Compounding

Compounding combines an ageless art with the latest medical knowledge and state-of-the-art technology, allowing specially trained professionals to prepare customized medications to meet each patient’s specific needs. Compounding is fundamental to the profession of pharmacy and was a standard means of providing prescription medications before drugs began to be produced in mass quantities by pharmaceutical manufacturers. The demand for professional compounding has increased as healthcare professionals and patients realize that the limited number of strengths and dosage forms that are commercially available do not meet the needs of many patients, and that these patients often have a better response to a customized dosage form that is "just what the doctor ordered".

Our compounding professionals can prepare unique dosage forms containing the best dose of medication for each individual. medications in dosage forms that are not commercially available, such as transdermal gels, troches, "chewies", and lollipops. medications free of problem-causing excipients such as dyes, sugar, lactose, or alcohol. combinations of various compatible medications into a single dosage form for easier administration and improved compliance. medications that are not commercially available. Quality Compounding Maximizes Therapeutic Outcomes The efficacy of any formulation is directly related to its preparation, which is why THE SELECTION OF YOUR COMPOUNDING PHARMACY IS CRITICAL.

Ongoing training for compounding pharmacists and technicians, state-of-the-art equipment, and high quality chemicals are essential. Experience and ingenuity are important factors as well. When tweaking a formula or developing a unique preparation, the compounding pharmacist must consider physical and chemical properties of both the active ingredient and excipients, solubility, tonicity, viscosity, and the most appropriate dosage form or device for administering the needed medication. Standard Operating Procedures should be in place, stability studies should be considered when compounding, and appropriate potency and sterility testing should be performed. Our compounding professionals can formulate suitable medications as sublingual drops, oral and nasal sprays, lollipops, rectal solutions and suppositories, and other customized dosage forms. Please contact us to discuss your patients’ needs.

Pain Management Compounding

  • Pain management is essential because even when the underlying disease process is stable, uncontrolled pain prevents patients from working productively, enjoying recreation, or taking pleasure in their usual roles in the family and society. Chronic pain may have a myriad of causes and perpetuating factors, and therefore can be much more difficult to manage than acute pain, requiring a multidisciplinary approach and customized treatment protocols to meet the specific needs of each patient.

    Optimal treatment may involve the use of medications that possess pain-relieving properties, including some antidepressants, anticonvulsants, antiarrhythmics, anesthetics, antiviral agents, and NMDA (N-methyl-D-aspartate) antagonists. NMDA-receptor antagonists, such as dextromethorphan and ketamine, can block pain transmission in dorsal horn spinal neurons, reduce nociception, and decrease tolerance to and the need for opioid analgesics. [Anesth Analg 2001 Mar;92(3):739-44]  By combining various agents which utilize different mechanisms to alter the sensation of pain, physicians have found that smaller concentrations of each medication can be used.

    Topical and transdermal creams and gels can be formulated to provide high local concentrations at the site of application (e.g., NSAIDs for joint pain), for trigger point application (e.g., combinations of medications for neuropathic pain), or in a base that will allow systemic absorption. Side effects associated with oral administration can often be avoided when medications are used topically. Studies suggest that there are no great restrictions on the type of drug that can be incorporated into a properly compounded transdermal gel.  When medications are administered transdermally, they are not absorbed through the gastrointestinal system and do not undergo first-pass hepatic metabolism.

    We work together with patient and practitioner to solve problems by customizing medications that meet the specific needs of each individual. Please contact our compounding pharmacist to discuss the dosage form, strength, and medication or combination that is most appropriate for your patient.
  • Neuropathic Pain

    • This study evaluated the effects of a topical gel containing baclofen 10 mg, amitriptyline HCL 40 mg, and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) on numbness, tingling, and pain caused by chemotherapy-induced peripheral neuropathy. The study concluded that BAK-PLO was well tolerated without evidence of systemic toxicity and appeared to somewhat improve symptoms of CIPN. Support Care Cancer. 2010 May 25. [Epub ahead of print]
      A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA.
      Barton DL et al. Click here to access the PubMed abstract of this article. Study subjects with moderate to severe peripheral neuropathic pain found that use of topical 2% amitriptyline/1% ketamine cream was well tolerated and was associated with long-term reduction in perceived pain. J Pain. 2005 Oct;6(10):644-9.
      Topical amitriptyline and ketamine in neuropathic pain syndromes: an open-label study.
      Lynch ME, Clark AJ, Sawynok J, Sullivan MJ. Click here to access the PubMed abstract of this article.
        Topical Clonidine for Diabetic Neuropathy A phase 2b double-blind, randomized, placebo-controlled clinical trial, showed that a topical clonidine 0.1% gel relieved pain in adults with painful diabetic neuropathy and no serious side effects were reported. http://www.hcplive.com/pain-management/articles/topical_ge_diabetic_neuropathy Accessed Aug 18, 2010   Amitriptyline/Ketamine Topical Cream for Treating Post-Herpetic Neuralgia (PHN)
        Combinations of synergistic drugs can be customized for the patient with chronic pain, and topical or transdermal formulations offer excellent alternatives, sometimes with fewer side effects compared to the same drugs when taken orally. A multicenter, double-blind, randomized, placebo controlled study was conducted to evaluate the efficacy and safety of amitriptyline 4%/ketamine 2% [NP-H] and amitriptyline 2%/ketamine 1% [NP-L] topical creams versus placebo in 251 PHN patients. NP-H was numerically superior to NP-L cream and placebo, and appears to be the optimal concentration for PHN treatment. Less than 5% of subjects who applied NP-H had detectable serum levels of amitriptyline or ketamine.
       
      This study was presented at the 2007 American Pain Society Annual Meeting, Poster #787
      http://www.ampainsoc.org/db2/abstract/view?poster_id=3208#787
      The following article discusses the use of topical ketamine 0.5% (5 mg/ml) gel, applied as a thin film two to three times daily over the skin where pain was severe. Topical ketamine reduced pain for patients with postherpetic neuralgia with no systemic side effects. Neurology 2003;60:1391-1392
      Topical ketamine treatment of postherpetic neuralgia
      No abstract available.  Click here to purchase the full article on line. The following randomized, double-blind, placebo-controlled study assessed the analgesic efficacy of topical administration of 3.3% doxepin hydrochloride, 0.025% capsaicin or a combination applied daily for 4 weeks in 200 adult patients with chronic neuropathic pain, and reported that all three preparations significantly reduced overall pain. Br J Clin Pharmacol 2000 Jun;49(6):574-9
      Topical application of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomized, double-blind, placebo-controlled study.
      Click here to access the PubMed abstract of this article.
  • Migraine

    • The following article concludes: A fixed combination of indomethacin 25 mg, prochlorperazine dimaleate 4 mg, and caffeine 75 mg is significantly more effective than sumatriptan in the acute treatment of migraine attacks versus sumatriptan 25 mg, both rectal suppositories. Headache. 2003 Sep;43(8):835-44
      Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine versus sumatriptan in acute treatment of multiple migraine attacks: a multicenter, randomized, crossover trial.
      Click here to access the PubMed abstract of this article.   The following article concludes: Oral therapy with a combination of LAS (equivalent to 900 mg ASA) and metoclopramide 10 mg was superior to placebo with therapeutic gains of 30% and 31% for the first treated attack, and was comparable to 100 mg sumatriptan. Funct Neurol. 2000;15 Suppl 3:196-201
      The effectiveness of combined oral lysine acetylsalicylate and metoclopramide (Migpriv) in the treatment of migraine attacks. Comparison with placebo and oral sumatriptan.
      Click here to access the PubMed abstract of this article.
  • NSAID Therapy

    • To avoid the risks of COX-2 inhibitors, our pharmacy can compound topically applied NSAIDs such as ibuprofen and ketoprofen. Topical NSAIDs have a safety profile which is superior to oral formulations. Topical NSAID administration offers the advantage of local, enhanced delivery to painful sites with a reduced incidence of systemic adverse effects. Topical preparations can be customized to contain a combination of medications to meet the specific needs of each patient.   This study concluded that topical NSAIDs, when used for treatment of pain resulting from strains, sprains or sports or overuse-type injuries, can provide good levels of pain relief without the systemic adverse events associated with oral NSAIDs. Cochrane Database Syst Rev. 2010 Jun 16; 6: CD007402.
      Topical NSAIDs for acute pain in adults.
      Massey T, Derry S, Moore RA, McQuay HJ. Click here to access the PubMed abstract of this article.

      "Topical non-steroidal anti-inflammatory drugs have a lower incidence of gastrointestinal adverse effects than the same drugs when they are taken orally. The low incidence of systemic adverse effects for topical NSAIDs probably results from the much lower plasma concentration from similar doses applied topically to those administered orally. Topical application of ibuprofen resulted in measurable tissue concentrations in deep tissue compartments, more than enough to inhibit inflammatory enzymes." BMJ. 1995 Jul 1;311(6996):22-6
      Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study. Free full text article available at bmj.com:
      http://bmj.bmjjournals.com/cgi/content/full/311/6996/22 This study concludes that topical NSAIDs have not been associated with renal failure. QJM. 1995 Aug;88(8):551-7
      Non-steroidal anti-inflammatory drugs and hospitalization for acute renal failure.
      Click here to access the PubMed abstract of this article. The following article concludes: "Topical non-steroidal anti-inflammatory drugs are effective in relieving pain in acute and chronic conditions." BMJ. 1998 Jan 31;316(7128):333-8
      Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs.
      Click here to access the PubMed abstract of this article. The following article reports "The systemic concentrations of ketoprofen have also been found to be 100 fold lower compared to tissue concentrations below the application site in patients undergoing knee joint surgery. Topically applied ketoprofen thus provides high local concentration below the site of application but lower systemic exposure." Pharm Res. 1996 Jan;13(1):168-72
      Percutaneous absorption of ketoprofen from different anatomical sites in man.
      Free full text article available at bmj.com:
      www.bmj.bmjjournals.com/cgi/content/full/316/7128/333 Sever disease is the most common cause of heel pain in pre-pubertal children. This inflammatory condition is a result of minor repetitive trauma and typically occurs during a growth spurt or at the beginning of a new sport season. A case report described the use of topical ketoprofen 10% gel to relieve pain and inflammation. Phys Ther. 2006 Mar;86(3):424-33
      Ketoprofen gel as an adjunct to physical therapist management of a child with Sever disease.
      Click here to access the PubMed abstract of this article.
  • Topical Anesthetics

    • This study suggests that due to its prompt analgesia, lack of systemic side effects, and convenience, xylocaine pump spray provides a significant improvement in posttraumatic peripheral neuropathy. Anesth Analg. 2009 Mar;108(3):987-91.
      The analgesic effect of a metered-dose 8% lidocaine pump spray in posttraumatic peripheral neuropathy: a pilot study.
      Kanai A, Segawa Y, Okamoto T, Koto M, Okamoto H. Click here to access the PubMed abstract of this article.
       
      A double-blind placebo-controlled crossover trial showed that in patients with Complex Regional Pain Syndrome (CRPS; also known as Reflex Sympathetic Dystrophy), topical application of ketamine 10% cream caused a reduction in allodynia, a most unpleasant aspect of this condition. This study shows promise for the use of topical ketamine as opposed to parenteral and oral forms which often result in undesirable side effects.
       
      Pain. 2009 Nov;146(1-2):18-25.
      Reduction of allodynia in patients with complex regional pain syndrome: A double-blind placebo-controlled trial of topical ketamine. Finch PM, Knudsen L, Drummond PD.
      Click here to access the PubMed abstract of this article.

       
      “Lidocaine lollipop is a promising form of local oropharyngeal anesthesia for EGD. Its use resulted in sparing the use of intravenous sedation. It is well tolerated and safe and may be particularly important in the elderly, patients with comorbidities, and office-based endoscopy. “
       
      Gastrointest Endosc. 2007 Oct;66(4):786-93.
      Lidocaine lollipop as single-agent anesthesia in upper GI endoscopy.
      Click here to access the PubMed abstract of this article.
        Topical piroxicam 0.5% gel was associated with fewer inflammatory side effects than was EMLA cream, because of its anti-inflammatory effect after the procedure. Lasers Med Sci. 2008 Aug 21. [Epub ahead of print]
      A clinical comparison of topical piroxicam and EMLA cream for pain relief and inflammation in laser hair removal.
      Click here to access the PubMed abstract of this article.
      The following article concludes: "LAT gel (4% lidocaine, 1:2000 adrenaline, 0.5% tetracaine) worked as well as TAC gel (0.5% tetracaine, 1:2000 adrenaline, 11.8% cocaine) for topical anesthesia in facial and scalp lacerations. Considering the advantages of a noncontrolled substance and less expense, LAT gel appears to be better suited than TAC gel for topical anesthesia in laceration repair in children." Pediatrics 1995 Feb;95(2):255-8
      Lidocaine adrenaline tetracaine gel versus tetracaine adrenaline cocaine gel for topical anesthesia in linear scalp and facial lacerations in children aged 5 to 17 years.
      Click here to access the PubMed abstract of this article.   The following article reported that a triple-anesthetic gel containing benzocaine, lidocaine, and tetracaine ("BLT") applied prior to treatment with a 532-nm KTP laser resulted in significantly lower pain scores than with 3 other topical anesthetics at 15, 30, 45, and 60 minutes after application. Cosmetic Dermatology 2003 Apr;16(4):35-7
      Topical Triple-Anesthetic Gel Compared With 3 Topical Anesthetics

  • Topical Opioids

    •   
      The discovery of peripheral opioid receptors has become the scientific basis for topical use of opioids in malignant and nonmalignant ulcers and oropharyngeal mucositis. A systematic review assessed the quality of published literature and examined whether topical opioids are effective in controlling pain in palliative care settings. Eighteen studies favored topical opioids in pain relief, but time to onset and duration of analgesia varied widely, perhaps due to variances in formulations. “N-of-1 trials should be encouraged for specific clinical circumstances.”
       
      J Pain Symptom Manage. 2009 May;37(5):913-7.
      Effectiveness of topical administration of opioids in palliative care: a systematic review.
      Click here to access the PubMed abstract of this article.  
      B&O Suppositories B&O Suppositories are used for relief of moderate to severe pain associated with rectal or bladder spasms that may occur postoperatively or secondary to cancer. Periodically, these have been on back order. When medications are not commercially available, call our compounding pharmacy. At Columbia- New York Presbyterian Hospital, physicians examined whether acetaminophen with codeine administered per rectum is an effective alternative for pain control compared with oral administration after an adenotonsillectomy. Equivalent postoperative pain control was achieved with suppositories and oral medication, with few side effects and good tolerance. Furthermore, many parents preferred the suppositories to oral medication in maintaining postoperative pain control because of ease of administration. Laryngoscope 2006 Aug;116(8):1485-8
      Comparison of oral versus rectal administration of acetaminophen with codeine in postoperative pediatric adenotonsillectomy patients.
      Click here to access the PubMed abstract of this article.




      The use of topical morphine gel is reported in two children with epidermolysis bullosa, where acute inflammatory pain is a major symptom and where effective analgesia is a major clinical problem. Arch Dis Child. 2004 Jul;89(7):679-81
      Peripheral opioids in inflammatory pain.
      Click here to access the PubMed abstract of this article.  
        Morphine sulfate 10 mg in Intrasite gel was applied topically to skin ulcers of hospice inpatients. The topical morphine was not absorbed in the majority of patients, suggesting any analgesic effect was mediated locally rather than systemically. J Pain Symptom Manage. 2004 May;27(5):434-9
      The bioavailability of morphine applied topically to cutaneous ulcers.
      Click here to access the PubMed abstract of this article.
  • Iontophoresis / Phonophoresis

    • Iontophoresis and phonophoresis are technologies that are capable of enhancing drug penetration through the skin. Phonophoresis uses ultrasonic waves to transmit molecules of drug through the skin, as opposed to iontophoresis, which uses low level electric current. Both techniques are used to treat inflammatory conditions such as arthritis, plantar fasciitis, tendonitis, bursitis, and carpal tunnel syndrome.

      Iontophoresis: Many ionic drugs are available including several antivirals, various antibiotics, and other specific drugs. Iontophoresis of ionized drugs provided a 20-60 fold increase in penetration over topical application. Examples of successful applications of iontophoresis include:
      •    treatment of inflammation/pain of muscles and tendons, including the Achilles tendon
      •    rapid, noninvasive local anesthesia, particularly for children
      •    relief of heel pain from bone spurs
      •    controlling the pain of tennis elbow
      •    relief of pain from rheumatoid arthritis of the knee
      •    relief of pain associated with plantar fasciitis
      •    improvement of jaw function in patients with temporomandibular joint (TMJ) disorders
      •    management of hip pain in patients with sickle cell disorders (SCD)
      •    an alternative to steroid injections for therapy of Carpal Tunnel Syndrome
      •    treatment for scar and tendon adhesions

      Phonophoresis (or sonophoresis) combines ultrasound with topical drug therapy to achieve therapeutic drug concentrations at target sites below the skin. A cream or gel containing medications such as corticosteroids, local anesthetics, electrolytes, or antibiotics is applied to the treatment area and then massaged with a transducer head. The technique has been widely used in sports medicine since the 1960s by podiatrists, orthopedists, and physical therapists.

      The method of preparation and quality of ingredients used for solutions or gels for iontophoresis or phonophoresis are critical to the success of the therapy and minimizing side effects.

      Am J Sports Med. 1997 May-Jun;25(3):312-6
      Treatment of plantar fasciitis by iontophoresis of 0.4% dexamethasone. A randomized, double-blind, placebo-controlled study.
      Click here to access the PubMed abstract of this article.
  • Examples of Compound Medications

    • All formulations are customized per prescription to meet the unique needs of each patient. Please call us to discuss the dosage form, medication, and strength which are most appropriate for your patient.
      • Ketoprofen topical or transdermal gel
      • Ketamine transdermal gel
      • Ketamine/Ketoprofen/Gabapentin transdermal gel
      • Lidocaine/Prilocaine topical gel
      • Triple-Anesthetic gel - benzocaine/lidocaine/tetracaine (“BLT”)
      • Gabapentin/Clonidine in PLO (Pluronic Lecithin Organogel)
      • Piroxicam tablet triturates
      • Ibuprofen suppositories
      • Ketoprofen/Cyclobenzaprine topical gel

Hormone Replacement Therapy for Women

  • Dr. Kent Holtorf is a leading authority in the field of hormone replacement therapy, and is also a board examiner for the American Board of Anti-Aging Medicine (ABAAM). Dr. Holtorf talked to Sunday Magazine about HRT on February 15, 2009. Click here to play or download the discussion. Click here to read Dr. Holtorf’s article about the benefits of customized Hormone Replacement Therapy. Protect your right to free prescribing and every patient’s access to customized medications. Visit www.savemymedicine.org for more information.
    Structural differences exist between human, and synthetic and animal hormones. In order for a replacement hormone to fully replicate the function of hormones which were originally naturally produced and present in the human body, the chemical structure must exactly match the original.  There are significant differences between hormones that are natural to humans and synthetic or horse preparations. Side chains can be added to a naturally-occurring hormone to create a synthetic drug that can be patented by a manufacturer. A patented drug can be profitable to mass produce, and therefore a drug company can afford to fund research as to the medication's use and effectiveness. However, naturally-occurring substances can not be patented, so scientific studies are less numerous on natural hormones, because medical research is usually funded by drug companies. Natural hormones include estrone (E1), estradiol (E2), progesterone, testosterone, dehydroepiandrosterone (DHEA), and pregnenolone. Our compounding specialists work together with patients and prescribers to provide customized hormone replacement therapy that provides the needed hormones in the most appropriate strength and dosage form to meet each woman's specific needs. Hormone replacement therapy should be initiated carefully after a woman's medical and family history has been reviewed. Every woman is unique and will respond to therapy in her own way. Close monitoring and medication adjustments are essential.
  • Research

    • The findings of numerous studies on hormone replacement therapy (HRT) conflict and, as a result, have raised serious questions regarding the appropriateness of HRT. Hormone replacement is an approved therapy for relief from moderate to severe hot flashes and symptoms of vulvar and vaginal atrophy. Numerous studies have confirmed that estrogen replacement decreases the risk of colon cancer, estrogen and progesterone decrease fracture risk, and various hormones increase energy levels and enhance libido. Reputable sources offer conflicting reports regarding issues such as memory, Alzheimer's disease, and stroke. With the exception of the Postmenopausal Estrogen/Progestin Intervention (PEPI) study, major studies have either failed to distinguish among types and dosages of HRT used in the study, or examined only the use of synthetic HRT preparations (as in the case of the Women's Health Initiative). The Women's Health Initiative (WHI) study was designed to identify the potential risks and benefits of HRT. The estrogen-progestin portion of the clinical trial was stopped in 2002 after results showed that a synthetic hormone combination containing conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) increased the women's risks of developing invasive breast cancer, heart disease, stroke, and pulmonary embolism. The data and safety monitoring board concluded that the risks outweighed the evidence of benefit for fractures and colon cancer. Utilizing data from the WHI, researchers later concluded that synthetic CEE plus MPA does not improve mental functioning and may increase the risk of dementia in women over age 65. They suggest these hormones increase the risk of stroke, which is known to increase the risk of dementia. With regard to the risk of dementia, typical HRT users are in their 50s and the WHI study focused on women aged 65 and over, who have a higher risk for dementia. The "estrogen-only" portion of the WHI study was halted in March 2004 after analysis of data suggested that synthetic CEE alone had no impact either way on heart disease (the main focus of the study), but may increase the risk of stroke. Many patients and medical professionals are unaware of the availability of alternatives. In reality, women's experiences and clinical outcomes of HRT differ vastly depending on the dose, dosage form, and route of administration, and also the type of hormone that is used. As a result of concerns and doubts generated by studies that use synthetic hormones, many women who could substantially benefit from customized hormone replacement may never have the opportunity. Published research delineating the differences between natural and synthetic HRT is now more abundant, but studies of natural HRT will probably never be as plentiful as those dealing with patented synthetic hormones. Our pharmacy welcomes your questions.
  • References

    • Reviewers conclude that the choice of transdermal route of administration of estradiol and the use of natural progesterone might offer significant benefits and added safety. Maturitas. 2008 Jul-Aug;60(3-4):185-201. Epub 2008 Sep 5.
      Could transdermal estradiol + progesterone be a safer postmenopausal HRT? A review.
      L'hermite M, Simoncini T, Fuller S, Genazzani AR. Click here to access the PubMed abstract of this article.
      Literature reviewers conclude that oral postmenopausal estrogen replacement is associated with an increased risk for venous thromboembolism. The review did not address transdermal estrogen therapy. Ann Intern Med. 2002 May 7;136(9):680-90.
      Postmenopausal estrogen replacement and risk for venous thromboembolism: a systematic review and meta-analysis for the U.S. Preventive Services Task Force.

      Miller J, Chan BK, Nelson HD. Click here to access the PubMed abstract of this article. The use of oral estrogen plus progestin hormone therapy in postmenopausal women was associated with doubling the risk of development of venous thrombosis. JAMA. 2004 Oct 6;292(13):1573-80.
      Estrogen plus progestin and risk of venous thrombosis.
      Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty BM, Stafford RS, Sidney S, Rosendaal FR; Women's Health Initiative Investigators. Click here to access the PubMed abstract of this article. According to this study's findings, oral postmenopausal estrogen/progesterone replacement may increase the risk of venous thromboembolism, but the risk of developing deep vein thrombosis (DVT) or pulmonary thromboembolism (TE) with transdermal estrogen therapy is negligible in comparison. Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):3071-8.
      Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial.
      Scarabin PY, Alhenc-Gelas M, Plu-Bureau G, Taisne P, Agher R, Aiach M. Click here to access the PubMed abstract of this article. The PEPI trial demonstrated that micronized progesterone is as effective as the synthetic progestin medroxyprogesterone acetate (MPA) in preventing endometrial hyperplasia.
      JAMA. 1995 Jan 18;273(3):199-208.
      Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. Click here to access the PubMed abstract of this article. Mark E. Johnson et al of Massachusetts Institute of Technology finds that: “Steroids are an important class of pharmacologically active drugs which have been found to be well suited for transdermal delivery.” Steroid hormones, including (in increasing order of permability) estriol, estradiol, testosterone, pregnenolone, progesterone, and estrone, are low molecular weight, highly lipophyllic molecules, therefore, good candidates for absorption across the skin. J Pharm Sci. 1995 Sep;84(9):1144-6.
      Permeation of steroids through human skin.
      Johnson ME, Blankschtein D, Langer R. Click here to access the PubMed abstract of this article. Stanczyk et al. of Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, report: "antiproliferative effects on the endometrium have been demonstrated with progesterone creams when circulating levels of progesterone are low. Thus, effects of topical progesterone creams on the endometrium should not be based on serum progesterone levels, but on histologic examination of the endometrium. Despite the low serum progesterone levels achieved with the creams, salivary progesterone levels are very high, indicating that progesterone levels in serum do not necessarily reflect those in tissues" Menopause. 2005 Mar;12(2):232-7.
      Percutaneous administration of progesterone: blood levels and endometrial protection.
      Stanczyk FZ, Paulson RJ, Roy S. Click here to access the PubMed abstract of this article.
      “These findings suggest that the choice of the progestagen component in combined HRT is of importance regarding breast cancer risk; it could be preferable to use progesterone.” Breast Cancer Res Treat. 2008 Jan;107(1):103-11. Epub 2007 Feb 27.
      Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study.
      Fournier A, Berrino F, Clavel-Chapelon F. Click here to access the PubMed abstract of this article. Ovarian androgens normally protect mammary epithelial cells and the addition of testosterone (not METHYLtestosterone) to conventional hormone therapy for postmenopausal women does not increase and may indeed reduce the hormone therapy-associated breast cancer risk-thereby returning the incidence to the normal rates observed in the general, untreated population. Menopause. 2004 Sep-Oct;11(5):531-5.
      Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy.
      Dimitrakakis C, Jones RA, Liu A, Bondy CA.
      Developmental Endocrinology Branch, National Institutes of Health Click here to access the PubMed abstract of this article.   Chang et al. studied influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo and reported that progesterone decreases estrogen-induced breast cell proliferation by 400%.

      Fertil Steril. 1995 Apr;63(4):785-91.
      Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo.
      Chang KJ, Lee TT, Linares-Cruz G, Fournier S, de Ligniéres B.
      Click here to access the PubMed abstract of this article. According to Fitzpatrick et al "A micronized progesterone-containing HRT regimen offers the potential for improved QOL as measured by improvement of menopause-associated symptoms."
      J Womens Health Gend Based Med. 2000 May;9(4):381-7.
      Comparison of regimens containing oral micronized progesterone or medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey.
      Fitzpatrick LA, Pace C, Wiita B. Click here to access the PubMed abstract of this article.
      While none of the hormone treatments used in this study had a detectable effect on mood, Cummings et al conclude "the lesser side effects of the micronized progesterone-containing regimen suggest that some women may prefer it to an MPA-containing regimen." Menopause. 2002 Jul-Aug;9(4):253-63.
      Comparison of physical and emotional side effects of progesterone or medroxyprogesterone in early postmenopausal women.
      Cummings JA, Brizendine L.
      Click here to access the PubMed abstract of this article. “This study demonstrates that the daily administration of a combination of micronized E2 and progesterone results in symptomatic improvement, minimal side effects, an improved lipid profile, and amenorrhea without endometrial proliferation or hyperplasia in menopausal women." Obstet Gynecol. 1989 Apr;73(4):606-12.
      Menopausal hormone replacement therapy with continuous daily oral micronized estradiol and progesterone.
      Hargrove JT, Maxson WS, Wentz AC, Burnett LS. Click here to access the PubMed abstract of this article.   This trial indicates that the use of natural progesterone does not increase the risk of breast cancer, as opposed to synthetic progestins. Fertil Steril. 1998 May;69(5):963-9.
      Estradiol and progesterone regulate the proliferation of human breast epithelial cells.
      Foidart JM, Colin C, Denoo X, Desreux J, Béliard A, Fournier S, de Lignières B. Click here to access the PubMed abstract of this article. A growing body of medical literature suggests that various progestogens are not equivalent. Furthermore, trials indicate that the use of natural progesterone alone or combined with estradiol does not increase the risk of breast cancer while use of medroxyprogesterone acetate or norethisterone acetate stimulate proliferation of breast cancer cells. Maturitas. 2003 Dec 10;46 Suppl 1:S55-8.
      Differential effects of progestogens on breast cancer cell lines.
      Franke HR, Vermes I. Click here to access the PubMed abstract of this article. Estrogen deficiency during menopause contributes to the development of abdominal obesity and insulin resistance, and could represent a major step in the development of diabetes in women. In a 2006 meta-analysis of 107 trials, Salpeter et al. concluded that appropriate HRT reduces abdominal obesity, insulin resistance, new-onset diabetes, lipids, pro-inflammatory adhesion molecules and pro-coagulant factors in women without diabetes. Diab Obes Metab 2006;8:538–54.
      Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women.
      Salpeter SR, Walsh JME, Ormiston TM, Greyber E, Buckley NS, Salpeter EE. Click here to access the PubMed abstract of this article. Glucose metabolism and insulin sensitivity can be improved by estrogen replacement therapy but the addition of an androgenic progestin, such as MPA or NETA, may reduce the beneficial effect of estrogens. While MPA is known to increase insulin resistance and impair glucose tolerance, natural progesterone does not. Maturitas 2008;59:249–58.
      Effects of estradiol and norethisterone on lipids, insulin resistance and carotid flow.
      Fernandes CE, Pompei LM, Machado RB, Ferreira JA, Melo NR, Peixoto S. Click here to access the PubMed abstract of this article.
      Neuroprotective effects of progesterone include prevention and reversal of age-dependent changes and dysfunction. Some of these actions, particularly those mediated by conversion to neurosteroids such as allopregnanolone, may not be shared by synthetic progestins since progesterone behaves differently in the brain than synthetic progestins (particularly MPA), through direct effects, as well as indirectly through effects on the vascular endothelium. This may have important implications for the effective use of HRT in the maintenance of neuronal function during menopause and aging and for protection against neurodegenerative diseases. Endocr Rev. 2007 Jun;28(4):387-439. Epub 2007 Apr 12.
      Novel perspectives for progesterone in hormone replacement therapy, with special reference to the nervous system.
      Schumacher M, Guennoun R, Ghoumari A, Massaad C, Robert F, El-Etr M, Akwa Y, Rajkowski K, Baulieu EE. Click here to access the PubMed abstract of this article. This study of the aftermath of the Women’s Health Initiative (WHI) found that 70% of women who were taking hormone therapy (conjugated equine estrogens and medroxyprogesterone acetate) discontinued it, and 26% of women lost confidence in medical recommendations in general. Many women have sought alternatives in the form of compounded bio-identical hormones. Womens Health Issues. 2005 Jul-Aug;15(4):187-95.
      After the Women's Health Initiative: decision making and trust of women taking hormone therapy.
      Schonberg MA, Davis RB, Wee CC. Click here to access the PubMed abstract of this article.   As women age and estrogen levels decline, cutaneous changes such as dryness, atrophy, fine wrinkling and poor healing occur. This article reviews the effects of declining estrogen levels on the skin and the effects of estrogen supplementation. J Am Acad Dermatol. 2005 Oct;53(4):555-68
      Estrogen and skin: the effects of estrogen, menopause, and hormone replacement therapy on the skin.
      Hall G, Phillips TJ. Click here to access the PubMed abstract of this article. Ninety-seven percent of the 189 women participating in this study experienced varying degrees of symptom control, but complications described with traditional HRT did not develop in these patients using bio-identical hormones. The findings of this study point out a need for larger controlled trials of bio-identical hormones in the management of menopause. Gynecol Endocrinol. 2009 Aug 19:1-5. [Epub ahead of print]
      Natural Hormone Therapy for Menopause
      Click here to access the PubMed abstract of this article.

      Transdermal estradiol was similarly effective as raloxifene in preventing bone loss at the lumbar spine, was well tolerated, and had no clinically significant effect on endometrium or breast density. Menopause. 2009 May-Jun;16(3):559-65.
      Effect of microdose transdermal 17beta-estradiol compared with raloxifene in the prevention of bone loss in healthy postmenopausal women: a 2-year, randomized, double-blind trial.
      Schaefers M, Muysers C, Alexandersen P, Christiansen C. Click here to access the PubMed abstract of this article. The objective of this analysis was to determine the effects of conjugated equine estrogens/medroxyprogesterone acetate on breast cancer mortality after a total mean follow-up of 11.0 years, through August 14, 2009. The analysis did not track or review patients taking bio-identical estrogens (estriol, estradiol) or progesterone. JAMA. 2010 Oct 20;304(15):1684-92.
      Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women.
      Chlebowski RT et al; WHI Investigators. Click here to access the PubMed abstract of this article. Breast cancer incidence and mortality is increased in women using conjugated equine estrogens and medroxyprogesterone acetate (a synthetic progestin). Lancet. 2003 Aug 9;362(9382):419-27.
      Breast cancer and hormone-replacement therapy in the Million Women Study.
      Beral V; Million Women Study Collaborators. Click here to access the PubMed abstract of this article. In this 2005 review of clinical studies comparing synthetic progestins to natural progesterone, Campagnoli et al concluded: "The balance of the in vivo evidence is that progesterone does not have a cancer-promoting effect on breast tissue. ...We therefore suggest that when HRT is indicated, preparations containing progesterone and not a synthetic progestin should be used, according to a sequential or cyclic-combined regimen. In this way the risk of endometrial cancer is minimized without increasing the risk of BC [breast cancer]." J Steroid Biochem Mol Biol. 2005 Jul;96(2):95-108.
      Progestins and progesterone in hormone replacement therapy and the risk of breast cancer.
      Campagnoli C, Clavel-Chapelon F, Kaaks R, Peris C, Berrino F. Click here to access the PubMed abstract of this article. In this 2005 clinical trial, Fournier et al compared synthetic progestins to the natural progesterone and reported: "The risk was significantly greater… with HRT containing synthetic progestins than with HRT containing micronized progesterone, the relative risk being 1.4 and 0.9, respectively." Int J Cancer. 2005 Apr 10;114(3):448-54.
      Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort.
      Fournier A, Berrino F, Riboli E, Avenel V, Clavel-Chapelon F. Click here to access the PubMed abstract of this article. This large French study raises the possibility that micronized progesterone, when combined with human estrogens such as estradiol or estriol, may have less impact on breast cancer mortality. J Clin Oncol. 2008 Mar 10;26(8):1260-8.
      Use of different postmenopausal hormone therapies and risk of histology- and hormone receptor-defined invasive breast cancer.
      Fournier A, Fabre A, Mesrine S, Boutron-Ruault MC, Berrino F, Clavel-Chapelon F. Click here to access the PubMed abstract of this article. Studies of women using HRT, including either micronized progesterone or synthetic medroxyprogesterone acetate (MPA), compared efficacy, patient satisfaction and quality of life. Women reported greater satisfaction, fewer side effects and improved quality of life when they were switched from synthetic progestins to micronized progesterone. J Womens Health Gend Based Med. 2000 May;9(4):381-7.
      Comparison of regimens containing oral micronized progesterone or medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey.

      Fitzpatrick LA, Pace C, Wiita B. Click here to access the PubMed abstract of this article. Transdermal Progesterone and Estrogen Improve Blood Pressure in Menopausal Women with High Stress
       
      Dr. Kenna Stephenson of the University of Texas Health Science Center has shown luteal phase levels of progesterone and estrogen administered via transdermal delivery improve blood pressure in perimenopausal and menopausal women with prehypertension and stress related to work or home.

      http://sanjay-kapur.blogspot.com/2009_09_01_archive.html

      Progesterone vs Synthetic Progestins: Clinical Options

      James A. Simon, MD, Clinical Professor, George Washington University, Washington, DC, notes: “Clinicians have numerous options in selecting a progestogen for the individual patient. The specific properties of progesterone or synthetic progestins may result in differing side-effect profiles for individual patients. Route of administration also offers differing systemic or local effects that should be considered for some uses and specific patients.” Differences exist among the exogenous progestogens, which include both natural progesterone and synthetic and semi-synthetic progestins, drugs which are “structurally related - but are not identical - to either progesterone or testosterone... Progesterone and progestins differ not only in their structure, but also in their potency, as determined by standard bioassays... Additionally, studies often do not evaluate the effects of progestogens on specific organs or compare the side-effect profiles of individual agents. These characteristics constitute an important, although rarely discussed, aspect of the differences among progestogens.” The Journal of Family Practice 2007 Feb; 2(7):S3-S5
       

      Comparison of Different Routes of Progesterone Administration for Luteal Phase Support in Infertility Treatment
       
      Different routes of natural progesterone supplementation have been tried as luteal phase support in infertility treatments. Orally administered progesterone is rapidly metabolized in the gastrointestinal tract and oral administration has proven to be inferior to intramuscular (IM) and vaginal routes. Progesterone IM achieves serum progesterone values that are within the range of luteal phase and results in sufficient secretory transformation of the endometrium and satisfactory pregnancy rates. The comparison between IM and vaginal progesterone has led to controversial results as regards the superiority of one or the other in inducing secretory endometrial transformation. However, there is increasing evidence in the literature to favor the use of vaginal progesterone. Vaginally administered progesterone achieves adequate endometrial secretory transformation but its pharmacokinetic properties are greatly dependent on the formulation used. After vaginal progesterone application, discrepancies have been detected between serum progesterone values and histological endometrial features. Vaginally administered progesterone results in adequate secretory endometrial transformation, despite serum progesterone values lower than those observed after IM administration, even if they are lower than those observed during the luteal phase of the natural cycle. This discrepancy is indicative of the first uterine pass effect and therefore of a better bioavailability of progesterone in the uterus, with minimal systematic undesirable effects.
       
      Hum Reprod Update. 2000 Mar-Apr;6(2):139-48.
      Comparison between different routes of progesterone administration as luteal phase support in infertility treatments.
      Click here to access the PubMed abstract of this article.


      Uses of Progesterone in Clinical Practice
       
      Progesterone is the natural progestogen produced by the corpus luteum during the luteal phase. It is absorbed when administered orally, but is greater than 90% metabolized during the first hepatic pass. This greatly limits the efficacy of once-daily administration and also results in “unphysiologically” high levels of progesterone metabolites which can cause dizziness and drowsiness to the point of preventing the operation of a motor vehicle. Synthetic progestins, such as medroxyprogesterone acetate and norethindrone acetate, have been specifically designed to resist enzymatic degradation and remain active after oral administration. However, according to Drs. Warren and Shantha of the Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, these synthetic progestins exert undesirable effects on the liver and often cause severe psychological side effects. Transvaginal administration of progesterone is a practical non-oral route available for administering progesterone. Early experience was gained with vaginal suppositories. The clinical acceptance of progesterone administered as a vaginal gel was enhanced by the characteristics of a polycarbophil-based gel, which conveys controlled and sustained-released properties. Investigations have shown that because of local direct vagina-to-uterus transport, which results in a preferential uterine uptake of progesterone, progesterone vaginal gel given in conjunction with physiological amounts of estradiol produces endometrial changes similar to those seen in the luteal phase, despite plasma progesterone levels that remain subphysiologic. Studies in infertility show that vaginal progesterone in this form allows secretory transformation of the endometrium and the development of pregnancy despite providing low systemic progesterone concentrations. Fewer side effects occur when vaginal progesterone is used for hormone replacement than are typically encountered with progestins and oral progesterone.
       
      Int J Fertil Womens Med. 1999 Mar-Apr;44(2):96-103
      Uses of progesterone in clinical practice.
      Click here to access the PubMed abstract of this article.
           Pregnenolone – The Parent Hormone Affecting Memory, Sleep, Anxiety, and Mood
       
      • Pregnenolone is at the top of the hormone cascade, the “parent hormone” from which neurosteroids and sex hormones are formed, and gives rise to important “neurohormones” that affect learning, memory, mood, sleep, and many other functions.
      • Pregnenolone may relieve anxiety, help to fight depression, and reduce symptoms of withdrawal from nicotine and alcohol addiction.
      • Hormone levels naturally decline with advancing age. People with lower pregnenolone levels are more likely to suffer from memory deficits, mood disorders, and even some mental illnesses.
      • Pregnenolone and other neuroactive steroids can protect brain cells against the long-term damage that can lead to Alzheimer’s disease and other forms of dementia.
       
         The conversion of cholesterol to pregnenolone constitutes the first of many steps in the synthesis of some of the body’s key hormones, including dehydroepiandrosterone (DHEA), testosterone, progesterone, estrogen, and cortisol. Pregnenolone’s metabolites fulfill a myriad of essential roles in the body, from stimulating memory via excitatory pathways to easing anxiety through inhibitory mechanisms.1,2
       
         Pregnenolone has vast potential for maintaining healthy cognitive function and may be “the most potent memory enhancer yet reported.”3 Alzheimer’s disease patients have lower levels of pregnenolone, allopregnanolone (a pregnenolone metabolite) and DHEA-sulfate (DHEAS) in all the main memory-related areas of their brains, compared with control patients. Furthermore, the brains of patients with the highest neurosteroid levels display the lowest collections of the destructive amyloid-beta proteins. 4,5,6
       
         Researchers have also shown that pregnenolone increases brain levels of acetylcholine, a key neurotransmitter required for optimal brain function, which is deficient in patients with Alzheimer’s disease. 7 Acetylcholine is not only vital for thought and memory, it is also involved in controlling sleep cycles, especially the phase of sleep that is associated with memory (called paradoxical sleep or the random eye movement [REM] phase).
       
         Neurosteroids are known to affect anxiety in humans.8 Researchers from the University of California in San Francisco performed two studies of pregnenolone and anti-anxiety medications and concluded that pregnenolone, taken as a supplement while using an anti-anxiety medication, could reduce many adverse effects of the medication, such as sedation and memory impairment. 9
       
         There is increasing evidence that lower levels of pregnenolone are associated with a variety of mental health conditions beyond anxiety, including depression, phobias, and even schizophrenia.10,11,12,13 One study revealed that schizophrenic patients with the lowest levels of pregnenolone were also most likely to have high levels of anxiety.14
       
         Pregnenolone and other neurosteroids have also been shown to counteract the anxiety-like behavior that is associated with nicotine or morphine withdrawal, due to their potent effects on sigma receptors, and may offer relief to individuals seeking to overcome these addictions. 15,16 Please click on the links below for more information.
      http://www.lef.org/magazine/mag2007/nov2007_report_pregnenolone_01.htm    
      1 Pharmacol Biochem Behav. 2006 Aug;84(4):555-67.
      2 Jpn J Pharmacol. 1999 Oct;81(2):125-55.
      3 Proc Natl Acad Sci USA. 1995 Nov 7;92(23):10806-10.
      4 Prog Neurobiol. 2003 Sep;71(1):3-29.
      5 J Clin Endocrinol Metab. 2002 Nov;87(11):5138-43.
      6 Biol Psychiatry. 2006 Dec 15;60(12):1287-94.
      7 Prog Neurobiol. 2003 Sep;71(1):43-8.
      8 Neuropsychobiology. 2004;50(1):6-9.
      9 Psychoneuroendocrinology. 2004 May;29(4):486-500.
      10 Prog Neuropsychopharmacol Biol Psychiatry. 2005 Feb;29(2):169-92.
      11 Neuropsychopharmacology. 2005 Jun;30(6):1181-6.
      12 Pharmacol Biochem Behav. 2006 Aug;84(4):644-55.
      13 Am J Psychiatry. 2002 Jan;159(1):145-7.
      14 Eur Neuropsychopharmacol. 2007 Apr;17(5):358-65.
      15 J Pharmacol Sci. 2006 Feb;100(2):93-118.
      16 Brain Res Brain Res Rev. 2001 Nov;37(1-3):116-32.
      Researchers at The University of Texas at Tyler, led by Kenna Stephenson, M.D., showed that use of progesterone in a topical cream (20 mg per day) relieved menopausal symptoms. In addition, in a subpopulation of hypercortisolemic women, nocturnal cortisol levels were reduced to normal range while they were using the progesterone cream as compared to placebo. Stress activates cortisol, and an abnormal cortisol pattern has been associated with an increased risk of heart attacks, cancer, obesity and other diseases. Blood 2004 Nov; 104(11):16
      Progesterone Relieves Menopausal Symptoms and Normalizes Nocturnal Cortisol Levels


      The French E3N-EPIC cohort study assessed the risk of breast cancer associated with HRT use in 54,548 postmenopausal women.
       
      Breast Cancer Res Treat. 2008 Jan;107(1):103-11
      Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study.
      Click here to access the PubMed abstract of this article.


      The neuroprotective and promyelinating effects of progesterone are promising not only for preventing, but also for reversing, age-dependent changes and dysfunctions. Endocr Rev. 2007 Jun;28(4):387-439.
      Novel perspectives for progesterone in hormone replacement therapy, with special reference to the nervous system.
      Click here to access the PubMed abstract of this article.

      Clinical evidence shows that, during menopause, estrogen withdrawal gives rise to modifications in mood, behavior and cognition and that estrogen administration is able to improve mood and cognitive efficiency in post-menopause. There may be a critical period of time for HRT-related neuroprotection, and early initiation of estrogen therapy may be necessary for cognitive benefit.
       
      Hum Reprod Update. 2007 Mar-Apr;13(2):175-87
      Estrogen, cognition and female ageing.
      Click here to access the PubMed abstract of this article.

      J Clin Endocrinol Metab. 2006 Jan;91(1):136-44.
      Pharmacokinetics of Testosterone Gel in Healthy Postmenopausal Women
      Click here to access the PubMed abstract of this article. Absorption and Efficacy of Multiple Hormones Delivered in a Single Cream This study is the first documenting systemic absorption of multiple hormones by both saliva and blood as well as improvement of health-related quality of life. Gynecol Obstet Invest. 2008 Apr 29;66(2):111-118.
      Click here to access the PubMed abstract of this article.   New research from the Women's Health Initiative Memory Study (WHIMS) links the use of hormone replacement therapy (HRT) before the age of 65 years to a reduced risk of all-cause dementia and Alzheimer's disease (AD) in women. At the American Academy of Neurology’s 59th Annual Meeting, researchers presented an analysis that showed early HRT use was associated with a 46% overall reduction in dementia risk and a 64% reduction in AD. WHIMS also included 2 studies that looked at cognitive outcomes and HRT in women over 65 years old. At an average 5-year follow-up, both the conjugated equine estrogens plus medroxyprogesterone acetate (CEE + MPA) and the CEE-alone trials showed conjugated estrogens, with or without MPA, increased dementia risk when therapy was initiated after age 65 years. In the CEE + MPA trial the risk doubled, while in the CEE-alone trial there was about a 50% increased risk. There is evidence from animal models suggesting estrogen at an earlier age may be beneficial, and these results are intriguing because they seem to support that evidence.
       
      While studies describe the therapies used in the WHI as “estrogen with or without progesterone”, the WHI actually used only synthetic CEE and MPA (which is chemically different than progesterone). HRT Before Age 65 May Decrease Risk of Dementia and Alzheimer’s Disease 
      American Academy of Neurology 59th Annual Meeting: Abstract S31.004. April 28 – May 5, 2007
      Click here to access the Medscape article. (accessed April 4, 2008)
      Progesterone Therapy for Catamenial Epilepsy
       
      Catamenial epilepsy refers to seizures that occur or worsen around menstruation. Researchers at North Carolina State University evaluated the hypothesis that neurosteroid "replacement" is an effective and a rational therapy for catamenial epilepsy. It is well known that progesterone possesses anticonvulsant properties. The clustering of seizures around the beginning of menstruation corresponds with a significant drop in the levels of progesterone circulating in the body and an increase in the estrogen:progesterone ratio. Recent studies have shown that progesterone is metabolized to the neurosteroid allopregnanolone which plays a crucial role in seizure protection. Declining levels of allopregnanolone, which occur during the menstrual cycle, can provoke seizures. “Cyclic natural progesterone use has been demonstrated as an effective treatment for catamenial and non-catamenial seizures in women. Progesterone is efficiently absorbed after oral administration as lozenges, and rectal administration as suppositories.” Progesterone was given at 100 to 200 mg, t.i.d. on days 15 to 28 of the menstrual cycle. In a 3 month investigation of cyclic natural progesterone therapy, 23 of 25 (92%) women continued on the same AED and progesterone protocol and continued to have a very substantial (62% to 74%) reduction in seizure frequency. Epilepsy Behav. 2008 Mar 16 [Epub ahead of print]
      Click here to access the PubMed abstract of this article.

      Seizure. 2008 Mar;17(2):176-80.
      Click here to access the PubMed abstract of this article.

      Indian Journal of Pharmacology 2005; 37(5):288-293
      Click here to access this article.

      Neurology 1995;45:1660-2
      Click here to access the PubMed abstract of this article.

      Neurology 1999;52:1917-8
      Click here to access the PubMed abstract of this article.  
      The Women's Health Initiative Memory Study (WHIMS) links the use of hormone replacement therapy (HRT) before the age of 65 years to a reduced risk of all-cause dementia and Alzheimer's disease (AD) in women. AmericanAcademyof Neurology 59th Annual Meeting: Abstract S31.004.
      April 28 - May 5, 2007 Click here to read a Medscape article on this topic.

        The following finding that conjugated equine estrogen was associated with venous thrombotic risk may have implications for the choice of hormones in perimenopausal and postmenopausal women. JAMA. 2004 Oct 6;292(13):1581-7
      Esterified estrogens and conjugated equine estrogens and the risk of venous thrombosis.
      Click here to access the PubMed abstract of this article.     These observations suggest that the addition of testosterone to conventional hormone therapy for postmenopausal women does not increase and may indeed reduce the hormone therapy-associated breast cancer risk-thereby returning the incidence to the normal rates observed in the general, untreated population. Menopause. 2004 Sep-Oct;11(5):531-5
      Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy.
      Click here
      to access the PubMed abstract of this article.     The pharmacodynamic differences of testosterone and methyltestosterone are briefly reviewed in the context of choice for individualized clinical use. Mayo Clin Proc. 2004 Apr;79(4 Suppl):S8-13
      Hot flashes and androgens: a biological rationale for clinical practice.
      Click here
      to access the PubMed abstract of this article.     The results of this study suggest a significant reduction in the incidence of type 2 diabetes in our population of non-obese, healthy postmenopausal women who used transdermal 17-beta-estradiol. This could suggest that, in some women, the estrogen deficiency that occurs after menopause could represent a fundamental step in the process of diabetogenesis. Diabetes Care. 2004 Mar;27(3):645-9
      Transdermal 17-beta-estradiol and risk of developing type 2 diabetes in a population of healthy, nonobese postmenopausal women.
      The full text article is available FREE online: http://care.diabetesjournals.org/cgi/content/full/27/3/645     Mayo Clinic researchers surveyed 176 women taking natural micronized progesterone who had previously taken synthetic progestins. After one to six months, the women reported an overall 34% increase in satisfaction on micronized progesterone compared to their previous HRT, reporting these improvements: 50% in hot flashes, 42% in depression, and 47% in anxiety. Micronized progesterone was also more effective in controlling breakthrough bleeding. J Womens Health Gend Based Med 2000 May;9(4):381-7
      Comparison of regimens containing oral micronized progesterone or medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey.
      Click here
      to access the PubMed abstract of this article. Fertil Steril 1999 Sep;72(3):389-97
      Micronized progesterone: clinical indications and comparison with current treatments.
      Click here
      to access the PubMed abstract of this article.     J Am Coll Cardiol 2000 Dec;36(7):2154-9
      Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women. (This is not a "claim", it is the title of the article.) 
      Click here to access the PubMed abstract of this article.    An extensive federally sponsored double-blind study was conducted at 19 academic medical centers that comprise the Maternal-Fetal Medicine Units Network under the National Institutes of Health and found that 17-alpha-hydroxyprogesterone caproate (17P) provides substantial benefit for decreasing the risk of pre-term birth at less than 37 weeks gestation.
        N Engl J Med 2003;348:2379-85 Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. Click here to access the PubMed abstract of this article.


      Am J Obstet Gynecol 2007;196:224.e1-224.e4. Increased recurrence of preterm delivery with early cessation of 17-alpha-hydroxyprogesterone caproate. Click here to access the PubMed abstract of this article.  Vaginal progesterone suppositories have also been shown to decrease the rate of preterm birth in patients at increased risk. Da Fonseca et al noted that among 142 women who had one prior preterm birth, prophylactic cerclage, or uterine malformation, daily use of a 100-mg vaginal progesterone suppository compared with placebo significantly decreased the likelihood of delivery prior to 37 weeks.   Am J Obstet Gynecol. 2003; 188(2):419-424. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study.
      Click here to access the PubMed abstract of this article. Other related articles: Obstet Gynecol 2005 May;105(5 Pt 1):1128-35 Am J Obstet Gynecol. 2007 May;196(5):453.e1-4  
      The PEPI Trial, a 3-year multicenter, randomized, double-blind, placebo-controlled study of 875 healthy postmenopausal women, stated that synthetic progestins partially negate the beneficial effects on cholesterol levels that result from taking estrogen. Natural progesterone maintained the benefits of estrogen on cholesterol without side effects. JAMA 1995 Jan 18;273(3):199-208
      Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial.
      The Writing Group for the PEPI Trial.
      Click here to access the PubMed abstract of this article.     Certain progestogens, such as micronized progesterone, can be administered concurrently with estrogen replacement therapy, providing protection against endometrial hyperplasia without significantly affecting the beneficial effects of estrogen on lipid profiles, atherosclerosis and vascular reactivity. J Reprod Med 2000 Mar;45(3 Suppl):245-58
      Rationale for hormone replacement therapy in atherosclerosis prevention.
      Click here to access the PubMed abstract of this article. J Clin Endocrinol Metab 2002;87:1062-1067
      Estrogen status correlates with the calcium content of coronary atherosclerotic plaques in women.
      Click here
      to access the PubMed abstract of this article. J Neurosci. 2003 Dec 10;23(36):11420-6
      Estradiol attenuates programmed cell death after stroke-like injury.
      Click here
      to access the PubMed abstract of this article. Endocrinology 2001 Mar 1;142(3):969-973
      Minireview: Neuroprotective Effects of Estrogen-New Insights into Mechanisms of Action.
      Click here
      to access the PubMed abstract of this article.     The use of conjugated equine estrogen plus medroxyprogesterone acetate in a double-blind, randomized, controlled trial of 16,608 postmenopausal women between the ages of 50 and 79 years doubled the risk of venous thrombosis. This estrogen, which is derived from pregnant mares' urine, plus synthetic progestin therapy increased the risks associated with age, overweight or obesity, and factor V Leiden. JAMA. 2004 Oct 6;292(13):1573-80
      Estrogen plus progestin and risk of venous thrombosis.
      Click here to access the PubMed abstract of this article. Chem Res Toxicol 1998 Sep;11(9):1105-11
      The equine estrogen metabolite 4-hydroxyequilenin causes DNA single-strand breaks and oxidation of DNA bases in vitro.
      Click here
      to access the PubMed abstract of this article.     The following study concluded that in non-human primates, medroxyprogesterone increases the risk of coronary vasospasm. Progesterone plus estradiol protected against vasospasm. Nat Med 1997 Mar;3(3):324-7
      Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm.
      Click here
      to access the PubMed abstract of this article.     MPA reduces the dilatory effect of estrogens on coronary arteries, increases the progression of coronary artery atherosclerosis, accelerates low-density lipoprotein uptake in plaque, increases the thrombogenic potential of atherosclerotic plaques and promotes insulin resistance and its consequent hyperglycemia. These effects may be largely limited to MPA and not shared with other progestogens. J Reprod Med 1999 Feb;44(2 Suppl):180-4
      Progestogens and cardiovascular disease. A critical review.
      Click here to access the PubMed abstract of this article.     Significant bone loss occurs during the 10 to 15 years before menopause when estrogen levels are still normal. Progesterone can stimulate new bone formation in women with osteoporosis. Dr. Prior measured estrogen and progesterone levels in female marathon runners who had osteoporosis. Although their estrogen levels were still high, they had stopped ovulating (common in female athletes) and progesterone levels had fallen, triggering the onset of osteoporosis. This can indicate a role for progesterone use, alone or combined with estrogen which reduces bone loss, in improving Bone Mineral Density. Endocr Rev 1990 May;11(2):386-98
      Progesterone as a bone-trophic hormone.
      Click here to access the PubMed abstract of this article.     The WHI assessed the major health benefits and risks of the most commonly used combined hormone preparation in the United States, the synthetic combination of conjugated equine estrogens and medroxyprogesterone acetate. Absolute excess risks per 10,000 person-years attributable to this synthetic hormone combination were 7 more CHD events, 8 more strokes, 8 more pulmonary emboli, and 8 more invasive breast cancers, while absolute risk reductions per 10,000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. JAMA. 2002 Jul 17;288(3):321-33
      Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial.
      Click here
      to access the PubMed abstract of this article.     Among postmenopausal women aged 65 years or older, synthetic estrogen plus progestin did not improve cognitive function when compared with placebo. However, typical HRT users are in their 50s and this study focused on women aged 65 and over, who have a higher risk for dementia. JAMA 2003 May 28;289(20):2663-72
      Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.
      Click here
      to access the PubMed abstract of this article.     In the following study, estrogen plus progestin increased the risk of ischemic stroke in generally healthy postmenopausal women. JAMA 2003 May 28;289(20):2673-84
      Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial.
      Click here
      to access the PubMed abstract of this article.
  • Estrogens

    • Estrogens actually refers to a group of related hormones, each with a unique profile of activity. Under normal circumstances, a woman's circulating estrogen levels fluctuate based on her menstrual cycle. For Hormone Replacement Therapy, these hormones are often prescribed in combination to re-establish a normal physiologic balance. The three main estrogens produced in female humans are:
      • E1 (Estrone; 10-20% of circulating estrogens) is the primary estrogen produced after menopause.
      • E2 (Estradiol; 10-30% of circulating estrogens) is the most potent and major secretory product of the ovary, and the predominant estrogen produced before menopause.
      • E3 (60-80% of circulating estrogens)  
  • Progesterone

    • Progesterone is a term that is incorrectly used interchangeably to describe both progesterone which is "chemically identical" to what the body naturally produces, and synthetic derivatives. Synthetic progestins are analogues of progesterone, and have been developed because they are patentable, more potent, and have a longer duration. Medroxyprogesterone acetate, the most commonly used synthetic progestin, was shown in a large study to cause significant lowering of HDL "good" cholesterol, thereby decreasing the cardioprotective benefit of estrogen therapy. Side effects are a frequent cause for discontinuation of HRT.  Only about 20% of women who start synthetic HRT remain on it two years later. Progesterone:
      • is commonly prescribed for perimenopausal women to counteract "estrogen dominance" which occurs when a woman produces smaller amounts of progesterone than normal relative to estrogen levels.
      • alone, or combined with estrogen, may improve Bone Mineral Density.
      • minimizes the risk of endometrial cancer in women who are receiving estrogen.
      • is preferred by women who had previously taken synthetic progestins.
      The benefits of progesterone are not limited to prevention of endometrial cancer in women who are receiving estrogen replacement. Progesterone therapy is not only needed by women who have an "intact uterus",  but is also valuable for women who have had a hysterectomy. Vasomotor flushing is the most bothersome complaint of menopause, and is the most common reason women seek HRT and remain compliant. For over 40 years, estrogens have been the mainstay of treatment of hot flashes, but progesterone may be effective as well.
  • Androgens

    • asd

Adrenal Fatigue / Thyroid Imbalance

  • Armour Thyroid® Shortage is Affecting your Patients. Armour Thyroid® has been plagued by unexplained product shortages and back orders. Nature-Throid™ and Westhroid™ are also unavailable. Many patients have tried synthetic thyroid hormones, such as levothyroxine and liothyronine, and have found that Natural Thyroid is the only form that works adequately for them, reporting  that they simply do not feel as well when they take levothyroxine alone or with liothyronine.  Currently, certain forms and strengths of Natural Thyroid are available only through compounding pharmacies.  In addition, we can blend T4 and T3 pure powders in a specific ratio by prescription. Commercially available tablets contain fillers and excipients that may not be tolerated by all patients. When we compound customized dosages, we have the ability to omit any problem-causing inactive ingredients and substitute non-reactive fillers. We welcome your questions and the opportunity to help your patients. Adrenal Fatigue
    The adrenal glands secrete hormones such as cortisol, estrogen, and testosterone that are essential to health and vitality and significantly affect total body function. After mid-life, the adrenal glands gradually become the major endogenous source of sex hormones in both men and women. Intense or prolonged physical or emotional stress commonly associated with modern lifestyles or chronic illness can lead to Adrenal Fatigue, which is an important contributing factor in health conditions ranging from allergies to obesity. Anti-inflammatory and anti-oxidant adrenal hormones like cortisol help to minimize allergic and negative reactions, such as cancer and autoimmune disorders. These hormones closely affect the utilization of carbohydrates and fats, the conversion of fats and proteins into energy, and cardiovascular and gastrointestinal function. Proper adrenal support is essential to complete the hormonal pathway to optimal health, and includes proper nutrition, getting plenty of sleep, regular moderate exercise, stress management, slowing down to regain a proper perspective on life, and replacement of deficient hormones. Thyroid Hormone Therapy
    Symptoms of hypothyroidism (low levels of thyroid hormone) include fatigue, cold and heat intolerance, hypotension, fluid retention, dry skin and/or hair, constipation, headaches, low sexual desire, infertility, irregular menstrual periods, aching muscles and joints, depression, anxiety, slowed metabolism and decreased heart rate, memory impairment, enlarged tongue, deep voice, swollen neck, PMS, weight gain, hypoglycemia, and high cholesterol and triglycerides. Yet, more than half of all people with thyroid disease are unaware of their condition. Although both T4 (thyroxine, an inactive form that is converted to T3 in other areas of the body) and T3 (triiodothyronine, the active form) are secreted by the normal thyroid gland, many hypothyroid patients are treated only with levothyroxine (synthetic T4). Some hypothyroid patients remain symptomatic, and T3 may also be required for optimal thyroid replacement therapy. However, the only commercially available form of T3 is synthetic liothyronine sodium in an immediate release formulation which is rapidly absorbed, and may result in higher than normal T3 concentrations throughout the body causing serious side effects, including heart palpitations. Research indicates there is a need for sustained-release T3 preparations in order to avoid adverse effects. A randomized, double-blind, crossover study found inclusion of T3 in thyroid hormone replacement improved cognitive performance, mood, physical status, and neuropsychological function in hypothyroid patients. Two-thirds of patients preferred T4 plus T3, and tended to be less depressed than after treatment with T4 alone. Patients and their physicians may wish to consider the use of sustained-release T3 in the treatment of hypothyroidism, particularly when the response to levothyroxine (T4) has not been complete. J Endocrinol Invest 2002 Feb;25(2):106-9
    Levothyroxine therapy and serum free thyroxine and free triiodothyronine concentrations.
    Click here to access the PubMed abstract of this article. N Engl J Med 1999 Feb 11;340(6):424-9
    Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism.
    Click here to access the PubMed abstract of this article.
    Also, the FREE full text of this article is available online.



    Rectal Administration of Propylthiouracil for Patients with Thyrotoxicosis and Critical Illness
     
    The Division of Endocrinology and Metabolism, Beth Israel Medical Center, University Hospital and Manhattan Campus for the Albert Einstein College of Medicine, reported the successful management of thyrotoxicosis in a seriously ill 47-year-old man with a perforated gastric ulcer in whom oral intake was contraindicated. Specially prepared suppositories containing 400 mg of propylthiouracil (PTU) were administered rectally every 6 hours. PTU was substantially absorbed from the rectal suppositories, with serum levels of PTU maintained within the high therapeutic range for 5 days until the patient was able to tolerate orally administered therapy. The patient improved clinically during this treatment. They concluded that this case strongly supports the rectal administration of PTU in suppository form as an appropriate alternative route in any patient with thyrotoxicosis, including the critically ill patient, when oral administration is not possible.
     
    Endocr Pract. 2006 Jan-Feb;12(1):43-7.
    Rectal administration of propylthiouracil in suppository form in patients with thyrotoxicosis and critical illness: case report and review of literature.
    Click here to access the PubMed abstract of this article.  

    Chronic Fatigue Syndrome (CFS, Chronic Fatigue and Immuno-Deficiency Syndrome, CFIDS) and Fibromyalgia (FM, formerly called fibrositis) may manifest as hypothalamic, pituitary, and immune dysfunction. A study in the Annals of Allergy, Asthma and Immunology [2000 Jun;84(6):639-40] demonstrated that supplementation with NADH for one month resulted in significant improvement, and other studies have shown some minimal improvement with magnesium. Ann Allergy Asthma Immunol. 1999 Feb;82(2):185-91
    Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome.
    Click here to access the PubMed abstract of this article.  
    The combination of pituitary dysfunction, high reverse T3, and thyroid resistance, leads to inadequate thyroid effect in most, if not all, CFIDS/FM patients. T4 (levothyroxine) preparations are often ineffective for CFIDS/FM patients. A T4/T3 combination preparation or straight T3 (triiodothyronine) may be preferable. T3 works the best for many of these patients, but Cytomel, a very short acting T3 available at retail pharmacies, is also a poor choice because the varying blood levels cause problems such as heart palpitations. Compounded, sustained-release T3 may be the best treatment. However, standard blood tests may lead one to dose incorrectly and not obtain significant benefits. Ultimately, it is the expertise and dosing of the T3 or T4/T3 combinations and the makeup of the medications that determines the success of treatment. Natural Therapies for CFIDS/FM: Proper nutritional supplements, proteins, and hormones can protect and enhance the immune system. Antioxidants may also be beneficial because free radicals play a role in causing damage to the immune system. Vitamin B-12 levels are often low in patients with CFIDS/FM. A malfunctioning thyroid or adrenal gland can decrease the ability of the body to absorb and utilize vitamin B-12. Vitamin B-12 is necessary for a healthy nervous system; it has been known for many years that depression and fatigue can be caused by low B-12 levels. D-ribose significantly reduced clinical symptoms in patients suffering from fibromyalgia and chronic fatigue syndrome, with an average increase in energy on the VAS of 45% and an average improvement in overall well-being of 30%. J Altern Complement Med. 2006 Nov;12(9):857-62
    The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. 
    Click here to access the PubMed abstract of this article.
    For more information about patient-specific Hormone Replacement Therapy, please contact our compounding pharmacist.

Hormone Replacement Therapy for Men

  • Symptoms of testosterone deficiency affect approximately 1 in 200 men and may include:
    • Weakness
    • Fatigue
    • Reduced libido
    • Osteoporosis
    This condition is commonly referred to as "Andropause" and less often as "Androgen Deficiency in the Aging Male" (ADAM).
     
    A man may be considered hypogonadal at any age if total testosterone is less than 200 ng/dl, or bioavailable testosterone is less than 60 ng/dl. Basaria and Dobs of Johns Hopkins University recommend that elderly men with symptoms of hypogonadism and a total testosterone level < 300 ng/dl should be started on hormone replacement.
  • Testosterone

    • What is the Optimal Form of Testosterone for Replacement Therapy? Testosterone USP is natural bio-identical testosterone that has been approved by the United States Pharmacopoeia and is available as a bulk chemical. Upon a prescription order, compounding pharmacists can use Testosterone USP to prepare numerous dosage forms. Natural Testosterone Replacement is Central to the Treatment of All Facets of Andropause. The term "testosterone" is often used generically when referring to numerous synthetic derivatives, as well as natural bio-identical testosterone. Confusion is responsible for conflicting data in the medical literature about the benefits and risks of testosterone therapy. Studies must be reviewed carefully to determine the form of testosterone that was used. Natural testosterone must not be confused with synthetic derivatives or "anabolic steroids," which when used by athletes and body builders have caused disastrous effects. For example, administration of synthetic non-aromatizable androgens, like stanozolol or methyltestosterone, causes profound decreases in HDL-C ("good cholesterol") and significant increases in LDL-C ("bad cholesterol"). Yet, hormone replacement with aromatizable androgens, such as testosterone, results in lower total cholesterol and LDL cholesterol levels while having little to no impact on serum HDL cholesterol levels. Proper monitoring of laboratory values and clinical response are essential when prescribing testosterone replacement therapy. The only absolute contraindications to androgen replacement therapy are the presence of prostate or breast cancer. "Although it is known that the clinical course of prostate cancer is accelerated by testosterone, its incidence is not increased by [testosterone] administration... There is even no clear evidence that testosterone replacement accelerates the development of BPH." Drugs & Aging 1999 Aug;15(2):131-42
  • Goals and Therapy

    • Goals of Testosterone Replacement Therapy in Adult Hypogonadal Men (age 50 or older)
      • Improvement in psychological well-being and mood
      • Improvement in erectile dysfunction
      • Improvement in libido
      • Increased muscle mass
      • Increased strength and stature
      • Preservation of bone mass
      • Possible decrease in cardiovascular risk
      A man may be considered hypogonadal at any age if total testosterone is less than 200 ng/dl, or bioavailable testosterone is less than 60 ng/dl. Basaria and Dobs of Johns Hopkins University recommend that elderly men with symptoms of hypogonadism and a total testosterone level < 300 ng/dl should be started on hormone replacement.
  • Supporting Literature

    • High estradiol levels can suppress testosterone production, and play a role in Metabolic Syndrome. Aromatase inhibitors such as anastrozole can reduce estradiol and increase serum bioavailable and total testosterone levels to the youthful normal range in older men with mild hypogonadism. Suppression of estradiol in men using low-dose anastrozole has been shown to have a positive effect on testosterone production without adverse effects during short term administration. J Clin Endocrinol Metab. 2004 Mar;89(3):1174-80.
      Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels.
      Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C. Click here to access the PubMed abstract of this article. In this case study anastrozole was used to restore fertility in a 29-year-old obese man who presented with a low sperm count in the setting of morbid obesity. Roth et al report "Treatment with an aromatase inhibitor, anastrozole, led to normalization of the patient's testosterone, luteinizing hormone and follicle-stimulating hormone levels, suppression of serum estradiol levels, and to normalization of spermatogenesis and fertility." Nat Clin Pract Endocrinol Metab. 2008 Jul;4(7):415-9.
      Treatment of male infertility secondary to morbid obesity.
      Roth MY, Amory JK, Page ST. Click here to access the PubMed abstract of this article. Testosterone Replacement Therapy for Men and Treatment of Depression
       
        
      Testosterone replacement therapy (TRT) may be efficacious treatment for subthreshold depression in older men with hypogonadism. 1, 2
       
      Dysthymia is a chronic type of depression in which a person's moods are regularly low. Testosterone replacement may be an effective antidepressant strategy for late-onset male dysthymia.3
       
      1 Ther Clin Risk Manag. 2009 Jun;5(3):427-48.
       The benefits and risks of testosterone replacement therapy: a review.
      Click here to access the PubMed abstract of this article.

      2 J Clin Psychiatry. 2009 Jul;70(7):1009-16.
      A randomized, double-blind, placebo-controlled study of testosterone treatment in hypogonadal older men with subthreshold depression (dysthymia or minor depression).
      Click here to access the PubMed abstract of this article.
       
      3  J Clin Psychopharmacol. 2009 Jun;29(3):216-21.
      Effects of testosterone replacement in middle-aged men with dysthymia: a randomized, placebo-controlled clinical trial.
      Click here to access the PubMed abstract of this article.



      Low Free Testosterone as a Potentially Treatable Cause of Depression in Older Men
       
      Arch Gen Psychiatry. 2008 Mar;65(3):283-9
      Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men.
      Click here to access the PubMed abstract of this article. 


      Low Testosterone Increases Mortality Risk in Men
       
      A population-based cohort study followed 1954 men aged 20 to 89 years for an average of 7.2 years, and has demonstrated a link between low levels of testosterone and increased risk for mortality in adult men of all ages.
       
      http://www.medscape.com/viewarticle/576267   (accessed 10/08)
      Administration of a transdermal testosterone (T) gel formulation to hypogonadal men provided dose-proportional increases in serum T levels to the normal adult male range. Testosterone 1% gel (50 or 100 mg/day) was compared to the permeation-enhanced T patch. After 180 days, skin irritation was reported in 5.5% of subjects treated with T gel and in 66% of subjects in the permeation-enhanced T patch group. This research at UCLA concluded that T gel replacement improved sexual function and mood, increased lean mass and muscle strength (principally in the legs), and decreased fat mass in hypogonadal men with less skin irritation and discontinuation compared with the recommended dose of the permeation-enhanced T patch. J Clin Endocrinol Metab. 2000 Aug;85(8):2839-53
      Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. Testosterone Gel Study Group.
      Click here to access the PubMed abstract The following study concluded that replacing testosterone in hypogonadal men increases bone mineral density of the spine and hip, fat-free mass, prostate volume, erythropoiesis, energy, and sexual function. The full effect of testosterone on bone mineral density took 24 months, but the full effects on the other tissues took only 3-6 months.

      J Clin Endocrinol Metab 2000 Aug;85(8):2670-7
      Effects of testosterone replacement in hypogonadal men.
      Click here to access the PubMed abstract Am J Med 2001 May;110(7):563-72
      Hypogonadism and androgen replacement therapy in elderly men.
      Click here to access the PubMed abstract Drugs Aging 1999 Aug;15(2):131-42
      Risks versus benefits of testosterone therapy in elderly men.
      Click here to access the PubMed abstract The findings below suggest that low levels of testosterone and SHBG play some role in the development of insulin resistance and subsequent type 2 diabetes.

      Diabetes Care 2000 Apr;23(4):490-4
      Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study.
      Click here to access the PubMed abstract

      Manifestations of testosterone deficiency have included depression, anxiety, irritability, insomnia, weakness, diminished libido, impotence, poor memory, reduced muscle and bone mass, and diminished sexual body hair. Although testosterone levels decline with age, there is great interindividual variability.

      Am J Psychiatry 1998 Oct;155(10):1310-8
      Age-associated testosterone decline in men: clinical issues for psychiatry.
      Click here to access the PubMed abstract.
      Massive obesity in males is associated with decreased total and free testosterone levels as well as elevated estradiol levels.

      Med Hypotheses 1999 Jan;52(1):49-51
      The hypogonadal-obesity cycle: role of aromatase in modulating the testosterone-estradiol shunt-a major factor in the genesis of morbid obesity.
      Click here to access the PubMed abstract.
      These results suggest that testosterone treatment might improve depressed mood in older men who have low levels of bioavailable testosterone.

      J Clin Endocrinol Metab 1999 Feb;84(2):573-7
      Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study.
      Click here to access the PubMed abstract
      The following results suggest that until the age of 60 years, the mean serum level of DHEAS is lower in patients with ED than in healthy volunteers.

      Urology 2000 May;55(5):755-8
      Serum dehydroepiandrosterone sulfate concentrations in men with erectile dysfunction.
      Click here to access the PubMed abstract
      Sublingual sildenafil in the treatment of erectile dysfunction: faster onset of action with lower dose  Forty consecutive patients with erectile dysfunction (mean age was 55 years) for more than three months were included in this study. Sixty-five percent of patients (13/20) who received sublingual sildenafil achieved satisfying erections and coitus, whereas the rate was 15% in the placebo group (3/20). The mean onset of action with sublingual sildenafil was 15.5 minutes and lasted for an average of 40 minutes. Minimal headaches, sweating and flushing were noted as the side-effects.  The conclusion: "20 mg sublingual sildenafil is safe and effective in the treatment of erectile dysfunction. Sublingual administration has some advantages as it is not effected by food ingestion and quickly appears in the circulation. These advantages provide a faster onset of action with a lower dose when compared to oral sildenafil. Sublingual use of sildenafil may be more cost-effective and possibly provides a more predictable onset of action."  Int J Urol. 2004 Nov;11(11):989-92 
      Sublingual sildenafil in the treatment of erectile dysfunction: faster onset of action with less dose.  Click here to access the PubMed abstract of this article.  The International Journal of Pharmaceutical Compounding [March/April 2007;11(2):121] reported a formula for Sildenafil 20mg Troches (flavored) with a recommended beyond-use date of 180 days.

Palliative Care

  • Palliative Care is "the active total care of patients whose disease is not responsive to curative treatment." The goal of palliative care is the achievement of the best possible quality of life for patients and their families. Symptom Control involves therapies for nausea & vomiting, dry mouth & stomatitis, excessive pulmonary secretions/death rattle, radiation mucositis and proctitis, and wound care. We work together with patient and practitioner to solve problems by customizing medications that meet the specific needs of each individual. Please contact our compounding pharmacist to discuss the dosage form, strength, and medication or combination that is most appropriate for your patient.
  • Anti-Emitics

    • Nausea & Vomiting Persistent nausea can often be effectively controlled by using a combination of medications tailored to meet that individual's specific needs. Dosage forms include transdermal gels, suppositories, lollipops, and more. Promethazine is commonly compounded for topical or transdermal application to treat nausea, vomiting, and vertigo, but this preparation may be used as an antiemetic for cases ranging from chemotherapy to motion sickness. The dose is typically 25mg for adults, and the dose is decreased for children. The gel is applied to an area of soft skin, such as the inside of the wrist or arm, the side of the torso, or the inside of the thigh. For children, doses are often applied to the inside of one wrist, and then the wrists are rubbed together.
      US Pharmacist, August 1999; 74-5 Lorazepam, diphenhydramine, haloperidol, and metoclopramide (known in combination as "ABHR") have been prepared as a rectal suppository and in other transdermal dosage forms. The rationale is to use a variety of medications which target various pathways such as vagal nerve stimulation, the vomiting center, and the CTZ for more severe cases. Researchers at Memorial Sloan-Kettering Cancer Center have studied the antiemetic activity and safety of the antiemetic regimen of metoclopramide, dexamethasone, and diphenhydramine in patients receiving standard outpatient chemotherapy programs. Vomiting was prevented in over 70% of patients. Cancer 1995 Sep 1;76(5):774-8
      Oral combination antiemetics in patients with small cell lung cancer receiving cisplatin or cyclophosphamide plus doxorubicin.
      Click here to access the PubMed abstract of this article.   Intranasal metoclopramide may significantly reduce the frequency of acute vomiting in patients receiving highly emetogenic chemotherapy, such cisplatin-induced delayed emesis. Intranasal metoclopramide caused minor irritation of the nasal membrane and unpleasant taste in some patients, but was otherwise well tolerated, with no report of serious extrapyramidal effects. Drugs 1999 Aug;58(2):315-22; discussion 323-4
      Intranasal metoclopramide.
      Click here to access the PubMed abstract of this article.




      ABH Transdermal Gel for Chemotherapy-Induced Nausea/Vomiting
       
      Chemotherapy-induced nausea and vomiting (CINV) is commonly cited by patients as being among the “most unpleasant and distressing” side effects associated with chemotherapy. CINV may impair quality of life significantly and necessitate chemotherapeutic dose reductions, treatment delays, and discontinuation of therapy.  Finally, it may cause a substantial number of lost work days for patients and considerable costs to the healthcare system, resulting in a substantial economic burden.
       
      Bleicher et al. of the Hematology/Oncology Division, Creighton University Medical Center, Omaha, NE, investigated the efficacy of "ABH," a topical gel containing lorazepam (Ativan®), diphenhydramine (Benadryl®), and haloperidol (Haldol®), in reducing breakthrough CINV. Adults receiving standard recommended prophylactic antiemetics as outpatients were instructed to apply 0.5 mL of a transdermal gel (containing lorazepam 2 mg, diphenhydramine 25 mg, and haloperidol 2 mg) when they experienced significant CINV. When the severity of CINV was quantified on a scale of 0-10, the mean CINV score decreased significantly from a 6.1 before gel application to a 1.7 as evaluated 30 minutes following gel application. Topical use of ABH gel appears to be a promising and safe rescue therapy for breakthrough CINV that occurs despite prophylactic antiemetic therapy.1
       
      Weschules noted that of 11,181 ABHR (ABH plus metoclopramide [Reglan®]) prescriptions provided for patients, 6,529 (58.4%) were for a topical gel, and 4,312 (38.6%) were for a rectal suppository.2 Less than 0.5% of patients discontinued treatment due to adverse side effects. Another retrospective study reported use of an ABHR gel to be 98% effective in hospice patients.3 There were no adverse reactions; however, problems arose when patients with bowel obstructions were treated.
       
      1 J Support Oncol. 2008 Jan;6(1):27-32.
      Lorazepam, diphenhydramine, and haloperidol transdermal gel for rescue from chemotherapy-induced nausea/vomiting: results of two pilot trials.
      Click here to access the PubMed abstract of this article. 2 J Palliat Med 2008;8:1135–1143.
      Tolerability of the compound ABHR in hospice patients.
      Click here to access the PubMed abstract of this article. 3 Int J Pharm Compounding 2006;10:95–99.
      ABHR Gel in the Treatment of Nausea and Vomiting in the Hospice Patient
      Click here to access the abstract of this article.
  • Therapy for Dry Mouth (Xerostomia)

    • Dry Mouth & Stomatitis There are many factors that can interfere with the ability to eat when a person is receiving chemotherapy. Malnutrition may result, yet it is often preventable. Our pharmacy can compound medications to help combat mouth tenderness and infections, which may enable patients to enjoy eating again. Cancer. 2002 Nov 15;95(10):2230-6
      Effect of topical morphine [mouthwash] for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma. Cerchietti LC, Navigante AH, Bonomi MR, Zaderajko MA, Menendez PR, Pogany CE, Roth BM.
      Supportive Care Division, Department of Medical Oncology, Angel H. Roffo Cancer Institute, University of Buenos Aires, Buenos Aires, Argentina. Click here to access the PubMed abstract of this article.   A three-drug mouthwash (lidocaine, diphenhydramine and sodium bicarbonate in normal saline) can provide effective symptomatic relief in patients with chemotherapy-induced mucositis. Support Care Cancer. 2000 Jan;8(1):55-8
      Efficacy of treatment to relieve mucositis-induced discomfort. Turhal NS, Erdal S, Karacay S.
      Department of Medicine, Marmara University Hospital, Istanbul, Turkey. Click here to access the PubMed abstract of this article.   Loss of saliva (xerostomia) is one of the most common complaints among patients who have received radiation therapy of the head and neck. Xerostomia contributes to radiation-induced periodontal infection, dental caries, osteoradionecrosis, and poor digestion of carbohydrates. Ask us about sialogogues (saliva stimulants) in customized dosage forms. The following article discusses the benefits of using pilocarpine in a sustained release dosage form to treat xerostomia. Yakugaku Zasshi. 1997 Jan;117(1):59-64
      [Preparation and evaluation of solid dispersions of pilocarpine hydrochloride for alleviation of xerostomia]
      [Article in Japanese] Oda M, Sato M, Yagi N, Ohno K, Miyazaki S, Watanabe S, Takada M.
      Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan. Click here to access the PubMed abstract of this article.
  • Anti-Secretory Agents

    • Excessive Secretions/Death Rattle Transdermal Anticholinergics for the Treatment of "Death Rattle" and Excessive Secretions Difficulty clearing upper airway secretions (death rattle) is a problem for half of all dying patients. Treatment often includes the use of anticholinergic drugs, such as scopolamine (also known as hyoscine) or atropine. Transdermal scopolamine has several indications for symptom control in patients with end-stage disease: control of excess salivary secretions, management of terminal secretions, and control of nausea.
      Palliat Med. 2002 Sep;16(5):369-74
      Using anti-muscarinic drugs in the management of death rattle: evidence-based guidelines for palliative care. 
      Click here to access the PubMed abstract.


      J Pain Symptom Manage. 2002 Apr;23(4):310-7
      Death rattle: prevalence, prevention and treatment.
      Click here to access the PubMed abstract.


      Prescrire Int. 2001 Aug;10(54):99-101
      Scopolamine: new preparations. Reference treatment for death rattle.
      Click here to access the PubMed abstract. Otolaryngol Head Neck Surg. 1990 Oct;103(4):615-8
      Reduction of salivary flow with transdermal scopolamine: a four-year experience.
      Click here to access the PubMed abstract of this article.
        Drooling is a serious social handicap experienced by some neurologically impaired patients. No one method has been identified to control drooling for all patients, however, anticholinergic drugs have been utilized. In the following case study, transdermal scopolamine was found to be effective for controlling drooling in a traumatic brain-injured patient for whom more conservative methods failed. From a baseline saliva flow rate, saliva flow decreased up to 59%. No significant side effects were observed with treatment, and the decrease in drooling was maintained for a 4-month period. Although transdermal scopolamine may represent one acceptable facet of long-term treatment, it must be stressed that efficacy is variable across patient populations and that treatment approaches must be individualized. Am J Phys Med Rehabil. 1991 Aug;70(4):220-2
      The use of transdermal scopolamine to control drooling. A case report.
      Click here to access the PubMed abstract of this article.
  • Pain Management

    • Pain management is essential because, even when the underlying disease process is stable, uncontrolled pain prevents patients from working productively, enjoying recreation, or taking pleasure in their usual roles in the family and society. Chronic pain may have a myriad of causes and perpetuating factors, and therefore can be much more difficult to manage than acute pain, requiring a multidisciplinary approach and customized treatment protocols to meet the specific needs of each patient. Optimal treatment may involve the use of medications that possess pain-relieving properties, including some antidepressants, anticonvulsants, antiarrhythmics, anesthetics, antiviral agents, and NMDA (N-methyl-D-aspartate) antagonists. Palliative care often involves the use of opioid analgesics. NMDA-receptor antagonists, such as dextromethorphan and ketamine, can block pain transmission in dorsal horn spinal neurons, reduce nociception, and decrease tolerance to and the need for opioid analgesics. [Anesth Analg 2001 Mar;92(3):739-44]  By combining various agents which utilize different mechanisms to alter the sensation of pain, physicians have found that smaller concentrations of each medication can be used. Topical and transdermal creams and gels can be formulated to provide high local concentrations at the site of application (e.g., NSAIDs for joint pain), for trigger point application (e.g., combinations of medications for neuropathic pain), or in a base that will allow systemic absorption. Side effects associated with oral administration can often be avoided when medications are used topically. Studies suggest that there are no great restrictions on the type of drug that can be incorporated into a properly compounded transdermal gel.  When medications are administered transdermally, they are not absorbed through the gastrointestinal system and do not undergo first-pass hepatic metabolism. We work together with prescriber and patient to solve problems by customizing medications that meet the specific needs of each individual. Please contact our compounding pharmacist to discuss the dosage form, strength, and medication or combination that is most appropriate for your patient.




      Effectiveness of Topical Administration of Opioids in Palliative Care
        
      The discovery of peripheral opioid receptors has become the scientific basis for topical use of opioids in malignant and nonmalignant ulcers and oropharyngeal mucositis. A systematic review assessed the quality of published literature and examined whether topical opioids are effective in controlling pain in palliative care settings. Eighteen studies favored topical opioids in pain relief, but time to onset and duration of analgesia varied widely, perhaps due to variances in formulations. “N-of-1 trials should be encouraged for specific clinical circumstances.”
       
      J Pain Symptom Manage. 2009 May;37(5):913-7.
      Effectiveness of topical administration of opioids in palliative care: a systematic review.
      Click here to access the PubMed abstract of this article.
  • Wound Care

    • Per a prescription order, a formulation can be compounded to contain the proper combination of active ingredients, in the most appropriate base, to treat a specific type of wound. We customize medications to meet each individual's specific needs. For example, the choice of cream, ointment, or gel can be clinically significant. Each time a wound needs to be cleaned, there is the potential for disruption of new tissue growth. Gels, which are more water soluble than creams or ointments, may be preferable for wound use because a gel can be rinsed from the wound by irrigation.  Ointments may contain polyethylene glycol (PEG), which can be absorbed from open wounds and damaged skin. If the wound is quite large and too much PEG is absorbed, it can lead to renal toxicity.  Another useful dosage form is the "polyox bandage" - which can be puffed onto a wound and will adhere even if exudate is present.  A polyox bandage can be compounded to contain the active ingredient(s) of your choice.  Decubitus Ulcers Phenytoin has been used topically to speed the healing of decubitus ulcers, pressure sores, venous stasis and diabetic ulcers, traumatic wounds, skin autograft donor sites, and burns. Ketoprofen may be used to control inflammation and pain, lidocaine provides topical anesthesia, and pentoxifylline may improve microcirculation at the wound margins and promote healing of the injured area. Misoprostol, a prostaglandin analog, is often included in wound care formulations to promote healing. Debridement of necrotic eschar with 40% urea paste may also speed healing. Medications which improve capillary blood flow can be added to a compounded medication to enhance circulation at the wound margins and promote healing of the injured area. Topical Phenytoin for Wound Healing Phenytoin may promote wound healing by a number of mechanisms, including stimulation of fibroblast proliferation, facilitation of collagen deposition, glucocorticoid antagonism, and antibacterial activity. Rhodes et al compared the healing of stage II decubitus ulcers with topically applied phenytoin and two other standard topical treatment procedures in 47 patients in a long-term care setting. Ulcers were examined for the presence of healthy granulation tissue, reduction in surface dimensions, and time to healing. Topical phenytoin therapy resulted in a shorter time to complete healing and formation of granulation tissue when compared with DuoDerm dressings or triple antibiotic ointment applications. The mean time to healing in the phenytoin group was 35.3 +/- 14.3 days compared with 51.8 +/- 19.6 and 53.8 +/- 8.5 days for the DuoDerm and triple antibiotic ointment groups, respectively. Healthy granulation tissue in the phenytoin group appeared within 2 to 7 days in all subjects, compared to 6 to 21 days in the standard treatment groups. The phenytoin-treated group showed no detectable serum phenytoin concentrations. Anstead et al. described a patient with a massive grade IV pressure ulcer that was unresponsive to conventional treatment, yet responded rapidly to treatment with topical phenytoin. Song and Cheng reported phenytoin improved wound breaking strength in normal and radiation-impaired wounds. The results of their study indicated that topical phenytoin accelerated normal and irradiation-impaired wound healing by increasing the number of wound macrophages and improving the macrophage function. Pendse et al evaluated the effectiveness of topical phenytoin in healing chronic skin ulcers in a controlled trial of 75 inpatients. At the end of the fourth week, 29 of 40 phenytoin-treated ulcers had healed completely versus 10 of 35 controls. They concluded: "topical phenytoin appears to be an effective, inexpensive, and widely available therapeutic agent in wound healing." The effectiveness of topical phenytoin as a wound healing agent was compared with that of OpSite and a conventional topical antibiotic dressing (Soframycin) in a controlled study of 60 patients with partial-thickness skin autograft donor sites on the lower extremities. Mean pain scores were lower and mean time to complete healing (complete epithelialization) was best in the phenytoin-treated group (6.2 +/- 1.6 days).  Topical phenytoin compared very favorably with, and in some aspects was superior to, occlusive dressings. No study reported any significant adverse effects secondary to topical phenytoin therapy. Phenytoin references: Ann Pharmacother 2001 Jun;35(6):675-81
      Topical phenytoin treatment of stage II decubitus ulcers in the elderly.
      Click here to access the PubMed abstract of this article. Biochem Pharmacol 1999 May 15;57(10):1085-94
      Role of phenytoin in wound healing--a wound pharmacology perspective.
      Click here to access the PubMed abstract of this article. Ann Pharmacother 1996 Jul-Aug;30(7-8):768-75
      Phenytoin in wound healing.
      Click here to access the PubMed abstract of this article. Int J Dermatol 1993 Mar;32(3):214-7
      Topical phenytoin in wound healing.
      Click here to access the PubMed abstract of this article. Chung Hua I Hsueh Tsa Chih 1997 Jan;77(1):54-7
      [The effect of systemic and local irradiation on wound macrophages and the repair promoting action of phenytoin sodium]
      Click here to access the PubMed abstract of this article. Burns 1993 Aug;19(4):306-10
      Topical phenytoin in the treatment of split-thickness skin autograft donor sites: a comparative study with polyurethane membrane drape and conventional dressing.
      Click here to access the PubMed abstract of this article. Diabetes Care 1991 Oct;14(10):909-11
      Topical phenytoin in diabetic foot ulcers.
      Click here to access the PubMed abstract of this article.



      Benzoyl Peroxide for Treatment of Decubitus Ulcers  Benzoyl peroxide is a powerful oxidizing agent with broad spectrum germicidal activity and good liposolubility. Therefore, it may represent a good agent for prevention of wound infection in areas with high density of sebaceous glands. Topical treatment of pressure sore with 20% benzoyl peroxide in O/W emulsion yielded very satisfactory results. In another study, 10% benzoyl peroxide gel was used prophylactically once a day for 7 days before surgery. The researchers concluded that topical benzoyl peroxide is an efficacious, harmless, and inexpensive agent for prevention of wound infections in seborrheic regions.

      Med Cutan Ibero Lat Am 1988;16(5):427-9.
      [Benzoyl peroxide in the treatment of decubitus ulcers]
      Click here to access the PubMed abstract of this article.
  • Dyspnea

    • When illness is incurable or the cause is irreversible and the goal is palliation, systemic opioids are the first-line therapy for symptomatic management of dyspnea. Palliat Med. 1997 Jul;11(4):277-81.
      Oral morphine as symptomatic treatment of dyspnoea in patients with advanced cancer.
      Click here to access the PubMed abstract of this article. N Engl J Med. 1981 Dec 31;305(27):1611-6.
      Effects of dihydrocodeine, alcohol, and caffeine on breathlessness and exercise tolerance in patients with chronic obstructive lung disease and normal blood gases.
      Click here to access the PubMed abstract of this article. Education for Physicians on End-of-life Care (EPEC) Participant’s Handbook
      EPEC Project, 1999. The Project to Educate Physicians on End-of-life Care from the Institute for Ethics at the American Medical Association.BMJ. 2003 Sep 6;327(7414):523-8
      Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea
      Click here to access the PubMed abstract of this article.
  • Prevention/Treatment of Radiation Mucositis/Proctitis

    • Radiation proctitis is a known complication of radiation therapy for prostate cancer. Commercially available treatments are often ineffective and have focused on relieving symptoms after damage has occurred, although options exist for prevention. A prospective, randomized, placebo-controlled, double-blinded trial concluded that misoprostol rectal suppositories significantly reduce acute and chronic radiation proctitis symptoms in patients receiving radiation therapy for prostate cancer. Am J Gastroenterol 2000 Aug;95(8):1961-6
      A prospective randomized placebo-controlled double-blinded pilot study of misoprostol rectal suppositories in the prevention of acute and chronic radiation proctitis symptoms in prostate cancer patients.
      Click here to access the PubMed abstract of this article.   Seven patients with radiation proctitis completed an open pilot study to evaluate the effectiveness of short chain fatty acid (SCFA) enemas. Four weeks of treatment resulted in clinical improvement in all patients, and modest changes in endoscopic and pathological parameters. Am J Gastroenterol. 1996 Sep;91(9):1814-6
      Evaluation of short-chain fatty acid enemas: treatment of radiation proctitis.
      Click here to access the PubMed abstract of this article.   Topical sucralfate may induce a lasting remission in a majority of patients with moderate to severe rectal bleeding due to radiation proctosigmoiditis. Dig Dis Sci 1999 May;44(5):973-8
      Natural history of late radiation proctosigmoiditis treated with topical sucralfate suspension.
      Click here to access the PubMed abstract of this article.   Topical morphine is effective in relieving mucositis-associated pain following concomitant chemoradiotherapy in head and neck carcinoma. Three patients, who had been treated previously with oral morphine with no relief from esophagitis pain, swallowed from 2 to 10 mL of 0.1% morphine viscous gel three times a day, 5 to 60 minutes before eating. The gel covered esophageal surfaces and produced topical anesthesia. Benefit continued to increase over several days of use. In prior studies, relief of oral mucositis pain was obtained by a topical 0.1% morphine solution. The major advantages of topical morphine administration are simplicity, low incidence of side effects, and low cost.

      J Pain Symptom Management 30;2 (Aug 2005); 107-9



      Ketamine Mouthwash for Mucositis Pain
       
        “Mucositis is a common adverse event related to many antineoplastic regimens... Ketamine is a potent N-methyl-D-aspartate (NMDA) receptor channel blocker that can lead to decreased nocioception and inhibit the inflammatory cascade… Also, ketamine acts on a number of other pathways that may attenuate pain.”
       
         Ketamine mouthwash (20 mg/5 ml) administered using the “swish and spit” technique may be a viable treatment option in refractory mucositis pain.
       
      J Palliat Med. 2009 Nov;12(11):989-91.
      Ketamine mouthwash for mucositis pain.
      Click here to access the PubMed abstract of this article.




      Doxepin Rinse Relieves Oral Mucositis Caused by Cancer Therapy
       
         Oral mucositis negatively impacts quality of life and as reported by patients, is the most debilitating complication of head and neck radiation therapy, chemotherapy, and hematopoietic cell transplantation. In many patients, oral mucositis is cancer therapy dose- and rate-limiting, which can lead to modification, delay, or cessation of cancer therapy and ultimately impact cure rates. Management of oral mucositis can be very costly due to the need for systemic opioids, parenteral nutrition, antibiotics, and hospital utilization.
       
         Systemic doxepin, a tricyclic antidepressant, has been used for pain management of patients with chronic pain. Tricyclics lead to increased serotonin and norepinephrine in neuronal synapses that may affect mood and pain. In addition, tricyclics have been shown to be potent sodium channel blockers and may inhibit spinal N-methyl-d-aspartate receptors.
       
         Practitioners at major US universities and in private practice assessed pain reduction after topical doxepin rinse in fifty-one patients with painful oral mucositis attributable solely to cancer therapy. Doxepin suspension (5 mg/mL) was prepared as an oral rinse containing 0.1% alcohol and sorbitol. A significant reduction of oral pain was recorded after doxepin was administered. At 5 minutes, on average, patients reported a 41% decrease in pain, obtaining a 55.6% reduction in pain from baseline at 15 minutes. The median duration of pain reduction lasted for almost 2½ hours. Taste was acceptable and discomfort/burning with use was minimal. These findings are in contrast to typical complaints of taste and discomfort/burning associated with topical application of local anesthetics.
       
      Anesth Analg 2006;103:465–70
      Oral Doxepin Rinse: The Analgesic Effect and Duration of Pain Reduction in Patients with Oral Mucositis Due to Cancer Therapy
      Click here to access the PubMed abstract of this article.
  • Examples of Compounded Medications

    • The following list is just a few of the preparations that we can compound for palliative care. All formulations are customized per prescription to meet the unique needs of each patient. Please call us to discuss the dosage form, medication, and strength which are most appropriate for your patient.
      • ABHR - gel and troche
      • Cholestyramine ointment
      • Dextromethorphan
      • single agent and oral modified release preparations
      • Hydrocodone without acetaminophen
      • Lidocaine -Tetracaine spray
      • Metoclopramide- nasal spray and suppository
      • Misoprostol – suppository and oral preparations
      • Morphine transdermal
      • Pilocarpine – gel, lollipop, or oral modified release preparations
      • Promethazine gel
      • Scopolamine gel
      • Short chain fatty acid enemas
      • Sucralfate oral adhesive paste, cream, and enema

Dermatology

  • Our compounding professionals can prepare individualized therapies for a myriad of dermatologic problems. Compounding pharmacists continue to improve both the aesthetic and therapeutic aspects of customized medications, offering alternatives and advantages for dermatology. We can compound medications into cosmetically appealing creams, topical sprays and powders, as well as create customized oral dosage forms (such as flavored troches or lollipops) and various preparations for other routes of administration. Compatible drugs can be combined into a single dosage form to simplify a medication administration schedule and improve compliance. USP approved chemicals can be utilized to enhance the absorption of topically applied medications. We commonly prepare unique formulations that physicians develop to meet specific needs of their patient population, or "tried and true" formulas acquired during medical training.
  • Acne

    • We can compound customized formulations which contain numerous medications to provide a synergistic effect for treatment of resistant acne. Int J Dermatol 1995 Jun;34(6):434-7
      Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris.
      Click here to access the PubMed abstract of this article. J Dermatol 1996 Apr;23(4):243-6
      Topical spironolactone reduces sebum secretion rates in young adults.
      Click here to access the PubMed abstract of this article.
  • Athlete's Foot

    • Various synergistic combinations are used for antifungal therapy. Research points to the practicality "of using ibuprofen, alone or in combination with azoles, in the treatment of candidosis, particularly when applied topically, taking advantage of the drug's antifungal and anti-inflammatory properties." J Med Microbiol 2000 Sep;49(9):831-40
      Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species.
      Click here to access the PubMed abstract of this article.
  • Chemical Peels

    • Chemical peelings with kojic acid, glycolic acid, and trichloroacetic acid, either alone or in combination, are effective therapy for diffuse melasma and localized hyperpigmentations (lentigo). Dermatol Surg 1999 Jun;25(6):450-4
      The use of chemical peelings in the treatment of different cutaneous hyperpigmentations.
      Click here to access the PubMed abstract of this article.
  • Diaper Rash/Incontinence

    • Ann Pharmacother 1996 Sep;30(9):954-6
      Cholestyramine ointment to treat buttocks rash and anal excoriation in an infant.
      Click here to access the PubMed abstract of this article. Dis Colon Rectum 1987 Feb;30(2):106-7
      Cholestyramine ointment in the treatment of perianal skin irritation following ileoanal anastomosis.
      Click here to access the PubMed abstract of this article.
  • Head Lice and Scabies

    • Concerns about emerging resistance and the potential harm of using permethrins have prompted a search for effective pediculicidal therapies that are not harmful to children with repeated use. An herbal formulation has been shown to be effective for head lice. Ivermectin can also be compounded for topical application or as an oral dose titrated for each patient for the treatment of head lice and scabies. Clin Exp Dermatol 2002 Jun;27(4):264-7
      Treatment of 18 children with scabies or cutaneous larva migrans using ivermectin.
      Click here to access the PubMed abstract of this article.

      Twenty six male and female patients aged 5 to 17 years had head lice infestation confirmed by eggs presence and received treatments with a single 200 microgram/kg oral dose of. At day 14 after treatment, 20 had responded to the treatment (77%), and 6 patients (23%) presented with a complete disappearance of eggs and all clinical symptoms. At day 28, 7 patients appeared clear of infestation (27%), but 4 of the 6 patients with no eggs at day 14 presented with signs of reinfestation. This study suggests that ivermectin is a promising treatment of head lice, and a second dose at day 10 may be appropriate.

      Trop Med Parasitol 1994 Sep;45(3):253-4
      Efficacy of ivermectin for the treatment of head lice (Pediculosis capitis).
      Click here to access the PubMed abstract of this article.   Two hundred scabies patients were randomly allocated to receive either oral ivermectin in a single dose of 200 micrograms/kg body weight, or 1% lindane lotion for topical application overnight. Patients were assessed after 48 hours, two weeks and four weeks. After a period of four weeks, 82.6% of the patients in the ivermectin group showed marked improvement; only 44.44% of the patients in the lindane group showed a similar response. Oral ivermectin is easy to administer as a single oral dose, induces an early and effective improvement in signs and symptoms, and compliance is accordingly increased.

      J Dermatol 2001 Sep;28(9):481-4
      Oral ivermectin in scabies patients: a comparison with 1% topical lindane lotion.
      Click here to access the PubMed abstract of this article.   Isr Med Assoc J. 2002 Oct;4(10):790-3
      The in vivo pediculicidal efficacy of a natural remedy.
      Click here to access the PubMed abstract of this article.
  • Molluscum Contagiosum

    • The following study found that 5% KOH aqueous solution proved to be as effective and less irritating when compared to the 10% KOH solution. This trial also emphasizes the effectiveness of topical KOH in the treatment of molluscum contagiosum, sparing affected children from more aggressive physical modalities of treatment. Pediatr Dermatol 2000 Nov-Dec;17(6):495
      Evaluation of the effectiveness of 5% potassium hydroxide for the treatment of molluscum contagiosum.
      Click here to access the PubMed abstract of this article.
  • Nail Infection/Removal

    • Treatment of Fingernail Lichen Planus
       
      Nail lichen planus most commonly occurs during the fifth and sixth decade of life and can be notoriously recalcitrant to many forms of treatment. Prevost and English of the University of Pittsburgh Department of Dermatology reported a case of successful treatment of destructive inflammatory lichen planus of the nails with combined topical therapy of tazarotene gel and clobetasol gel, without the occurrence of potential adverse affects of systemic treatments.
       
      J Drugs Dermatol. 2007 Feb;6(2):202-4.
      Palliative treatment of fingernail lichen planus.
      Click here to access the PubMed abstract of this article.




      Although surgical excision is the most popular method for removing nails, the use of concentrated urea plasters applied under occlusion may be superior. The use of urea plasters has inherent advantages - they are inexpensive, several nails can be treated in one session, and the procedure is essentially painless. Various synergistic combinations and topical medications with penetrant enhancers can be compounded for antifungal therapy. Topical medications usually have a lower adverse drug-reaction profile than systemic medications. Cutis. 1980 Jun;25(6):609-12
      Urea ointment in the nonsurgical avulsion of nail dystrophies--a reappraisal.
      Click here to access the PubMed abstract of this article. Cutis. 1980 Apr;25(4):397, 405
      Combination urea and salicyclic acid ointment nail avulsion in nondystrophic nails: a follow-up observation.
      Click here to access the PubMed abstract of this article. JAMA 1979 Apr 13;241(15):1559, 1563
      Urea plasters alternative to surgery for nail removal.
      PMID: 430701 (No abstract available) Clin Exp Dermatol 1982 May;7(3):273-6
      The treatment of fungus and yeast infections of nails by the method of "chemical removal".
      PMID: 7105479 (No abstract available)   Management of onychomycosis, a fungal infection of the fingernails and toenails, usually consists of systemic antifungal medications, topical therapy (e.g., urea ointment, desiccating solutions, keratolytics, vital dyes), or surgical intervention (e.g., nail plate avulsion, laser therapy). Topical prescription antifungal preparations, containing the active ingredient of your choice, may be less likely to cause the serious systemic side effects that can occur with oral antifungal therapy and can provide a more economical alternative, as lower doses are needed when the medication is applied topically at the site. Penetrant enhancers can be included in the preparation to improve the effectiveness of topical antifungals.  Trop Med Int Health 1999 Apr;4(4):284-7
      Treatment of toenail onychomycosis with 2% butenafine and 5% Melaleuca alternifolia (tea tree) oil in cream.
      Click here to access the PubMed abstract of this article.
  • Pigmentation Abnormalities

    • Patients with vitiligo have low catalase levels in their epidermis in association with high levels of hydrogen peroxide. Topical application of a UVB-activated pseudocatalase cream can successfully remove epidermal H2O2 resulting in a remarkable repigmentation. J Investig Dermatol Symp Proc 1999 Sep;4(1):91-6
      In vivo and in vitro evidence for hydrogen peroxide (H2O2) accumulation in the epidermis of patients with vitiligo and its successful removal by a UVB-activated pseudocatalase.
      Click here to access the PubMed abstract of this article.
      Researchers concluded that "although hydroquinone showed a better response, ascorbic acid may play a role in the therapy of melasma as it is almost devoid of side-effects; it could be used alone or in combination therapy." Int J Dermatol. 2004 Aug;43(8):604-7.
      A double-blind randomized trial of 5% ascorbic acid vs. 4% hydroquinone in melasma.
      Espinal-Perez LE, Moncada B, Castanedo-Cazares JP. Click here to access the PubMed abstract of this article.   Melasma is a circumscribed brown macular hyperpigmentation of areas of the face and neck that are exposed to light, and is aggravated by sunlight, birth control pills, and pregnancy. This study demonstrates that a cream containing hydroquinone, glycolic acid, vitamins C and E, and sunscreen is a safe and effective treatment therapy for melasma. Int J Dermatol. 2003 Dec;42(12):966-72.
      Safety and efficacy of 4% hydroquinone combined with 10% glycolic acid, antioxidants, and sunscreen in the treatment of melasma.
      Guevara IL, Pandya AG. Click here to access the PubMed abstract of this article.
      The antioxidant N-acetyl cysteine (NAC) has an antiproliferative effect on human keratinocytes and NAC has been used topically to satisfactorily treat lamellar ichthyosis. Lancet. 1999 Nov 27;354(9193):1880.
      Topical N-acetylcysteine for lamellar ichthyosis.
      Redondo P, Bauzá A. Click here to access the PubMed abstract of this article. Topically applied NAC can prevent skin irritation resulting from radiotherapy and protects from sun-induced erythema. Semin Oncol. 1983 Mar;10(1 Suppl 1):86-92.
      Topical use of N-acetylcysteine for reduction of skin reaction to radiation therapy.
      Kim JA, Baker DG, Hahn SS, Goodchild NT, Constable WC. Click here to access the PubMed abstract of this article.  
  • Plantar Warts/Warts

    • Topical 5-fluorouracil (5-FU) 5% with tape occlusion produced complete eradication of all plantar warts within 12 weeks of treatment in 19 of 20 patients. It was concluded that use of topical 5% 5-fluorouracil cream for plantar warts is safe, efficacious, and accepted by the patient.
       
      J Drugs Dermatol. 2006 May;5(5):418-24.
      Topical 5% 5-fluorouracil cream in the treatment of plantar warts: a prospective, randomized, and controlled clinical study.
      Click here to access the PubMed abstract of this article.
      A medical record review was conducted by the Podiatry Division, Department of Orthopedics, Cabrini Medical Center, New York, NY to determine the clinical outcome and average time to resolution of verruca plantaris (plantar warts) in 20 patients treated with twice-daily applications of topical fluorouracil (5-FU) combined with topical 17% and 40% salicylic acid. Twice-daily application of topical fluorouracil and salicylic acid is a safe and effective treatment for verruca plantaris. J Am Podiatr Med Assoc. 2005 Jul-Aug;95(4):366-9.
      Treatment of verruca plantaris with a combination of topical fluorouracil and salicylic acid.
      Click here to access the PubMed abstract of this article. Phys Ther. 2002 Dec;82(12):1184-91
      Treatment of plantar verrucae using 2% sodium salicylate iontophoresis.
      Click here to access the PubMed abstract of this article.   Cantharidin in a collodion vehicle has been used by dermatologists as a treatment for molluscum contagiosum and warts since the 1950s. Cantharidin lost FDA approval in 1962 because its manufacturers failed to submit data attesting to cantharidin's efficacy. However, in 1999, the FDA included cantharidin on its "Bulk Substances List" of drugs which although not available as commercial products, were approved for compounding on a customized basis for individual patients. Because of cantharidin's potential for toxicity, the FDA has proposed that cantharidin should be limited to "topical use in the professional office setting only." Severe blistering can result from improper use, and ingestion, especially by children, can be fatal. Treatment of mucous membranes is contraindicated and placement of cantharidin near the eyes and eyelids should be avoided to prevent scleral erosion. Caution: The treatment of plantar warts with cantharidin is NOT recommended and may have a higher rate of significant complications including lymphangitis and refractory lymphedema. Arch Dermatol. 2001;137:1357-1360
      Cantharidin revisited: a blistering defense of an ancient medicine.
      Click here to access the PubMed abstract J Am Acad Dermatol. 2000;43:503-507
      Childhood molluscum contagiosum: experience with cantharidin therapy in 300 patients.
      Click here to access the PubMed abstract   Squaric Acid Dibutylester (SADBE) for Cutaneous Warts in Children Warts are a common pediatric skin infection and clearance may be enhanced by contact sensitizers, such as squaric acid dibutylester (SADBE). Contact immunotherapy with SADBE is relatively safe and an effective alternative in the management of multiple and resistant cutaneous warts in children. J Am Acad Dermatol. 2000 May;42(5 Pt 1):803-8
      Squaric acid immunotherapy for warts in children.
      Click here to access the PubMed abstract
      Pediatr Dermatol. 2000 Jul-Aug;17(4):315-8
      Use of squaric acid dibutylester (SADBE) for cutaneous warts in children.
      Click here to access the PubMed abstract

      J Am Acad Dermatol. 1999 Oct;41(4):595-9
      Contact immunotherapy with squaric acid dibutylester for the treatment of recalcitrant warts.
      Click here to access the PubMed abstract
  • Rosacea

    • Clin Exp Dermatol 2003 Jan;28(1):61-3
      Topical application of NADH for the treatment of rosacea and contact dermatitis.
      Click here to access the PubMed abstract of this article.
  • Scarring and Keloids

    • Br J Plast Surg 1998 Sep;51(6):462-9
      Topical tamoxifen--a potential therapeutic regime in treating excessive dermal scarring?
      Click here to access the PubMed abstract of this article.
  • Topical Anesthetics

    • Topical anesthesia is needed for common procedures such as suturing, wound cleaning, and injection administration. The ideal topical anesthetic would provide complete anesthesia following a simple pain-free application, not contain narcotics or controlled substances, and have an excellent safety profile. The combination of topical anesthetics lidocaine and tetracaine and the vasoconstrictor epinephrine has been used successfully for anesthesia prior to suturing linear scalp and facial lacerations in children. A triple-anesthetic gel containing benzocaine, lidocaine, and tetracaine ("BLT") has also been reported to be effective when applied prior to laser and cosmetic procedures. Convenience of application without need for occlusion is an advantage of these topical anesthetics. The following article concludes: "LAT gel (4% lidocaine, 1:2000 adrenaline, 0.5% tetracaine) worked as well as TAC gel (0.5% tetracaine, 1:2000 adrenaline, 11.8% cocaine) for topical anesthesia in facial and scalp lacerations. Considering the advantages of a noncontrolled substance and less expense, LAT gel appears to be better suited than TAC gel for topical anesthesia in laceration repair in children." Pediatrics 1995 Feb;95(2):255-8
      Lidocaine adrenaline tetracaine gel versus tetracaine adrenaline cocaine gel for topical anesthesia in linear scalp and facial lacerations in children aged 5 to 17 years.
      Click here to access the PubMed abstract of this article.
        The following article reported that a triple-anesthetic gel containing benzocaine, lidocaine, and tetracaine ("BLT") applied prior to treatment with a 532-nm KTP laser resulted in significantly lower pain scores than with 3 other topical anesthetics at 15, 30, 45, and 60 minutes after application. Cosmetic Dermatology 2003 Apr;16(4):35-7
      Topical Triple-Anesthetic Gel Compared With 3 Topical Anesthetics
  • Sun Protection/Photoaged Skin/Wrinkles

    • Topically applied antioxidants exert their benefits by offering protection from damaging free radicals produced when skin is exposed to ultraviolet light or allowed to age naturally. Appropriate formulation and use which is supervised by a knowledgeable healthcare professional will maximize the benefits while minimizing any potential side effects of these therapies.
       
      Biofactors 1999;9(2-4):371-8 
      Coenzyme Q10, a cutaneous antioxidant and energizer.
      Click here to access the PubMed abstract of this article.
      Coenzyme Q10 (ubiquinone, CoQ10) is an important antioxidant that is taken to strengthen immune and cardiac function. The processes of aging and photoaging of the skin (due to sunlight) are associated with an increase in cellular oxidation, which may occur as the body’s own levels of CoQ10 decline. A reduction in wrinkle depth was shown following topical application of CoQ10 0.3%, and results indicated that CoQ10 has the efficacy to prevent many of the detrimental effects of photoaging. Wrinkles around the region of the eyes (“crow’s feet”) may be reduced by long-term application of CoQ10.
       
      Z Gerontol Geriatr 1999 Apr;32(2):83-8
      Modulation of oxidative stresses in human aging skin
      Click here to access the PubMed abstract of this article.
      Vitamin C has been incorporated into a variety of cosmeceuticals designed to protect and rejuvenate photoaged skin. Ascorbyl Palmitate (Vitamin C Ester) is a lipid soluble, neutral pH, non-acidic (thus, non-irritating and non-stinging) form of Vitamin C which can reach cells within the skin rapidly in amounts greater than can be achieved by water soluble Vitamin C (L-Ascorbic Acid).

      Dermatol Surg. 2005 Jul;31(7 Pt 2):814-7
      Topical vitamin C: a useful agent for treating photoaging and other dermatologic conditions.
      Click here to access the PubMed abstract of this article.
        Alpha Lipoic Acid (ALA) is a powerful antioxidant and scavenger with anti-inflammatory properties that promotes optimum efficiency for production of energy and removal of intracellular waste products, essential for cellular healing and elimination of wrinkles and facial scars. Twelve weeks of treatment with a cream containing 5% ALA improves clinical characteristics related to photoaging of facial skin.
       
      Br J Dermatol. 2003 Oct; 149(4): 841-9
      Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoageing of facial skin.
      Click here to access the PubMed abstract of this article.
        Topical niacinamide 5% (vitamin B3) reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in aging facial skin.
        
      Int J Cosmet Sci. 2004 Oct;26(5):231-8.
      Topical niacinamide reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in aging facial skin.
      Click here to access the PubMed abstract of this article.
      Topical application of 0.01% estradiol and 0.3% estriol markedly improved elasticity and firmness of the skin, substantially decreased  pore sizes, increased skin moisture, and decreased wrinkle depth.
       
      Eur J Obstet Gynecol Reprod Biol. 2007 Feb;130(2):202-5.
      Effects of topical estradiol on the facial skin collagen of postmenopausal women under oral hormone therapy: a pilot study.
      Click here to access the PubMed abstract of this article. Int J Dermatol. 1996 Sep;35(9):669-74.
      Treatment of skin aging with topical estrogens.
      Click here to access the PubMed abstract of this article. Topical 2% progesterone increases elasticity and firmness in the skin of peri- and postmenopausal women.
       
      Br J Dermatol. 2005 Sep;153(3):626-34.
      Effects and side-effects of 2% progesterone cream on the skin of peri- and postmenopausal women: results from a double-blind, vehicle-controlled, randomized study.
      Click here to access the PubMed abstract of this article.
        DMAE (2-dimethylaminoethanol, deanol), when applied topically to the skin, may improve the appearance of sagging skin, boost the effects of other antioxidants, increase smoothness, reduce fine lines and give facial muscles a leaner look. In a randomized clinical study, 3% DMAE facial gel applied daily for 16 weeks has been shown to be safe and efficacious in the mitigation of forehead lines and periorbital fine wrinkles, and in improving lip shape and fullness and the overall appearance of aging skin. Br J Dermatol. 2007 Mar;156(3):433-9.
      The antiwrinkle effect of topical concentrated 2-dimethylaminoethanol involves a vacuolar cytopathology.
      Click here to access the PubMed abstract of this article. Am J Clin Dermatol. 2005;6(1):39-47.
      The role of dimethylaminoethanol in cosmetic dermatology.
      Click here to access the PubMed abstract of this article.

      Antioxidants such as vitamins E and C, coenzyme Q10, alpha-lipoic acid, glutathione, and others can reduce signs of aging.
       
      Acta Dermatovenerol Alp Panonica Adriat. 2008 Jun;17(2):47-54.
      Skin aging.
      Click here to access the PubMed abstract of this article.

        Alpha-lipoic acid (ALA) 0.5% and proanthocyanidin (PA) 0.3% administered transdermally in a cosmetic formulation supplemented with 2% benzyl alcohol as a penetration enhancer,  significantly enhanced collagen synthesis and deposition.      
              
      Connect Tissue Res. 2005;46(4-5):251-7.
      Transdermal delivery of amino acids and antioxidants enhance collagen synthesis: in vivo and in vitro studies.
      Click here to access the PubMed abstract of this article.


      Topical Application of Phytonadione, Retinol and Vitamins C and E to Reduce Infraorbital Dark Circles and Wrinkles of the Lower Eyelids
       
       Infraorbital dark circles and wrinkles of the lower eyelids are cosmetic problems that worsen with age. Fifty-seven healthy adult volunteers with dark under-eye circles and wrinkles were enrolled in an open label study to determine whether a gel containing 2% phytonadione, 0.1% retinol and 0.1% vitamins C and E is effective in reducing dark under-eye circles and wrinkles of the lower eyelids. The gel formulation was applied twice daily to the lower eyelid site for 8 weeks. Hemostasis, pigmentation and wrinkles were evaluated by a physician and by the patients after 4 and 8 weeks of treatment. Topical application of the gel decreased not only hemostasis but also wrinkles after 8 weeks of treatment. Of 57 patients, 27 (47%) had reductions in hemostasis. However, pigmentation was not clearly removed by this gel.
       
      J Cosmet Dermatol. 2004 Apr;3(2):73-5
      The effects of topical application of phytonadione, retinol and vitamins C and E on infraorbital dark circles and wrinkles of the lower eyelids.
      Click here to access the PubMed abstract of this article.
       
      Protection and Reversal of Photodamage with Topical Antioxidants
       
      Topical vitamins C and E, as well as topical selenium, protect skin against sunburn, suntan and skin cancer and also reverse the mottled pigmentation and wrinkles of photoaging. However, only certain forms of these antioxidants are stable and active after percutaneous absorption. Benefits of topical application are that the skin attains far higher levels of each antioxidant than can be achieved by taking these vitamins orally and topical application arms the skin with a reservoir of antioxidants that cannot be washed or rubbed off, protecting the skin for several days after application.
       
      J Cosmet Dermatol. 2004 Jul;3(3):149-55 
      Photodamage of the skin: protection and reversal with topical antioxidants.
      Click here to access the PubMed abstract of this article.



      Topical application of niacinamide (such as in a 2% cream) has a stabilizing effect on epidermal barrier function, seen as a reduction in transepidermal water loss and an improvement in the moisture content of the horny layer, and it may be used as a treatment adjunct in atopic dermatitis. In aging skin, topical application of niacinamide improves the surface structure and pigmentary disorders, smoothes out wrinkles and inhibits photocarcinogenesis.  Cutis 2006 Jan;77(1 Suppl):11-6.
      Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review. Click here to access the PubMed abstract of this article.  Int J Dermatol 2005 Mar;44(3):197-202.
      Moisturizing effects of topical nicotinamide on atopic dry skin. Click here to access the PubMed abstract of this article.  J Cosmet Dermatol 2004 Apr;3(2):88-93
      Nicotinic acid/niacinamide and the skin.  Click here to access the PubMed abstract of this article.   


      Niacinamide can be combined with other active ingredients such as DMAE, sodium hyaluronate, benzoyl peroxide, or metronidazole in a customized medication that can be used as anti-wrinkle or anti-aging therapy or to treat acne or rosacea Br J Dermatol. 2003 Oct; 149(4): 841-9
      Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoageing of facial skin.
      Click here to access the PubMed abstract of this article.


      Estrogen Therapy to Prevent or Reverse Skin Aging  Declining estrogen levels are associated with a variety of cutaneous changes, many of which can be reversed or improved by topical or systemic estrogen supplementation. Studies of postmenopausal women indicate that estrogen deprivation is associated with declining dermal collagen content, diminished elasticity and skin strength, loss of moisture in the skin, epidermal thinning, atrophy, fine wrinkling, and impaired wound healing. Keratinocytes, Langerhans' cells, melanocytes, sebaceous glands, collagen content and the synthesis of hyaluronic acid are under hormonal influence. Estrogen may attenuate inflammation in psoriatic lesions. Alone or together with progesterone, estrogen prevents or reverses skin atrophy, dryness and wrinkles associated with chronological or photo-aging. Estrogen and progesterone stimulate proliferation of keratinocytes while estrogen suppresses apoptosis and thus prevents epidermal atrophy. Estrogen maintains skin moisture by increasing acid mucopolysaccharide or hyaluronic acid levels in the dermis, and accelerates cutaneous wound healing.  Low estrogen levels that accompany menopause exacerbate the deleterious effects of both intrinsic and environmental aging. Estrogens clearly have a key role in skin aging homeostasis as evidenced by the accelerated decline in skin appearance seen in the perimenopausal years.  At Yale University School of Medicine, the effects of long-term hormone replacement therapy (HRT) on skin rigidity and wrinkling at 11 facial locations was assessed using the Lemperle scale by a plastic surgeon who was blinded to HRT use. Skin rigidity at the cheek and forehead was measured with a durometer. Demographics including age, race, sun exposure, sunscreen use, tobacco use, and skin type were similar. Rigidity was significantly decreased in HRT users compared to nonusers at both the cheek and forehead. Average wrinkle scores were lower in hormone users than in nonhormone users. The study concluded that long-term postmenopausal HRT users have more elastic skin and less severe wrinkling than women who never used HRT, suggesting that hormone therapy may have cosmetic benefits.     In another study, the dermal collagen of 15 postmenopausal women who had received systemic estrogen replacement was analyzed before and after using a topical 0.01% estrogen treatment. Epithelial and dermal thickness improved after topical estrogen therapy. Facial skin collagen significantly increased after 16 weeks of treatment. Systemic estrogen levels did not significantly increase after topical therapy. 
      Exp Dermatol. 2004;13 Suppl 4:36-40
      Skin aging and sex hormones in women -- clinical perspectives for intervention by hormone replacement therapy.
      Click here to access the PubMed abstract of this article.

      Exp Dermatol. 2006 Feb;15(2):83-94
      Biology of estrogens in skin: implications for skin aging.
      Click here to access the PubMed abstract of this article.

      Eur J Obstet Gynecol Reprod Biol. 2006 Jun 22

      J Am Acad Dermatol. 2005 Oct;53(4):555-68; quiz 569-72
      Estrogen and skin: the effects of estrogen, menopause, and hormone replacement therapy on the skin.
      Click here to access the PubMed abstract of this article.

      Fertil Steril. 2005 Aug;84(2):285-8
      Long-term effects of hormone therapy on skin rigidity and wrinkles.
      Click here to access the PubMed abstract of this article.

      Am J Clin Dermatol. 2003;4(6):371-8
      Skin aging and menopause : implications for treatment.
      Click here to access the PubMed abstract of this article.

      Am J Clin Dermatol. 2001;2(3):143-50
      Estrogen and skin. An overview.
      Click here to access the PubMed abstract of this article.

      J Dermatol Sci. 2005 Apr;38(1):1-7
      Regulatory roles of sex hormones in cutaneous biology and immunology.
      Click here to access the PubMed abstract of this article.




      In the following study, the effects of topical 0.01% estradiol and 0.3% estriol compounds were measured in preclimacteric women with skin aging symptoms. After treatment for 6 months, elasticity and firmness of the skin had markedly improved; wrinkle depth and pore sizes had decreased by 61 to 100%; skin moisture had increased; and wrinkle depth decreased significantly. Int J Dermatol 1996 Sep;35(9):669-74
      Treatment of skin aging with topical estrogens.
      Click here to access the PubMed abstract of this article.

      A low-dose, topical gel form of diclofenac sodium has been developed in Europe for pain relief and reduction of redness after sunburn. Eur J Dermatol. 2004 Jul-Aug;14(4):238-46
      The efficacy and safety of low-dose diclofenac sodium 0.1% gel for the symptomatic relief of pain and erythema associated with superficial natural sunburn.
      Click here to access the PubMed abstract of this article.
  • Pruritis

    • Pramoxine Reduces Uremic Pruritus
       
      Wake Forest University School of Medicine conducted a randomized, double-blind, controlled comparative trial in a community hemodialysis center to evaluate the efficacy of 1% pramoxine hydrochloride lotion versus control lotion in the treatment of uremic pruritus in adult hemodialysis patients. Pramoxine 1% lotion was applied twice daily to all affected areas of pruritus for 4 weeks, resulting in a 61% decrease in itch intensity. “This safe, convenient and effective topical lotion may potentially benefit the large number of patients affected by pruritus associated with end-stage renal disease.”
       
      J Dermatolog Treat. 2008 Sep 24:1-5.
      A pramoxine-based anti-itch lotion is more effective than a control lotion for the treatment of uremic pruritus in adult hemodialysis patients.
      Click here to access the PubMed abstract of this article.

      Hydroxyethyl Starch-Induced Pruritus Relieved by Menthol/Camphor Lotion
       
         Hydroxyethyl starch (HES) is a key component of many colloid volume expanders used in hypovolemic shock and otologic disease. Pruritus is a common side effect. Although classically refractory to treatment with corticosteroids and antihistamines, some benefit has been achieved with topical capsaicin, ultraviolet light therapy, and oral naltrexone.
          A man with severe symptoms and refractory course was treated with a topical lotion containing 0.5% camphor and 0.5% menthol, which was dramatically successful.
         A randomized, double-blind, placebo-controlled trial showed a combination of menthol and phenol to be beneficial in mustard-gas induced pruritis.
       
      J Am Acad Dermatol. 2008 Jul;59(1):151-3.
      Hydroxyethyl starch-induced pruritus relieved by a combination of menthol and camphor.
      Click here to access the PubMed abstract of this article. Singapore Med J 2007;48:392-5.
      Phenol and menthol in the treatment of chronic skin lesions following mustard gas exposure.
      Click here to access the PubMed abstract of this article.

      Naltrexone for Post-Burn Pruritus and Severe Generalized Pruritus in Biliary Atresia 
       
      “Severe pruritus is one of the many complications that burn survivors endure as a consequence of healing or healed burn or donor site wounds, [and] continues to be a clinical challenge that is inadequately addressed by traditional therapies. The success of naltrexone, an opioid antagonist, in treating pruritus in other patient populations, supported the concept that it may also be effective in burn survivors.” Opioid antagonists have been shown to suppress pruritus in patients with chronic cholestasis, uremia, atopic dermatitis, and chloroquine-induced itching.
        
      “Naltrexone is a well-tolerated medication with little adverse effects [and] may be an effective adjuvant treatment in the management of cholestatic pruritus in the pediatric population.” Two studies used a topical formulation of 1% naltrexone (or placebo) for 2 weeks to treat patients with localized and generalized atopic dermatitis with severe itching. More than 70% of the patients using the 1% naltrexone cream experienced a significant reduction of pruritus. The cream containing naltrexone had an overall 29.4% better effect than placebo.
       
      Burns. 2008 Sep;34(6):797-802.
      Add article title
      Click here to access the PubMed abstract of this article. Pediatr Dermatol. 2008 May-Jun;25(3):403-4.
      The use of naltrexone in the management of severe generalized pruritus in biliary atresia: report of a case.
      Click here to access the PubMed abstract of this article. J Am Acad Dermatol. 2007 Jun;56(6):979-88 
      Treatment of pruritus with topically applied opiate receptor antagonist.
      Click here to access the PubMed abstract of this article.

      The following studies evaluated a topical formulation of 1% naltrexone to treat patients with localized and generalized atopic dermatitis with severe itching, and more than 70% of patients using the 1% naltrexone cream experienced a significant reduction of pruritus.J Am Acad Dermatol. 2007 Jun;56(6):979-88 
      Treatment of pruritus with topically applied opiate receptor antagonist.
      Click here to access the PubMed abstract of this article. J Cutan Med Surg. 2005 Oct;9(5):215-6           
      Successful treatment of refractory aquagenic pruritus with naltrexone.
      Click here to access the PubMed abstract of this article.




      Itching Relieved with Topical Naltrexone Pruritus is a very common and distressing skin problem. More than 70% of patients with localized and generalized atopic dermatitis with severe itching who used topical naltrexone 1% cream experienced a significant reduction of pruritus. J Am Acad Dermatol. 2007 Jun;56(6):979-88 
      Treatment of pruritus with topically applied opiate receptor antagonist.
      Click here to access the PubMed abstract of this article.

      Aquagenic pruritus is an intense prickling sensation that develops in affected individuals immediately after contact with water at any temperature. Endogenous opiates, like naltrexone, can modify pruritus by influencing the peripheral and central sensation of itch, and have been found to be successful in suppressing the perception of pruritus from many diverse origins including aquagenic pruritus. J Cutan Med Surg. 2005 Oct;9(5):215-6
      Successful treatment of refractory aquagenic pruritus with naltrexone
      Click here to access the PubMed abstract of this article.
  • Psoriasis

    • Results from this study indicate that coal tar can be maintained as a safe treatment in dermatological practice. J Invest Dermatol. 2010 Apr;130(4):953-61. Epub 2009 Dec 17.
      No increased risk of cancer after coal tar treatment in patients with psoriasis or eczema.
      Roelofzen JH, Aben KK, Oldenhof UT, Coenraads PJ, Alkemade HA, van de Kerkhof PC, van der Valk PG, Kiemeney LA. Click here to access the PubMed abstract of this article. Two double-blind, randomized, clinical evaluations were conducted to investigate the anecdotal belief that tachyphylaxis occurs in long-term treatment of scalp seborrheic dermatits and dandruff when using a single pyrithione zinc-based product. Evaluation of data showed a consistent benefit for all products at all time points; therefore, no evidence of decreased benefit over time was found within 48 weeks of treatment. Int J Dermatol. 2009 Jan;48(1):79-85.
      Does tachyphylaxis occur in long-term management of scalp seborrheic dermatitis with pyrithione zinc-based treatments?
      Schwartz JR, Rocchetta H, Asawanonda P, Luo F, Thomas JH. Click here to access the PubMed abstract of this article. Traditionally used in an ointment vehicle for psoriasis, clobetasol propionate 0.05% is also available in spray, foam, lotion, and shampoo formulations, which may provide for improved convenience and acceptance with similar efficacy, safety, and tolerability as the traditional ointment and cream formulations. For patients who prefer a less messy vehicle, adherence and outcomes are likely to be better with the formulations other than the traditionally recommended ointment.
      Am J Clin Dermatol. 2009;10(6):397-406.
      Topical clobetasol propionate in the treatment of psoriasis: a review of newer formulations.
      Feldman SR, Yentzer BA. Click here to access the PubMed abstract of this article. Topical vitamin B12 offers a new therapeutic approach for eczema (atopic dermatitis) and psoriasis, and may be suitable for long-term therapy as no long term adverse effects have been reported.  
      Topical vitamin B12--a new therapeutic approach in atopic dermatitis-evaluation of efficacy and tolerability in a randomized placebo-controlled multicentre clinical trial.         Click here to access the PubMed abstract of this article.Dermatology 2001;203:141-147
      Vitamin B(12) cream containing avocado oil in the therapy of plaque psoriasis.              Click here to access the PubMed abstract of this article.
      Salicylic acid has been used alone as a treatment for psoriasis, but is most commonly used to increase the penetration of other topical preparations, primarily corticosteroids. In this small study, the use of 6% salicylic acid gel in conjunction with tacrolimus ointment showed statistically significant improvement for the treatment of plaque psoriasis compared with the use of salicylic acid alone. "For patients with localized psoriasis, and for many of those with moderate psoriasis as well, the mainstay of treatment is still topical therapy. The quality of life is greatly affected in such patients, and they often express high levels of dissatisfaction with current treatment options. Safe, convenient, and effective topical regimens, such as combination therapy with topical tacrolimus and salicylic acid, can be of great benefit in this large population." Arch Dermatol. 2005;141:43-46
      Topical tacrolimus ointment combined with 6% salicylic acid gel for plaque psoriasis treatment.
      Click here to view the abstract or FREE FULL TEXT of this complete article. "Methotrexate has been used as an effective systemic chemotherapeutic drug for psoriasis by dermatologists for over 30 years. Nevertheless, pharmacokinetic data indicate that oral methotrexate can cause a decrease in red and white blood cell and platelet counts and can also cause severe liver damage, diarrhea, and stomach irritation, as dose-related drug-induced side effects. Such indications have limited its prescription by physicians. However, [Syed and Nordstrom of the Department of Dermatology, University of California-San Francisco, and researchers from three other locations note that] if its incorporation in a gel as a topical agent, in a proper dosage. imparts better results without the cited side effects, then such a formulation appears to justify a clinical evaluation. Furthermore, published data have indicated that 70% of patients prefer topical therapy for treating psoriasis." This article concludes: "methotrexate 0.25% in a hydrophilic gel is well tolerated and significantly more effective than placebo as a patient-applied topical medication to treat psoriasis vulgaris." J Cutan Med Surg 2001; 299-302
      Management of psoriasis vulgaris with methotrexate 0.25% in a hydrophilic gel: a placebo-controlled, double-blind study.
      Click here to view the PubMed abstract for this article. This article concludes: "Methotrexate 0.25% in a hydrophilic gel is well tolerated but is not very effective in controlling the lesions of psoriasis on the palms and soles; however, a higher concentration in a different base with better penetration could possibly provide better results."
       
      J Dermatol 2004 Oct;31(10):798-801
      Topical 0.25% methotrexate gel in a hydrogel base for palmoplantar psoriasis.
      Click here to access the PubMed abstract of this article. Tiwari, Kumar, et al. published a case report of topical methotrexate delivered by iontophoresis for the treatment of recalcitrant palmoplantar psoriasis. In a 46 y.o. male with well-defined bilateral palmar plaques of 6 years duration which were resistant to several therapies, the right palm was treated, as it had more severe lesions. Iontophoresis was performed using cotton gauze soaked in 4 to 6 ml of methotrexate disodium solution 10 mg/ml, once a week for four weeks. The researchers reported 75% improvement after four weeks of therapy. Iontophoresis allows high concentrations of drug to be delivered to a limited area, and may offer a method of reducing total drug accumulation and reduced side effects.

      Int J Dermatol. 2003 Feb;42(2):157-9
      Topical methotrexate delivered by iontophoresis in the treatment of recalcitrant psoriais--a case report.
      Click here to view the citation for this article.
  • Vitiligo

    • Treatment Options for Vitiligo

      Pseudocatalase Cream
      Vitiligo is a spontaneous irregular depigmentation of skin. Patients with vitiligo have low catalase levels in their epidermis with high levels of hydrogen peroxide. Pseudocatalase cream is an externally applied UVB-activated product that can lead to recovery of the oxidative damage in the epidermis and remarkable repigmentation. Skin Pharmacol Appl Skin Physiol 1999 May-Jun;12(3):132-8
      Successful treatment of oxidative stress in vitiligo.
      Click here to access the PubMed abstract J Pathol 2000 Aug;191(4):407-16
      Melanocytes are not absent in lesional skin of long duration vitiligo.
      Click here to access the PubMed abstract J Investig Dermatol Symp Proc 1999 Sep;4(1):91-6
      In vivo and in vitro evidence for hydrogen peroxide (H2O2) accumulation in the epidermis of patients with vitiligo and its successful removal by a UVB-activated pseudocatalase.
      Click here to access the PubMed abstract Dermatology 1995;190(3):223-9
      Treatment of vitiligo with a topical application of pseudocatalase and calcium in combination with short-term UVB exposure: a case study on 33 patients.
      Click here to access the PubMed abstract



      Topical Phenylalanine 
       
      Melanocytes may still be present in long-standing (>25 years) depigmented skin of patients with vitiligo. L-phenylalanine uptake and turnover in the pigment forming melanocytes is vital for initiation of melanogenesis. Phenylalanine hydroxylase activities increase linearly with inherited skin color yielding eightfold more activities in black skin compared to white skin.  Camacho and Mazuecos performed an uncontrolled retrospective survey of a group of 193 patients (171 participants after screening) with evolving vitiligo who were treated with oral (50 or 100 mg/kg daily) and topical (10% gel) phenylalanine plus sun exposure . When the study closed, 100% repigmentation was achieved in 122 patients on the face, 35 on the trunk, and 33 on the limbs. Patients who were treated during the months of high solar radiation (and therefore also used the topical phenylalanine) achieved greater repigmentation. No side effects were reported. Arch Dermatol. 1999;135:216-217
      Treatment of vitiligo with oral and topical phenylalanine: 6 years of experience.
      Click here to access the PubMed abstract J Drugs Dermatol 2002 Sep;1(2):127-31
      Oral and topical L-phenylalanine, clobetasol propionate, and UVA/sunlight--a new study for the treatment of vitiligo.
      Click here to access the PubMed abstract Mol Genet Metab 2005 Dec;86(4):27-33
      Decreased phenylalanine uptake and turnover in patients with vitiligo.
      Click here to access the PubMed abstract
  • Examples of Compounded Medications

    • The following list is just a few of the preparations that we can compound for dermatology. We work together with prescriber and patient to solve problems, and all formulations are customized per prescription to meet the unique needs of each patient. Therapeutic results depend not only on the selection of drug, but also the use of a proper base and preparation technique. Please contact our compounding pharmacist to discuss the dosage form, strength, and medication or combination that is most appropriate for your patient.
      • Alpha Lipoic Acid cream
      • "BLT" gel (benzocaine, lidocaine, and tetracaine)
      • Cholestyramine ointment
      • 2-Deoxy D-Glucose (2-DDG) in various dosage forms such as creams, lip balms, and oral rinses
      • Dapsone cream
      • Ivermectin - oral or topical
      • KOH solution - 5% and 10%
      • Kojic Acid, Hydroquinone, Retinoic Acid gel
      • Pseudocatalase cream
      • Tamoxifen topical
      • Trichloroacetic Acid/Lactic Acid/Azelaic Acid topical solution
      • Urea 40% ointment

Pediatrics

  • We work together with prescribers, children, and their families to customize medications and meet specific needs. Children pose many challenges when it comes to medication: they may resist having to take a medication, dislike the taste or texture, have difficulty swallowing solid dosage forms, and are fearful of injections. The limited pediatric market for most drugs may be the leading reason for the lack of investment in drug development for this population by the pharmaceutical industry. Most medications are not labeled for pediatric populations, and when a medication is not approved for use in infants and children, it usually is not available in a suitable pediatric dosage form. Fortunately, our compounding pharmacy is able to help. We can compound oral medications into pleasantly flavored suspensions, solutions, concentrates, freezerpops, "gummy bears" or lozenges, in colors that entice the child to take the medication. A palatable formulation is more likely to improve compliance and minimize spillage or waste during administration. Lollipops are an ideal alternative to "swish and swallow" medications that need to be retained in the mouth for a prolonged period of time. Most drugs can be compounded into transdermal gels that can easily be applied to an appropriate site, such as the child's wrist, for absorption through the skin. Professional compounding is not just diluting existing medications, or mixing powders with bases. We must consider physical and chemical properties of each active and inactive ingredient in order to prepare an effective and safe customized medication with the desired taste, color, fragrance, viscosity, uniformity, texture, and stability. The efficacy of any compounded medication is influenced by the technique and equipment used in preparing the formulation, the purity and quality of the ingredients, choice of vehicle (base), and proper use of additives such as penetration enhancers.
  • Acne

    • Emergence of resistant pathogens emphasizes the need for alternatives to antimicrobial agents for acne therapy. We can compound cosmetically-appealing customized formulations which can contain numerous medications to provide a synergistic effect for treatment of resistant acne. Int J Dermatol 1995 Jun;34(6):434-7
      Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris.
      Click here to access the PubMed abstract of this article. J Dermatol 1996 Apr;23(4):243-6
      Topical spironolactone reduces sebum secretion rates in young adults.
      Click here to access the PubMed abstract of this article.
  • Attention Deficit Hyperactivity Disorder

    • The use of medications to treat ADHD has greatly increased, yet the dosage requirements for many children differ from strengths that are commercially available. This often necessitates a midday dose at school, which can be embarrassing to a child. Slow-release dosage forms can be compounded to contain the precise dose of medication needed by each child. Pediatr Clin North Am 1999;46:945-963
      Management of stimulant medications in children with attention-deficit/hyperactivity disorder.
      Click here to access the PubMed abstract of this article.
  • Autism

    • Autism spectrum disorder (ASD) is diagnosed on the basis of behavioral parameters, yet there are many underlying biomedical factors which can contribute to these symptoms. Therapies directed at these underlying factors may be helpful in decreasing symptoms of autism. For example, recent studies have found chronic inflammation in the brains of children with autism, raising the possibility that treatments directed against inflammation may be helpful.  The Autism Research Institute asked parents to rate the effectiveness of numerous biomedical treatments. As of 2008, over 26,000 parents had evaluated more than 80 interventions. Detoxification was considered helpful by 74% of parents. Other highly rated therapies included gluten/casein-free diet, food allergy treatment, methylcobalamin, and essential fatty acid therapy. It is thought that the earlier treatment is started, the better the results. Gluten-Free and Casein-Free Preparations
      Children with autism may benefit from a gluten-free and casein-free diet. Many commonly used medications contain gluten. Some probiotics contain casein. We can compound preparations that are free of gluten and casein to solve problems for sensitive individuals.
       
      Therapy for Gut Dysbiosis
      Autistic children frequently have abnormalities in gut permeability, defects or deficiencies in intestinal enzymes, and/or abnormal intestinal flora. Yeast overgrowth can be prevented or treated by oral administration of Lactobacillus or other probiotics. If response is insufficient, oral antifungals may be needed. Prescription medications can be compounded for oral administration to help reduce yeast in the gut. Compromised digestive function, often secondary to inflammation of the bowel, may lead to the absorption of toxins (“leaky gut”). Children can benefit from balanced nutrition, treatment of imbalanced gut flora, and enhancement of immune function.
       
      Nutritional Therapy for Autism
      Most children with autism have a need for increased amounts of vitamins, minerals, and some amino acids. Some detoxification agents may remove essential minerals, creating a need for additional minerals. Vitamin C, vitamin B6, vitamin A, omega-3 fatty acids, calcium, magnesium, zinc, and selenium are often needed in addition to a broad-spectrum vitamin/mineral supplement. Copper should be avoided in many cases, since the levels in autistic children are sometimes high. Amino acid, nutritional, and supplemental therapies can be customized for each child. Once the physician has determined the specific nutrients that are needed, compatible supplements can be combined in flavored suspensions to simplify administration. Many children with autism are zinc deficient. Zinc deficiency affects taste perception and children then become averse to eating certain foods and taking supplements. In this case, transdermal preparations can be very helpful by completely bypassing the oral route of administration. Commonly needed nutrients which can easily be given in a transdermal form include vitamin A, vitamin D, and zinc.
       
      Glutathione is the major antioxidant in cells and is important for detoxification and elimination of environmental toxins.  Its active form is reduced in about 80 percent of autistic children. Oxidative stress, a suspected contributor in many disease processes like heart disease and cancer, also plays a role in autism, and occurs when antioxidants are not present in sufficient levels to clear the body of free radicals. Free radicals can damage cells in the brain, gastrointestinal tract and immune system. Children with low glutathione levels may be more vulnerable to this damage, so supplementation with oral or transdermal glutathione and other antioxidants may be beneficial.
       
      Methylcobalamin – Vitamin methyl-B12 helps support the methylation pathway, which is important for detoxification. This pathway is often not working optimally in children with ASD. Melatonin appears to be a safe and well-tolerated treatment for insomnia in children with ASD.


      J Child Neurol. 2008 Jan 8 [Epub ahead of print]
      Melatonin for Insomnia in Children With Autism Spectrum Disorders.
      Click here to access the PubMed abstract of this article.

      Detoxification (including chelation)
      Some children with autism may suffer from heavy metal toxicity, and may potentially benefit from therapies which support detoxification. Some may also benefit from chelation (removal of heavy metals). Oral DMSA (dimercaptosuccinic acid) is approved by the FDA for treating lead poisoning in children as young as one year of age. It has also been demonstrated to be able to bind and remove a wide range of toxic metals, including mercury, arsenic, tin, nickel, and antimony. Oral DMSA has been used off-label for this purpose. It is important to monitor kidney and liver function and complete blood counts when using DMSA, and although rare, serious side effects may occur.
       
       Please note: These therapies have not been approved by the FDA for the treatment of autism, and should be used only under direct supervision of an experienced and knowledgeable health care professional after parents or guardians have received adequate information and given consent.
       
      References:
      http://www.autism.com/treatable/form34qr.htm (accessed April 2008)

      Ann Neurol 2005;57:67–81
      Neuroglial activation and neuroinflammation in the brain of patients with autism.
      Click here to access the PubMed abstract of this article.

      Ann N Y Acad Sci. 2007 Jun;1107:92-103.
      Brain-specific autoantibodies in the plasma of subjects with autistic spectrum disorder.
      Click here to access the PubMed abstract of this article.

      Cell Mol Neurobiol. 2004 Apr;24(2):219-41
      Secretin: hypothalamic distribution and hypothesized neuroregulatory role in autism.
      Click here to access the PubMed abstract of this article.

      Neuroendocrinology Letters 2002;23:303-8
      Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: a pilot study.
      Click here to access the PubMed abstract of this article.

      Dev Brain Dysfunction 1997;10:40-43
      Biochemical parameters in autistic children.

      J Inherit Metab Dis.1993;16(4):762-770

      Pediatrics 1995;95:255-8
      Lidocaine adrenaline tetracaine gel versus tetracaine adrenaline cocaine gel for topical anesthesia in linear scalp and facial lacerations in children aged 5 to 17 years.
      Click here to access the PubMed abstract of this article.

      J Nutr Env Med 2000;10:25-32
      Sulphur metabolism in autism.  
  • Diaper Rash

    • Approximately two-thirds of infants experience diaper rash (dermatitis). Customized diaper rash preparations -ointments, powders, or creams- can be compounded to treat each child’s specific symptoms, using ingredients which will protect the skin from additional irritation, soothe and encourage healing, and prevent secondary infections. Skin protectants (zinc oxide, petrolatum) provide a physical barrier against external irritants such as urine or gastrointestinal enzymes in stool. Antifungal creams can be used when a yeast (Candida) infection is suspected.

      We can also compound a bile acid sequestrant, such as cholestyramine ointment, to prevent skin irritation, which is especially helpful for ostomy patients. Ann Pharmacother 1996 Sep;30(9):954-6
      Cholestyramine ointment to treat buttocks rash and anal excoriation in an infant.
      Click here to access the PubMed abstract of this article.
  • Eosinophillic Esophagitis

    • Oral Viscous Budesonide (OVB) for Treatment of Eosinophilic Esophagitis Eosinophilic esophagitis (EE) is a disease most likely due to an immunologic response to ingested and inhaled allergens. Presenting symptoms of EE often mimic those of gastroesophageal reflux disease (GERD) and include vomiting, dysphagia, pain, and food impaction. However, because the treatment of EE and GERD differs, it is important to distinguish between them. Swallowed topical steroids, such as fluticasone propionate, have been administered using a metered-dose inhaler (MDI) without a spacer, with instructions to not inhale, but to puff and swallow, thus delivering a topical antiinflammatory product to the esophageal mucosa. Although effective in lowering eosinophil levels, this technique of administering aerosolized corticosteroids, which are often bitter to taste, may be complicated for young children, and twice daily administration is necessary. However, this treatment is attractive because only 1% of the steroid is absorbed systemically and it undergoes rapid hepatic processing. The main potential side effect is oral/esophageal Candida infection that developed in 3 of 20 patients in one series.1 Budesonide is a corticosteroid with high topical anti-inflammatory activity but low systemic activity due to extensive hepatic metabolism. Aceves et al. of Children’s Hospital and the Department of Pediatrics, University of California, San Diego, reported the successful treatment of EE using an oral viscous suspension of budesonide in 2 patients who were unable to utilize fluticasone propionate for developmental reasons.2 Researchers noted: “Our data suggest that OVB is an effective and safe treatment for young children with proven EE. It may have advantages over other therapies in that it is palatable, its volume (8–12 ml) provides pan-esophageal mucosal coverage, and it requires only once daily administration.”3 The increased viscosity of OVB may prolong budesonide’s contact time with the esophageal mucosa. No significant adverse events were reported. Morning cortisol levels were within normal limits. 1 J Pediatr Gastroenterol Nutr 1998;27:90–3.
      Treatment of eosinophilic esophagitis with inhaled corticosteroids.
      Click here to access the PubMed abstract of this article. 2 J Allergy Clin Immunol 2005;116:705–6.
      Topical viscous budesonide suspension for treatment of eosinophilic esophagitis.
      Click here to access the PubMed abstract of this article

      3
      Am J Gastroenterol. 2007 Oct;102(10):2271-9.
      Oral viscous budesonide: a potential new therapy for eosinophilic esophagitis in children.
      Click here to access the PubMed abstract of this article.
  • Fungal Infections

    • Athlete's foot, jock itch, and onychomycosis (fungal nail) are common, particularly in athletes. Research points to the practicality "of using ibuprofen, alone or in combination with azoles, in the treatment of candidosis, particularly when applied topically, taking advantage of the drug's antifungal and anti-inflammatory properties." Various synergistic combinations are used for antifungal therapy. J Med Microbiol 2000 Sep;49(9):831-40
      Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species.
      Click here to access the PubMed abstract of this article.
  • Head Lice/Scabies

    • Concerns about emerging resistance and the potential harm of using permethrins have prompted a search for effective pediculicidal therapies that are not harmful to children with repeated use. An herbal formulation has been shown to be effective for head lice. Ivermectin can also be compounded for topical application or as an oral dose titrated for each patient for the treatment of head lice and scabies. Clin Exp Dermatol 2002 Jun;27(4):264-7
      Treatment of 18 children with scabies or cutaneous larva migrans using ivermectin.
      Click here to access the PubMed abstract of this article.   Twenty six male and female patients aged 5 to 17 years had head lice infestation confirmed by eggs presence and received treatments with a single 200 microgram/kg oral dose of. At day 14 after treatment, 20 had responded to the treatment (77%), and 6 patients (23%) presented with a complete disappearance of eggs and all clinical symptoms. At day 28, 7 patients appeared clear of infestation (27%), but 4 of the 6 patients with no eggs at day 14 presented with signs of reinfestation. This study suggests that ivermectin is a promising treatment of head lice, and a second dose at day 10 may be appropriate.

      Trop Med Parasitol 1994 Sep;45(3):253-4
      Efficacy of ivermectin for the treatment of head lice (Pediculosis capitis).
      Click here to access the PubMed abstract of this article.   Two hundred scabies patients were randomly allocated to receive either oral ivermectin in a single dose of 200 micrograms/kg body weight, or 1% lindane lotion for topical application overnight. Patients were assessed after 48 hours, two weeks and four weeks. After a period of four weeks, 82.6% of the patients in the ivermectin group showed marked improvement; only 44.44% of the patients in the lindane group showed a similar response. Oral ivermectin is easy to administer as a single oral dose, induces an early and effective improvement in signs and symptoms, and compliance is accordingly increased.

      J Dermatol 2001 Sep;28(9):481-4
      Oral ivermectin in scabies patients: a comparison with 1% topical lindane lotion.
      Click here to access the PubMed abstract of this article.   Isr Med Assoc J. 2002 Oct;4(10):790-3
      The in vivo pediculicidal efficacy of a natural remedy.
      Click here to access the PubMed abstract of this article.
  • Molluscum Contagiosum

    • Resistant warts and molluscum contagiosum have been treated successfully with compounded topical medications, avoiding discomfort associated with freezing, scraping, electrocautery and laser therapy. The following study found that 5% KOH aqueous solution proved to be as effective and less irritating when compared to the 10% KOH solution. This trial also emphasizes the effectiveness of topical KOH in the treatment of molluscum contagiosum, sparing affected children from more aggressive physical modalities of treatment. Pediatr Dermatol 2000 Nov-Dec;17(6):495
      Evaluation of the effectiveness of 5% potassium hydroxide for the treatment of molluscum contagiosum.
      Click here to access the PubMed abstract of this article.
  • Nausea Vomiting

    • Orally administered anti-emetics can be difficult for a nauseated child to "keep down", and rectal suppositories may not be well accepted by children. Even persistent nausea can often be effectively controlled by using a combination of medications tailored to meet an individual's specific needs. Dosage forms include transdermal gels, suppositories, lollipops, and more. Promethazine is commonly compounded for topical or transdermal application to treat nausea, vomiting, and vertigo, but this preparation may be used as an antiemetic for cases ranging from chemotherapy to motion sickness. The dose is typically 25mg for adults, and the dose is decreased for children. The gel is applied to an area of soft skin, such as the inside of the wrist or arm, the side of the torso, or the inside of the thigh. For children, doses are often applied to the inside of one wrist, and then the wrists are rubbed together.
      US Pharmacist, August 1999; 74-5
  • Topical Anesthesia

    • Topical anesthesia is needed for common pediatric procedures such as suturing, wound cleaning, and injection administration. The ideal topical anesthetic would provide complete anesthesia following a simple pain-free application, not contain narcotics or controlled substances, and have an excellent safety profile. The combination of topical anesthetics lidocaine and tetracaine and the vasoconstrictor epinephrine has been used successfully for anesthesia prior to suturing linear scalp and facial lacerations in children. A triple-anesthetic gel containing benzocaine, lidocaine, and tetracaine ("BLT") has also been reported to be effective when applied prior to laser and cosmetic procedures. Convenience of application without need for occlusion is an advantage of these topical anesthetics. The following article concludes: "LAT gel (4% lidocaine, 1:2000 adrenaline, 0.5% tetracaine) worked as well as TAC gel (0.5% tetracaine, 1:2000 adrenaline, 11.8% cocaine) for topical anesthesia in facial and scalp lacerations. Considering the advantages of a noncontrolled substance and less expense, LAT gel appears to be better suited than TAC gel for topical anesthesia in laceration repair in children." Pediatrics 1995 Feb;95(2):255-8
      Lidocaine adrenaline tetracaine gel versus tetracaine adrenaline cocaine gel for topical anesthesia in linear scalp and facial lacerations in children aged 5 to 17 years.
      Click here to access the PubMed abstract of this article.   The following article reported that a triple-anesthetic gel containing benzocaine, lidocaine, and tetracaine ("BLT") applied prior to treatment with a 532-nm KTP laser resulted in significantly lower pain scores than with 3 other topical anesthetics at 15, 30, 45, and 60 minutes after application. Cosmetic Dermatology 2003 Apr;16(4):35-7
      Topical Triple-Anesthetic Gel Compared With 3 Topical Anesthetics
  • Pulmonary Arterial Hypertension

    • Sildenafil has the potential to improve hemodynamics and exercise capacity for up to 12 months in children with Pulmonary arterial hypertension (PAH), and this medication can be compounded as a stable oral suspension. Circulation. 2005 Jun 21;111(24):3274-80
      Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single-drug, open-label, pilot study.
      Click here to access the PubMed abstract of this article.
      Am J Health Syst Pharm. 2006 Feb 1;63(3):254-7
      Extemporaneous sildenafil citrate oral suspensions for the treatment of pulmonary hypertension in children.
      Click here to access the PubMed abstract of this article.
  • Seizures/AED

    • Intranasal Delivery of Antiepileptic Medications for Treatment of Seizures
       
         Acute isolated seizure, repetitive or recurrent seizures, and status epilepticus are medical emergencies. Mortality and poor neurologic outcome are directly associated with the duration of seizure activity. The rapidity by which a medication can be delivered to the systemic circulation and then to the brain plays a significant role in reducing the time needed to treat seizures and reduce opportunity for damage to the CNS. Speed of delivery, particularly outside of the hospital, is enhanced when transmucosal routes of delivery are used in place of an intravenous injection. Diazepam rectal gel was developed due to the need for non-injection-based delivery; however, the aesthetics of rectal delivery are not popular with patients and caregivers.
         Benzodiazepines, such as lorazepam, diazepam, midazolam, and clonazepam are considered to be medications of first choice. Intranasal transmucosal delivery of benzodiazepines is useful in reducing time to drug administration and cessation of seizures at home or when actively seizing patients arrive in the emergency room. There are many factors that a practitioner and compounding pharmacist must consider when choosing a benzodiazepine for intranasal administration, including solubility of the drug, ease of passing the blood-brain barrier, and pharmacokinetic/pharmacodynamic profiles. Concentration is important as the nasal cavity can retain approximately 0.1-0.15 ml.
         Under ideal conditions, most medication is absorbed from the nasal cavity and into the bloodstream within 15 to 20 minutes, thus generally avoiding the first-pass gut metabolism. Increased nasal mucus production is commonly observed with actively seizing patients, so it may be prudent to suction mucus from the nasal cavity prior to administration of intranasal midazolam. Intranasal midazolam has been extensively studied in epilepsy patients. Various devices have been used to deliver 0.2 mg/kg of midazolam injection intranasally.
         Morbidity and mortality, as well as health-care resources and expenses associated with treatment of epileptic patients, could be reduced if an effective and safe transmucosal treatment was available for use by caregivers.
       
      Neurotherapeutics. 2009 Apr;6(2):352-8.
      Intranasal delivery of antiepileptic medications for treatment of seizures.
      Click here to access the PubMed abstract of this article.
       
      Midazolam nasal spray has been used to reduce procedural anxiety in children, anxiety-related dyspnea, and to prevent MRI-induced claustrophobia.
       
      AJR 2001; 176:865-868
      Using Intranasal Midazolam Spray to Prevent Claustrophobia Induced by MR Imaging
      Click here to access the PubMed abstract of this article. Pediatrics. 2000 Jan;105(1 Pt 1):73-8. Click here to access the PubMed abstract of this article.




      Intranasal Midazolam for Managing Prolonged Seizures Intranasal midazolam is a safe and practical alternative to rectal diazepam for managing prolonged seizures in non-hospitalized patients. J Intellect Dev Disabil 2006 Sep;31(3):131-8
      Community use of intranasal midazolam for managing prolonged seizures.
      Click here to access the PubMed abstract of this article. Am J Emerg Med 2006 May;24(3):343-6 
      Intranasal midazolam therapy for pediatric status epilepticus.
      Click here to access the PubMed abstract of this article.
  • Examples of Compounded Medications

      • BLT or LAT topical gel or spray
      • Cholestyramine ointment
      • Clotrimazole in DMSO solution
      • Fluconazole/Ibuprofen topical
      • Ivermectin topical
      • KOH solution - 5% and 10%
      • Nicotinamide/Spironolactone topical
      • Promethazine transdermal gel
      • Urea 40% plasters
      The above list is just a few of the preparations that we can compound for pediatric use. We work together with prescriber and patient to solve problems, and all formulations are customized per prescription to meet the unique needs of each child.

Podiatry

  • Podiatrists and other health care professionals encounter numerous problems that may be helped with compounded medications. We commonly prepare unique formulations that prescribers develop to meet specific needs of their patient population, or "tried and true" formulas acquired during professional training. Penetrant enhancers can be added to improve the extent of absorption of topically applied medications. Numerous compatible medications can be combined into a single dosage form for ease of administration. Also, a synergistic effect can be achieved when certain medications are used concomitantly.
  • Anti-Fungal Therapy

    • Topical Therapy for Nail Infections
       
         Yeast and bacterial infections of the nails are usually the result of microscopic damage to the nail plates. The nails will have either a white, thin discoloration at the tip of the nail that starts to extend toward the cuticle, or may have a greenish-black color to the nail. A mixture of 4% thymol in alcohol used twice daily until the affected area has grown out is excellent for this condition.1 Thymol is an antibacterial and antifungal, and alcohol also reduces moisture in skin folds and cuticles.
       
         For treatment of onychomycosis, penetration of the topical antifungal agent through the nail plate from the surface of the nail and diffusion of the systemic antifungal drug through the nail bed may increase the total amount of antifungal activity at the site of infection. Results from an initial study in patients with onychomycosis suggest that this approach can enhance the overall efficacy of therapy. Using a combination of antifungal drugs in this manner may potentially reduce the duration of therapy and allow a reduction in dose of the oral agent, which may reduce systemic adverse effects. Physicians may also consider combining topical antifungal therapy with topical urea. Urea degrades protein, including keratin -- a major component of the nail plate. Potentially, urea can soften the nail plate, making it more porous and penetrable to topical antifungal drugs.2  Urea ointment (40 to 55%) can be applied to the nail twice daily for two weeks. Then, topical formulations such as clotrimazole 2% and ibuprofen 2% in DMSO USP (“apply to affected nails BID for 6 weeks”)3 or  butenafine 2% and tea tree oil 5% cream can be applied to the affected nail.
       
         A randomized, double-blind, placebo-controlled study examined the clinical efficacy and tolerability of 2% butenafine hydrochloride and 5% Melaleuca alternifolia (tea tree) oil incorporated into a cream base to manage toenail onychomycosis. Sixty outpatients (39 M, 21 F) aged 18-80 years (mean 29.6) with 6 to 36 months duration of disease were randomized to two groups (40 active therapy and 20 placebo). After 16 weeks, 80% of patients using medicated cream were cured, as opposed to none in the placebo group. Four patients in the active treatment group experienced subjective mild inflammation without discontinuing treatment. During follow-up, no relapse occurred in cured patients and no improvement was seen in medication-resistant and placebo participants.4
       
      1 Audrey Kunin, M.D. http://www.dermadoctor.com/article_Nail-Fungus_57.html (accessed June 19, 2009)
      http://www.medscape.com/viewarticle/452687_8 (accessed September 16, 2008)
      3 Timothy J. Scott, DPM, FACFAS, Clarion, PA
      4 Trop Med Int Health. 1999 Apr;4(4):284-7.
      Treatment of toenail onychomycosis with 2% butenafine and 5% Melaleuca alternifolia (tea tree) oil in cream.
      Click here to access the PubMed abstract of this article.   A recent large prospective study has shown that onychomycosis is among the most significant predictors of foot ulcer. If left untreated, toenails can become thick, causing pressure and irritation, and thus act as a trigger for more severe complications. In the treatment of onychomycosis, compliance and drug interactions are important considerations, as diabetic patients frequently take concomitant medications.
      Am J Clin Dermatol. 2009;10(4):211-20.
      Toenail onychomycosis in diabetic patients: issues and management.
      Mayser P, Freund V, Budihardja D.
      Click here to access the PubMed abstract of this article.   Study participants were treated with a solution of 1% fluconazole and 20% urea in a mixture of ethanol and water, applied once daily at bedtime. The response to this local therapy was appreciable. J Dermatolog Treat. 2005 Feb;16(1):52-5. Combination of fluconazole and urea in a nail lacquer for treating onychomycosis.
      Baran R, Coquard F.
      Click here to access the PubMed abstract of this article.
      Studies have shown that antifungal agents can be of benefit in treating onychomycosis in patient populations that include the elderly, children, and immunocompromised individuals (e.g., transplant patients, Down's patients, HIV patients, and diabetics). The treatment modality in special patient populations should take into account the clinical presentation of onychomycosis, causative organism, patient and physician preference, concomitant medications that the patient is taking, and the potential for adverse events associated with antifungal therapy. J Cutan Med Surg. 2004 Jan-Feb;8(1):25-30. Epub 2004 Jan 23. Treatment of onychomycosis: pros and cons of antifungal agents.
      Gupta AK, Ryder JE, Skinner AR.
      Click here to access the PubMed abstract of this article.   Chemical nail destruction with a combination of urea and bifonazole, followed by treatment with an antifungal ointment, can be used when the nail is markedly thickened. Non-comparative trials have shown cure rates close to 70% at three months when the matrix is not involved, and 40% with matrix involvement. Prescrire Int. 2009 Feb;18(99):26-30. Fungal nail infections: diagnosis and management.
      Click here to access the PubMed abstract of this article.
      Fungal infections of the feet are commonly associated with dry, cracked skin surrounding the plantar surface and heel fissures. Hyperkeratosis can have various etiologies, and chronic conditions are often quite difficult to treat. Moccasin tinea pedis is typically resistant to topical antifungal therapy when used as sole therapy, because the scale on the plantar surface of the foot impedes or limits the absorption of the antifungal agent. However, one study showed a 100% cure rate was achieved in 12 patients with confirmed moccasin tinea pedis who were treated with topical 40% urea cream and antifungal cream concomitantly for 2 to 3 weeks. Cutis 2004 May;73(5):355-7
      The use of 40% urea cream in the treatment of moccasin tinea pedis.
      Click here to access the PubMed abstract  
  • Arthritis/Inflammation

    • The following article concludes: "Topical non-steroidal anti-inflammatory drugs are effective in relieving pain in acute and chronic conditions." BMJ. 1998 Jan 31;316(7128):333-8
      Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs.
      Click here to access the PubMed abstract of this article. Free full text article available at bmj.com: http://bmj.bmjjournals.com/cgi/content/full/316/7128/333   The following article reports "The systemic concentrations of ketoprofen have also been found to be 100 fold lower compared to tissue concentrations below the application site in patients undergoing knee joint surgery. Topically applied ketoprofen thus provides high local concentration below the site of application but lower systemic exposure." Pharm Res. 1996 Jan;13(1):168-72
      Percutaneous absorption of ketoprofen from different anatomical sites in man.
      Click here to access the PubMed abstract of this article.
  • Athlete's Foot

    • Various synergistic combinations are used for antifungal therapy. Research points to the practicality "of using ibuprofen, alone or in combination with azoles, in the treatment of candidosis, particularly when applied topically, taking advantage of the drug's antifungal and anti-inflammatory properties." J Med Microbiol 2000 Sep;49(9):831-40
      Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species.
      Click here to access the PubMed abstract of this article.
  • Diabetic Neuropathy

    • Neuropathic pain includes a variety of conditions such as diabetic neuropathy, phantom limb pain, reflex sympathetic dystrophy (RSD or Complex Regional Pain Syndrome), and pain caused by blunt trauma or crushing injuries. Symptoms of neuropathic pain may not be evident for weeks to months after the injury. Optimal treatment may involve not only the use of traditional analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, but may also include medications that possess pain-relieving properties, including some antidepressants, anticonvulsants, antiarrhythmics, anesthetics, antiviral agents, and NMDA antagonists. "Combination therapy is frequently the only effective approach for managing the complex array of chemical mediators and other contributors to the individual pain experience."1 "As topical formulations are developed, they provide hope for more effective drug combinations, with fewer systemic adverse drug effects and drug-drug interactions."1 For example, research has shown that topically applied ketoprofen provides a high local concentration of drug below the site of application but decreases systemic exposure and significantly reduces the risk of gastrointestinal upset or bleeding. When properly compounded into an appropriate base, tissue concentrations of ketoprofen were found to be 100-fold greater below the application site (knee) compared to systemic concentrations.2 Sever disease is the most common cause of heel pain in pre-pubertal children. A case report described the use of topical ketoprofen 10% gel as an adjunct to physical therapy to relieve pain and inflammation.3

      1 Advanced Studies in Medicine 2003 July;3(7A):S639
      2 Pharmaceutical Research (1996) 13: 1; 168-172
      3 Phys Ther. 2006 Mar;86(3):424-33
      Ketoprofen gel as an adjunct to physical therapist management of a child with Sever disease.
      Click here to access the PubMed abstract of this article.



      Neuropathy Foot Cream

      The following testimonial appeared in the December 1999 issue of Neuropathy News, a patient newsletter: "My local [compounding pharmacist] has created a cream to help alleviate the pain of foot neuropathy. It reduces the burning and sharp, needle-like pain. All you need is a very thin coat. The directions call for using it four times a day, but I find it particularly helpful at night. [The formulation contains] 2% amitriptyline and 2% baclofen in a transdermal gel."
      "Compounding pharmacists have the unique training and ability to create medications that address the individual needs of patients. One of the most helpful products they use are transdermal gels that allow for the passage of medication directly through the tissue into the area of pain. Many of the medications typically prescribed for neuropathy patients such as amitriptyline, lidocaine, mexilitene, ketamine and [gabapentin] can cause significant side effects when taken orally. Transdermal gel minimizes systemic side effects and maximizes local pain relief. Compounding pharmacists have many resources that offer relief from neuropathic pain."

      In Diabetes Interviews, January 2000, Neil A. Burrell, DPM, CDE, of Beaumont, Texas, writes "We have a very high success rate using amitriptyline and baclofen mixed in a gel component. This compound is applied to the feet three times per day, and offers immediate relief... [For] recalcitrant neuropathic pain, many times we use a combination of tramadol, gabapentin and amitriptyline." At our compounding pharmacy, we work together with physicians and patients to prepare formulations containing the medications and doses that are most appropriate to meet each patient's specific needs. Let us know how we can be of service.

      Arginine Transdermal

      Diabetes Care, January 2004; 27(1):284-5
      Improvement of Temperature and Flow in Feet of Subjects with Diabetes With Use of a Transdermal Preparation of L-Arginine - A pilot study
      Click here for the full article.
      Topical doxepin could be an alternative and relatively safe treatment in alleviating neuropathic pain in the diabetic patient, especially when the use of systemic treatment is contraindicated. In the following case study, the soles of the patient's feet were treated with topical doxepin 5% twice daily for four weeks. The patient responded dramatically with loss of the severe burning sensation and no side effects reported. Wounds 15(8):272-276, 2003. © 2003 Health Management Publications, Inc.
      Burning Feet Due to Diabetic Neuropathy
      Click here for the full article.
  • Molluscum Contagiosum

    • tant warts and molluscum contagiosum have been treated successfully with compounded topical medications, avoiding discomfort associated with freezing, scraping, electrocautery and laser therapy. The following study found that 5% KOH aqueous solution proved to be as effective and less irritating when compared to the 10% KOH solution. This trial also emphasizes the effectiveness of topical KOH in the treatment of molluscum contagiosum, sparing affected children from more aggressive physical modalities of treatment. Pediatr Dermatol 2000 Nov-Dec;17(6):495
      Evaluation of the effectiveness of 5% potassium hydroxide for the treatment of molluscum contagiosum.
      Click here to access the PubMed abstract of this article.
  • Nail Infection/Removal

    • Although surgical excision is the most popular method for removing nails, the use of concentrated urea plasters applied under occlusion may be superior. The use of urea plasters has inherent advantages - they are inexpensive, several nails can be treated in one session, and the procedure is essentially painless. Various synergistic combinations and topical medications with penetrant enhancers can be compounded for antifungal therapy. Topical medications usually have a lower adverse drug-reaction profile than systemic medications. Cutis. 1980 Jun;25(6):609-12
      Urea ointment in the nonsurgical avulsion of nail dystrophies--a reappraisal.
      Click here to access the PubMed abstract of this article. Cutis. 1980 Apr;25(4):397, 405
      Combination urea and salicyclic acid ointment nail avulsion in nondystrophic nails: a follow-up observation.
      Click here to access the PubMed abstract of this article. JAMA 1979 Apr 13;241(15):1559, 1563
      Urea plasters alternative to surgery for nail removal..
      PMID: 430701 (No abstract available) Clin Exp Dermatol 1982 May;7(3):273-6
      The treatment of fungus and yeast infections of nails by the method of "chemical removal".
      PMID: 7105479 (No abstract available)     Management of onychomycosis, a fungal infection of the fingernails and toenails, usually consists of systemic antifungal medications, topical therapy (e.g., urea ointment, desiccating solutions, keratolytics, vital dyes), or surgical intervention (e.g., nail plate avulsion, laser therapy). Topical prescription antifungal preparations, containing the active ingredient of your choice, may be less likely to cause the serious systemic side effects that can occur with oral antifungal therapy and can provide a more economical alternative, as lower doses are needed when the medication is applied topically at the site. Penetrant enhancers can be included in the preparation to improve the effectiveness of topical antifungals.  Trop Med Int Health 1999 Apr;4(4):284-7
      Treatment of toenail onychomycosis with 2% butenafine and 5% Melaleuca alternifolia (tea tree) oil in cream.
      Click here to access the PubMed abstract of this article.
  • Plantar Warts `5`/Warts

    • Phys Ther. 2002 Dec;82(12):1184-91
      Treatment of plantar verrucae using 2% sodium salicylate iontophoresis.
      Click here to access the PubMed abstract of this article.   Cantharidin in a collodion vehicle has been used by dermatologists as a treatment for molluscum contagiosum and warts since the 1950s. Cantharidin lost FDA approval in 1962 because its manufacturers failed to submit data attesting to cantharidin's efficacy. However, in 1999, the FDA included cantharidin on its "Bulk Substances List" of drugs which although not available as commercial products, were approved for compounding on a customized basis for individual patients. Because of cantharidin's potential for toxicity, the FDA has proposed that cantharidin should be limited to "topical use in the professional office setting only." Severe blistering can result from improper use, and ingestion, especially by children, can be fatal. Treatment of mucous membranes is contraindicated and placement of cantharidin near the eyes and eyelids should be avoided to prevent scleral erosion. Caution: The treatment of plantar warts with cantharidin is NOT recommended and may have a higher rate of significant complications including lymphangitis and refractory lymphedema. Arch Dermatol. 2001;137:1357-1360
      Cantharidin revisited: a blistering defense of an ancient medicine.
      Click here to access the PubMed abstract J Am Acad Dermatol. 2000;43:503-507
      Childhood molluscum contagiosum: experience with cantharidin therapy in 300 patients.
      Click here to access the PubMed abstract   Squaric Acid Dibutylester (SADBE) for Cutaneous Warts in Children Warts are a common pediatric skin infection and clearance may be enhanced by contact sensitizers, such as squaric acid dibutylester (SADBE). Contact immunotherapy with SADBE is relatively safe and an effective alternative in the management of multiple and resistant cutaneous warts in children. J Am Acad Dermatol. 2000 May;42(5 Pt 1):803-8
      Squaric acid immunotherapy for warts in children.
      Click here to access the PubMed abstract
      Pediatr Dermatol. 2000 Jul-Aug;17(4):315-8
      Use of squaric acid dibutylester (SADBE) for cutaneous warts in children.
      Click here to access the PubMed abstract

      J Am Acad Dermatol. 1999 Oct;41(4):595-9
      Contact immunotherapy with squaric acid dibutylester for the treatment of recalcitrant warts.
      Click here to access the PubMed abstract
  • Wound Care

    • Wounds and pressure sores may heal more quickly if treated with topical phenytoin. Medications which improve capillary blood flow can be added to a compounded medication to enhance circulation at the wound margins and promote healing of the injured area. Topical Phenytoin for Wound Healing The stimulatory effect of orally administered phenytoin on gingival tissue prompted its assessment in wound healing. Phenytoin may promote wound healing by a number of mechanisms, including stimulation of fibroblast proliferation, facilitation of collagen deposition, glucocorticoid antagonism, and antibacterial activity. Phenytoin has been used topically in the healing of pressure sores, venous stasis and diabetic ulcers, traumatic wounds, skin autograft donor sites, and burns. Rhodes et al compared the healing of stage II decubitus ulcers with topically applied phenytoin and two other standard topical treatment procedures in 47 patients in a long-term care setting. Ulcers were examined for the presence of healthy granulation tissue, reduction in surface dimensions, and time to healing. Topical phenytoin therapy resulted in a shorter time to complete healing and formation of granulation tissue when compared with DuoDerm dressings or triple antibiotic ointment applications. The mean time to healing in the phenytoin group was 35.3 +/- 14.3 days compared with 51.8 +/- 19.6 and 53.8 +/- 8.5 days for the DuoDerm and triple antibiotic ointment groups, respectively. Healthy granulation tissue in the phenytoin group appeared within 2 to 7 days in all subjects, compared to 6 to 21 days in the standard treatment groups. The phenytoin-treated group showed no detectable serum phenytoin concentrations. Anstead et al. described a patient with a massive grade IV pressure ulcer that was unresponsive to conventional treatment, yet responded rapidly to treatment with topical phenytoin. Song and Cheng reported phenytoin improved wound breaking strength in normal and radiation-impaired wounds. The results of their study indicated that topical phenytoin accelerated normal and irradiation-impaired wound healing by increasing the number of wound macrophages and improving the macrophage function. Pendse et al evaluated the effectiveness of topical phenytoin in healing chronic skin ulcers in a controlled trial of 75 inpatients. At the end of the fourth week, 29 of 40 phenytoin-treated ulcers had healed completely versus 10 of 35 controls. They concluded: "topical phenytoin appears to be an effective, inexpensive, and widely available therapeutic agent in wound healing." The effectiveness of topical phenytoin as a wound healing agent was compared with that of OpSite and a conventional topical antibiotic dressing (Soframycin) in a controlled study of 60 patients with partial-thickness skin autograft donor sites on the lower extremities. Mean pain scores were lower and mean time to complete healing (complete epithelialization) was best in the phenytoin-treated group (6.2 +/- 1.6 days). Topical phenytoin compared very favorably with, and in some aspects was superior to, occlusive dressings. The efficacy of topical phenytoin in the treatment of diabetic foot ulcers was evaluated in a controlled inpatient study. Fifty patients were treated with topical phenytoin, and 50 patients received dry sterile occlusive dressings. Both groups improved, but the ulcers treated with topical phenytoin healed more rapidly. Mean time to complete healing was 21 days with phenytoin and 45 days with control. No study reported any significant adverse effects secondary to topical phenytoin therapy. Ann Pharmacother 2001 Jun;35(6):675-81
      Topical phenytoin treatment of stage II decubitus ulcers in the elderly.
      Click here to access the PubMed abstract of this article.

      Biochem Pharmacol 1999 May 15;57(10):1085-94
      Role of phenytoin in wound healing--a wound pharmacology perspective.
      Click here to access the PubMed abstract of this article.

      Ann Pharmacother 1996 Jul-Aug;30(7-8):768-75
      Phenytoin in wound healing.
      Click here to access the PubMed abstract of this article.

      Int J Dermatol 1993 Mar;32(3):214-7
      Topical phenytoin in wound healing.
      Click here to access the PubMed abstract of this article.

      Chung Hua I Hsueh Tsa Chih 1997 Jan;77(1):54-7
      [The effect of systemic and local irradiation on wound macrophages and the repair promoting action of phenytoin sodium]
      Click here to access the PubMed abstract of this article. 

      Burns 1993 Aug;19(4):306-10
      Topical phenytoin in the treatment of split-thickness skin autograft donor sites: a comparative study with polyurethane membrane drape and conventional dressing.
      Click here to access the PubMed abstract of this article

      Diabetes Care 1991 Oct;14(10):909-11
      Topical phenytoin in diabetic foot ulcers.
      Click here to access the PubMed abstract of this article
  • Iontophoresis & Phonophoresis

    • Iontophoresis facilitates delivery of medications into the tissues beneath the skin by electronic transport of ionized drugs in solution. Acetic acid iontophoresis is effective in the treatment of heel pain. Iontophoresis of dexamethasone for plantar fasciitis should be considered when more immediate results are needed. Iontophoresis has also been used to successfully treat plantar hyperhidrosis. Phonophoresis is a technique that combines topical drug therapy with ultrasound to achieve therapeutic drug concentrations in muscle and other tissues beneath the skin. Ultrasound gels can be formulated to contain medications such as anti-inflammatories and/or anesthetics. J Am Podiatr Med Assoc. 1999 May;89(5):251-7
      Management of heel pain syndrome with acetic acid iontophoresis.
      Click here to access the PubMed abstract of this article. Am J Sports Med 1997 May-Jun;25(3):312-6
      Treatment of plantar fasciitis by iontophoresis of 0.4% dexamethasone. A randomized, double-blind, placebo-controlled study.Click here to access the PubMed abstract of this article.
  • Examples of Compounded Medications

    • The following list is just a few of the preparations that we can compound for podiatry. We work together with prescriber and patient to solve problems, and all formulations are customized per prescription to meet the unique needs of each patient. Therapeutic results depend not only on the selection of drug, but also the use of a proper base and preparation technique. Please contact our compounding pharmacist to discuss the dosage form, strength, and medication or combination that is most appropriate for your patient.
      • Clotrimazole in DMSO solution
      • Dexamethasone iontophoresis solution
      • Fluconazole/Ibuprofen topical gel
      • Ketamine/Gabapentin transdermal gel
      • Ketoprofen 10% topical gel
      • KOH solution - 5% and 10%
      • Phenytoin topical
      • Urea 40% ointment

Sports Medicine

  • Athletes, coaches, trainers, team physicians, physical therapists, and even the “weekend warrior” are faced with problems including inflammation and muscle spasms. We work together with these individuals and other health care professionals to customize medications which meet specific needs. Our compounding specialists can help to solve medication problems using customized preparations that contain the most appropriate ingredients in the best vehicle to most efficiently provide the needed drug to the affected area. Please contact our compounding pharmacist for more information.
  • Benefits of Transdermal Therapy

    • Topical
      Peripheral tissue activity
      Systemic side effects less likely
      If analgesic, applied directly over painful site
      Insignificant serum levels Transdermal
      Systemic activity
      Potential for adverse effects
      If analgesic, may be applied away from painful site
      Serum levels necessary for effect Medications that relieve pain, reduce inflammation, and relax muscles can have side effects that are detrimental to athletic performance, such as drowsiness. However, when these medications are administered topically, the therapeutic benefit can be enhanced while significantly reducing the risk of adverse effects. For example, research has shown that topically-applied ketoprofen provides a high local concentration of drug below the site of application but decreases systemic exposure and significantly reduces the risk of gastrointestinal upset or bleeding. When properly compounded into an appropriate base, tissue concentrations of ketoprofen were found to be 100-fold greater below the application site (knee) compared to systemic concentrations. Muscle relaxants can be similarly prepared to minimize the risk of drowsiness.
  • Benefits of Transdermal NSAIDs

    • Topical
      Peripheral tissue activity
      Systemic side effects less likely
      If analgesic, applied directly over painful site
      Insignificant serum levels Transdermal
      Systemic activity
      Potential for adverse effects
      If analgesic, may be applied away from painful site
      Serum levels necessary for effect Medications that relieve pain, reduce inflammation, and relax muscles can have side effects that are detrimental to athletic performance, such as drowsiness. However, when these medications are administered topically, the therapeutic benefit can be enhanced while significantly reducing the risk of adverse effects. For example, research has shown that topically-applied ketoprofen provides a high local concentration of drug below the site of application but decreases systemic exposure and significantly reduces the risk of gastrointestinal upset or bleeding. When properly compounded into an appropriate base, tissue concentrations of ketoprofen were found to be 100-fold greater below the application site (knee) compared to systemic concentrations. Muscle relaxants can be similarly prepared to minimize the risk of drowsiness.
  • Topical Anesthetics

    • To avoid the risks of COX-2 inhibitors, our pharmacy can compound topically applied NSAIDs such as ibuprofen and ketoprofen. Topical NSAIDs have a safety profile which is superior to oral formulations. Topical NSAID administration offers the advantage of local, enhanced delivery to painful sites with a reduced incidence of systemic adverse effects. Topical preparations can be customized to contain a combination of medications to meet the specific needs of each patient.

      Topical NSAIDs for Acute Pain
      “Topical non-steroidal anti-inflammatory drugs have a lower incidence of gastrointestinal adverse effects than the same drugs when they are taken orally. The low incidence of systemic adverse effects for topical NSAIDs probably results from the much lower plasma concentration from similar doses applied topically to those administered orally. Topical application of ibuprofen resulted in measurable tissue concentrations in deep tissue compartments, more than enough to inhibit inflammatory enzymes.”1 Topical NSAIDs have not been associated with renal failure.2 1BMJ. 1995 Jul 1;311(6996):22-6
      Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study.
      Free full text article available at bmj.com:  http://bmj.bmjjournals.com/cgi/content/full/311/6996/22   2QJM 1995;88:551–557
      Non-steroidal anti-inflammatory drugs and hospitalization for acute renal failure.
      Click here to access the PubMed abstract of this article.   The following article concludes: “Topical non-steroidal anti-inflammatory drugs are effective in relieving pain in acute and chronic conditions.” BMJ. 1998 Jan 31;316(7128):333-8
      Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs.
      Click here to access the PubMed abstract of this article.
      Free full text article available at bmj.com:  http://bmj.bmjjournals.com/cgi/content/full/316/7128/333     The following article reports “The systemic concentrations of ketoprofen have also been found to be 100 fold lower compared to tissue concentrations below the application site in patients undergoing knee joint surgery. Topically applied ketoprofen thus provides high local concentration below the site of application but lower systemic exposure.” Pharm Res. 1996 Jan;13(1):168-72
      Percutaneous absorption of ketoprofen from different anatomical sites in man.
      Click here to access the PubMed abstract of this article. Findings of this study demonstrate that "following topical application in a patch, ketoprofen shows rapid and sustained delivery to the underlying tissues without a significant increase of the plasma drug concentration." AAPS PharmSciTech. 2010 Mar;11(1):154-8. Epub 2010 Jan 20.
      Ketoprofen absorption by muscle and tendon after topical or oral administration in patients undergoing anterior cruciate ligament reconstruction.
      Sekiya I, Mo.rito T, Hara K, Yamazaki J, Ju YJ, Yagishita K, Mochizuki T, Tsuji K, Muneta T. Click here to access the PubMed abstract of this article.
      Reduction of spontaneous pain and pain on active movement in the topical ketoprofen spray group was significantly greater than in the oral ketoprofen treatment group, irrespective of sprain severity. Regarding mobility impairment and ankle swelling, topically-applied ketoprofen treatment turned out to be significantly superior to orally administered ketoprofen treatment. Additionally, the topical preparation was well tolerated, whereas ketoprofen tablets caused gastrointestinal side effects in some patients. Minerva Cardioangiol. 2008 Oct;56(5 Suppl):47-53.
      Management of uncomplicated ankle sprains with topical or oral ketoprofen treatment. A registry study.
      Vinciguerra G et al. Click here to access the PubMed abstract of this article. Topical NSAIDs have a safety profile which is superior to oral formulations. Topical NSAID administration offers the advantage of local, enhanced delivery to painful sites with higher tissue levels beneath the site of application and a reduced incidence of systemic (such as gastrointestinal) adverse effects. Advanced Studies in Medicine, Johns Hopkins University, Volume 3 (7A), July 2003
  • Iontophoresis & Phonophoresis

    • Iontophoresis facilitates delivery of medications into the tissues beneath the skin by electronic transport of ionized drugs in solution. Acetic acid iontophoresis is effective in the treatment of heel pain. Iontophoresis of dexamethasone for plantar fasciitis should be considered when more immediate results are needed. Iontophoresis has also been used to successfully treat plantar hyperhidrosis. Phonophoresis is a technique that combines topical drug therapy with ultrasound to achieve therapeutic drug concentrations in muscle and other tissues beneath the skin. Ultrasound gels can be formulated to contain medications such as anti-inflammatories and/or anesthetics. J Am Podiatr Med Assoc. 1999 May;89(5):251-7
      Management of heel pain syndrome with acetic acid iontophoresis.
      Click here to access the PubMed abstract of this article. Am J Sports Med 1997 May-Jun;25(3):312-6
      Treatment of plantar fasciitis by iontophoresis of 0.4% dexamethasone. A randomized, double-blind, placebo-controlled study.
      Click here to access the PubMed abstract of this article.
  • Pregame Rubs

    • Pregame rubs can be compounded to contain substances such as emu oil and anti-spasmodic drugs. Emu oil is a moisturizer that can improve healing of injured skin. Plast Reconstr Surg 1998 Dec;102(7):2404-7
      Promotion of second intention wound healing by emu oil lotion: comparative results with furasin, polysporin, and cortisone.
      Click here to access the PubMed abstract of this article.
  • Hemmorhoids

    • Hemorrhoids are particularly problematic for catchers, coaches, and others who are regularly in a squatting position. Treatment often involves use of a novel dosage form known as the "rectal rocket", a suppository that permits simultaneous internal and external application of anti-inflammatories, anesthetics, antibiotics, or other medications.
  • Excessive Perspiration

    • Hyperhidrosis therapy Excessive perspiration is a concern for many athletes, as well as members of dance teams and marching bands. Numerous topical treatment options exist. Primary hyperhidrosis (excessive perspiration) is a physically and emotionally distressing condition which involves mainly the palms, soles, and axillae. Oral anticholinergic agents and beta-blockers may be effective for controlling or reducing profuse sweating, but also carry significant side effects. Topical therapies may be the most practical and most common treatment for hyperhidrosis, but many agents that have proven useful in clinical trials are not commercially available. Placebo-controlled trials have shown that topically applied 20% aluminum chloride hexahydrate significantly reduces the symptoms of hyperhidrosis in 60%-100% of patients. Skin irritation can be minimized with 1% hydrocortisone cream or by compounding 20% aluminum chloride in a 4% salicylic acid gel base, instead of in anhydrous alcohol base (as is the commercial product Drysol®). Luh and Blackwell of the Dept. of Internal Medicine, University of Texas Medical Branch at Galveston describe a healthy, active 27-year-old male resident physician who had excessive facial sweating with minimal exertion or stress. The sweating was especially pronounced on the forehead, nose, and upper lip. Daily topical application of a 0.5% glycopyrrolate solution to the face and forehead significantly reduced facial sweating after the first treatment, without any discomfort to the skin. No loss of efficacy was seen after multiple face washings. Facial hyperhidrosis recurred after withdrawal of the glycopyrrolate for 2 days, confirming its therapeutic effect. Two years later, he continues to use glycopyrrolate as needed. Mayo Clin Proc 1986 Dec;61(12):951-6
      Treatment of primary hyperhidrosis.
      Click here to access the PubMed abstract of this article.

      South Med J 2002 Jul;95(7):756-8
      Craniofacial hyperhidrosis successfully treated with topical glycopyrrolate.
      Click here to access the PubMed abstract of this article.

      Ann Pharmacother 1995 May;29(5):489-92
      Propantheline bromide in the management of hyperhidrosis associated with spinal cord injury.
      Click here to access the PubMed abstract of this article.

      Intl J Pharm Comp 2001 Jan/Feb;5(1):28-9
      Glycopyrrolate 1% Cream
      Click here to access the abstract of this article.
  • Transdermal

    • Transdermal therapy to decrease side effects Medications that relieve pain, reduce inflammation, and relax muscles can have side effects that are detrimental to athletic performance, such as drowsiness. However, when these medications are administered transdermally, the therapeutic benefit can be enhanced while significantly reducing the risk of adverse effects. For example, research has shown that topically applied ketoprofen provides a high local concentration of drug below the site of application but decreases systemic exposure and significantly reduces the risk of gastrointestinal upset or bleeding. When properly compounded into an appropriate base, tissue concentrations of ketoprofen were found to be 100-fold greater below the application site (knee) compared to systemic concentrations. Muscle relaxants can be similarly prepared to minimize the risk of drowsiness.   A symposium held during the 93rd Annual Congress of the Italian Society of Orthopedics and Traumatology (SIOT) in Rome, Italy in November 2008, noted that topical anti-inflammatory therapy is a promising therapeutic strategy in the treatment of muscle strains, since it provides local analgesic and anti-inflammatory effects while minimizing systemic adverse events. Adv Ther. 2009 Dec;26(12):1072-83. Epub 2010 Feb 4.
      New therapeutic approaches for management of sport-induced muscle strains.
      De Carli A et al.
      Click here to access the PubMed abstract of this article.
  • Examples of Compounded Medications

    • The following list is just a few of the preparations that we can compound for sports medicine. All formulations are customized to meet the unique needs of each individual; therefore, we can consider the athlete’s lifestyle and environmental factors when formulating medications. Our compounding professionals can choose the best base to administer the active ingredients, or consult with the prescriber to determine the most appropriate route of administration to solve a specific problem.
      • Clotrimazole in DMSO solution
      • Cyclobenzaprine/Ketoprofen transdermal gel
      • Dexamethasone iontophoresis solution
      • Fluconazole/Ibuprofen topical gel
      • Ketamine/Gabapentin transdermal gel
      • Ketoprofen 10% transdermal gel
      • LAT topical gel
      • Lidocaine/Hydrocortisone "rectal rocket" suppository
      • Nutritional Supplements
      • Rehydration Drinks

Wound Care

  • Per a prescription order, a formulation can be compounded to contain the proper combination of active ingredients, in the most appropriate base, to treat a specific type of wound. We customize medications to meet each individual’s specific needs. For example, the choice of cream, ointment, or gel can be clinically significant. Each time a wound needs to be cleaned, there is the potential for disruption of new tissue growth. Gels, which are more water soluble than creams or ointments, may be preferable for wound use because a gel can be rinsed from the wound by irrigation.  Ointments may contain polyethylene glycol (PEG), which can be absorbed from open wounds and damaged skin. If the wound is quite large and too much PEG is absorbed, it can lead to renal toxicity. Another useful dosage form is the “polyox bandage” - which can be puffed onto a wound and will adhere even if exudate is present.   A polyox bandage can be compounded to contain the active ingredient(s) of your choice. 
  • Therapy for Wounds, Ulcerations, Donor Sites and Burns

    • Decubitus Ulcers; Venous Stasis and Diabetic Ulcers; Traumatic Wounds; Skin Autograft Donor Sites; and Burns Phenytoin has been used topically to speed the healing of decubitus ulcers, pressure sores, venous stasis and diabetic ulcers, traumatic wounds, skin autograft donor sites, and burns. Ketoprofen may be used to control inflammation and pain, lidocaine provides topical anesthesia, and pentoxifylline may improve microcirculation at the wound margins and promote healing of the injured area. Misoprostol, a prostaglandin analog, is often included in wound care formulations to promote healing. Debridement of necrotic eschar with 40% urea paste may also speed healing. Medications which improve capillary blood flow can be added to a compounded medication to enhance circulation at the wound margins and promote healing of the injured area. Topical Phenytoin for Wound Healing The stimulatory effect of orally administered phenytoin on gingival tissue prompted its assessment in wound healing. Phenytoin may promote wound healing by a number of mechanisms, including stimulation of fibroblast proliferation, facilitation of collagen deposition, glucocorticoid antagonism, and antibacterial activity. Phenytoin has been used topically in the healing of pressure sores, venous stasis and diabetic ulcers, traumatic wounds, skin autograft donor sites, and burns. Rhodes et al compared the healing of stage II decubitus ulcers with topically applied phenytoin and two other standard topical treatment procedures in 47 patients in a long-term care setting. Ulcers were examined for the presence of healthy granulation tissue, reduction in surface dimensions, and time to healing. Topical phenytoin therapy resulted in a shorter time to complete healing and formation of granulation tissue when compared with DuoDerm dressings or triple antibiotic ointment applications. The mean time to healing in the phenytoin group was 35.3 +/- 14.3 days compared with 51.8 +/- 19.6 and 53.8 +/- 8.5 days for the DuoDerm and triple antibiotic ointment groups, respectively. Healthy granulation tissue in the phenytoin group appeared within 2 to 7 days in all subjects, compared to 6 to 21 days in the standard treatment groups. The phenytoin-treated group showed no detectable serum phenytoin concentrations. Anstead et al. described a patient with a massive grade IV pressure ulcer that was unresponsive to conventional treatment, yet responded rapidly to treatment with topical phenytoin. Song and Cheng reported phenytoin improved wound breaking strength in normal and radiation-impaired wounds. The results of their study indicated that topical phenytoin accelerated normal and irradiation-impaired wound healing by increasing the number of wound macrophages and improving the macrophage function. Pendse et al evaluated the effectiveness of topical phenytoin in healing chronic skin ulcers in a controlled trial of 75 inpatients. At the end of the fourth week, 29 of 40 phenytoin-treated ulcers had healed completely versus 10 of 35 controls. They concluded: "topical phenytoin appears to be an effective, inexpensive, and widely available therapeutic agent in wound healing." The effectiveness of topical phenytoin as a wound healing agent was compared with that of OpSite and a conventional topical antibiotic dressing (Soframycin) in a controlled study of 60 patients with partial-thickness skin autograft donor sites on the lower extremities. Mean pain scores were lower and mean time to complete healing (complete epithelialization) was best in the phenytoin-treated group (6.2 +/- 1.6 days).  Topical phenytoin compared very favorably with, and in some aspects was superior to, occlusive dressings. The efficacy of topical phenytoin in the treatment of diabetic foot ulcers was evaluated in a controlled inpatient study. Fifty patients were treated with topical phenytoin, and 50 patients received dry sterile occlusive dressings. Both groups improved, but the ulcers treated with topical phenytoin healed more rapidly. Mean time to complete healing was 21 days with phenytoin and 45 days with control. No study reported any significant adverse effects secondary to topical phenytoin therapy. Phenytoin references: Ann Pharmacother 2001 Jun;35(6):675-81
      Topical phenytoin treatment of stage II decubitus ulcers in the elderly.
      Click here to access the PubMed abstract of this article. Biochem Pharmacol 1999 May 15;57(10):1085-94
      Role of phenytoin in wound healing--a wound pharmacology perspective.
      Click here to access the PubMed abstract of this article. Ann Pharmacother 1996 Jul-Aug;30(7-8):768-75
      Phenytoin in wound healing.
      Click here to access the PubMed abstract of this article. Int J Dermatol 1993 Mar;32(3):214-7
      Topical phenytoin in wound healing.
      Click here to access the PubMed abstract of this article. Chung Hua I Hsueh Tsa Chih 1997 Jan;77(1):54-7
      [The effect of systemic and local irradiation on wound macrophages and the repair promoting action of phenytoin sodium]
      Click here to access the PubMed abstract of this article. Burns 1993 Aug;19(4):306-10
      Topical phenytoin in the treatment of split-thickness skin autograft donor sites: a comparative study with polyurethane membrane drape and conventional dressing.
      Click here to access the PubMed abstract of this article. Diabetes Care 1991 Oct;14(10):909-11
      Topical phenytoin in diabetic foot ulcers.
      Click here to access the PubMed abstract of this article.

      Benzoyl Peroxide for Treatment of Decubitus Ulcers 
      Benzoyl peroxide is a powerful oxidizing agent with broad spectrum germicidal activity and good liposolubility. Therefore, it may represent a good agent for prevention of wound infection in areas with high density of sebaceous glands. Topical treatment of pressure sore with 20% benzoyl peroxide in O/W emulsion yielded very satisfactory results. In another study, 10% benzoyl peroxide gel was used prophylactically once a day for 7 days before surgery. The researchers concluded that topical benzoyl peroxide is an efficacious, harmless, and inexpensive agent for prevention of wound infections in seborrheic regions. Med Cutan Ibero Lat Am 1988;16(5):427-9
      [Benzoyl peroxide in the treatment of decubitus ulcers].
      Click here to access the PubMed abstract of this article. J Dermatol Surg Oncol 1994 Aug;20(8):538-40
      Utility of topical benzoyl peroxide for prevention of surgical skin wound infection.
      Click here to access the PubMed abstract of this article.   Miscellaneous Arch Dermatol. 2001 Oct;137(10):1288-90
      Debridement of necrotic eschar with 40% urea paste speeds healing of residual limbs and avoids further surgery.
      PMID: 11594851 No Abstract Available.
  • Odor Control

    • Odor from malignant cutaneous wounds, ulcerated tumors, some pressure ulcers, and fungating tumors can cause great distress and embarrassment for patients. Topical metronidazole is one medication that has been used to eliminate this odor, greatly improving the patient’s quality of life.  Exudate and associated cellulitis may also decrease significantly with appropriate topical therapy. Ostomy Wound Manage 1997 Jan-Feb;43(1):56-60, 62, 64-6
      Malignant Cutaneous Wounds: a Management Protocol
      Click here to access the PubMed abstract of this article.
  • Skin Irritation

    • Numerous topical preparations containing cholestyramine or sucralfate (creams, adhesive pastes, enemas, suppositories) have been used for their protectant properties or for treatment of a variety of dermatologic and mucosal problems, including oral and esophageal ulcers, peristomal and perineal excoriation, decubitus ulcers, and radiation-induced rectal and vaginal ulcerations, and second and third degree burns. Ann Pharmacother 1996 Sep;30(9):954-6
      Cholestyramine ointment to treat buttocks rash and anal excoriation in an infant.
      Click here to access the PubMed abstract of this article. Dis Colon Rectum 1987 Feb;30(2):106-7
      Cholestyramine ointment in the treatment of perianal skin irritation following ileoanal anastomosis.
      Click here to access the PubMed abstract of this article.   Clin Exp Dermatol. 2000 Nov;25(8):584-8
      Topical sucralfate in the management of peristomal skin disease: an open study.
      Click here to access the PubMed abstract of this article.   Burns. 2001 Aug;27(5):465-9
      Topical use of sucralfate cream in second and third degree burns.
      Click here to access the PubMed abstract of this article.

Dentistry

  • We work together with dentists and their patients to solve problems using customized medications. Upon a prescription order, we can compound:
    • lip balms for viral lesions
    • topical muscle relaxants/analgesics
    • topical anesthetics
    • non-staining antibacterial rinses
    • oral sedation in lollipops and freezer pops
    • lollipops for oral thrush
    • mouth rinses for aphthous ulcers or chemotherapy-induced stomatitis
    • mouth rinse to stop oral bleeding during dental procedures for patients who take anticoagulants
    • dry socket preparations
    • "mucosal bandages" to cover ulcerated, infected, or tender mucosa
    • lozenges that help to prevent gagging
    • and many more unique preparations and novel delivery systems
    Medications are manufactured in a limited number of strengths and dosage forms that will satisfy the needs of most patients due to stability concerns, and the cost of stocking and distributing numerous formulations of each drug. Using pharmaceutical grade chemicals and specialized equipment not found in most pharmacies, we can compound medications in doses and dosage forms that are not commercially available. We want to optimize the care of every patient. Just let us know what you need!
  • Topical Therapy For Pain and Infection

    • The options to help patients with oral and perioral pain problems such as neuropathies, burning mouth syndrome, neuromas and neuralgias. Vehicle-carrier agents and bases have been developed that can penetrate the mucosa and cutaneous tissues and transport the active medication to the treatment site. Dentists have been using topical agents with increasing frequency as part of the therapeutic protocol for orofacial painful neuropathy. Several topical intraoral medications are used in the treatment of oral ulcerations and infections, including antifungals; nonsteroidal anti-inflammatory drugs (NSAIDs); and corticosteroids. Because of their rapid onset and low side-effect profile, topical medications offer a distinct advantage over systemic administration for orofacial disorders. Medicated lollipops, lozenges, and adhering powders are ideal for keeping an antibiotic or antifungal in contact with an infected area in the mouth.


      Topical Anesthetics -Combinations of your Choice Methemoglobinemia (MHb) is a potentially serious blood condition and an uncommon adverse reaction known to be associated with benzocaine. This condition reduces the ability of red blood cells to deliver oxygen throughout the body, which can lead to bluish discoloration of the skin, nausea and fatigue. It can progress to stupor, coma and death. Almost all reported cases of benzocaine-induced MHb were associated with high-concentration preparations (14 percent to 20 percent benzocaine). Compounding pharmacies can formulate low concentration or benzocaine-free topical anesthetics, including combinations of other topical anesthetics such as lidocaine and tetracaine or prilocaine.


        Treatment for Recurrent Aphthous Stomatitis In a clinical randomized crossover trial, minocycline 0.2% and tetracycline 0.25% aqueous oral rinses were assessed in patients with frequent episodes of RAS. Minocycline mouthwashes as compared to topical tetracycline rinses resulted in significantly improved pain control, by reducing the severity and duration of pain. Topical minocycline rinse may be a potential treatment for other non-infectious inflammatory ulcerative oral mucosal diseases. Dermatol Online J. 2007 May 1;13(2):1.
      Click here to read the PubMed abstract of this article.
      Spec Care Dentist. 2008 Jan-Feb;28(1):27-31.
      Click here to read the PubMed abstract of this article.

      A single-blind controlled study evaluated the therapeutic efficacy and safety of lactic acid 5% mouthwash, one teaspoonful three times daily before meals, and concluded that this is an effective therapy for patients with RAS and significantly reduced the signs and symptoms of the disease. Dermatol Online J. 2006 Dec 10;12(7):2.
      Click here to read the PubMed abstract of this article.

        Dyclonine Topical Anesthetic Solution Dyclonine HCl 0.5% and 1.0% Topical Solutions are listed in the “Discontinued Drug Product List” section of the Orange Book as Dyclone™ products were NOT withdrawn from commercial manufacture for reasons of safety or effectiveness.Unlike the original product which had an unpleasant taste, compounded dyclonine topical anesthetic solution can be formulated in mint and several other pleasing flavors.

        Topical Medication to Treat Orofacial Neuropathic Pain The Department of Diagnostic Sciences, Division of Orofacial Pain, University of Medicine and Dentistry of New Jersey, Newark, conducted a study to evaluate the effect of topical medications alone or in combination with systemic medications in the treatment of orofacial neuropathic pain conditions. A retrospective chart review was performed for 39 patients who were diagnosed with a neuropathic pain condition such as deafferentation pain, traumatic neuroma, or trigeminal or glossopharyngeal neuralgia, and were treated for orofacial neuropathic pain at the Orofacial Pain Clinic. The review concluded that topical medication as single treatment or in combination with systemic medications can reduce orofacial neuropathic pain severity. “The topical medication can be ordered from a compounding pharmacy where it can be formulated to contain carbamazepine 4%, lidocaine 1%, ketoprofen 4%, ketamine 4%, and gabapentin 4%. Carbamazepine and gabapentin ... act by suppressing paroxysmal discharges and reducing neuronal hyperexcitability. Lidocaine, which is a local anesthetic, acts by blocking sodium channels, preventing nerve depolarization.Ketoprofen has anti-inflammatory activity.Last, ketamine blocks N-methyl-D-aspartate (NMDA) receptors, whose hyperactivity contributes to maintenance of neuropathic pain.” The topical preparation should utilize penetration enhancers such as anhydrous gel base and bio-adhesive copolymers. These are used to carry the medication transdermally and transmucosally. “ Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Apr;105(4):466-9.
      Click here to read the PubMed abstract of this article.

      Update on Burning Mouth Syndrome

      Burning mouth syndrome (BMS), also referred to as glossopyrosis or glossodynia (when the burning occurs on the tongue only) is usually described as oral burning pain, sometimes with dysesthetic qualities similar to those present in other neuropathic pain conditions. The dorsal tongue, palate, lips and gingival tissues, individually or in combination, are the most common sites involved. Bilateral or unilateral oral burning pain has been found to be associated with jaw pain or uncontrollable tightness, taste changes, subjective dry mouth, geographic and fissured tongue, painful teeth, headache, neck and shoulder pain, difficulty speaking, nausea, gagging and swallowing difficulties. BMS has been reported to follow dental treatment, antibiotic usage and a severe upper respiratory infection. The lack of pathology to account for the pain can be frustrating. Pain is constant, progressively increases over the day, and usually decreases during eating. Patients, who are frequently distressed by their unremitting symptoms, may demonstrate psychological abnormalities including anxiety and depression. Therapy for BMS involves the use of centrally acting medications for neuropathic pain, such as tricyclic antidepressants, benzodiazepines or gabapentin. Clonazepam is a benzodiazepine used either topically or in low doses orally, which appears to have excellent efficacy in the relief of the symptoms related to BMS. Topical medications, including clonidine, may be considered for application to local sites. A combination of oral medications for the management of BMS (clonazepam, gabapentin, baclofen, and lamotrigine) significantly decreased pain in 38 or 45 patients. The most common adverse effect reported with the medication protocol was drowsiness followed by dizziness and perceived changes in mood. These results suggest that BMS may be treated with lower doses of a combination of medications rather than higher doses of a single medication, which may help to limit adverse effects such as drowsiness or dizziness.

      Adv Otorhinolaryngol. 2006, 63:278�287 

      The formulation for a mouthrinse containing clonazepam 1 mg per 5 ml has been reported. It is hypothesised that clonazepam acts locally to disrupt the mechanism(s) underlying stomatodynia. Topical formulations of gabapentin, ketamine, clonidine, and baclofen have been used to treat chronic neuropathic pain at various bodily sites. Int J of Pharmaceutical Compounding July/Aug 2005, 9(4):310
      Pain 2004 Mar;108(1-2):51-7       (click for abstract)
      Pain Med. 2000 Mar;1(1):97-100  



      Triamcinolone Acetonide Oral Rinse for Treating Oral Lichen Planus   Corticosteroids are the class of drug most commonly used for the treatment of oral lichen planus. Triamcinolone acetonide paste is the most widely available commercial preparation for the treatment of oral lichen planus, but is difficult to apply to mucosa and patients have reported an unpleasant sticky sensation. Delivery of corticosteroids via an oral rinse has the advantage of providing drug contact with the distal, hard-to-reach crevices and surfaces of the oral cavity, which can prevent new eruptions. The use of a 0.1% triamcinolone acetonide aqueous suspension as an oral rinse in the treatment of symptomatic oral lichen planus has proven to be more effective than the 0.1% dental paste. This preparation must be compounded extemporaneously and should not contain flavorings (which stimulate salivation and therefore dilute the preparation in the mouth, decreasing its effectiveness) or preservatives (which may sting or burn the mucosa). Also, researchers have formulated a triamcinolone acetonide solution for use as an oral rinse, which is more convenient to use and more palatable than the commercially available triamcinolone acetonide paste, with similar therapeutic efficacy.

       Am J Health-Syst Pharm.  2005;62(5):485-491
      Click here
      to access the PubMed abstract of this article. 
  • Dry Mouth, Stomatitis and Mucositis

    • Topical Oral Solutions for the Treatment of Chemo-Induced Oral Mucositis
       
      “Magic mouthwashes” are topical solutions or suspensions prepared to relieve symptoms of various oral pathologies. As compounding pharmacists, we recognize the need for practitioners to have the ability to prescribe customized preparations to meet specific patient needs. We can compound various medications into a stable, pleasantly-flavored, alcohol-free suspension.
       
      J Oncol Pharm Pract. 2005 Dec;11(4):139-43.
      Survey of topical oral solutions for the treatment of chemo-induced oral mucositis.
      Click here to access the PubMed abstract of this article.  
      Misoprostol: Mucosal Protectant and Anti-Secretory

      Misoprostol is a synthetic prostaglandin E1 analogue, with mucosal cytoprotectant and antisecretory properties. A mouthrinse containing misoprostol and lidocaine in a non-irritating neutral vehicle can be used to provide immediate pain relief and aid in the healing of the oral cavity. A mucoadhesive powder containing misoprostol can be used to aid in the healing of mucosal ulcers and irritations. It is applied by using a powder "puffer" or by direct application of the powder to the affected area. The carriers will hydrate and adhere to the mucosal surface, keeping the misoprostol in prolonged contact with the area. Int'l J Pharm Compounding. May/June 2000; 4(3):211
      Misoprostol 0.001% and Lidocaine 0.5% Oral Rinse
      Click here to access the abstract of this article.

      Int'l J Pharm Compounding. May/June 2000; 4(3):212
      Misoprostol 0.0027% Mucoadhesive Powder
      Click here to access the abstract of this article.

      Int'l J Pharm Compounding. Jan/Feb 1999; 3(1):48
      Misoprostol 0.0024% and Lidocaine 1% in Glycerin Mouth Paint               
      Click here to access the abstract of this article




      Burning Mouth Syndrome (BMS) Relieved with Alpha Lipoic Acid (ALA)
      A double blind, controlled study compared alpha lipoic acid with placebo for two months on 60 patients with constant BMS, in whom there was no laboratory evidence of deficiencies in iron, vitamins or thyroid function and no hyperglycemia. Following treatment with alpha lipoic acid 600 mg orally daily, there was a significant symptomatic improvement compared with placebo. This improvement was maintained in over 70% of patients at the 1 year follow-up. J Oral Pathol Med. 2002 May;31(5):267-9.
      Burning mouth syndrome (BMS): double blind controlled study of alpha-lipoic acid (thioctic acid) therapy.
      Click here to access the PubMed abstract of this article. 

      Saliva Substitute for Dry Mouth/Throat Saliva replacement is an important adjunct to relieving the symptoms of xerostomia in patients with Sjogren's Syndrome. Saliva substitutes which contain thickening agents like carboxymethylcellulose are used because water alone can not adequately moisten and lubricate the oral mucosa and teeth. Dry mouth or throat secondary to a number of conditions can be relieved with a customized saliva substitute that can be administered throughout the day and night and can be flavored to please each patient. Keeping the mucosal membranes moist can improve comfort for the patient and minimize irritation and the risk of infection. Int'l J Pharm Compounding. May/June 2000; 4(3):215
      Saliva Substitute for Dry Mouth/Throat                  
      Click here to access the abstract of this article.

      Int'l J Pharm Compounding. Sep/Oct 2000; 4(5):340
      Saliva Substitute
      Click here to access the abstract of this article.   Pilocarpine Troches for Xerostomia Pilocarpine is indicated for the treatment of xerostomia secondary to radiation therapy of the head and neck. Pilocarpine is a cholinergic agent that stimulates residual-functioning exocrine glands. In a study by Vivino et al., pilocarpine at oral doses of 2.5mg and 5mg four times daily significantly increased saliva production and alleviated symptoms of dry mouth when compared to placebo. The higher dose produced the most improvement but also the highest incidence of adverse effects, such as sweating, diarrhea, and urinary frequency. Arch Intern Med. 1999; 159:174-181
      Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjogren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group.
      Click here to access the PubMed abstract of this article.


      Int'l J Pharm Compounding. Sep/Oct 2000; 4(5):381
      Pilocarpine HCl 2-mg Troches                      
      Click here to access the abstract of this article.
       

      Treatment for Dry Mouth, Stomatitis, and Mucositis
      Loss of saliva (xerostomia) is one of the most common complaints among patients who have received radiation therapy of the head and neck. Xerostomia contributes to radiation-induced periodontal infection, dental caries, osteoradionecrosis, and poor digestion of carbohydrates. Ask us about sialogogues (saliva stimulants) in customized dosage forms. Aust Dent J 2002 Sep;47(3):249-53
      An investigation into the use of pilocarpine as a sialagogue in patients with radiation induced xerostomia.
      Click here to access the PubMed abstract of this article.   When a person is receiving chemotherapy or radiation, mouth tenderness and infections can interfere with the ability to eat. Malnutrition may result, yet it is often preventable. Our pharmacy can compound medications which may enable patients to enjoy eating again. We can compound numerous medications into a preparation such as an oral rinse that contains the needed concentrations of each drug. A three-drug mouthwash (lidocaine, diphenhydramine and sodium bicarbonate in normal saline) can provide effective symptomatic relief in patients with chemotherapy-induced mucositis. Support Care Cancer. 2000 Jan;8(1):55-8
      Efficacy of treatment to relieve mucositis-induced discomfort.
      Click here to access the PubMed abstract of this article.
  • Therapy for TMJ

    • New, Noninvasive Approach for Successfully Treating Pain and Inflammation of TMJ Disorders A topical gel containing 18% potassium complex, 10% dimethylisosorbide, and 72% aqueous hydroxyethyl cellulose gel was applied and gently rubbed onto the facial skin over the painful TMJ, muscles of mastication, and myofacial area. Complete pain relief occurred in 45 of 54 patients in this study within 5 minutes of the first application of the gel, and in all 54 patients after the third day of twice daily application of the treatment gel. J Oral Implantol. 2007;33(6):365-70.
      A new, noninvasive approach for successfully treating the pain and inflammation of TMJ disorders.
      Click here to read the PubMed abstract of this article.


      Transdermal application of NSAIDs such as ketoprofen results in significantly higher tissue levels beneath the site of application than are achieved with oral administration. Additionally, side effects such as gastrointestinal irritation are avoided. The following article concludes: "Topical non-steroidal anti-inflammatory drugs are effective in relieving pain in acute and chronic conditions." BMJ. 1998 Jan 31;316(7128):333-8
      Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs.
      Click here to access the PubMed abstract of this article. Free full text article available at bmj.com: http://bmj.bmjjournals.com/cgi/content/full/316/7128/333   The following article reports "The systemic concentrations of ketoprofen have also been found to be 100 fold lower compared to tissue concentrations below the application... Topically applied ketoprofen thus provides high local concentration below the site of application but lower systemic exposure." Pharm Res. 1996 Jan;13(1):168-72
      Percutaneous absorption of ketoprofen from different anatomical sites in man.
      Click here to access the PubMed abstract of this article.   Iontophoretic delivery of dexamethasone and lidocaine may be effective in improving mandibular function in patients with temporo-mandibular disorders who have concurrent temporo-mandibular joint capsulitis and disc displacement without reduction. J Orofac Pain 1996 Spring;10(2):157-65
      Temporomandibular joint iontophoresis: a double-blind randomized clinical trial.
      Click here to access the PubMed abstract of this article.
  • Surpressing the Gag Reflex

    • The gag reflex can cause a patient considerable discomfort as well as interfere with dental procedures. An electrolyte tablet administered and retained intraorally a few minutes before the start of a procedure can suppress the gag reflex, allowing a mandibular block to be given with much greater ease, which further reduces the gagging reflex. Tablets can be prescribed for home use for patients who can not properly perform oral hygiene procedures due to the gagging problem. Severe gaggers may need to repeat a dose in 15 to 20 minutes. Some patients and dentists prefer to use electrolyte lollipops.


      Dent Today. 1991 Dec;10(9):68-71
      The gagging patient: a method for success.
      Click here to access the PubMed abstract of this article.
  • Transdermal Anti-Emetics

    • Topical application of anti-emetics in a gel formulation provides a rapid onset and offers an effective alternative to oral administration. Oral surgeons have found this formulation to be particularly useful. Promethazine is commonly compounded for topical or transdermal application to treat nausea, vomiting, and vertigo, but this preparation may be used as an antiemetic for cases ranging from chemotherapy to motion sickness. The dose is typically 25mg for adults, and the dose is decreased for children. The gel is applied to an area of soft skin, such as the inside of the wrist or arm, the side of the torso, or the inside of the thigh. For children, the gel is often applied to the inside of one wrist, and then the wrists are rubbed together.
      US Pharmacist, August 1999; 74-5 Other dosage forms include suppositories and lollipops
  • Periodontal Therapy

    • Compounding allows countless active ingredients to be incorporated into customized mouthwashes, gels, troches, etc. For example, to treat periodontal disease, antibiotics can be formulated as a mouthwash, or added to an oral adhesive paste or a plasticized gel that will maintain the contact between the tissue and medication for a prolonged period of time.


      Metronidazole 25% in a lipogel-type base provides an efficient treatment of anaerobic infection when applied topically in the periodontal pockets.

      J Int Acad Periodontol. 2000 Jul;2(3):64-70
      Clinical evaluation of subgingival application of metronidazole 25%, and adjunctive therapy.
      Click here to access the PubMed abstract of this article.

      Vojnosanit Pregl. 2005 Jul-Aug;62(7-8):565-8
      Effects of topical application of metronidazole-containing mucoadhesive lipogel in periodontal pockets.
      Click here to access the PubMed abstract of this article.

      Minerva Stomatol. 2000 Jan-Feb;49(1-2):59-67
      [Topical treatment of peri-implantitis with metronidazole dental gel 25%. Clinical analysis and microbiological control]
      Click here to access the PubMed abstract of this article.

      J Clin Periodontol. 1992 Oct;19(9 Pt 2):693-7
      Systemic absorption of metronidazole after application of a metronidazole 25% dental gel.
      Click here to access the PubMed abstract of this article.
  • "Miracle Mouthwashes"

    • Compounding dental mouthwashes or rinses may offer numerous advantages over commercially available dosage forms. Elixirs, syrups, and suspensions often contain preservatives such as alcohol which can cause reactions or gastrointestinal irritation, or sugar which makes the preparation undesirable for prolonged use in the mouth or for diabetic patients. A customized preparation without unnecessary excipients - i.e., a sugar-free, dye-free, lactose-free, and preservative-free dosage form - can eliminate concerns of palatability, alcohol content, and dyes which may stain exposed mucosa. Various preparations are also available to treat burning mouth syndrome and anesthetic/analgesic and antibiotic/anti-infective mouthwashes are commonly requested. Tranexamic acid solution (4.8%) used as a mouthwash has been used successfully to prevent postsurgical bleeding after oral surgery without dose modification of oral anticoagulants. J Oral Maxillofac Surg 1993 Nov;51(11):1211-6
      Prevention of postsurgical bleeding in oral surgery using tranexamic acid without dose modification of oral anticoagulants.
      Click here to access the PubMed abstract of this article.
  • Examples of Comounded Medications

    • We are dedicated to meeting the unique needs of dental patients, and we welcome your questions and medication problems. Our compounding professionals are problem-solving specialists! Examples of Customized Medications for Dental Care
      • Anti-Viral Lip Balms
      • Ketamine/Ketoprofen/Gabapentin gel
      • Ketoprofen/Cyclobenzaprine topical gel
      • Lidocaine/Prilocaine gel in plasticized base
        Mucosal Bandages
      • Oxytetracycline/Hydrocortisone Suspension
      • Peruvian Balsam/Eugenol
      • Sucralfate Oral Adhesive Paste
      • Tranexamic Acid Mouthwash
      • Triple-Anesthetic gel - benzocaine/lidocaine/tetracaine ("BLT")
      • Pressure Indicating Paste (PIP)
      All formulations are customized per prescription to meet the unique needs of each patient. Please contact our compounding pharmacist to discuss the dosage form, strength, and medication or combination that is most appropriate for your patient.

Veterinary

  • Pharmacists Helping Vets and Pets Our "specialty service should not be viewed as competition with local veterinarians; rather, compounding allows veterinarians to broaden their prescribing abilities and to offer [dosage] forms that are patient-specific in strength and formulation. Therefore, the goal of compounding for the veterinary patient is to enhance the veterinarian's ability to treat patients in a more effective and efficient manner... "Compounding can make medicating animals easier if the pharmacist prepares flavored chews that animals accept readily. For example, tranquilizing a feral cat with a liver-flavored chew eliminates the possibility of over- or underdosing. If a chew contains 10mg acepromazine and the dose fails to gain a response, a second flavored chew can be given to the animal. Furthermore, the amount of medication incorporated into the chews, capsules, [topical or transdermal], or liquid preparations can be formulated to the specific request of the veterinarian, thereby eliminating the need to cut-up tablets and divide the contents of commercially prepared capsules... As manufacturers decide that certain products are no longer economically rewarding to market, the list of commercially prepared veterinary medication becomes smaller. At present, the armamentarium of medications available for animals is less than perfect. Cherry-flavored amoxicillin or orange-flavored cephalexin may not be [appealing to a cat or monkey]..."

    Veterinary Forum October 2002, (pp. 62-65) Our compounding pharmacy can prepare:
    • Flavored medication
    • Medicine in ideal size, strength, and dosage form
    • Unavailable medications
    • Combinations to improve compliance
    • Novel devices and delivery systems
    Compounding is actually a means to an end. We work together with veterinarians and their clients and patients to solve medication problems by compounding specialized medications that meet the unique needs of each animal - pets, exotics, horses, or zoo animals. Let us know how we can help you and the animals in your care.
  • Transdermal Medications

    • Have you ever thought about applying a transdermal preparation to the inside of an animal's ear or another hairless area as an alternate route of systemic administration? It's quick and easy, and many medications are compatible with transdermal bases. Transdermal delivery is particularly useful for animals who should not be stressed due to cardiovascular or hypertensive illness. Also, it is appreciated by owners who no longer have to deal with an animal who resists being medicated, and the resulting scratches! We can also prepare topical medications for application at the site of inflammation or infection. Advantages of Transdermal Dosage Forms
      Various alternative dosage forms permit medication to be absorbed via non-oral routes to meet an animal's specific needs. Although the parenteral and rectal routes are traditional alternatives to oral administration, transdermal absorption offers many advantages. For example:
      • When medication is absorbed directly into the bloodstream without first entering the gastrointestinal system, a smaller amount of active ingredient may be required for therapeutic effect.
      • Direct application and absorption at the target site can mean higher tissue levels and lower blood levels of various medications. Side effects such as GI irritation can be eliminated.
      • Various types of drug interactions may be avoided when one or more interacting medications are administered transdermally.
      A substantial number of references exist in human medical literature with regard to the efficacy of transdermal administration of non-steroidal anti-inflammatory drugs and other types of analgesics, antiemetics, and other medications. We can compound transdermal and topical medications using a suitable base, and add penetrant enhancers if desired.



      Transdermal Atenolol and Feasibility of Transdermal Administration Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol. “In theory, the transdermal route of administering medications has many potential advantages. It is noninvasive and not demanding technically, avoids first-pass hepatic metabolism and gastrointestinal breakdown, has potential for sustained release formulations, and can be administered over a large surface area. Transdermal administration of medication has been shown to achieve blood concentrations of drug that are considered to be therapeutic (eg, fentanyl) or efficaciously affect physiologic surrogates (eg, methimazole, nitroglycerine, and lidocaine). Feasibility of transdermal medication varies on a drug-by-drug basis.” Discussion: In spite of these results, investigators did not conclude that transdermally administered atenolol is not feasible.Because two cats did achieve therapeutic blood concentrations of atenolol after transdermal administration, the authors called for further research to find a transdermal formulation and dosing regimen for atenolol that will consistently result in plasma atenolol concentrations of >260ng/ml.Investigators offered several considerations for future studies. This study utilized a hydrophilic carbomer/propylene glycol/glycerin gel vehicle which has been used in human delivery of transdermal medications. As pluronic lecithin organogel (PLO) is the transdermal vehicle used almost exclusively in veterinary medicine, investigators encouraged future transdermal atenolol research utilizing PLO as the vehicle.Investigators also noted that higher doses of atenolol (3mg/kg) have been reported to consistently result in blood levels providing adequate adrenergic blockade at 12 hours in all cats studied.Since the median atenolol dose administered in this study was 1.1mg/kg, researchers suggest studying transdermal atenolol at the 3.3mg/kg dose. Because daily oral administration of atenolol to cats is challenging and often results in a lack of compliance, a non-invasive dosage form such as transdermal atenolol will most likely result in better compliance, less stress to the cat, and reveal a positive therapeutic effect. Am J Vet Res. 2008 Jan;69(1): 39-44.
      Comparision of pharmacodynamic variables following oral versus transdermal administration of atenolol to healthy cats.
      Click here to read the PubMed abstract of this article.



      Transdermal Carbimazole Gel for the Treatment of Feline Hyperthyroidism The aim of a study conducted by Buijtels et al. of Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, The Netherlands, and presented at the 16th ECVIM-CA Congress, 2006, was to develop a carbimazole gel for application at the inner pinna of the ear and to study its effectiveness in cats with hyperthyroidism. The results of this study indicate that twice daily administration of carbimazole gel at the inner pinna of the ear is an effective treatment of cats with hyperthyroidism. Tijdschrift voor Diergeneeskunde. 2006; 131(13):478-82
      [Transdermal carbimazole for the treatment of feline hyperthyroidism]
      Click here to read the PubMed abstract of this article.
  • Anti Infective

    • Penicillin Gelatin Guttural Pouch Lavage
       
        
      Streptococcus equi is the bacterial pathogen responsible for a highly contagious equine disease known as strangles.  Strangles most commonly occurs in younger horses, but can be seen in horses of any age, particularly performance horses encountering sites where high density and high turnover of horses occurs (competition grounds, fairs, auctions, and boarding facilities). Infection by S. equi causes a severe inflammatory response manifesting as fever (102°-106°F), inappetance, lymphadenopathy with abscessation and resulting stridor, and a copious, mucopurulent nasal discharge. The guttural pouch has been identified as the site most likely to harbor S. equi organisms after infection due to draining abscesses from the mandibular lymph nodes.  While systemic beta-lactam therapy has proven very valuable in treatment of active disease, antibiotics do not achieve high enough concentrations in the guttural pouch to eliminate organisms.  Recently, the use of penicillin G sodium impregnated gelatin has been utilized to fill the guttural pouches following guttural pouch lavage in order to allow prolonged, bacteriocidal concentrations of penicillin in the guttural pouch after a single application.  The penicillin sodium gel should be prepared in an aseptic environment and refrigerated for at least 24 hours prior to administration. Our compounding pharmacists are able to provide this preparation for equine veterinary patients.
       
      For further reading on equine strangles consult the American Association of Equine Practitioners at http://www.aaep.org/strangles.htm.
       
      Clotrimazole 1% in Pluronic Gel for Nasal Aspergillosis
       
         Nasal aspergillosis is a common fungal condition in dogs that results in massive turbinate destruction, pain and death or euthanasia due to lysis of surrounding skeletal structures such as the cribiform plate. Systemic treatment with oral antifungals is very expensive and often accompanied with serious adverse effects, and often is not successful (40-70% success).  Traditionally, the treatment of choice for nasal aspergillosis in dogs was a one-hour intranasal irrigation of 1% clotrimazole solution while the patient was anesthetized. The prolonged anesthesia was necessary to allow maximal contact time of the 1% clotrimazole solutions that immediately ran out of the sinuses once introduced. This therapy resulted in a success rate of almost 70% after a single treatment, but many dogs require multiple treatments for complete resolution.  Because of the expense and risk of multiple surgical and prolonged anesthetic procedures, a method to provide prolonged contact of 1% clotrimazole solutions in the nasal sinuses has been considered. A recent study assessed the retention, toxicity and stability of several viscous preparations of clotrimazole 1% in canine frontal sinus. Six compounds were evaluated including commercially available 1% clotrimazole cream, and 1% clotrimazole in varying concentrations of hydroxypropyl methylcellulose, carboxymethylcellulose, and poloxamer gel.  Results of this study indicate that clotrimazole 1% delivered in 25% poloxamer gel resulted in the least amount of sinus inflammation and was accompanied by a reasonable retention time.  Researchers concluded that use of poloxamer gels holds much promise for prolonged delivery of clotrimazole in nasal sinuses, potentially reducing anesthetic time as well as accomplishing fungal organism eradication after a single course of treatment. Veterinarians interested in pursuing use of this therapy for nasal aspergillosis can contact our compounding pharmacist to prescribe clotrimazole 1% in 25% poloxamer gel.
       
      Am J Vet Res 2009:70:640–647
      Assessment of clotrimazole gels for in vitro stability and in vivo retention in the frontal sinus of dogs.
      Click here to access the PubMed abstract of this article.




      Antibiotic/Antifungal/Antiviral Therapy
      Please scroll down for more information on the following topics:
      Metronidazole
      Esophageal Strictures Secondary to Administration of Doxycycline Tablets
      Oral Itraconazole for Therapy of Dermatophytosis Caused by Microsporum canis
      Chloramphenicol Suspension for Birds & Small Animals
      Fluoroquinolone Antibiotics
      Antibiotic Treats for Feline Abscess
      Intranasal Clotrimazole for Treatment of Nasal Aspergillosis in Dogs
      Azithromycin
      Azithromycin for R. equi Infections in Foals
      Idoxuridine Ophthalmic Drops for Cats
      Feline Ocular Toxoplasmosis
      Itraconazole/DMSO for Fungal Keratitis in Horses Metronidazole
      Metronidazole is effective against a variety of obligate anaerobic bacteria as well as anaerobic protozoa such as Giardia and Trichomonas. "Various salts of metronidazole with improved palatability are now available for veterinary patients... Cats and birds accept the benzoate salt much more willingly than they accept metronidazole HCl and do not seem to be stressed by its administration."
      Metronidazole should be used with caution in patients with hepatic dysfunction. Therapy should be promptly discontinued if abnormal neurological signs appear, including nystagmus, ataxia, seizures, and rigidity. All benzene moieties must be conjugated with glucuronide to facilitate elimination and this pathway is inefficient in cats. Therefore, doses of metronidazole benzoate above 200 mg/kg/day may produce signs of cumulative toxicity in cats within 48 to 72 hours. Compendium Dec. 2000: 22(12); pp. 1104, 1105, 1107, 1130

      Esophageal Strictures Secondary to Administration of Doxycycline Tablets

      "The most common causes of esophageal strictures in dogs and cats are gastroesophageal reflux during anesthesia, persistent vomiting, or ingestion of foreign bodies or caustic agents. In humans, esophageal retention of oral medication is a common cause of severe esophagitis. Of the medications proven to lead to esophageal ulceration, doxycycline is most often implicated. It has been suggested that pill-induced esophagitis also could occur in small animals..." Drug-induced esophageal ulceration usually occurs when tablets are taken with little or no water and adhere to the esophageal mucosa. Once this occurs, flushing with large quantities of liquid fails to wash the medication into the stomach. Melendez et al. of Colorado State University College of Veterinary Medicine report on three cases of presumptive doxycycline-induced esophagitis in cats, with resultant stricture formation. All cats had been administered fractions of doxycycline tablets one to three weeks before presenting with a chief complaint of regurgitation. "Two of the cases developed regurgitation within 7 days after initiation of therapy with doxycycline. One cat, which was treated while at an animal shelter, was noted to be regurgitating the day that it was adopted, approximately 2 weeks after being treated with doxycycline. No other cause of esophageal stricture formation could be identified." If a pet that has received a doxycycline tablet shows sign of esophagitis (dysphagia, excessive salivation, inappetence, and regurgitation), the doxycycline tablets should be discontinued. Suggested therapy for esophagitis includes sucralfate slurries, a prokinetic agent (i.e. cisapride) to increase lower esophageal sphincter tone, and anti-inflammatory doses of glucocorticoids to prevent stricture formation.
      Doxycycline can be compounded as a stable flavored liquid preparation or other palatable dosage form to meet the specific needs of each animal and owner.

      Feline Practice 28:2; 10-12 (Mar/Apr 2000)   Oral Itraconazole for Therapy of Dermatophytosis Caused by Microsporum canis
      Itraconazole could be an effective alternative to griseofulvin that has toxic effects (particularly in puppies based on this author's experience) and frequent therapeutic relapses. Itraconazole has also been used to successfully treat M. canis infection of cats and guinea pigs. J Am Vet Med Assoc 1998;213:993-995

      Chloramphenicol Suspension for Birds & Small Animals

      by J. Terry McGrath, VMD, Pennsylvania Since chloramphenicol palmitate is no longer commercially available, we contacted our compounding pharmacist for an alternative for use in our avian and other small patients, such as rabbits and rodents. The pharmacist prepared a cola flavored suspension containing 30 mg/ml of chloramphenicol palmitate, which could be administered using a small oral syringe. However, birds did not like the taste and it was reformulated into a tutti fruitti and pina colada syrup. The "animal appropriate" flavor has really helped with compliance, because now the birds and small animals like to take their medicine! Note: To avoid potential antagonism, chloramphenicol should not be administered simultaneously with penicillin or streptomycin. Chloramphenicol-containing preparations should not be administered in conjunction with, or two hours prior to, the induction of general anesthesia with pentobarbital. When administered orally in dogs, chloramphenicol is well-tolerated, has high clinical efficacy, and a low incidence of side effects. The recommended canine dosage is 25 mg/lb of body weight every six hours. Precautions: Chloramphenicol should be administered cautiously to animals with hematopoietic dysfunction, or impaired kidney or liver function.

      Antibiotic Treats for Feline Abscess

      Submitted by: Michael Briggs, Pharm.D. Veterinarian: Rich Marchetti, D.V.M.
      Patient: One year old non-castrated short-haired male cat with abscess from wound received in fight. The owner reported that the cat, who is usually affectionate and friendly toward the owner and house dog, had been withdrawn, on guard, and growling for approximately three days. A thorn-like projection near the tail was found by the owner, who immediately took the cat to the veterinarian. The cat was anesthetized and the veterinarian cleaned, debrided, and shaved the area of the wound, and prescribed amoxicillin 100 mg daily for ten days. The owner was instructed to keep the cat inside for the duration of therapy, to minimize the risk of superinfection and avoid additional injury.
      Medication Problem: The cat refused to take liquids, and was also resistant to taking tablets ("pilling"). The required dose of antibiotic was too high for transdermal treatment (due to the amount of gel that would need to be applied for each dose). Solution: The veterinarian called our compounding pharmacy and asked if we could come up with a palatable dosage form. We formulated a fish-flavored chewable treat containing amoxicillin 100 mg to be given once daily for ten days. This dosage form offers the advantage of ease of administration, decreases the potential for dosing errors, and greatly increases patient compliance. The cat readily consumed the amoxicillin "treat". The wound did not heal in a ten day period, so five additional days of therapy were required.
      Comment: Our pharmacy has compounded this preparation more than ten times with a 100% success rate.

      Intranasal Clotrimazole for Treatment of Nasal Aspergillosis in Dogs

      "Treatment of nasal aspergillosis with systemic antifungal medications, such as thiabendazole, ketoconazole, and fluconazole, has been disappointing because the response rate is only 43 to 60%. Response to oral administration of itraconazole has been approximately 60 to 70%... Topical administration of the imidazoles, enilconazole, and clotrimazole is more effective than orally administered antifungal medications." Topical administration of clotrimazole resulted in resolution of clinical disease in 65% of dogs after 1 treatment and 87% of dogs after one or more treatments. Topical administration of clotrimazole, using either technique, was an effective treatment for nasal aspergillosis in dogs. Use of non-invasive intranasal infusion of clotrimazole eliminated the need for surgical trephination of frontal sinuses in many dogs and was associated with fewer complications. Nasal discharge ceased in most dogs 2 weeks after topical treatment, and the authors now recommend re-treatment with clotrimazole if nasal discharge has not improved 2 weeks after treatment. "[Damage] of the cribriform plate may contraindicate use of topical treatment; complications arising from leakage of antifungal medications into the CNS in dogs with fungal rhinitis have not been evaluated." J Am Vet Med Assoc 1998 Aug 15;213(4):501-6
      Comparison of topical administration of clotrimazole through surgically placed versus nonsurgically placed catheters for treatment of nasal aspergillosis in dogs: 60 cases (1990-1996).
      Click here to access the PubMed abstract of this article. J Am Anim Hosp Assoc 1998 Nov-Dec;34(6):487-92
      Management of nasal aspergillosis in a dog with a single, noninvasive intranasal infusion of clotrimazole.
      Click here to access the PubMed abstract of this article.   Azithromycin
      is a form of erythromycin with improved action against gram-negative organisms, resistance to acid degradation, improved tissue penetration, and a prolonged elimination half-life. Azithromycin shows potential for use in veterinary medicine, particularly in cats and certain avian and exotic species.
      "Lacking the prokinetic action of erythromycin, azithromycin appears to cause fewer GI side effects and is generally well tolerated after oral administration. Cats appear to tolerate the drug particularly well... Animals with a history of arrhythmias should be monitored while receiving the drug. Some reduction in dose may be warranted in patients with hepatic or biliary dysfunction, although no reduction appears necessary in patients with renal dysfunction." Please consult our compounding pharmacist regarding dosing. Compendium of Continuing Education 23:3 (March 2001), pp. 242-7


      Azithromycin for R. equi Infections in Foals
      On the basis of pharmacokinetic values, minimum inhibitory concentrations of R. equi isolates, and drug concentrations in pulmonary epithelial lining fluid (PELF) and bronchoalveolar cells, a single daily oral dose of 10 mg/kg may be appropriate for treatment of R. equi infections in foals. Persistence of high azithromycin concentrations in PELF and bronchoalveolar cells 48 hours after discontinuation of administration suggests that after 5 daily doses, oral administration at 48-hour intervals may be adequate. Am J Vet Res 2001 Dec;62(12):1870-5
      Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar cells in foals.
      Click here to access the PubMed abstract of this article. The Capsule Report, Mixed Practice/Exotic Edition Jan 2002;15, 10: page 1

      Itraconazole/DMSO for Fungal Keratitis in Horses
      Fungal keratitis is a serious complication of trauma to the eye. Approximately one-half of the cases of fungal infections have involved the use of eye ointments containing corticosteroids after trauma to the globe of the eye.

      "Itraconazole is a third generation triazole that has superior penetration properties and a wide spectrum of activity. A 1% solution of itraconazole in a 30% DMSO and petroleum base has been shown to reach high concentrations within the stroma of the cornea when administered every 4 to 6 hours. In general, every 6 hours is suitable for all but Fusarium sp which requires every 4 hour administration." Disease which is rapidly ulcerating "should also receive treatment that helps block the enzymes (collagenase) responsible for ulceration. A 5% acetylcysteine solution and autologous serum in which 4 mg/ml of EDTA has been added has been recommended. These need to be instilled hourly for best effect. The antimicrobial can be added to the serum." This information has been abstracted from an article by Robert N. Oglesby, DVM, which appears on his webpage, "The Horseman's Advisor."
      For more information, references and complete text, see http://www.horseadvice.com/horse/messages/4/5506.html   Idoxuridine Ophthalmic Drops for Cats
      The ocular signs of feline herpesvirus I (FHV-1) infection include bilateral conjunctivitis, serous ocular discharge which may become mucoid or mucopurulent, and blepharospasm. If corneal involvement is present, topical antivirals are prescribed. Research indicates that idoxuridine is effective against FHV-1. Prolonged contact with the infected tissue is required. The 0.1% solution must be applied five times daily. Previously marketed as Stoxil�, the ophthalmic solution is not commercially available at this time.

      Michael Zigler, DVM, Cert.V.Ophthal  http://www.eyevet.ca/herpes.html

      Am J Vet Res 1989 Jan;50(1):158-60
      In vitro susceptibility of feline herpesvirus-1 to vidarabine, idoxuridine, trifluridine, acyclovir, or bromovinyldeoxyuridine.
      Click here to access the PubMed abstract of this article.
        Feline Ocular Toxoplasmosis
      "The anterior uveitis seen in cats with a positive serum titer to Toxoplasma gondii may result from immune-mediated mechanisms and not the presence or replication of the organism itself. As a result, it is unclear whether systemic antitoxoplasmic therapy is beneficial in these cases." Michael G. Davidson, DVM, of North Carolina State University, College of Veterinary Medicine reports in Vet Clin N Amer, Sep 2000, that he "usually treats cats with ocular lesions and concurrent systemic findings of toxoplasmosis with systemic clindamycin (12.5 mg/kg PO twice daily for 14-21 days) and anti-inflammatory therapy. Other sources recommend clindamycin 10-12.5 mg/kg every 12 hours for 4 weeks. Oral trimethoprim-sulfonamide combination therapy (15 mg/kg every 12 hours for 2 to 4 weeks) can also be used to treat toxoplasmosis but is less suitable because of potential side effects caused by folic acid deficiency in cats.2 In T gondii seropositive cats exhibiting anterior uveitis alone and with no systemic signs, Dr. Davidson recommends topical steroids and atropine alone. If the cat fails to respond to topical therapy alone within 1-3 weeks, systemic clindamycin should be added to the treatment regimen. The rationale for the use of corticosteroids is to suppress the damaging inflammation in the retina, which may affect vision. Corticosteroids are typically administered 1-2 days after antibiotic therapy has been initiated to allow adequate tissue levels of the antimicrobial agent to be achieved. [Dr. Davidson] does not recommend systemic steroids in cats with suspected ocular toxoplasmosis because of the risk of exacerbating systemic replication of T gondii."1
      Swift and aggressive treatment of uveitis is necessary to avoid such secondary complications as glaucoma, cataract formation, and retinal degeneration or detachment.3 1 The Capsule Report 19:10 (Jan 2001), p. 4
      2, 3 Compendium of Continuing Education 23:3 (March 2001), pp. 258-66
  • Behavioral Medicine

    • Transdermal Treatment for Aggressive Cat
      Donald Tummons, D.V.M. An 11 year-old male cat showed aggressive behavior towards other cats and also started urinary spraying.  Buspirone 2.5mg/ml flavored suspension was tried.  It was extremely difficult for the owner to give the oral suspension and after a few days the cat was vomiting the medication. Treatment
      The owner was instructed to apply 0.1ml of transdermal buspirone 2.5mg/0.1ml pluronic lecithin organogel (PLO) topically inside the tip of the ear twice a day. Outcome
      After the first dose, the owner noticed the medication made the cat too sleepy and the dose was decreased to 0.05ml (1.25mg of buspirone).  The cat's aggressive behavior has been controlled on the lower dose with a few exceptions and the owner then increased the dose to 2.5mg of buspirone for a couple of doses.  The owner is amazed how easy it is to apply the medication.


      Amitriptyline for Behavioral and Urinary Disorders
      Amitriptyline hydrochloride is one of the most widely used  tricyclic antidepressants (TCAs) in companion animal behavioral medicine, exerting antihistaminic, anti-inflammatory, analgesic, and antidepressant effects. Amitriptyline increases synaptic activity of serotonin and norepinephrine, has significant central and peripheral anticholinergic activity, and stimulates beta-adrenergic receptors in smooth muscle (e.g. the bladder), causing a decrease in smooth muscle excitability and a subsequent increase in bladder capacity and storage. Although amitriptyline has been used successfully to treat behavior-related and urinary tract disorders in cats and dogs, the drug is not approved by the FDA for veterinary use and therefore is not available as a veterinary preparation. Compendium 23(5) May 2001: 433-7

      Imipramine
      In animals, tricyclic antidepressants have actions similar to those of phenothiazines in altering avoidance behaviors. Imipramine has been used for the following indications: Cats:  urethral incompetence Dogs: treatment of separation anxiety and other behaviors, cataplexy, urethral incompetence Horses:  narcolepsy and ejaculatory dysfunction


      Naltrexone for Self-Mutilating Behavior
      "Naltrexone may be useful in the treatment of self-mutilating or tail-chasing behaviors in dogs or cats... [A synthetic opiate antagonist,] naltrexone is generally considered to be contraindicated in patients physically dependent on opiate drugs, in hepatic failure or with acute hepatitis." Doses for Dogs: As adjunctive therapy in behavior disorders: For tail chasing or excessive licking: First give 0.01mg/kg SubQ of naloxone to determine if narcotic antagonists may be effective. If so, give naltrexone PO at 1 - 2 mg/kg daily. Long-term therapy may be required. (Crowill-Davis 1992) For the adjunctive treatment of acral pruritic dermatitis: 2.2mg/kg PO once daily for one month trial. Some dogs exhibit drowsiness and minor changes in behavior. 50-60% of patients have benefited...    (Rosychuck 1991)


      Canine Acral Lick Dermatitis
      involves excessive licking of the paws or flank, even to the point of self-mutilation, and can produce ulcerations and infections that require medical treatment. Based on patterns of behavior and response to medication, veterinary scientists propose that canine acral lick dermatitis, also known as canine compulsive disorder (CCD), is an animal model of human obsessive-compulsive disorder. A randomized, placebo-controlled, double-blind crossover clinical study evaluated the efficacy of the medication clomipramine for treatment of CCD. Fifty one dogs with CCD were given clomipramine 3 mg/kg [1.3 mg/lb] of body weight orally every 12 hours for 4 weeks and then placebo for 4 weeks. While drug therapy can be helpful, therapy may need to include behavior modification to optimally manage CCD. J Am Vet Med Assoc 1998 Dec 15;213(12):1760-6
      Efficacy of clomipramine in the treatment of canine compulsive disorder.
      Click here to access the PubMed abstract of this article. Arch Gen Psychiatry 1992 Jul;49(7):517-21
      Drug treatment of canine acral lick. An animal model of obsessive-compulsive disorder.
      Click here to access the PubMed abstract of this article.   Fluoxetine for Refractory Owner-Directed Dominance Aggression
      Evidence suggests that social dominance aggression may be modulated by serotonergic mechanisms. Fluoxetine (Prozac�), a specific inhibitor of serotonin reuptake, is a popular human antidepressant which has been used successfully to decrease social aggression in dogs and monkeys. J Am Vet Med Assoc 1996;209:1585-1587
      Use of fluoxetine to treat dominance aggression in dogs.
      Click here to access the PubMed abstract of this article.   Fluoxetine for Urine Spraying in Cats
      Administration of fluoxetine hydrochloride for treatment of urine spraying in cats can be expected to considerably reduce the rate of urine marking. Pryor et al. recommend that most cats should be treated more than eight weeks before treatment is withdrawn. Cats that vertically marked a mean of > or = 3 times per week were treated for 8 weeks with fluoxetine (1mg/kg PO daily- dosage individualized for each cat by a compounding pharmacy) or fish-flavored liquid placebo. When treatment was discontinued after 8 weeks, the spraying rate of cats that had received treatment varied. The main adverse reaction to the drug was a reduction in food intake, which was observed in 4 of 9 treated cats. J Am Vet Med Assoc 2001 Dec 1;219(11):1557-61
      Effects of a selective serotonin reuptake inhibitor on urine spraying behavior in cats.
      Click here to access the PubMed abstract of this article.   Inappropriate Elimination in Cats: Fluorescein to Find the Culprit
      In a multi-cat household, it is important to determine which cat is inappropriately eliminating so that the proper intervention can be made. Even if one cat is observed marking or urinating outside the box, it does not rule out the possibility that other cats are also behaving inappropriately. When it is necessary to identify which cat in a multi-cat household is spraying or inappropriately eliminating, fluorescein can be orally administered once daily in the evening with food for three days. That cat's urine will fluoresce under ultraviolet light for approximately 24 hours. To detect urine containing the fluorescein indicator, the client needs to scan the household with a commercial black light or black light purchased from a novelty store. Although urine will commonly glow, fluorescein treated urine fluoresces a characteristic bright yellow. Caution clients that they may reveal previously undiscovered sites of elimination; advise them not to become alarmed or angry. By administering the dye to different cats at two day intervals, the culprit can be identified. Pharmacological support for urine spraying or marking is usually needed only for cases with underlying anxiety or problems with social interactions between cats (clomipramine), or for cats with interstitial cystitis (amitriptyline, doxepin). Administration of fluoxetine hydrochloride for treatment of urine spraying in cats may also considerably reduce the rate of urine marking.


      Cyproheptadine to Control Urine Spraying and as an Antipruritic in Cats
      A 10-year-old castrated male domestic cat was admitted to the hospital at the School of Veterinary Medicine, Tufts University. A diagnosis of territorial urine marking was made. Treatment included behavior modification and the administration of cyproheptadine, which resulted in the immediate arrest of undesirable urine marking. Cyproheptadine administration was adjusted to determine the lowest dosage that effectively maintained the cat's consistent use of the litter box. It was recommended to continue cyproheptadine administration for at least 1 year before any attempt to withdraw its use. Another study recommended a dose of 2 mg, p.o., every 12 hours. This antihistamine, also prescribed for its appetite stimulant effects in cats, has antiandrogenic effects in other species. J Am Vet Med Assoc 1999 Aug 15;215(4):501-2, 482
      Use of cyproheptadine to control urine spraying in a castrated male domestic cat.
      Click here to access the PubMed abstract of this article. J Am Vet Med Assoc 1999 Feb 1;214(3):369-71, 351-2
      Use of cyproheptadine to control urine spraying and masturbation in a cat.
      Click here to access the PubMed abstract of this article.   Cyproheptadine hydrochloride was administered to 20 presumed or proven allergic cats to determine its efficacy in controlling pruritus. Each cat received 2 mg, orally, every 12 hours. The pruritus was satisfactorily controlled in 9 cats. Side effects were seen in 8 cats, and included polyphagia, sedation, vocalization, affectionate behavior, and vomiting.  Can Vet J 1998 Oct;39(10):634-7
      Observations on the use of cyproheptadine hydrochloride as an antipruritic agent in allergic cats.
      Click here to access the PubMed abstract of this article.   Clomipramine for Feline Anxiety
      A study of 11 cats assessed the clinical response to a treatment regimen that included clomipramine and behavior modification in cats diagnosed with anxiety-related or obsessive-compulsive disorders. Presenting signs were urine spraying in seven cases, overgrooming in three and excessive vocalization in one. Clomipramine was administered orally once daily, with a mean starting dose of 0.4 mg/kg. If necessary, the dose was adjusted according to the clinical response of each cat. The average maintenance dosage was 0.3 mg/kg once daily. The researchers concluded that clomipramine was effective in controlling the signs of anxiety-related and obsessive-compulsive disorders in 10 of 10 assessable cases when used in combination with behavior modification, and the drug was well tolerated. Aust Vet J 1998 May;76(5):317-21
      Use of clomipramine in the treatment of anxiety-related and obsessive-compulsive disorders in cats.
      Click here to access the PubMed abstract of this article.   Selegiline
      is a monoamine oxidase (MAO) inhibitor indicated for use in dogs to control signs associated with canine cognitive dysfunction syndrome and uncomplicated pituitary-dependent hyperadrenocorticism (PDH). Studies suggest that selegiline may enhance survival rates. The recommended dose for cognitive dysfunction is 0.5 to 1 mg/kg, and for PDH is 1 mg/kg, orally each morning. If no improvement is seen after 2 months, the dose can be increased to the maximum of 2mg/kg/day. If there is no clinical improvement after 1 month at 2mg/kg/day, alternative therapy or further evaluation should be considered. "Overall, selegiline is well tolerated... Gastrointestinal disturbances, particularly vomiting and diarrhea, are the most common side effects reported. Diarrhea may resolve when the drug is discontinued or the dose decreased. Other adverse effects include hyperactivity, agitation, restlessness, and insomnia. A dose reduction or discontinuation of therapy also resolves these problems." Compendium March 2000; 22(3):204-5
  • Cardioology/Hypertension

    • Transdermal Diltiazem for Treatment of Hypertrophic Cardiomyopathy in Cats
       
      Diltiazem has direct coronary vasodilating properties, a beneficial therapeutic effect not provided by the beta-adrenergic blocking agents for the management of feline hypertrophic cardiomyopathy (HCM). “Orally administered diltiazem appears to have sustained beneficial effects on left ventricular filling and cardiac performance based on its ability to reduce resting heart rate, decrease blood lactate concentration, increase venous oxygen tension, improve echocardiographic parameters, and resolve radiographic abnormalities. Long-term diltiazem administration may also reverse myocardial hypertrophy in some patients. There appear to be few if any side effects of this drug. Diltiazem, therefore, provides a safe and effective approach for the management of feline HCM.”1
       
      At North Carolina State University, College of Veterinary Medicine, analysis of diltiazem in Lipoderm® transdermal gel showed that diltiazem was stable at a concentration of 246 mg/ml for 30 days and at a concentration of 99.6 mg/ml for 60 days, no matter the storage conditions explored in the study.2
       
       A formula is available for Diltiazem 5% for veterinary use.3
       
      1 Vet Clin North Am Small Anim Pract. 1991 Sep;21(5):1023-34.
      Evidence for or against the efficacy of calcium channel blockers for management of hypertrophic cardiomyopathy in cats.
      Click here to access the PubMed abstract of this article. 2 J Pharm Biomed Anal. 2005 Jun 1;38(1):60-5. Epub 2004 Dec 25.
      Analysis of diltiazem in Lipoderm transdermal gel using reversed-phase high-performance liquid chromatography applied to homogenization and stability studies.
      Click here to access the PubMed abstract of this article. 3 International Journal of Pharmaceutical Compounding. Jan/Feb 2008; 12(1):67
      Diltiazem 5% in Lipoderm, Veterinary
      Click here to access the abstract of this article.




      Transdermal Atenolol and Feasibility of Transdermal Administration Am J Vet Res. 2008 Jan;69(1): 39-44.
      Comparision of pharmacodynamic variables following oral versus transdermal administration of atenolol to healthy cats.
      Click here to read the PubMed abstract of this article.PMID: 18167085 Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol. “In theory, the transdermal route of administering medications has many potential advantages. It is noninvasive and not demanding technically, avoids first-pass hepatic metabolism and gastrointestinal breakdown, has potential for sustained release formulations, and can be administered over a large surface area. Transdermal administration of medication has been shown to achieve blood concentrations of drug that are considered to be therapeutic (eg, fentanyl) or efficaciously affect physiologic surrogates (eg, methimazole, nitroglycerine, and lidocaine). Feasibility of transdermal medication varies on a drug-by-drug basis.” Discussion: In spite of these results, investigators did not conclude that transdermally administered atenolol is not feasible.Because two cats did achieve therapeutic blood concentrations of atenolol after transdermal administration, the authors called for further research to find a transdermal formulation and dosing regimen for atenolol that will consistently result in plasma atenolol concentrations of >260ng/ml.Investigators offered several considerations for future studies. This study utilized a hydrophilic carbomer/propylene glycol/glycerin gel vehicle which has been used in human delivery of transdermal medications. As pluronic lecithin organogel (PLO) is the transdermal vehicle used almost exclusively in veterinary medicine, investigators encouraged future transdermal atenolol research utilizing PLO as the vehicle.Investigators also noted that higher doses of atenolol (3mg/kg) have been reported to consistently result in blood levels providing adequate adrenergic blockade at 12 hours in all cats studied.Since the median atenolol dose administered in this study was 1.1mg/kg, researchers suggest studying transdermal atenolol at the 3.3mg/kg dose. Because daily oral administration of atenolol to cats is challenging and often results in a lack of compliance, a non-invasive dosage form such as transdermal atenolol will most likely result in better compliance, less stress to the cat, and reveal a positive therapeutic effect.


      Enalapril for Cardiomyopathy and CHF
       "Enalapril maleate is an angiotensin-converting enzyme (ACE) inhibitor labeled to treat mild to severe heart failure in dogs." Research has shown that enalapril in combination with diuretics - with or without digitalis glycosides - "produces statistically significant clinical improvement in dogs with advanced heart failure due to mitral regurgitation or dilated cardiomyopathy" and has demonstrated "beneficial hemodynamic and clinical effects of adding enalapril to conventional therapy for dogs with CHF... Dogs treated with enalapril and conventional CHF therapy survived two times as long as did those receiving standard therapy alone." Enalapril has also "been effective in treating cardiomyopathy and CHF in cats and ferrets, and its effects on blood pressure in horses and camels have been studied." Because enalapril is a prodrug and can not be converted to its active form enalaprilat in patients with severe liver dysfunction, captopril or lisinopril might be a better choice in those patients. Renal function should be checked before starting enalapril therapy and at least every two months thereafter. The most common side effects are gastrointestinal, but there have been reports of enalapril-induced cough in dogs and a bird. Hypotension is a major concern if overdose occurs. NSAIDs, including aspirin, may reduce enalapril's effect. The injectable form (enalaprilat) should not be given orally because it is very poorly absorbed. "The recommended dose for enalapril in dogs is 0.5 mg/kg orally every 12 to 24 hours. The dose for cats is 0.25 to 0.5 mg/kg orally every 12 to 24 hours." Compendium, Dec. 1999


      Amlodipine to Treat Feline Systemic Hypertension
      Amlodipine, a calcium channel blocker, has an antihypertensive effect in cats with coexistent systemic hypertension and renal insufficiency. Its use may improve the prognosis for cats with systemic hypertension by decreasing the risk of ocular injury or neurologic complications induced by high blood pressure (BP). In a retrospective study, medical records from 69 cats with systemic hypertension and hypertensive retinopathy were reviewed. 68.1% of the cats were referred because of vision loss; retinal detachment, hemorrhage, edema, and degeneration were common findings. Amlodipine decreased BP in 31 of 32 cats and improved ocular signs in 18 of 26 cats. Primary hypertension in cats may be more common than currently recognized. In a study at the Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, amlodipine was shown to be a safe and effective once-daily antihypertensive agent when administered to cats at a dosage of 0.18 +/- 0.03 mg/kg daily as monotherapy. Researchers at the Department of Medical Sciences, University of Wisconsin-Madison, administered amlodipine at an oral daily dosage of 0.625 mg per cat (range = 0.08 to 0.23 mg/kg body weight). Average indirect systolic blood pressure measurements in those 12 cases decreased significantly from 198 to 155 mmHg during amlodipine treatment. Significant changes in body weight and serum creatinine and potassium concentrations were not detected. Relationship between ocular lesions and hypertension
      Retinal lesions, caused predominantly by choroidal injury, are common in cats with hypertension. Hypertension should be considered in older cats with acute onset of blindness; retinal edema, hemorrhage, or detachment; cardiac disease; or neurologic abnormalities. Cats with hypertension-induced ocular disease should be evaluated for renal failure, hyperthyroidism, diabetes mellitus, and cardiac abnormalities. Blood pressure measurements and funduscopic evaluations should be performed routinely in cats at risk for hypertension (preexisting renal disease, hyperthyroidism, and age > 10 years). Am J Vet Res 2002 Jun;63(6):833-9
      Effects of the calcium channel antagonist amlodipine in cats with surgically induced hypertensive renal insufficiency.
      Click here to access the PubMed abstract of this article. J Am Vet Med Assoc 2000 Sep 1;217(5):695-702
      Ocular lesions associated with systemic hypertension in cats: 69 cases (1985-1998).
      Click here to access the PubMed abstract of this article. J Vet Intern Med 1998 May-Jun;12(3):157-62
      Amlodipine: a randomized, blinded clinical trial in 9 cats with systemic hypertension.
      Click here to access the PubMed abstract of this article. J Am Anim Hosp Assoc 1997 May-Jun;33(3):226-34
      Treatment of systemic hypertension in cats with amlodipine besylate.
      Click here to access the PubMed abstract of this article.
  • Dermatologics

    • Alternative Therapies for Atopy
      Dogs with atopic dermatitis (AD) often have concurrent allergies and are prone to relapsing skin and ear infections, which significantly contribute to their discomfort level. Much research has been done in recent years to identify effective and safe alternative treatments. Percutaneous absorption of allergens may be the most relevant route of exposure in dogs. Topical therapy may reduce the amount of allergen absorption through the skin. Several preparations, including glucocorticoids and anesthetics, can be used to reduce pruritus and provide analgesia.
      Cyclosporine , misoprostol, pentoxifylline, and various antihistamines have been effective. Compendium 2001 May 23(5):454-60 Tetracycline/Niacinamide for Dermatology
      The combination of tetracycline and niacinamide is being used for a continually expanding list of dermatologic disorders thought to be of immune-mediated origin. Diseases that may be controlled with this combination include discoid lupus erythematosus, pemphigus erythematosus, vesicular cutaneous lupus erythematosus (idiopathic ulcerative dermatosis) in Collies and Shetland Sheepdogs, pemphigus foliaceus, lupoid onychodystrophy, metatarsal fistulae in German Shepherds, sterile panniculitis, sterile granulomatous/pyogranulomatous dermatitis, vasculitis, cutaneous histiocytosis, idiopathic lymphocytic/plasmacytic ear margin dermatitis, and nodular granulomatous episcleral keratitis. The Capsule Report (Small Animal/Exotic Edition) 21:9, December 2002, reporting on Proceedings of the Friskies Pet Care Symposium 10:01 J Am Anim Hosp Assoc 1997 Nov-Dec;33(6):540-3
      Tetracycline and niacinamide for the treatment of sterile pyogranuloma/granuloma syndrome in a dog.
      Click here to access the PubMed abstract of this article. J Am Vet Med Assoc 1992 May 15;200(10):1497-500
      Use of tetracycline and niacinamide for treatment of autoimmune skin disease in 31 dogs.
      Click here to access the PubMed abstract of this article.   Antihistamines in Horses
      Practitioners may prefer to use antihistamines to reduce urticarial reactions and reduce pruritus in horses because these drugs usually have fewer side effects than steroids. The American Quarter Horse Association recommends a 10 day withdrawal prior to any competition. Vet Prac News, Apr 2001

      Prednisone Administered as a Transdermal Gel to Treat Allergic Dermatitis in a Cat

      Submitted by Janna L. Love, Pharm.D. A 5 y.o. female feline presented with allergic dermatitis accompanied by severe scratching and hair loss. The cat had previously been treated with oral prednisone tablets. As the owner was unable to "pill the cat", she had tried to crush the tablets and mix with milk or tuna juice, but the cat still would not take the medication. It has been our experience that transdermal gels work wonderfully in cats. An owner does not have to fight the animal to get a tablet down the cat's throat, and does not have to worry about whether the animal has received the correct dose, as the prescribed amount of gel can be massaged into the vascular surface inside the cat's ear. The veterinarian prescribed Prednisone 5 mg/0.1 ml in a transdermal gel. We dispensed 3 ml, with instructions to apply 0.1 ml (5 mg) daily to the inside of the cat's ear. The benefits of transdermal administration include the ability to reliably administer the prescribed dose, and ease of administration to a calm, relaxed cat. The therapy was very successful. The cat's dermatitis resolved and the hair began to regrow within a few weeks. There were no complications and no modification in dosage was necessary. The owner periodically uses the preparation when she first notices signs of a relapse. Relapses have promptly resolved with transdermal prednisone therapy.
  • Endocrinology

    • Low Dose Trilostane for Canine Cushing’s Disease
       
         Cushing's Disease (hyperadrenocorticism) is a common condition in older dogs, often mistaken for the aging process itself. Dogs get pot bellies, lose hair, drink and eat excessively, urinate in the house, and make owners begin to prematurely consider euthanasia. Yet, Cushing's disease is treatable and that treatment can result in a longer, more comfortable life for the dog and its owner.
       
        Trilostane is the most promising FDA-approved treatment for canine Cushing’s disease. Current FDA approved labeling for trilostane (Vetoryl™) lists the recommended dose at 3-6mg/kg body weight orally once daily, and Vetoryl™ capsules are available in strengths of 10mg, 30mg and 60mg.  Several studies conducted prior to US-approval of trilostane referenced effective doses ranging from 6-12mg/kg orally per day.  After noting that many dogs treated with trilostane at the labeled dose demonstrated symptoms of hypoadrenocorticism (Addison’s Disease), clinical endocrinologists at the University of California Davis College of Veterinary Medicine evaluated the safety and efficacy of lower doses of trilostane.  Investigators in this trial administered trilostane to dogs diagnosed with Cushing’s disease at doses ranging from 0.5-2.5mg/kg orally every 12 hours and evaluated dogs for therapeutic progress at 3 different treatment intervals over a total treatment period of 8-16 weeks. After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [n =3]).
       
         Since many dogs that develop Cushing’s disease are smaller breed dogs weighing less than 9kg (e.g. terriers and poodles), the commercially available capsules (10mg, 30mg and 60mg) are too large for appropriate therapy. As a result of the UC-Davis study, many veterinarians are requesting compounding pharmacists to compound smaller doses of trilostane as capsules or oral suspensions. On September 11, 2009, the Center for Veterinary Medicine division of the Food and Drug Administration issued a statement to veterinarians and pharmacists that “trilostane can only be legally compounded by using FDA-approved VETORYL™ as the starting material”, and that “…trilostane should not be imported from other countries or compounded from (the) bulk (chemical)”. As Vetoryl™ is only available for sale to licensed veterinarians in the US, and use of the bulk chemical to compound trilostane will not be tolerated by FDA, veterinarians and pharmacists are advised to collaborate to ensure availability of safe and legal compounded dosage forms of trilostane for dogs requiring lower doses than are commercially available.
       
      J Am Vet Med Assoc 2008;232:1321–1328.
      Evaluation of  twice-daily, low dose trilostane treatment in dogs with naturally occurring hyperadrenocorticism.
      Click here to access the abstract of this article.
       
      http://www.fda.gov/AnimalVeterinary/SafetyHealth/ProductSafetyInformation/ucm182038.htm




      Phenoxybenzamine for Dogs with Pheochromocytoma
       
       Some studies in dogs undergoing adrenalectomy for pheochromocytoma suggest that anesthetic complications and perioperative mortality are common. In humans, surgical outcome has improved with the use of phenoxybenzamine (PBZ) before adrenalectomy. Therefore, at the School of Veterinary Medicine, University of California, Davis, it was hypothesized that dogs treated with PBZ before adrenalectomy have increased survival compared with untreated dogs, and they conducted a retrospective medical record review of 48 dogs that underwent adrenalectomy for pheochromocytoma from January 1986 through December 2005. Twenty-three of 48 dogs were pretreated with PBZ (median dosage: 0.6 mg/kg PO q12h) for a median duration of 20 days before adrenalectomy. Duration of anesthesia and surgery, percentage of dogs with pheochromocytoma involving the right versus left adrenal gland, size of tumor, and presence of vascular invasion were similar for PBZ-treated and untreated dogs. Thirty-three (69%) of 48 dogs survived adrenalectomy in the perioperative period. PBZ-treated dogs had a significantly decreased mortality rate compared with untreated dogs (13 versus 48%, respectively). Additional significant prognostic factors for improved survival included younger age, lack of intraoperative arrhythmias, and decreased surgical time. Results from this retrospective study support treatment with PBZ before surgical removal of pheochromocytoma in dogs.
       
      J Vet Intern Med. 2008 Nov-Dec;22(6):1333-9.
      Predictive factors and the effect of phenoxybenzamine on outcome in dogs undergoing adrenalectomy for pheochromocytoma.
      Click here to access the PubMed abstract of this article.



      Transdermal Carbimazole Gel for the Treatment of Feline Hyperthyroidism The aim of a study conducted by Buijtels et al. of Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, The Netherlands, and presented at the 16th ECVIM-CA Congress, 2006, was to develop a carbimazole gel for application at the inner pinna of the ear and to study its effectiveness in cats with hyperthyroidism. The results of this study indicate that twice daily administration of carbimazole gel at the inner pinna of the ear is an effective treatment of cats with hyperthyroidism. Tijdschrift voor Diergeneeskunde. 2006; 131(13):478-82
      [Transdermal carbimazole for the treatment of feline hyperthyroidism]
      Click here to read the PubMed abstract of this article.


      PZI and Low-Dose Insulin
      The commercial production of traditional beef &/or pork insulins has declined as most human diabetic patients (the majority of the consumers) are being switched to human insulin products because of the reduced risk of allergic reactions. Protamine zinc insulin occurs as a sterile suspension of insulin modified by the addition of protamine sulfate and zinc chloride, and has a long duration of action (up to 30 hours). Therefore, treatment of many dogs and cats has been accomplished with once daily dosing of PZI.
      U-20 and U-40 insulin allow for more accurate measurement of smaller doses required by many pets and birds. Use of U-100 insulin can result in morbidity or mortality caused by dosing errors.
        Oral Anti-Diabetic Drugs
      "may be appropriate for cats that are in good overall health with early or mild clinical signs of diabetes and those with owners who are unwilling or unable to administer insulin injections."1 The oral hypoglycemic medication, glipizide, provides a viable therapeutic alternative to conventional insulin therapy with a positive therapeutic response in approximately 50% of diabetic cats with non-insulin-dependent disease. Response to glipizide therapy or lack thereof usually is evident within the first 4 to 6 weeks of treatment. Adverse side effects occurred in less than 10% of patients. The existence of residual beta cell function is necessary for response to glipizide therapy. Discontinuation of diabetogenic medications that may be contributing to insulin resistance is important.2 According to Deborah S. Greco, DVM, Ph.D., diplomate ACVIM, glipizide has been used successfully to treat diabetes mellitus in cats at a dosage of 2.5 to 5 mg two times daily, when combined with dietary fiber therapy. Dr. Greco recommends evaluating the patient weekly or every two weeks for a period of 2 to 3 months. If the fasting blood sugar decreases to less than 200 mg/dL, the glipizide should be continued at the same dosage and the cat reevaluated in 3 to 6 months. If the fasting blood glucose remains >200 mg/dL after 2 to 3 months of therapy and the cat is still symptomatic (polyuria, polydipsia, weight loss), glipizide should be discontinued and insulin therapy instituted. If the blood glucose remains >200 mg/dL and the cat becomes asymptomatic, glipizide should be continued indefinitely and the cat rechecked in 3-6 months.3 1 Compendium 23(7), July 2001, 633-640
      2 Vet Clin North Am Small Anim Pract 1995 May;25(3):599-615
      NIDDM in the cat: treatment with the oral hypoglycemic medication, glipizide.
      Click here to access the PubMed abstract of this article.
      3 presented at the 1999 Southern California VMA Seminar and the 116th Indiana VMA Seminar

      Methimazole for Feline Hyperthyroid Disease

      "Methimazole is the drug of choice for the medical management of feline hyperthyroid disease. It is safer and more potent than propylthiouracil in blocking thyroid hormone synthesis. Use of the drug generally will bring serum T4 into normal ranges within 2 to 3 weeks... Adverse effects have been observed in approximately 15% of cats and generally are transient. Anorexia, vomiting, and transient lethargy have been reported. Serum antinuclear antibodies develop in many cats with long-term use of the drug. A glucocorticoid-responsive pruritus involving the face, ears, and neck may occur. In less than 2% of cases, thrombocytopenia or agranulocytosis have been reported in cats treated with [methimazole]. Withdrawal of the drug and provision of care for thrombocytopenia or agranulocytosis generally results in resolution... Cats on chronic methimazole therapy should be rechecked every 3 to 6 months to assay serum T4 levels and to check for signs of drug toxicity." Handbook of Veterinary Drugs, 2nd edition, ©1998, pp. 239-240 According to the International Journal of Pharmaceutical Compounding (Vol. 5, No. 2, March/April 2001, p. 96), "it could be theorized that transdermal administration would produce a ... higher blood level of methimazole than that resulting from oral administration of the drug. A higher blood level of [methimazole] might result in a slightly greater risk of adverse effects, so drug therapy might need to be initiated at a slightly lower dose than that of the traditional oral dose." The author of the article (GiGi Davidson, R.Ph., DICVP, North Carolina State University, College of Veterinary Medicine) states that anecdotal evidence indicates that this is true of "most transdermally administered doses of methimazole. The most measurable parameter for efficacy is the response of the serum T4 level." Note: Methimazole is also used to decrease renal toxicity of cisplatin in dogs. Transdermal Methimazole Applied to Ear of Hyperthyroid Cats
      Francis Arsenault, D.V.M., New Brunswick The following six cats have received methimazole in a pluronic lecithin organogel (PLO) which the owners apply to the inner side of the ear. Overall, we have found this to be very effective therapy with good compliance. Transdermal administration can be particularly helpful for owners who have arthritis and those who have great difficulty "pilling" the cat. Methimazole doses have ranged from 2.5mg to 12.5 mg daily, divided into two doses. Cat #1 (S.A.): 17 years old, has been on methimazole 1.25mg/0.1 ml PLO to inside of ear twice daily for nine months. The owner reports that the medicine is easy to administer and absorbs well. I am pleased with the clinical results. Cat #2 (A.L.): 18 years old, has been using methimazole for six months. This cat was started on 3.5mg/0.1ml PLO BID. Several dosage adjustments were necessary. We increased the concentration of the transdermal gel to 5.0mg/0.1ml PLO, and the owner now applies 7.5mg/0.15ml PLO in the AM and 5mg/0.1ml in the PM. She places plastic wrap over her finger before applying the medication, which she has found to be much easier to use than pills, with no stress to the pet. She states the measurements on the topical dispenser are easy to read, and she needs to wash the cat's ear to remove the coating left by the medication. Cat #3 (B.M.): was started on methimazole eight months ago at 5mg/0.1ml PLO BID. The dose was decreased to 2.5mg BID. The cat's owner stated the medication was very easy to use. B.M. improved clinically and gained weight, and is no longer on the med. Cat #4 (S.O.): used medication once only. Cat #5 (D.O.): same owner as cat #4, received methimazole 2.5mg/0.05ml PLO BID for two months. No longer on medication. Cat #6 (M.B.): 19 years old, has received methimazole 1.25mg/0.1ml PLO BID for four months. The owner says the medication is easy to apply, and alternates ears. It is necessary to wipe the ear each day as the medication does leave a residue.

      Adrenal Disease in Male Ferrets

      Adrenal gland disease is a common problem in middle-aged to older ferrets. The disease results in one or both of the adrenal glands producing abnormal amounts of androgens and/or estrogens, and can cause hair loss, itching, vulvar enlargement in females, prostate enlargement in male ferrets which can block the flow of urine, and in rare cases, bone marrow suppression. Although not usually a serious health concern, ferrets may have no relief from the itching that is associated with this disease if it is not treated.
      Flutamide is an androgen blocker that may help relieve prostatic enlargement. It is dosed at 10 mg/kg, PO, every 12-24 hours. Liver enzymes should be checked at one month and every six months thereafter. Mitotane may be effective in younger ferrets but may cause nausea and lethargy. Ketoconazole is usually ineffective.1 1 Evelyn Ivey, DVM, Dip ABVP, San Diego Co VMA Conf Procd, Sep 2000

      Mitotane for Canine Hyperadrenocorticism

      In veterinary medicine, mitotane is used primarily for the medical treatment of pituitary-dependent hyper-adrenocorticism (PDH) and palliative therapy of adrenal carcinoma, usually in dogs. Systemic drug availability has been found to be very poor from intact tablets in fasted dogs, and best when the powdered drug is mixed in oil and poured on dog food. The interaction between food and mitotane probably contributes to the variation in clinical response of dogs treated with the drug, because it appears that the efficacy is improved considerably when the drug is given with food. Because of the potentially severe toxicity associated with mitotane, clients should be instructed to wear gloves during and wash their hands after administering the medication, and to keep the medication out of reach of children or pets. Dogs with concurrent diabetes mellitus may have rapidly changing insulin requirements during the initial treatment period, and should be closely monitored until they are clinically stable. Clients should be advised of the symptoms of acute hypoadrenocorticism. Because of the potential severe toxicity associated with mitotane, clients should be instructed to wash their hands after administration and to keep the medication out of reach of children or pets. Res Vet Sci 1987 Sep;43(2):160-5
      Systemic availability of o,p'-DDD in normal dogs, fasted and fed, and in dogs with hyperadrenocorticism.
      Click here to access the PubMed abstract of this article.

      Veterinary Drug Handbook, 2nd Edition, by Donald C. Plumb
  • Otitis

    • Therapy for Chronic Canine Otitis 

         Treatment errors, over and under treatment, or inappropriate use of antimicrobial medication can result in a chronically diseased ear. The key to successful management of chronic canine otitis is early intervention, identifying a cause of the condition, and employing specific and appropriate therapy.
         Ears with highly proliferative, chronic disease require deep cleaning and flushing before any topical therapy can be expected to help resolve the condition. Should a myringotomy be performed, the contents of the middle ear can be aspirated as soon as rupture occurs, and the middle ear can be flushed with normal saline or Tris-EDTA using a feline, open-tipped urinary catheter. "Just before the animal wakes, Tris-EDTA and a topical antimicrobial solution should be instilled and a parenteral prednisolone administered."
         "The pathogens isolated most frequently from chronic external and middle-ear infections include Staphylococcus intermedius, Malassezia pachydermatis, Pseudomonas species, Proteus species, Escherichia coli, and enterococcus. Selection of both systemic and topical antimicrobial medication is based on cytologic evaluation and culture and sensitivity results. Systemic antibiotics are mandatory... Treatment should continue until the infection is resolved (a minimum of 4 weeks). It is not uncommon for treatment of otitis media to continue uninterrupted for 8 to 12 weeks."
         Patricia D. White, DVM, MS of Atlanta Veterinary Skin & Allergy Clinic suggests that several compounded preparations may be appropriate. Compendium on Continuing Education 21:8 August 1999, pg 716-28


      Importance of Medication Vehicle
       

         "Topical antimicrobial therapy is an important part of the treatment regimen, and the vehicle is as important as the active ingredient. Most otic preparations are combination drugs (glucocorticoid plus antibiotic) in an oil or ointment base. Oils and ointments are occlusive, may hold or trap exudate, and may increase the risk of ototoxicity; such preparations are not desirable in cases of chronic otitis in which a moist exudate is present, the canal is stenotic, or the eardrum may be ruptured. The goal of treating a wet ear is to dry it. Solutions and suspensions are primarily composed of water; may contain an astringent (e.g., aluminum acetate); and are designed to evaporate over time, thus helping to dry the ear." Topical antibiotics that are selected initially should be adjusted when the culture and sensitivity results are known.
         "There is no single topical otic preparation that will satisfactorily treat all conditions. Practitioners tend to dispense a product based on clinical impressions or pick a favorite product rather than selecting one that has specific application for the current condition." Direct application of medication to the ear canal will result in a higher concentration than that obtained with systemic medication.
      Once you have identified the problem, we can compound an otic preparation to most appropriately treat each animal. Compendium on Continuing Education 21:8 August 1999, pgs. 716-728



      Antimicrobial/Anti-inflammatory Otic Suspensions Anhydrous Preparations without Aminoglycosides    It is desirable to move away from commercially available aminoglycoside-antifungal-steroid otic preparations to avoid animoglycoside induced ototoxicity. Use of a formulation that substitutes a fluoroquinolone for an aminoglycoside constitutes a more effective and less toxic therapy, and is preferred if a tympanum rupture is expected. The efficacy and tolerability of a fluoroquinolone-clotrimazole-dexamethasone (FCD) otic suspension (10 drops per affected ear once daily) was compared with a standard topical treatment containing polymyxin B, miconazole and prednisolone (PMP) in a total of 140 dogs with clinical signs of acute or subacute otitis externa, Staphylococcus, Pseudomonas, Enterobacteriaceae and Malassezia were isolated from samples taken at inclusion. Each group received treatment for 7 or 14 days according to the clinical outcome on day 7. Treatments were equally effective, with a cure rate of 58.3% for the FCD prep and 41.2% for the PMP combination. Both medications were equally well tolerated by dogs, but FCD was superior in terms of pain relief, decrease in pus quantity and smell, response rate and investigator's assessment on day 14. Vet Dermatol 2005 Oct;16(5):299-307 
      A comparative study of two antimicrobial/anti-inflammatory formulations in the treatment of canine otitis externa.
      Click here to access the PubMed abstract for this article.   While it is a common practice in some veterinary offices to add dexamethasone injection to clotrimazole solution to create an otic preparation with both antifungal and anti-inflammatory properties, it is more desirable to use an anhydrous preparation in the ear to reduce the risk of bacterial growth in the warm, moist environment. Anhydrous preparations also tend to have longer shelf lives. Avoid using products such as miconazole solution which has a high alcohol concentration to avoid irritating a sensitive ear.  Contact our compounding pharmacy for anhydrous otic preparations.




      Helpful Hints Regarding Otitis Therapy

         Ototoxicity manifested as deafness or vestibular toxicity is a potential adverse effect of some medications used to treat otitis, such as aminoglycosides (tobramycin, gentamicin, amikacin and neomycin) and chloramphenicol. Numerous alternatives exist.
         Enrofloxacin, a fluoroquinolone effective against Pseudomonas species, can be compounded as a solution and applied to the ear canal twice daily. "Topical enrofloxacin may achieve a higher antibiotic concentration at the site more economically than systemic medication."
         Silver sulfadiazine is effective in vitro against Pseudomonas species, Staph aureus, Proteus species, and others; a 0.1% to 1% emulsion every 12 hours is adequate to kill Pseudomonas.
         Topical otic products may contain potent glucocorticoids in ointment or oil bases. However, solutions may be a preferable vehicle, and it may be advisable to use a less potent steroid because the degree of absorption of topical steroids can not be controlled. We can compound a preparation containing your choice of steroid in the most appropriate vehicle to treat the condition.
         "Commercial otic drying agents should be avoided in inflamed, chronically diseased ears because most contain isopropyl alcohol and varying concentrations of benzoic, acetic, salicylic, or boric acid. Each of these products individually can be extremely irritating to an already traumatized epithelium."
         Acetic acid solution can be used to decrease the bacterial population by lowering the pH within the ear canal. Pseudomonas can be killed by 1 minute of contact with a 2% solution. This treatment is especially beneficial when the organism is resistant to other antibacterials. Staph and Strep may be killed by 5 minutes of contact with a 5% solution, according to Kirk's Current Veterinary Therapy XII Small Animal Practice. However, inflammation (which can be severe) is an occasional side effect of treatment with acetic acid concentrations higher than 2.5%. Compendium on Continuing Education 21:8 August 1999, pgs. 716-728
      Kirk's Current Veterinary Therapy XII Small Animal Practice, 1995, Bonagura & Kirk, ed.

      Treatment of Canine Otitis with Norfloxacin 1% & Ketoconazole 1%

      by T. D. Flack, D.V.M. Scottsdale, AZ    The common therapy for fungal otitis externa in dogs utilizes an antifungal and topical steroid, sometimes in combination with systemic antibiotics. The three organisms which have been isolated and are thought to be the most common pathogens in recurrent canine otitis externa are Malassezia, Pseudomonas, and Proteus spp. Using a fluoroquinolone along with an antifungal, we are able to have good coverage on all virulent pathogens. For treatment of resistant infections, the synergism of norfloxacin and ketoconazole provides a broader spectrum of coverage than many other therapies, as ketoconazole is a more active antifungal than clotrimazole. We have utilized a compounded otic gel containing norfloxacin 1% and ketoconazole 1% more than 20 times with a very high success rate.
         Infectious otitis externa is a common disease in dogs. Systemic antibiotic therapy is not always required. Thirty-six dogs of mixed sex, breed, and age were treated for... the purpose of evaluating the efficacy of a ketoconazole 1% and norfloxacin 1% otic gel... Treatment consisted of 0.5 to 1.0 ml of the otic gel in each affected ear twice a day for 7 days. Results showed 91.66% satisfactory responses at 7 and 14 days treatment... Failures (8.33%) were related to Staphylococcus associated with Proteus, Malassezia, and Candida... The 7-day treatment was successful in 21 cases. However, since 12 dogs required 14 days of treatment, it would be sensible to recommend a 14-day therapy." Canine Practice, Vol. 21, No. 2, pp. 26-28


      Tris-EDTA Solution for Canine Otitis

      Richard E. Wooley, D.V.M., Ph.D., Harry W. Dickerson, B.V.Sc., Ph.D., and William R. Engen, D.V.M.,
      Department of Medical Microbiology, College of Veterinary Medicine, Univ. of Georgia, Athens    The authors reported the successful use of Tris-EDTA in the treatment of otitis externa. In 24 dogs with clinical otitis, the Tris-EDTA (tris[hydroxymethyl] aminomethane and ethylenediaminetetraacetate) combination was tested against Bacillus spp., Staphylococcus aureus, Candida spp., Pseudomonas aeruginosa, Esherichia coli, Proteus vulgaris, Trichosporon spp., and an a-streptococcus. "Fifteen of the 24 cases were acute; all were evaluated with bacterial culture before and after treatment. The treatment consisted of applying lavage solution to the ears t.i.d. until resolution or for three weeks if there was no clinical response. Dogs were examined for irritation of the ears after treatment... 23 of 24 cases were resolved; no adverse effects were seen, but duration of follow-up was not specified. The case that failed to respond was a chronic, mixed infection of E. Coli and Proteus spp.; inflammation was reduced, but the infection persisted. Most cases responded within one week, but P. aeruginosa infections required one to three weeks of treatment." Veterinary Forum, June 1999, p. 52    Tris-EDTA solution (buffered to pH 8.0) has a direct bactericidal effect on some bacteria by chelating metal ions in the cell wall. "Dogs with chronic disease (e.g. atopy, idiopathic seborrhea) will be predisposed to recurrent otitis; a topical antibiotic solution or Tris-EDTA used two to three times weekly may prevent an infection from occurring with each flare-up of the primary disease."
         The bactericidal effects of Tris-EDTA are synergistic with aminoglycosides. Although an antibiotic can be added to the Tris-EDTA solution, Patricia D. White, DVM, MS states that she prefers to use Tris-EDTA 5 to 10 minutes before the topical antibiotic. The Tris-EDTA/antibiotic combination is ineffective against yeast. Compendium on Continuing Education 21:8 Aug. 1999, pgs. 716-728
  • Pain Management

    • Transmucosal Buprenorphine: More is Better For Dogs and Horses
       
         The pharmacokinetic profile of a buccally-administered (transmucosal) dose of buprenorphine to cats is almost identical to that of intravenously administered buprenorphine. The unusually alkaline salivary pH of cats prevents ionization of buprenorphine, allowing it to diffuse into systemic circulation in a non-ionized form. This discovery greatly facilitated outpatient feline pain relief, allowing owners to administer this drug to cats at home, without the need for hospitalization or injection.  Because the duration of analgesia from buprenorphine (4-12hrs) is longer than that provided by other opiates, buprenorphine is frequently used for provision of non-invasive, intermediate to long-term analgesia in cats.  It is typically administered at doses of 10-30mcg/kg applied to the oral mucosa (inside the cheek pouch) every 8 hours for up to 5 days (many cats experience anorexia after 5 days of therapy with buprenorphine). The commercially available 300mcg/ml solution for injection (Buprenex) works well for buccal administration with most cats receiving volumes of approximately 0.066ml/kg (e.g. 0.33ml for the average 5kg cat).1
       
        Buccal absorption of buprenorphine has also been examined in dogs at approximately the same dose (20mcg/kg) utilized in cats. Absorption was low at this dose, but a dose of 120 mcg/kg administered transmucosally to dogs produced drug concentrations equivalent to an intravenous dose of 20 mcg/kg. Dogs have a relatively more acidic salivary pH than cats, resulting in more ionization of buprenorphine, reducing the amount of drug available for diffusion across membranes. At doses of 120mcg/kg, a 25kg dog would require 3000mcg or 10ml of the commercially available buprenorphine solution for injection.  A canine patient would likely swallow a large portion of 10ml administered buccally, and since the oral absorption of buprenorphine is extremely low, analgesic effect would not be achieved. Recent work at NC State University (unpublished) also demonstrates that buccal buprenorphine provides effective analgesia in horses when administered at doses of 6.6mcg/kg (e.g. 11ml of the commercially available injection for a 500kg horse). Again, a significant portion of this dose is likely to be swallowed by an equine patient, precluding a full analgesic effect.
       
          For dogs and horses, a more concentrated solution of buprenorphine is greatly desirable for transmucosal use.  Compounded solutions of buprenorphine from 3-6mg/ml would allow for buccal administration of volumes of less than 1ml for both dogs and horses. Our compounding pharmacy can prepare concentrated solutions of buprenorphine for transmucosal use in dogs and horses.  Please call for more information.
       
      1 J Vet Pharmacol Ther. 2005; 28(5):453-460. 
      PK-PD modeling of buprenorphine in cats: intravenous and oral transmucosal administration
      Click here to access the abstract of this article.
       
      2 Vet Ther. 2008 Summer;9(2):83-93.
      Pharmacokinetics of buprenorphine following intravenous and oral transmucosal administration in dogs.
      Click here to access the PubMed abstract of this article.





      Gabapentin in a Xylitol-Free Formulation

      Gabapentin is only approved for use in humans, but is widely used in veterinary medicine for both analgesia and neuroleptic indications.Dosed at 10-15mg/kg orally up to three times daily, this drug has become a valuable adjunct in veterinary therapies.Historically, gabapentin was available as a 100 mg scored tablet, enabling dosing of small animals (e.g. those weighing 5 kg or less) by quartering or halving tablets. Recently, gabapentin 100 mg tablets have been discontinued by all manufacturers, resulting in gabapentin 100 mg capsules being the smallest solid dosage form of gabapentin on the market.Because these capsules cannot be easily divided into smaller doses by pet owners, veterinarians have considered using Neurontin® (gabapentin) 50mg/ml oral solution to dose smaller patients.Unfortunately, Neurontin® Solution contains 300mg/ml of xylitol, an artificial sweetener which is known to cause profound hypoglycemia and hepatic necrosis in dogs at single doses of 100mg/kg. Dogs receiving doses of 0.3ml/kg of Neurontin® daily will be exposed to potentially toxic doses of xylitol.For this reason, veterinarians are turning to compounding pharmacists to compound patient-specific doses of gabapentin in capsules or treats, or compounded suspensions of gabapentin that do not contain xylitol. Gabapentin is also used quite frequently in cats at small doses.  It is not known if cats have the same problems with xylitol that dogs do, but many cats dislike the strawberry taste of Neurontin® liquid, so the compounded preparation is often an appreciated alternative. Aust Vet J. 2005 Oct;83(10):602-8.
      Improving seizure control in dogs with refractory epilepsy using gabapentin as an adjunctive agent. 
      Click here to read the PubMed abstract of this article. JAVMA  229: 1113-1117, 2006.
      Acute hepatic failure and coagulopathy associated with xylitol ingestion in eight dogs.
      Click here to read the PubMed abstract of this article. Vet Clin North Am Small Anim Pract. 2005 Jan;35(1):129-46
      Managing Pain in Feline Patients.
      Click here to read the PubMed abstract of this article.



      Transmucosal Buprenorphine for Cats

      The majority of an oral dose of buprenorphine is removed by hepatic first pass metabolism, therefore effective oral doses in dogs and cats may be cost prohibitive. Buprenorphine�s uniquely alkaline pKa (8.24) allows it to be administered transmucosally (buccally) to cats by virtue of the high salivary pH of this species (8-9). Administered on the tongue or in the cheek pouch at doses of 0.01-0.03mg/kg up to every 8 hours, buprenorphine has become a widely used and easy to administer analgesic for cats.  For cats, oral buprenorphine administration is not appropriate, as dosage forms such as oral suspensions encourage complete swallowing of the drug, delivering it to the gastrointestinal system where it will be almost entirely extracted by hepatic first pass metabolism and likely will NOT achieve analgesic blood levels. A preferable dosage form is a 0.3mg/ml solution for transmucosal administration; concentrations should not be lower than 0.3mg/ml as larger administered volumes risk being swallowed before absorption across buccal mucosa. Some veterinarians also have reported anecdotal success by transdermal administration of buprenorphine at 0.03mg/kg every 8 hours. While there have been no scientific reports evaluating the efficacy of transdermally-administered buprenorphine in cats, a transdermal patch of buprenorphine is available in the United Kingdom and delivers buprenorphine transdermally to humans for up to 7 days.  Transdermal buprenorphine may prove to be a particularly effective analgesic for cats that have received extensive dental procedures and do not wish to have their mouths manipulated for buccal administration of drugs.




      Pain Management in Cats

      Pharmacokinetic data developed in other species cannot be safely extrapolated to the cat. Feline deficiency of glucuronidation pathways results in slow metabolism of several NSAIDs, which prolongs the duration of effect and may lead to drug accumulation and toxicity. Meloxicam, a COX2 selective NSAID, has demonstrated clinical efficacy for chronic pain, musculoskeletal pain, and routine soft tissue surgery with few side effects. Based on clinical experience, Lascelles of NCSU College of Veterinary Medicine, now recommends oral meloxicam doses for cats that are less than previously reported in the literature (0.1 mg/kg PO on day 1 followed by 0.05 mg/kg PO daily for 4-6 days, then 0.025 mg/kg daily for 10 days, then lowest effective dose).1 Five days of oral treatment with meloxicam or ketoprofen for cats with painful locomotor disorders provided similar analgesia2, but meloxicam drops were more palatable than ketoprofen tablets. Appropriately flavored preparations in a convenient dosage form are easier for owners to administer and allow for accurate dosing. According to Robertson and Taylor3, opioids have an unjustified reputation for causing mania in cats, but with refinements in dosing they are now used successfully in this species. The mu-opioid agonists are generally considered the best analgesics. Morphine (0.1 - 0.3 mg/kg) is effective in a clinical setting. Oxymorphone and hydromorphone (0.05 - 0.1 mg/kg) are widely used in the USA. These opioids are more potent (up to 10 times), and longer acting than morphine in cats. Buprenorphine (0.01 - 0.02 mg/kg), a partial mu-agonist, is the most popular opioid used in small animal practice in the UK, other parts of Europe, Australia and South Africa. In clinical studies it has produced better analgesia than several other opioids and appears to be highly suitable for perioperative pain management in cats. Amitriptyline (starting dose 2.5 mg/kg PO, once daily) has been used to treat feline interstitial cystitis with few side effects, and there are anecdotal reports of its use for cancer and neuropathic pain management. Some of the less conventional analgesics including the tricyclic anti-depressants and gabapentin may prove to play a useful role in chronic pain management, but controlled clinical trials are needed to establish the best doses for maximum efficacy. Other less traditional analgesics such as ketamine and local anesthetics are also used for clinical pain management. The transmucosal, transdermal and epidural routes offer novel methods for administration of analgesic drugs and have considerable potential for improving techniques in feline pain management. 1 http://www.vetmash.com/pdf_files/dr_duncan_lascelle04.pdf  (accessed June 2009)

      2J Small Anim Pract 2001 Dec;42(12):587-93
      Evaluation of the clinical efficacy of meloxicam in cats with painful locomotor disorders.
      Click here to access the PubMed abstract of this article.

      3Journal of Feline Medicine and Surgery; 6(5), Oct 2004: 321-333
      Pain management in cats—past, present and future. Part 2. Treatment of pain—clinical pharmacology
      Click here to access the PubMed abstract of this article.


      Meloxicam for Analgesia in Dogs

      A clinical trial was conducted to evaluate the safety and efficacy of  meloxicam in dogs with chronic osteoarthritis. A scoring system assessed specific lameness, general stiffness, painful rise, exercise intolerance, and behavior, and demonstrated significant reductions in clinical signs of osteoarthritis following 4 weeks of drug therapy. Side effects were minimal in extent and duration. The findings of this investigation suggest that the efficacy, tolerance, and formulation of meloxicam oral suspension make it well suited for the treatment of chronic osteoarthritis in the dog. Can Vet J 2000 Apr;41(4):296-300
      Clinical efficacy and tolerance of meloxicam in dogs with chronic osteoarthritis.
      Click here to access the PubMed abstract of this article.





      Ketoprofen

      is a potent anti-inflammatory and analgesic which can be used for the management of surgical pain or chronic pain. The drug should not be given to animals with GI ulceration, impaired renal or hepatic function, or coagulation disorders. Ketoprofen should not be used preoperatively when noncompressible bleeding may be a problem. Occasional vomiting has been reported. When an NSAID or other drug that is potentially irritating to the GI tract is needed, topical preparations offer an excellent alternative. Pharmaceutical Research, Vol. 13, No. 1, 1996 reports (in humans) "a topical formulation of ketoprofen has been developed for the temporary relief of minor aches and pains of muscle and joints and to minimize gastrointestinal side effects after oral administration."
  • Poisoning/Toxicosis

    • Compounding pharmacists are now receiving requests from veterinarians to compound oral medications for dogs and cats in vehicles that are known to be free of xylitol.  Xylitol is an artificial sweetener commonly used to sweeten human medications, gums, mouthwashes and candies, and while not toxic to humans, can be quite toxic to dogs.  Xylitol is not absorbed from the gastrointestinal tract of humans, but is easily absorbed in dogs.  Once in the bloodstream, xylitol acts like glucose, stimulating insulin secretion, which causes life-threatening hypoglycemia.  Profound hypoglycemia can last for 1-2 hours following xylitol ingestion, and has frequently resulted in death.  Many commercially available drugs labeled for humans, such as gabapentin oral suspension, contain xylitol as an inactive ingredient, and all human medications used in dogs should be scrutinized for xylitol content. Compounding pharmacists can play a valuable role for veterinarians and veterinary patients by providing xylitol-free suspensions of medications and by educating clients to avoid all xylitol-containing foods in their pets.  It is not currently known if xylitol is toxic in cats, but for the present, xylitol must also be assumed to be toxic to cats.  For more information, search "xylitol" at http://www.aspca.org/.

      Apomorphine to Stimulate Vomiting

      Emetic drugs are usually administered in emergency situations after ingestion of a toxin. "Apomorphine is an opiate drug that acts as a potent central dopamine agonist to directly stimulate the CTZ. It can be administered PO, IV, or SC; the IM route is not as effective. It can also be applied directly to conjunctival and gingival membranes, using the tablet formulation, which can easily be removed once emesis is initiated. Vomiting usually occurs in 5-10 min. Although apomorphine directly stimulates the CTZ, it has a depressant effect on the emetic center. Therefore, if the first dose does not induce emesis, additional doses are not helpful. Because the vestibular apparatus may also be involved in apomorphine-induced vomiting, animals that are sedate and motionless will not vomit as readily as animals that are active. Because it can cause CNS stimulation, apomorphine is used cautiously in cats. Opiate-induced excitement in cats can be treated with naloxone (an opiate antagonist)."
      Apomorphine dosage for dogs: 4 mg/kg PO; 0.02 mg/kg IV; 0.3 mg/kg SC (from Merck Veterinary Manual, 8th edition, p. 1681); 0.25mg/kg (as a tablet) into the conjunctival sac (from Plumb's Veterinary Drug Handbook, p.51)

      Accidental Poisoning

      "is not a rare event; and veterinarians need to have access to antidotes. However, there are relatively few products specifically labeled for use in these instances, so it has not really been legal for veterinarians to have previously prepared antidotes for poisonings on hand in emergency rooms. For example, if a case of lead poisoning is diagnosed and the veterinarian needs some calcium EDTA as an antidote, there is no product available labeled for use in animals... Compounding offers opportunities for facilities to have [items such as calcium EDTA] on hand ... for emergency treatment, in anticipation of a legitimate prescription."
      Intl J of Pharm Comp 1997 July/Aug; 1(4): 240 N-acetylcysteine as an Antidote for Acetaminophen Toxicosis 

         N-acetylcysteine (NAC) is the antidote of choice for the treatment of acetaminophen poisoning, one of the most common types of intoxication in dogs and cats. NAC acts principally by replenishment of intracellular glutathione stores and detoxification of the reactive metabolite (NAPQI). NAC acts as a scavenger of free radicals, blocks the conversion of hemoglobin to methemoglobin, and can reduce the extent of liver injury.
         Although NAC is most effective if administered less than 12 hours after ingestion of acetaminophen, the use of NAC as an antidote is still recommended up to 36 to 80 hours after acetaminophen ingestion.
         Oral NAC, IV NAC, and IV sodium sulfate were evaluated as treatments for cats who had received toxic sublethal doses of acetaminophen (APAP). At the dosage levels used, oral NAC, IV NAC, and IV sodium sulfate were equally effective antidotes, as measured by decreased methemo-globinemia, increased whole blood reduced glutathione, decreased APAP half-lives, and increased urinary excretion of the APAP-sulfate conjugate. All the antidotal treatments produced results significantly different from those in the control cats.
         To determine if rectally administered N-acetylcysteine (NAC) is absorbed into the systemic circulation, NAC was administered into the rectal vault (2.0 g/kg) of swine via a balloon-tipped Foley catheter inserted into the animals' rectums. NAC administered via the rectal route resulted in systemic absorption as determined by spectrophotometric methods in 5 of the 7 study animals. This study provides important information regarding the development of a potential alternative route for the administration of NAC to dogs.
         In dogs and cats, NAC can be administered intravenously or orally, but has a pungent odor. Oral administration of NAC typically causes nausea and vomiting. The oral solution can be compounded as a chicken-flavored preparation to improve palatability.
         Rapid intravenous administration of NAC can cause hypotension, bronchospasm, and flushing. Reactions can be minimized by slowing the rate of infusion.
         Activated charcoal may absorb NAC and reduce its effectiveness, so NAC should not be administered within two hours of giving activated charcoal. "Administration of activated charcoal may exacerbate vomiting and lead to aspiration. A strong antiemetic agent (metoclopramide 0.4 mg/kg IV) may be necessary to prevent emesis."
         NAC is currently not approved by the FDA for use in dogs and cats, but is available in human formulations, and upon a prescription order, can be compounded to meet specific veterinary needs. Compendium 2003 Apr;25(4):276-280

      Am J Vet Res
      1985 Jul;46(7):1485-9
      Comparison of N-acetylcysteine and methylene blue, alone or in combination, for treatment of acetaminophen toxicosis in cats.
      Click here to access the PubMed abstract of this article. 

      Vet Hum Toxicol 1997 Dec;39(6):329-31
      Rectal administration of N-acetylcysteine in swine: a pilot study.
      Click here to access the PubMed abstract of this article. 

      Vet Med 1997;92(2):158-165



      Dimercaptosuccinic Acid for Lead Poisoning in Cats

      Wright Veterinary Medical Center, Bethlehem, PA The owners of two nine-year-old cats moved to a new house. One week after moving, both cats were vomiting and losing weight so the owners brought the cats to the veterinary clinic. The veterinarian began intravenous hydration. Blood work showed a very high level of nucleated RBC's. The CBC revealed platelet clumps on feathered edge, few macrocytes, moderate anisocytosis, and occasional acanthocytes (54% and 45.1% NRBC). One cat had two seizures on the first day of hospitalization. Based on the initial signs and nucleated red cells, lead poisoning was suspected, although there was no radiographic evidence of lead ingestion. We tested for lead and began treatment with dimercaptosuccinic acid (DMSA) 40mg/cc. The cats improved clinically within 24 hours. There were no more seizures and the cats began to eat. The blood lead levels were 164.8 and 210 (normal is 0-25). The cats were treated with 40mg (1cc) of DMSA given orally three times per day for a total of 10 days. DMSA is not commercially available in an injectable or liquid form. Therefore, we worked together with our compounding pharmacist to prepare a sterile formulation that would be suitable for intravenous or oral use. The second day after therapy had begun, the owners informed us that they had been sanding the painted floors in their new house. The cats probably walked through the dust and in grooming themselves licked the lead paint off their paws. There have been no further problems with the cats to our knowledge. The owner declined to come in for a lead level recheck.


      Penicillamine for Long-Term Treatment of Lead Poisoning

      Penicillamine chelates a variety of metals, including copper, lead, iron and mercury, forming stable water-soluble complexes that are excreted by the kidneys. Used primarily for its chelating ability in veterinary medicine, it is the drug of choice for copper storage-associated hepatopathies in dogs at a dose of 15mg/kg PO twice daily. Penicillamine may also be used in cystine urolithiasis (penicillamine combines chemically with cystine to form a stable soluble complex that can be readily excreted) and in a different dose for the long-term oral treatment of lead poisoning. "This drug should preferably be given on an empty stomach, at least 30 minutes before feeding. If the animal develops problems with vomiting or anorexia, three remedies have been suggested. 1) Give the same total daily dose, but divide into smaller individual doses and give more frequently. 2) Temporarily reduce the daily dose and gradually increase to recommended dosage. 3) Give with meals (will probably reduce amount of drug absorbed)." Veterinary Drug Handbook, 2nd edition, Donald C. Plumb, Ed.

      4-Methylpyrazole for Ethylene Glycol (Antifreeze) Poisoning
       
      Therapy for ethylene glycol poisoning is aimed at preventing absorption, increasing excretion, and preventing metabolism of ethylene glycol to its toxic metabolites. Inhibition of liver alcohol dehydrogenase (ADH), the enzyme responsible for the initial reaction in the metabolic pathway, can be accomplished by giving a compound that combines with the enzyme and renders it inactive. The most effective ADH inhibitor in the dog is 4-methylpyrazole (4-MP), which unlike most competitive inhibitors (ethanol, propylene glycol, and 1,3-butanediol) does not contribute to CNS depression and increased serum osmolality. The recommended dose of 5% (50mg/ml) 4-methylpyrazole is 20 mg/kg body weight IV initially, followed by 15 mg/kg IV at 12 and 24 hr, and 5 mg/kg at 36 hr. While 4-MP is the recommended therapy in dogs, it is not appropriate for use in cats. Although it is non-toxic, it does not effectively inhibit EG metabolism unless administered to a cat at the same time as consumption of EG. Am J Vet Res 1995;56:825.
  • Seizure Control

    • Potassium Bromide for Seizures
      by Mollyann Holland, D.V.M., Oklahoma City, OK
      Diplomate, American College of Veterinary Internal Medicine
      Potassium bromide is frequently helpful in treating refractory seizures in animals. Because potassium bromide is excreted renally, it may also be preferable for use in animals that have developed hepatotoxicity while on other anticonvulsants. My compounding pharmacist prepares this as a liver flavored solution, which can easily be administered to dogs. I feel that it is important to inform my animal owners that potassium bromide solution is compounded from a reagent grade chemical, and is not a commercially available "drug." KBr is dosed on a weight basis. Maintenance doses range from 20-100 mg/kg body weight/day, and can be given as a single or divided dose. I usually dose at 30-40mg/kg/day as a single dose with food. Due to its long half-life, KBr can take up to four months to reach steady state; therefore, a loading dose may be required if therapeutic blood levels must be reached quickly. The loading dose is 400-600 mg/kg body weight and is administered orally over 30 to 60 minutes to avoid vomiting. A loading dose is not necessary if it is possible to keep the animal on other medications (as in a case of emerging hepatotoxicity) until levels of bromide are therapeutic (0.5-1.5 mg/ml), when the other anticonvulsant can be tapered off.

      Potassium Bromide Chewable "Treats" for Seizure Control

      Contributed by Steve Toney, R.Ph., Erin King, C.Ph.T. and Pam Woodin, D.V.M. Case Report: 5 y.o. male Golden Retriever with seizure disorder. The owners called our compounding pharmacy to see what we could do as they were having difficulty administering medications to their dog. We suggested medicated canine treats that we have compounded many times with a 100% success rate. The veterinarian was consulted and we prepared potassium bromide (KBr) 150 mg treats coated with liver and beef flavored powder. The owner administers two treats two times daily, and the dog now loves to take his medicine! Note: Chewable treats can be compounded to contain a variety of medications and flavored for the specific breed or pet. This dosage form has high patient acceptance and a low risk of owner misdosing. Potassium bromide (KBr) can be also compounded as an oral solution which is easy to flavor and convenient for use as a loading dose. However, the risk of owner misdosing is greater than with a chewie or capsule. Phenobarbital: Problems and Solutions

      While phenobarbital is often used in veterinary medicine to treat seizure disorders, there are several concerns with its use:
      • there are no commercially available veterinary approved products
      • phenobarbital tablets for human use are small, hard, and unscored, making them difficult to divide for individualized dosing
      • phenobarbital elixir has a high alcohol content, which is problematic for cats or any species when chronically administered
      • phenobarbital induces CYP450 hepatic enzymes which can result in substantial drug interactions with oral anticoagulants, steroids, antibiotics, beta-blockers, theophylline, etc.
      • phenobarbital is contraindicated in dogs with hepatic disease
      When you wish to prescribe phenobarbital, please be aware that our compounding pharmacy can prepare an alcohol-free, appropriately flavored oral suspension, which is highly bio-available and very easy to use when administering a loading dose or when a flexible dose is needed. Once the maintenance dose is established, the dosage form can be switched to a capsule (with a lower risk of misdosing by the owner) or a flavored chewable medicated "treat", with the added benefit of high patient acceptance
  • Urology

    • Treating Feline Urethral Spasm
       
         Feline lower urinary tract disease (FLUTD) is a spectrum of different diseases that present with a common set of clinical signs regardless of the underlying cause.  Cats with FLUTD, usually present with signs of dysuria (difficult urination), pollakiuria (increased frequency of urination), hematuria, agitation or vocalization (crying or howling) when unable to urinate due to urethral obstruction. Obstructive FLUTD can be a serious condition and may lead to post-renal azotemia, renal azotemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and acidemia. These combined metabolic and renal disruptions can rapidly prove fatal. Therefore, cats presenting with lower urinary tract obstruction require immediate treatment. Acute renal failure and death can result in 1-3 day if urinary tract obstruction is left untreated.
       
         Urethral spasm may occur in many cases of FLUTD, regardless of the underlying cause. Spasms may be initiated by local pain or inflammation, and may affect the smooth and/or skeletal muscle of the urethra. It may therefore be beneficial to give drugs to counter both smooth and skeletal muscle effects. While these drugs are rarely associated with side effects in young cats, the risk of concurrent renal or cardiac disease should be assessed before these drugs are given to older cats. Smooth muscle anti-spasmodics include prazosin 0.25-1.0 mg/cat PO q8-12h, and phenoxybenzamine  0.5-1.0 mg/kg PO q12h--give for 5 days before evaluating efficiency. The most commonly used skeletal muscle anti-spasmodic is dantrolene given at 0.5-2.0 mg/kg PO q12h.
       
         There have been only a limited number of studies into the use of anti-spasmodic drugs in the relief of urethral spasm in cats; however, prazosin, phenoxybenzamine and dantrolene have been shown to be most beneficial.  Unfortunately, all of these drugs are commercially available in capsule forms that cannot be safely and accurately administered to cats. Because prazosin and phenoxybenzamine are smooth muscle alpha adrenergic antagonists, profound hypotension is a potential adverse effect.  For this reason, these drugs have a very narrow therapeutic index, and veterinary clinicians prefer to only use these drugs in carefully titrated doses. Our compounding pharmacy is able to provide these valuable anti-spasmodic drugs in palatable, appropriately-sized dosage forms and optimal individualized strengths.  While none of these drugs are stable for long periods of time in liquid dosage forms, we can compound capsules containing one or more of the anti-spasmodics individualized for a specific patient, or provide as medicated treats.  Due to the delayed onset of transdermal medications, this dosage form is not appropriate for use in treating this potentially life-threatening condition. 
       
      AJVR 1995 Jul;56(7):919-23.
      Urethral pressure response to smooth and skeletal muscle relaxants in anesthetized, adult male cats with naturally acquired urethral obstruction.
      Click here to access the PubMed abstract of this article.

      AJVR 1992 Jul;53(7):1161-5.
      Urethral pressure response to alpha-adrenergic agonist and antagonist drugs in anesthetized healthy male cats.
      Click here to access the PubMed abstract of this article.

      AJVR 1996 Oct;57(10):1497-500.
      Effects of acepromazine maleate and phenoxybenzamine on urethral pressure profiles of anesthetized, healthy, sexually intact male cats.
      Click here to access the PubMed abstract of this article.




      Treatment for Urinary Incontinence Hormonal Therapy:
      Diethylstilbestrol (DES) has been used to treat estrogen responsive incontinence in spayed female dogs. The use of DES is contraindicated in cats as daily use has resulted in pancreatic, hepatic, and cardiac lesions. Dose for dogs:
      Initially 0.1-1.0 mg PO daily for 3-5 days, followed by maintenance therapy of approximately 1 mg PO per week. Some animals may require much higher initial dosages to obtain a response. DES can be given PO to female dogs at 0.1-0.3 mg/kg/day for 7-10 days, followed by a similar dose once weekly. Dogs should be maintained at the lowest possible dose because bone marrow suppression can develop when diethylstilbestrol is given in high doses. 1,4  When therapy is chronic or high dosages are used, packed cell volumes, white blood cell counts, and platelet counts should be done at least monthly. Liver function tests should be done at baseline, one month after therapy, and repeated 2 months after cessation of therapy if abnormal. Clients should be informed to contact the veterinarian if signs and symptoms of lethargy, diarrhea, vomiting, abnormal discharge from vulva, excessive water consumption and urination or abnormal bleeding occur. DES is not for human consumption and should be dispensed only in child-resistant containers and stored in a secure location.1 DES is not currently commercially available; however, the medication can be prepared by a compounding pharmacy.
      Adrenergic Agonists:
      Phenylpropanolamine (PPA) is a weak alphaagonist that increases urethral sphincter tone and produces closure of the bladder neck, and is used to treat urethral sphincter hypotonus and resulting incontinence in dogs and cats. Dose1: Dogs:  1.1 mg/kg PO every 8 hours       Cats:  12.5mg PO every 8 hours The effect is short-lived, and the dose needs to be titrated to effect. "Dogs that are older at the onset of clinical signs (median 5 years) and those with a longer period from the time of ovariohysterectomy to the onset of urinary incontinence (median 2.5 years) respond best. PPA is preferred to ephedrine because side effects are less severe; ephedrine has greater cardiovascular side effects and it tends to lose effectiveness over time."2 In a multicenter, blinded, placebo-controlled trial, 50 dogs that presented with clinical signs consistent with urinary sphincter mechanism incontinence were treated for 28 days with either PPA (1 mg/kg three times daily) or placebo. At day 28, 85.7 per cent of PPA-treated cases had no episodes of unconscious urination compared with 33.3 per cent of placebo-treated cases.3 Potential side effects include restlessness, irritability, hypertension and anorexia. Numerous drug interactions exist.   In November2000, human PPA preparations were removed from the market due to reports of serious side effects in humans. PPA continues to be available as a bulk chemical for veterinary use only. 1 Veterinary Drug Handbook, 3rd edition, Donald C. Plumb, ed. pp.193-5, and 508-9

      2 Handbook of Veterinary Drugs, 2nd edition, pp. 277-8

      3 J Small Anim Pract. 2002 Nov;43(11):493-6
      Evaluation of phenylpropanolamine in the treatment of urethral sphincter mechanism incompetence in the bitch.
      Click here to access the PubMed abstract of this article.

      4 http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/191024.htm&word=ppa Per your prescription, we can compound customized dosage forms to meet the specific needs and flavor/texture preferences of each animal.


      Piroxicam for Canine Bladder Cancer
      Traditional chemotherapy (using cisplatin, carboplatin, adriamycin, and others) has been used in canine Transitional Cell Carcinoma (TCC). The response has been rather disappointing with <20% of dogs having remission. Interest in non-steroidal anti-inflammatory (NSAID) therapy began when dogs with various forms of spontaneous cancer had remission while receiving the NSAID piroxicam for pain control, and no other therapy.  Two of the first dogs treated (one with metastatic carcinoma, one with undifferentiated sarcoma) had advanced cancer and had remission of their cancer when only receiving piroxicam. This has led to numerous studies of piroxicam in animals with cancer at Purdue University Veterinary Teaching Hospital (PUVTH). In an attempt to improve the response of TCC to therapy, PUVTH conducted a study comparing chemotherapy (cisplatin) alone to chemotherapy plus piroxicam. The combination of cisplatin and piroxicam was more effective against the cancer, but the combination treatment caused a rise in BUN. In several instances, the cisplatin therapy was withdrawn (so as to not cause renal damage) while the tumors were still shrinking. In a phase I study of piroxicam in 62 dogs with various histopathologically confirmed, measurable tumors, gastrointestinal toxicity was dose-related and dose limiting, but anti-tumor activity occurred at lower, less toxic doses of piroxicam. Partial remission occurred in 8 dogs, including 3 of 10 dogs with TCC. A phase II clinical trial of piroxicam in dogs with histologically confirmed, measurable, nonresectable TCC was performed. The dogs lived at home with their owners and were evaluated at the PUVTH at monthly intervals. Piroxicam was given orally at a dosage of 0.3 mg/kg every 24 hours (the accepted canine dosage prior to this trial). Tumor response in 34 dogs included 2 complete remissions (CR), 4 partial remissions (PR), 18 stable disease (SD), and 10 progressive disease (PD). Piroxicam therapy was generally well tolerated, with gastrointestinal toxicity noted in six dogs and renal papillary necrosis in two dogs. The median survival was 180 days. Fifty-five additional dogs were treated with piroxicam, and tumor response included 2 CR, 7 PR, 32 SD, and 14 PD. It is not known how long dogs with TCC that are not treated will live. Survival is affected by the growth rate of the tumor, the exact location of the tumor within the bladder, and whether the tumor has metasticized. The median survival in dogs treated with cisplatin or carboplatin at PUVTH was 130 days. Median survival with piroxicam treatment in 55 dogs with TCC was 190 days. The survival times in all of these studies, however, vary tremendously from only a few days to more than one year.  Longer survival times have been reached when chemotherapy is combined with piroxicam, but the optimal combination treatment is still being determined. Cancer Chemother Pharmacol 1992;29:214-218
      Phase I trial of piroxicam in 62 dogs bearing naturally occurring tumors.
      Click here to access the PubMed abstract of this article.

      J Vet Intern Med 1994;8:273-278
      Piroxicam therapy in 34 dogs with transitional cell carcinoma of the urinary bladder.
      Click here to access the PubMed abstract of this article.

      Cancer Chemother Pharmacol 2000;46:221-226
      Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer.
      Click here to access the PubMed abstract of this article.

      Urologic Oncology 2000;5:47-59
      Naturally-occurring canine transitional cell carcinoma of the urinary bladder: A relevant model of human invasive bladder cancer.


      Citrate Salts as Alkalinizing Agents
      Citrate salts are a source of bicarbonate, but are much more palatable than bicarbonate preparations. "They are used as urinary alkalinizers when an alkaline urine is desirable and in the management of chronic metabolic acidosis accompanied with conditions such as renal tubular acidosis or chronic renal insufficiency. Potassium citrate alone has been used for the prevention of calcium oxalate uroliths. The citrate can complex with calcium thereby decreasing urinary concentrations of calcium oxalate... When urine is alkalinized by citrate solutions, excretion of certain drugs (e.g. quinidine, amphetamines, ephedrine, ...tetracycline) is decreased, and excretion of weakly acidic drugs (e.g. salicylates) is increased. The solubility of ciprofloxacin and enrofloxacin is decreased in an alkaline environment [and patients] should be monitored for signs of crystalluria." (Plumb's Veterinary Drug Handbook, 2nd ed.)  In combination with potassium citrate preparations, these agents may lead to severe increases in serum potassium levels: NSAIDs, ACE-inhibitors, cyclosporine, digitalis, heparin and others. Fludrocortisone Acetate
      Fludrocortisone is a long-acting corticosteroid with potent mineralocorticoid and moderate glucocorticoid activity. It is used in small animal medicine for the treatment of adrenocortical insufficiency, where it promotes sodium retention and urinary potassium secretion. It is commercially available only as the human product, a tablet containing 0.1 mg  fludrocortisone acetate. The maintenance therapy for animals (particularly dogs) can require administration of multiple tablets for each daily dose.  Therefore, it may be more convenient for owner and animal to administer fludrocortisone acetate as a flavored suspension, or single flavored solid dosage form. Aluminum Hydroxide for Hyperphosphatemia
      For dogs and cats, aluminum hydroxide is initially dosed at 30 - 90 mg/kg orally one to three times daily. A preparation that can be mixed with food may be preferred as it is more easily dispersed throughout ingesta. Dosage must be individualized, and serum phosphate levels should be evaluated at 10-14 days to determine optimum dosage. Veterinary Drug Handbook, 3rd edition, Donald C. Plumb, editor. pp. 48-49

      Calcitriol for Chronic Renal Failure
      Submitted by Shirley Russman, D.V.M. Our protocol for treating chronic renal failure includes a special diet, adequate hydration, potassium supplementation, stomach acid control and calcitriol therapy to control phosphorus levels. Calcitriol (a vitamin D3 metabolite) may also be used to prevent or reverse secondary hyperparathyroidism in dogs and cats with chronic renal failure. Calcitriol is dosed in nanograms. Commercially available products are for humans, and the dose is much too high for dogs or cats (for example, the capsule contains 250 nanograms or 0.25 micrograms). Our compounding pharmacist has been able to prepare any capsule (8 nanograms and up) or liquid (i.e. 4 nanograms/0.25ml) necessary to meet our needs.  We have used this compounded remedy over one hundred times and have found it to be very successful in lowering phosphorus levels in our patients with chronic renal failure. Serum calcium levels should be monitored as hypercalcemia is a possible consequence of calcitriol administration. Editor's Note: Calcitriol "has a rapid onset of action (1-4 days) and a short half-life (4-6 hours). Oral calcitriol is administered to patients after initial stabilization with fluid therapy, dietary protein and phosphorus restriction, the use of intestinal phosphate binders and H-2 blockers as needed. Serum phosphorus should be less than 6 mg/dL (1.9 mmol/liter) before initiating calcitriol. "Hypercalcemia usually only occurs if calcitriol is used in conjunction with intestinal phosphate binders, especially calcium carbonate... Long-term use of phenytoin and the barbiturates may interfere with the action of the drug, necessitating higher doses of calcitriol... Thiazide diuretics may enhance the effects of calcitriol predisposing to hypercalcemia. Calcitriol-induced hypercalcemia may antagonize the antiarrhythmic effects of calcium channel-blocking agents." Handbook of Veterinary Drugs, 2nd edition, pp. 105-106
  • Wound Care

    • Would you like a topical medication that is difficult for an animal to lick off or that will adhere to a mucosal surface? You can prescribe a medicated "polyox bandage" or "mucosal bandage". When moistened, this medicated preparation will adhere to a wound or mucosal surface, thereby providing a protective barrier and increasing the contact between the medication and the affected area.
      Wound and Incision Care - Prevent Licking

      A common problem encountered by veterinarians and animal owners is preventing an animal from licking an incision or licking medication from the area to which it has been applied. In addition to injury to the wound, pharmacists and veterinarians must consider the consequences of internal consumption of an external preparation. To prevent an animal from licking, a medication can be compounded to contain an extremely bitter substance. Choices include diphenhydramine, quinine, or the non-therapeutic ingredient sucrose octaacetate. Sucrose octaacetate can be added at 1% to 5% to any topical dosage form and the bitterness usually prevents the animal from repeated licking of the area of application. Another way to protect a medicated area from licking is to incorporate the needed medication into CAP (Cellulose Acetate Hydrogen Phthlate) solution. Since CAP solution does not dissolve in an acidic pH, the animal's saliva does not remove it from the skin. CAP solution can also be sprayed directly onto a wound or over stitches to protect them.

      Phenytoin/Lidocaine Poly-Ox Bandage Used to Treat Leg Wound

      Problem: Twenty-four hours after an automobile accident, an eight-month old female pit bull presented with a leg injury that appeared as if it would have difficulty healing. The dog had been hit by an automobile, which had scraped a hole in the right front leg. The wound, which extended from the elbow to the carpus, was approximately 3/4" to 1" wide. Treatment: The tissue of the leg was stabilized using tension-relieving sutures. Because the veterinarian had prior successful experiences with other cases involving wound care, she requested we compound a topical preparation consisting of 2% phenytoin and 2% lidocaine in a methylcellulose/polyoxyethylene (poly-ox) bandage for the dog. The animal underwent hydrotherapy twice daily and the compounded medication was applied just before bandaging was secured. Outcome: The wound was completely healed after 2 months of therapy and the animal has full use of her leg with no visible ill effects. According to the veterinarian, the animal healed much quicker than usual due to the increased contact time of the medications and she was satisfied with the treatment process. We have also used this compound with the same positive success on a degloved feline after its paw had been caught in a fence overnight. Reference:
      Randy S. Carr, R.Ph., FIACP & Pamela Doskey, D.V.M.

      Therapy for Severe Chemical Burns

      by Barbara Espe, D.V.M., North Dakota
      In April 1998, I was called to euthanize a 1 1/2 year old female miniature schnauzer that had been burned with hot water from the bath tub and washed in Woolite? 3-4 weeks earlier. The full thickness burns involved about 80% of the skin on the dorsal trunk from neck to tail and elbows to midthigh. The owners were using aloe vera to treat the burns and she had a severe infection, was emaciated (5 lb.) and had not eaten for one week. Since she had survived so long without treatment, I had the owners sign ownership over to me and I contacted the Central Dakota Humane Society. They agreed to take on this project despite the many hours of labor and the potential cost. The dog was immediately given an analgesic and antibiotics. I literally stopped at the pharmacy with the dog so the compounding pharmacist could see what we were up against. At the pharmacist's suggestion, a Poly-Ox bandage containing phenytoin base 2% and misoprostol 0.002% was compounded and applied in a layered manner. Telfa? pads were used to cover the wound, and a T-shirt was put on to protect the bandages. The dog started eating canned food that night and in several days she was eating four large cans of food daily. In addition to the Poly-Ox bandage, she remained on Cefadrops? and Rimadyl?. She seemed to be uncomfortable and analgesics did not appear to control her pain. The powder was returned to the pharmacy and lidocaine 2% was added. Although this helped somewhat, the dog was becoming non-compliant at the time of her dressing changes. The compound was again modified to contain bupivacaine 0.2% to obtain an extended analgesic effect. This was a significant improvement and therapy continued for several months. As healing occurred, the dog began to experience itching in the regranulated skin and wound areas. Diphenhydramine was given orally along with the Rimadyl? and we began rubbing her stretched skin with Emu oil to keep it moist. Shortly thereafter, the dog "became a schnauzer again." Her activity level has increased greatly and we anticipate a complete recovery. When I began treating this dog, I thought that skin grafting would be necessary. Due to the success of this therapy, no grafting will be needed. However, I don't expect hair regrowth and the epithelium will remain scarred and easily bruised.
  • Equine

    • Reserpine for Compulsory Stall Rest
       
         Reserpine has clinical therapeutic value to sedate horses recovering from injuries that are confined to stall rest for long periods of time. Reserpine is a narrow therapeutic index drug. Recommended doses of reserpine range from 1-4mg/500kg horse once daily and may be administered orally or by intramuscular injection. Doses of 5-10mg/500kg horse have resulted in severe toxicity. Signs of toxicity can occur within three to six hours of administration. Initially, severe depression, sweating and flatulence are seen. There may be sporadic episodes of colic, sometimes violent, followed by somnolence. Injection frequently results in diarrhea, but both oral and parenteral routes may result in increased gastrointestinal sounds, muscle trembling, hypotension, decreased heart rate, arrhythmias, miosis, ptosis, and penile paralysis. Clinical signs will persist until norepinephrine stores are replenished which may be up to 60 hours after dosing.  Reserpine may be detected by drug assay for up to 5 days after administration.  No antidote is available for reserpine toxicity, although methamphetamine has been suggested as a possible therapy.
       
         Drug interactions with reserpine can be life-threatening. Horses treated with reserpine within the previous 60 days may be at risk for profound hypotension (even death) when exposed to xylazine, detomidine or ketamine.
       
         Reserpine is no longer commercially available as an injection, but is available in 0.1mg and 0.25mg tablets. However, reserpine has a bitter taste, and many horses will not accept these tablets voluntarily. Our compounding pharmacy is able to provide palatable oral gels and suspensions of reserpine as well as reserpine injection upon the order of a licensed veterinarian.
       
      Equine Clinical Pharmacology. Editors Joseph Bertone, DVM, MS and Linda J. I. Horspool BVMS PhD. WB Saunders, p. 152.



      Transmucosal Buprenorphine: More is Better For Dogs and Horses
       
         The pharmacokinetic profile of a buccally-administered (transmucosal) dose of buprenorphine to cats is almost identical to that of intravenously administered buprenorphine. The unusually alkaline salivary pH of cats prevents ionization of buprenorphine, allowing it to diffuse into systemic circulation in a non-ionized form. This discovery greatly facilitated outpatient feline pain relief, allowing owners to administer this drug to cats at home, without the need for hospitalization or injection.  Because the duration of analgesia from buprenorphine (4-12hrs) is longer than that provided by other opiates, buprenorphine is frequently used for provision of non-invasive, intermediate to long-term analgesia in cats.  It is typically administered at doses of 10-30mcg/kg applied to the oral mucosa (inside the cheek pouch) every 8 hours for up to 5 days (many cats experience anorexia after 5 days of therapy with buprenorphine). The commercially available 300mcg/ml solution for injection (Buprenex) works well for buccal administration with most cats receiving volumes of approximately 0.066ml/kg (e.g. 0.33ml for the average 5kg cat).1
       
        Buccal absorption of buprenorphine has also been examined in dogs at approximately the same dose (20mcg/kg) utilized in cats. Absorption was low at this dose, but a dose of 120 mcg/kg administered transmucosally to dogs produced drug concentrations equivalent to an intravenous dose of 20 mcg/kg. Dogs have a relatively more acidic salivary pH than cats, resulting in more ionization of buprenorphine, reducing the amount of drug available for diffusion across membranes. At doses of 120mcg/kg, a 25kg dog would require 3000mcg or 10ml of the commercially available buprenorphine solution for injection.  A canine patient would likely swallow a large portion of 10ml administered buccally, and since the oral absorption of buprenorphine is extremely low, analgesic effect would not be achieved. Recent work at NC State University (unpublished) also demonstrates that buccal buprenorphine provides effective analgesia in horses when administered at doses of 6.6mcg/kg (e.g. 11ml of the commercially available injection for a 500kg horse). Again, a significant portion of this dose is likely to be swallowed by an equine patient, precluding a full analgesic effect.
       
          For dogs and horses, a more concentrated solution of buprenorphine is greatly desirable for transmucosal use.  Compounded solutions of buprenorphine from 3-6mg/ml would allow for buccal administration of volumes of less than 1ml for both dogs and horses. Our compounding pharmacy can prepare concentrated solutions of buprenorphine for transmucosal use in dogs and horses.  Please call for more information.
       
      1 J Vet Pharmacol Ther. 2005; 28(5):453-460. 
      PK-PD modeling of buprenorphine in cats: intravenous and oral transmucosal administration
      Click here to access the abstract of this article.
       
      2 Vet Ther. 2008 Summer;9(2):83-93.
      Pharmacokinetics of buprenorphine following intravenous and oral transmucosal administration in dogs.
      Click here to access the PubMed abstract of this article.

      Stability of Compounded Pergolide  Pituitary pars intermedia dysfunction (PPID) is the most common endocrine disorder in equine species.The most life-threatening clinical sign of PPID is laminitis, which is thought to be related to cortisol and other hormonal effects on glucose utilization by tissues of the hoof wall. An integral part of PPID management is medical treatment.The most widely used drug is the dopamine agonist, pergolide. Unfortunately, pergolide was withdrawn from the human market in 2007 due to cardiovascular side effects in people. Pressured by the American Veterinary Medical Association, the American Association of Equine Practitioners, and thousands of horse owners in May 2007, the Food and Drug Administration decided to allow compounding of pergolide for horses utilizing the bulk chemical active pharmaceutical ingredient.As a result of this milestone decision, compounding pharmacists began providing various compounded dosage forms of pergolide for horses with PPID.Most horse owners prefer to utilize flavored oral suspensions of pergolide.This dosage form allows for both increased palatability to the patient, increased compliance by the horse owner, and allows for flexibility in dosage adjustment until an effective dosage is determined.Unfortunately, pergolide was never commercially available in a liquid oral dosage form.Commercial availability was limited to the tablet dosage form and until recently, no information was available to support the stability of a liquid dosage form of pergolide. In February 2009, researchers at the NC State College of Veterinary Medicine published results of a long-term stability study for aqueous suspensions of pergolide.In this study, pergolide was compounded into an aqueous formulation with a final target concentration of 1 mg/mL. Aliquots of the formulation were then stored at –20°, 8°, 25°, or 37°C without exposure to light or at 25°C with exposure to light for 35 days. Samples were assayed in triplicate by means of high-pressure liquid chromatography immediately after compounding and after 1, 7, 14, 21, and 35 days of storage.Results showed that samples exposed to light while stored at 25°C had undergone excessive degradation by day 14, samples stored at 37°C had undergone excessive degradation by day 21, and samples stored at 25°C without exposure to light had undergone excessive degradation by day 35. The decrease in expected concentration corresponded with the appearance of degradation peaks in chromatograms and with a change in color of the formulation.In light of these results, researchers concluded that compounded pergolide formulations in aqueous vehicles should be stored in a dark container, protected from light, and refrigerated and should not be used > 30 days after produced. It is also recommended that pharmacists and veterinarians do not add any excipients which would prevent an owner from detecting a color change in pergolide formulations.Formulations that have undergone a color change should be considered unstable and discarded. The results of this study should allow veterinarians and our compounding pharmacists to collaborate to provide more accurate control of this devastating equine disease. J Am Vet Med Assoc 2009;234:385–389
      Compounding and Storage Conditions on Stability of Pergolide Mesylate.
      Click here to access the abstract of this article.



      Sugar-Free Medications For Horses with EMS

      The term “equine metabolic syndrome” (EMS) has been adopted to describe a collection of clinical signs that contribute to the development of laminitis in horses, and has previously been described as peripheral equine Cushing’s syndrome, pseudo-Cushing’s syndrome, hypothyroidism, and insulin resistance syndrome. Causes of EMS are similar to those found to cause metabolic syndrome and insulin resistance in humans. Management and prevention of EMS primarily revolves around weight control and prevention of obesity. While there is no “cure” for EMS, there exist many supportive therapies including vitamin and mineral supplements, low starch feeds, and anti-inflammatory and analgesic medications. While the horse feed industry has quickly realized the need for sugar-free feeds, any change in drug formulation requires FDA approval, so the veterinary drug industry has not been able to respond quickly to the need for sugar-free medications and supplements for horses. Our compounding pharmacy can contribute significantly to the care of EMS horses by working with veterinarians to convert all medications and supplements to sugar-free dosage forms. Sugar-free powders and pastes of phenylbutazone, flunixin, pergolide, and vitamins are particularly valuable to veterinarians treating horses with EMS.

      Pergolide for Equine Cushing's Disease  Pergolide has proven to be a safe and effective therapy in long term management of equine Cushing's disease. The American Association of Equine Practitioners (AAEP) has been working with the FDA to develop options to provide veterinarians with continued access to pergolide to treat equine Cushing's patients. FDA has indicated willingness to utilize regulatory discretion to allow compounding pharmacists to provide pergolide compounded from the bulk substance until a manufactured source of pergolide can be made available.   J Vet Intern Med. 2002 Nov-Dec;16(6):742-6.
      Treatment with pergolide or cyproheptadine of pituitary pars intermedia dysfunction (equine Cushing's disease). 

      Click here
      to access the PubMed abstract of this article. 

      Electrolyte Paste to Restore Fluid and Acid Base Balance in Horses

        "Prolonged exercise in horses, particularly when performed in hot and humid conditions, brings about large fluid and electrolyte loses which, if not restored, may impair thermoregulatory responses and result in hyperthermia." In horses, administration of oral rehydration solutions (ORS) is problematic, because many horses refuse to drink fluids containing electrolytes. Therefore, administration of ORS typically requires placement of a nasogastric tube with its inherent risks. An alternative is to give a concentrated electrolyte mixture as a paste. Leon et al. of Department of Veterinary Clinical Sciences, University of Sydney, NSW, Australia studied six Thoroughbred geldings to determine "whether oral administration of a concentrated electrolyte paste would promote the restoration of fluid, electrolyte, and acid base balance as well as fluid and electrolyte deficits induced by furosemide administration" (a standard model which induces significant contraction of plasma volume and consistent electrolyte deficit against which the effects of treatment could be measured). 
        "As a general conclusion, horses that received concentrated electrolytes [and had free access] to water consumed more water, regained more weight, lost considerably less electrolytes in urine, and maintained plasma electrolyte concentrations and acid base balance closer to baseline values than did those that had ad libitum access to water only." Administration of electrolyte paste provided a more practical source than supplementation using feed or salt blocks. Am J Vet Res 1998 Jul;59(7):898-903
      Effects of concentrated electrolytes administered via a paste on fluid, electrolyte, and acid base balance in horses.
      Click here to access the PubMed abstract of this article.

      Progesterone for Estrus Induction in Mares

      According to Robert R. Foss, DVM, progesterone in sesame oil, 150 mg per day, IM is equally as efficacious as altrenogest. The optimal formulation is the combination of progesterone and estradiol 17-beta; the addition of estradiol provides a greater feedback than progesterone alone, so cessation produces a more dramatic response. The estradiol is somewhat protective against exacerbation of endometritis. Dr. Foss commonly uses this combination at 150 mg progesterone and 10 mg estradiol 17-beta, IM, daily for 10 days. Estrus will usually begin in 6-8 days with ovulation around day 10-12. This combination has been effective in situations where altrenogest has failed. 114th IL VMA Proceedings, February, 1996


      Prednisone (Oral) Ineffective in Horses

      Jackson et al. compared the effects of prednisone with environmental management to environmental management alone for the treatment of heaves (recurrent airway obstruction), and reported that oral prednisone has no additional benefit.1 To be effective, oral prednisone must be absorbed and metabolized to its active form prednisolone. Robinson et al. designed a study with two objectives:  1) to compare oral prednisone with intravenous dexamethasone for the treatment of horses with heaves; and 2) to measure serum prednisolone levels in horses after oral administration of prednisone and prednisolone. Each of five horses received five drug formulations (prednisone and prednisolone in tablet and liquid form, as well as intravenous prednisolone sodium succinate as a positive control, all at a dose of 2.2 mg/kg) in a Latin square design study. Severity of airway obstruction was measured, and there were no significant differences between prednisone administration and no medication at any time. Prednisolone was detectable in serum immediately after intravenous administration, peaking at around 1000 ng/ml at 12 min. Oral administration of prednisolone tablets or liquid yielded peak serum prednisolone concentrations of 377-1032 ng/ml at 30-45 min. When horses received oral prednisone tablets or liquid, prednisolone never reached detectable levels in the serum. The authors concluded, "In order for the drug prednisone to be effective after oral administration it must be absorbed from the gastrointestinal tract and converted to the active drug prednisolone by the liver. Although trace serum levels of prednisone were detected, prednisolone never appeared in the serum. Our data do not allow us to determine if prednisone is poorly absorbed, rapidly excreted, or not converted to prednisolone by the liver. However, it is clear that prednisone is unlikely to have any anti-inflammatory effect when administered by mouth. Oral administration of prednisolone is likely to be beneficial because it is rapidly absorbed and achieves serum levels close to those that result from intravenous administration."2 Robert N. Oglesby, DVM (The Horseman's Advisor, www.horseadvice.com) reports his reaction to hearing the above presentation at the November, 2000 meeting of the American Association of Equine Practitioners: "I was shocked and looking around me hundreds of other vets were also: oral prednisone doses are in every equine medicine text with many descriptions of its indications. Why has no one noticed the lack of effect before now? The reason is simple: no one believed it was possible that [prednisone] was not effective [in horses]. Its usefulness in other species was too well established... we did not even question its use. Looking back on it, it was the management changes that were responsible for the clinical improvement..." 1Equine Vet J 2000 Sep;32(5):432-8
       
      2 AAEP Proceedings, Vol. 46, 2000, pp. 266-267

      Equine Vet J. 2002 May;34(3):283-7
      Prednisone per os is likely to have limited efficacy in horses.
      Click here for access to the PubMed abstract. We can compound prednisolone into the most appropriate dosage form, including oral pastes or "chewies" that horses will love!


      Pentoxifylline
       
       
      In horses, a dose of 8.5 mg/kg orally two times daily is recommended for reducing the cytokine effects in endotoxemia. For the treatment of navicular disease, 6 g/day orally for 6 weeks should be used.    Compendium 23(7), July 2001, 603-4


      Anti-Diarrheals for Foals & Horses

      Treatment of diarrhea should always be based on establishing a diagnosis and correcting the basic cause. Anti-diarrheal products are not a substitute for adequate fluid and electrolyte therapy when dehydration or shock threatens. When the veterinarian deems anti-diarrheal therapy is appropriate, the following options may be considered. According to James L. Becht, D.V.M., M.S., Diplomat ACVIM, preparations containing bismuth subsalicylate seem superior to those containing kaolin, pectin, or activated charcoal for treating the foal with diarrhea. Bismuth subsalicylate neutralizes bacterial toxins, has some antibacterial activity, and may exert an antisecretory effect. It can be administered at a dosage of 4 oz q 6h; darkened feces will result. If no effect is seen within 48 hours, continued administration is probably not indicated. (105th Ohio VMA). Wendy E. Vaala, V.M.D., Diplomate ACVIM reports (ACVIM 16th Veterinary Medical Forum) that delayed gastric emptying and gastroduodenal dysmotility can be improved  in some foals with  metoclopramide (0.25-0.6 mg/kg, PO q4-6h), erythromycin (1.0-2.0 mg/kg  PO q6h), or cisapride (10 mg/kg PO q6h). If colic, ileus, and gastric reflux are present, Dr. Vaala recommends an abdominal sonogram to rule out the presence of an intussusception prior to initiating prokinetic therapy. Diarrhea may be treated symptomatically with bismuth subsalicylate (1-2 ml/kg, PO, q4-6h) and may also respond to psyllium administration. Intestinal probiotics containing Lactobacillus bacteria ... may be given to foals receiving antibiotics to help reestablish intestinal flora. Adult horses may be treated with bismuth subsalicylate 1 oz per 8 kg of body weight PO TID-QID (Clark and Becht 1987).

      Headshaking in Horses

      may include additional signs such as nose rubbing, striking at the nose with the forelegs, or active avoidance of light, warmth, or wind on the face. Newton et al studied 20 mature horses with typical headshaking of 2 week to 7 year duration, and concluded that the etiopathology may be a trigeminal neuritis or neuralgia. In 12 of 20 horses, drug therapy was initiated. Cyproheptadine (CP) alone was ineffective but the addition of carbamazepine (CM) resulted in 80-100% improvement in 80% of cases within 3 to 4 days of beginning drug therapy. Seven cases were treated with a combination of CM (4 mg/kg, three to four times daily) and CP (0.2-0.5 mg/kg  every 12 to 24 hours).  Carbamazepine alone has been effective in 88% of cases. Some headshaking horses have responded well to CM doses of 1.6 - 2.4 grams every six hours without apparent side effects. Horses are treated for 10 to 20 days and if they respond, the treatment is discontinued. If clinical signs of headshaking recur, treatment is restarted. In practice, there is a realistic possibility of controlling but not curing headshaking with carbamazepine therapy at the present time. Other studies have reported that cyproheptadine alone was beneficial in more than two thirds of treated horses. Equine Vet J  2000 May;32(3):208-16
      Headshaking in horses: possible aetiopathogenesis suggested by the results of diagnostic tests and several treatment regimes used in 20 cases.
      Click here for access to the PubMed abstract.

      Equine Vet J Suppl 1998 Nov;(27):28-9
      Characterisation of headshaking syndrome--31 cases.
      Click here for PubMed abstract.

      J Am Vet Med Assoc 
      2001 Aug 1;219(3):334-7
      Owner survey of headshaking in horses.
      Click here for access to the PubMed abstract.

      ISU Vet Med 
      Sept 2000

      The Pennsylvania State University Veterinary News
      , Dec 2000, pp 9-10




      Aust Vet J. 1991 Jul;68(7):221-4 
      Use of phenytoin to treat horses with Australian stringhalt  
      Click here for access to the PubMed abstract. 
  • Avian

    • Doxycycline Administered in Drinking Water for Treatment of Spiral Bacterial Infection in Birds
       
         Spiral bacteria have been found in various portions of the respiratory tracts of cockatiels and lovebirds.  Common signs of infection with this bacterium include red clogged nares, sneezing, reddened and blunted choanal papillae and pharyngeal redness. Infected birds may also show signs of lethargy, anorexia and weight loss. Conjunctivitis, sinusitis and periorbital swelling may also be noted but are less common signs.  A survey of 148 cockatiels seen by a veterinary practice in New York indicated that 37 (25%) were found to be infected with spiral bacteria with most of these having clinical signs of upper respiratory tract infection and red choana. The infection rate was higher in birds <2yrs old and in birds fed poor diets, suggesting that spiral bacteria are opportunistic organisms that cause clinical signs in young and compromised birds.
       
         Spiral bacterial infections in cockatiels have been successfully treated with oral administration of doxycycline hyclate at 25mg/kg orally every 12 hours for 3 weeks. However, this regimen requires twice-daily capture and forced administration of doxycycline liquid suspension, which is apparently not palatable to birds. The stress caused by this regimen to both birds and owners caused researchers at the North Carolina State University College of Veterinary Medicine to determine the feasibility of administering doxycycline via drinking water.  A group of 11 cockatiels naturally infected with spiral bacteria were offered solutions of doxycycline at 400mg per liter as the sole source of drinking water and 7 other naturally infected cockatiels acted as the control group receiving untreated tap water as the sole source of drinking water for a treatment period of 30 days.  For the first 14 days, spiral bacteria were isolated from all 18 birds in both the treatment and control group, but after day 21, spiral bacteria were no longer seen in the treatment group.
       
         For this study, doxycycline drinking water was prepared by emptying the contents of 4 x 100 mg doxycycline hyclate capsules into a liter of deionized water and stirring with a magnetized stirrer for 4 minutes and made fresh every 24-36 hours.  As most bird owners do not have magnetic stirrers at home, and as the doxycycline hyclate capsules contain excipients other than doxycycline that do not go into solution and settle out at the bottom of the drinking bowl, our compounding pharmacy can provide bird owners with a more efficient method of doxycycline hyclate delivery by preparing 400mg capsules or packets of pure doxycycline hyclate, which the owner can stir into a 1 liter bottle of sterile water for irrigation (eliminating the possibility of contamination as well as preventing any binding of doxycycline by cations in tap water). It is interesting to note that doxycycline monohydrate is more palatable than doxycycline hyclate, but unfortunately, doxycycline monohydrate is not soluble in water and would not be a useful salt for this method of drug administration.  
       
      J Am Vet Med Assoc. 2008 Feb 1;232(3):389-93
      Administration of doxycycline in drinking water for treatment of spiral bacterial infection in cockatiels.
      Click here to access the PubMed abstract of this article.




      Antifungal Therapy for Avian Species
      In avian species, the most frequent causes of infection have shifted from gram-negative bacteria to gram-positive bacteria and Candida (often non-albican) species. There is a decreased susceptibility of many non-albicans species to available antifungal drugs, perhaps as a consequence of nondiscriminate azole use. The efficacy of terbinafine has been improved when administered in combination with azoles for treatment of azole resistant oral candidiasis and aspergillosis. Because terbinafine was administered successfully in an African gray parrot at 15 mg/kg every 12 hours for 30 days without adverse effects, it may have potential for use in systemic aspergillosis in these azole-sensitive species. Caution should be used in avian patients with liver or renal disease. Veterinary Clin North Am Exot Anim Pract. 2003 May;6(2):337-50, vi
      Antifungal drug therapy in avian species.
      Click here to access the PubMed abstract of this article.


      Treatment of a Systemic Fungal Infection in a Parrot with Itraconazole Flavored Suspension and Nebulized Clotrimazole
      Submitted by Michael Briggs, Pharm.D. A Solomon Island Eclectus parrot, female aged 1.5 years, presented in a weakened state. Examination and culture revealed a systemic Aspergillus infection. Due to its significant cost as well as concern for the pet, the owner was highly motivated to treat the parrot. Treatment posed a challenge because the parrot only eats brightly-colored foods, and there was no commercially available clotrimazole solution for nebulization for veterinary use. The veterinarian contacted the local compounding pharmacy to discuss how compounded medications might help solve this therapeutic dilemma. It was decided that an oral suspension flavored with equal parts orange, banana, and strawberry could mask the bitter flavor of itraconazole, and that a customized dosage (20mg/ml) could be compounded for the parrot. The veterinarian also prescribed clotrimazole 1% for nebulization. The owner administered 0.2ml (4mg) of itraconazole suspension to the bird each day by mouth using an oral syringe. Therapy continued for three months. Clotrimazole 1% solution was nebulized (1ml BID to TID) by placing a pediatric nebulizer mask over the cooperative bird's head. After 30 days, the bird still had a productive cough. Therefore, nebulizer therapy with clotrimazole continued after total resolution of signs and symptoms of infection, for a total of four months (one month after the oral itraconazole was finished). The parrot fully recovered. This case represented the pharmacy's first attempt at avian therapy, and was 100% successful. The same therapy was used later for another bird that also fully recovered from a systemic Aspergillus infection.

      Enrofloxacin in Birds
      Enrofloxacin is highly active against most gram-negative bacteria. Doses of 15 mg/kg orally twice daily have maintained effective drug concentrations in most of the psittacine species that have been tested. Senegal parrots have required TID dosing for moderately resistant organisms. Keven Flammer, DVM, Dip ABVP, reports successful treatment of E coli, Klebsiella, and Proteus infections. He states that oral administration is well tolerated, but that IM administration should be avoided, and never used for repeated dosing, due to irritation at the site of injection. The IM formulation can be given orally but is unpalatable, even when mixed with flavoring. Dr. Flammer notes that an oral suspension can be compounded and appropriately flavored. 10th U Wisc Exotic Pet Conf Procd 04:01
      The Capsule Report, Small Animal/Exotic Edition Jan 2002;20, 10: page 3


      Haloperidol for Feather-Plucking and Self-Mutilation
      Neuropeptides, particularly dopamine, are implicated in many self-mutilating disorders. The 1993 Proceedings of the Association of Avian Veterinarians (pg. 119-120) reports the dopamine antagonist  haloperidol is currently being used on cockatiels, lovebirds, ring-neck parakeets, African Greys, and several species of cockatoos and Amazon parrots.  The indications for use in these birds have included severe feather plucking, mutilation of skin and muscle over the back, chest and legs, wing web mutilation, and Amazon foot necrosis syndrome.  Side effects from the use of haloperidol have included depression, depressed appetite, excitability and anorexia. (In most birds, side effects disappeared after discontinuing the drug for several days and then retrying at a lower dose.)  One study reported normal behavior was maintained "by administering haloperidol at approximately 0.4 mg/kg body weight/day for approximately seven months." Journal of Small Animal Practice 1993; 34:564-566
      Treatment of psychogenic feather picking in birds with a dopamine antagonist.




      Haloperidol for Feather Plucking
      by Stacie Fowler, D.V.M., Texas Signalment:  "Echo", adult male Eclectus Parrot Chief Complaint:  Feather picking of 4-6 years duration Diagnosis:  Previous veterinarian had done numerous tests in 1993 to rule out medical causes of feather picking and the final diagnosis was psychological behavioral feather picking. Feather Picking:  This is a common syndrome in pet "parrot-type" birds that can have medical and/or psychological causes. It is  important to rule out all medical causes of this condition before initiating psychotropic drug therapy. It is also important to institute appropriate dietary and environmental changes as well as behavioral therapy along with psychotropic drug use. Past History and Medications:  Echo first started picking at his feathers in 1991.  By November of 1994 he had pulled out all his feathers except those which he could not reach on his head. In December of 1994, Echo's previous veterinarian started him on naltrexone (dose unknown) for behavioral feather picking. He failed to respond to this drug and was placed in an Elizabethan collar on 4/20/95 to prevent further plucking.  The author first saw this patient on 1/10/97. He had been wearing the collar almost constantly since 4/95 and all his feathers were in place (but ragged and unkempt looking) except under the collar. Anytime the collar was removed the patient would rip his feathers out.  The owners wished to try Prozac? for Echo's problem but since this author has had little success with Prozac?, we started trials on other drugs. Along with changes in diet and environment and behavioral exercises, we started Echo on Aventyl? elixir at 1/4 teaspoon per 4 ounces of drinking water to be replaced with fresh twice daily. We also initiated every other daily misting of the feathers with a dilute Aloe and Penetran? suspension. By 3/8/97, Echo was still plucking too many feathers when the collar was removed.  To his Aventyl? therapy, we added naltrexone compounded to 5 mg/ml in a strawberry flavored base, 0.16 ml by mouth twice daily. By 3/20/97 he was still plucking badly when the collar was removed.  The Aventyl and naltrexone were discontinued and we did a brief trial on diazepam 2 mg per 4 ounces of drinking water. The diazepam is not meant to sedate and the owner was instructed to increase the dose to a maximum of 10 mg per 4 ounces of water if feather plucking continued but only if no sedation was noted. The diazepam produced no change in behavior and caused too much sedation for Echo.  On 4/10/97 we began a trial on haloperidol 2 mg/ml at .015 ml by mouth once daily. The owners were instructed that they could increase the dose to maximum of .06cc of 2 mg/ml haloperidol twice daily. By 5/7/97, Echo's owners reported that they were giving .075 cc of 2 mg/ml haloperidol twice daily and he seemed to be responding nicely. On 5/17/97 the haloperidol was refilled and compounded to 1 mg/ml to facilitate easier measuring.  As of 9/2/98, Echo is receiving haloperidol 0.15 mg by mouth twice daily. This is a higher dose than I have seen published in the literature but the owners are pleased with Echo's condition and do not wish to try a lower dose or even possibly wean him off the haloperidol. Echo is not experiencing any noticeable side effects from his haloperidol therapy. Currently, Echo never wears his Elizabethan collar and is totally feathered in except for his neck. I believe that 2 years of constant pressure from the collar has caused atrophy of the feather follicles around the neck.
  • Miscelaneous

    • Low Dose Anti-platelet Therapies for Feline Arterial Thromboembolism (FATE)
       
         Feline hypertrophic cardiomyopathy (HCM) is the most common form of heart disease in cats and is characterized by concentric thickening of the left ventricle. The clinical consequences of ventricular hypertrophy include arrhythmias, congestive heart failure, and feline aortic thromboembolism (FATE).  FATE carries an extremely poor prognosis with a 66% mortality rate.  The formation of aortic clots in FATE leads to paralysis, severe leg pain and, often, death.  There is no cure for HCM; hypertrophy of the heart wall is irreversible.  Therapies demonstrating benefit to HCM patients include beta-blockers, diuretics, ACE inhibitors, and antiplatelet drugs.  Because systemic warfarin therapy is associated with a high occurrence of hemorrhagic events, aspirin has historically been utilized as the primary oral antiplatelet therapy to prevent FATE in cats with HCM. It was initially dosed at 81mg every 72 hours as this was the smallest commercially available dosage form of aspirin. A study in 2003 revolutionized low dose aspirin therapy in cats through utilization of a compounded 5mg aspirin capsule administered orally every 72 hours. Results of this study indicated that the same degree of antiplatelet activity was achieved but the inhibition of endothelial production of prostacyclin (PGI), an antagonist to platelet aggregation and vasoconstriction, is not affected with the 5mg dose as is seen with the 81mg dose. This study also demonstrated a lower incidence of gastrointestinal adverse effects with the 5mg dose when compared to the 81mg dose of aspirin.
         Clopidogrel (Plavix™) has been shown to be more effective than aspirin in preventing myocardial infarction, stroke and peripheral vascular events in humans. Clopidogrel has recently been evaluated in cats and has been shown to significantly inhibit multiple platelet functions. Investigators concluded that a low dose of 18.75mg of clopidogrel (1/4 of a commercially available 75mg tablet) given orally once daily was safe and effective anti-platelet therapy for cats.  Investigators also commented that a considerably lower compounded dose of clopidogrel may prove to be as effective, safer, and considerably less expensive than quartering the commercially available tablets and recommended that studies be performed with lower doses of clopidogrel as were done with aspirin in 2003. Some veterinary teaching hospitals are utilizing doses of 6mg and 7mg clopidogrel orally once daily in combination with low dose aspirin therapy although the efficacy of these therapeutic regimens have not been evaluated.  The multi-centric Feline Arterial Thromboembolism – Clopidogrel vs. Aspirin Trial (FAT-CAT) initiated at Purdue University College of Veterinary Medicine has been accepting FATE cats for enrollment for the last two years to determine if there is clinical superiority of either agent when prophylaxing against recurrence of FATE.  Initial results show a significant (41.6%) reduction of FATE recurrence in one of the two treatment groups; however, study coordinators will not unblind the treatment arms to investigators until the full enrollment of 30 cats per treatment group is achieved. Clinicians interested in learning more about the FAT-CAT study should visit http://www.vin.com/FATCAT/    Veterinarians interested in exploring use of low dose aspirin and low dose clopidogrel therapy can collaborate with our compounding pharmacists regarding formulation of patient-specific doses. 
       
      J Vet Intern Med 2003;17:73-83
      Arterial thromboembolism in cats: acute crisis in 127 cases (1992-2001) and long-term management with low-dose aspirin in 24 cases.
      Click here to access the abstract of this article. 
       
      J Am Vet Med Assoc 2004;225:1406–1411
      Antiplatelet effects and pharmacodynamics of clopidogrel in cats.
      Click here to access the PubMed abstract of this article.
       
      Cornell University and NC State University



      Prednisone versus Prednisolone:  Which drug for which species?
       
      While prednisone and prednisolone have historically been considered therapeutically equivalent when used in veterinary medicine, recent studies have proven that they are not.  It is now well-accepted in veterinary medicine that while prednisone and prednisolone may be therapeutically equivalent in dogs and humans, they are not in cats and horses.  Researchers Graham-Mize and Rosser administered 10 mg total dose of either prednisone or prednisolone to cats in order to determine comparative pharmacokinetics of each drug. The AUC (ng/ml/hr) and Cmax (ng/ml) of oral prednisolone was 5 fold and 11 fold higher following administration of prednisolone compared to an equivalent oral dose of prednisone: 3230 and 1400, respectively, following oral prednisolone compared to 672.63 and 122, respectively following oral prednisone. Although the study was not designed to discriminate differences in oral absorption versus hepatic conversion, the authors nonetheless demonstrate the superiority of oral prednisolone to prednisone in cats.  Until further studies are conducted, most veterinary clinicians agree that prednisolone (not prednisone) should be utilized in feline patients.
       
         In 2002, researchers had demonstrated a superiority of prednisolone over prednisone in treating horses with recurrent airway obstruction (heaves). In this crossover study, 5 horses were given the following treatments: prednisone tablets, prednisone liquid, prednisolone tablets, prednisolone liquid and i.v. prednisolone sodium succinate (positive control). Blood samples were taken before drug administration and at selected time points during a 24 hour period. Serum concentrations of prednisone and prednisolone were determined in order to evaluate gastrointestinal absorption and hepatic metabolism. Serum concentrations of the endogenous glucocorticoid hydrocortisone were also determined as an indicator of the biological activity of the drugs. Both prednisolone tablets and liquid were absorbed rapidly, with prednisolone detectable in serum within 15 min of administration and with peak concentrations occurring within 45 min. Small amounts of prednisone were detected in the serum samples after administration of both prednisone tablets and liquid. The active metabolite prednisolone was not detected in serum samples after administration of prednisone liquid and was detected in serum samples from only one horse after administration of prednisone tablets. Endogenous hydrocortisone production was suppressed when horses received prednisolone. The results of these studies indicate that prednisone has poor efficacy for the treatment of heaves because it is poorly absorbed and the active metabolite prednisolone is rarely produced. In contrast, prednisolone tablets have excellent bioavailability and should be useful as a therapeutic agent in horses.
       
      Consult our compounding pharmacist about customized dosage forms and strengths. Caution: Transdermal application of prednisolone (or other corticosteroids) to the ear is not recommended due to a high likelihood of epidermal atrophy of the ear pinnae with chronic use.  The ear tips will flop with time and may not return to normal shape even after withdrawal of the prednisolone.
       
      Veterinary Dermatology 15 (s1) 2004, pp 10.
      Bioavailability and activity of prednisone and prednisolone in the feline patient.
      Click here to access the PubMed abstract of this article. 
       
      Equine Vet. J. 2002 May;34(3):283-7
      Prednisone per os is likely to have limited efficacy in horses.
      Click here to access the PubMed abstract of this article. 


      Safety and Efficacy of Ocular vs Parenteral Apomorphine for Induced Emesis in Dogs
       
         A study published in October 2008 retrospectively evaluated the efficacy of a compounded 2mg ocular insert of apomorphine versus a compounded 1mg/ml apomorphine injection. Either parenteral or ocular apomorphine dosage forms were sent to veterinary clinics with a case study report form requesting case-specific information. Information collected included breed, body weight, time from placement of the insert until emesis, and any information available regarding the nature of the toxin and clinical signs. Clinicians were asked to grade the severity of adverse effects on a subjective scale of 0 to 5, with 5 being most severe and 0 being absent. The adverse effects listed included prolonged vomiting, tachycardia, excitation, respiratory depression, bradycardia, sedation, and ocular irritation. Hypotension was not specifically included because of the difficulty of monitoring this while treating the dog. The clinician was also asked to grade the ease of product use for each case. Case reports for more than 5000 dogs were ultimately reviewed.
         For the ocular insert group, approximately 67% of dogs developed emesis between 3 and 10 minutes following placement of the insert. Approximately 83% of the dogs had emesis within the 15-minute time interval. Median time to emesis was 6 minutes, 7.2% of dogs experienced emesis after 15 minutes, and 9.3% did not have emesis at all. When the drug was administered IV, emesis occurred rapidly with a success rate of 90.6% and a median time to emesis of 1 minute. Difference in success rate between the IV and ocular insert groups was not significant (p=0.399).
         The prevalence of adverse effects with the IV route was less than the ocular route; however, the prevalence of tachycardia and sedation were higher with the IV group. Tachycardia was detected in 0.6% of dogs treated with the ocular insert and 15.6% of those treated IV. In the ocular insert group, sedation occurred with a frequency of 11.1%, whereas the IV group had a frequency of 43.8%. For the ocular insert group, ocular irritation in 82% of dogs was also reported, but of these, 80% had severity scores of 1, which meant detected but not clinically relevant. If reports with a score of 1 were disregarded, the frequency of irritation decreased to 16.2%. In 6.3% of dogs, the clinician experienced some difficulty with use of the insert, either in placing the insert or in maintaining the insert in the conjunctival sac; and some dogs actively resisted placement of the insert while other dogs were successful in dislodging the insert once it had been placed, leading to discontinuous administration. The ease of use scores seemed to become better with time, suggesting that with experience, the clinicians became more skilled in using the inserts.
         Researchers also observed that dogs weighing more than 25kg seemed less responsive to a 2mg ocular dose of apomorphine. Researchers concluded that an insert with a larger quantity of apomorphine should be utilized for larger dogs and that safeguards should be employed to prevent administration of larger dose inserts to smaller dogs.
         Apomorphine has not been commercially available to veterinarians for several years. For this reason, compounding pharmacists have been supplying apomorphine to veterinarians in various dosage forms to have immediately available for emergency use. Dosage forms include compressed tablets, powders for reconstitution into ocular or injectable solutions, and injectable solutions for parenteral administration.  In light of the results of this study, it would appear that compounded ocular solutions might be superior to either injections or solid ocular tablets or inserts. Kits can be prepared containing apomorphine that can be reconstituted for use as an isotonic ophthalmic solution and subsequently can be administered as an injection if emesis is not successfully induced after ophthalmic administration. Veterinarians interested in obtaining these dosage forms or kits may contact our compounding pharmacy. Am J Vet Res. 2008 Oct;69(10):1360-5.
      Safety and efficacy of an ocular insert for apomorphine-induced emesis in dogs.
      Click here to access the PubMed abstract of this article.

        Pyridostigmine Oral Liquid for Treatment of Myasthenia Gravis

      Myasthenia gravis (MG) is a common cause of generalized weakness in dogs and cats. With optimal care, the prognosis for remission and a normal life are good. “Unfortunately, drugs used to diagnose and treat myasthenia gravis are frequently unavailable” but during manufacturer shortages, compounding pharmacists can provide needed medications.1

      The drug used most commonly to treat MG is pyridostigmine bromide at a dose of 1-3 mg/kg orally two to three times daily. “It is extremely important to note, however, that pyridostigmine bromide should not be compounded with methylcellulose-containing vehicles, as methylcellulose has been shown to completely inhibit the oral absorption of pyridostigmine from the gastrointestinal tract.2 For animals not responding to pyridostigmine, corticosteroids (e.g., prednisone for dogs, prednisolone for cats) can be administered at 0.5 mg/kg orally every other day. Immunosuppressive doses of corticosteroids are not recommended as they may worsen muscle weakness.”3
       
      1,3 International Journal of Pharmaceutical Compounding. Sep/Oct 2008; 12(5):398-401
      Veterinary Compounding for Myasthenia Gravis
      Click here to access the abstract of this article. 2 Neurology 1981; 31(2):145-149.

      Compounding for Feline Lymphoma

      Feline lymphoma is one of the most common cancers in cats and presents with a variety of lesions and symptoms. Feline lymphoma, like human lymphoma, is classified into low, medium and high-grade categories depending on the anatomic location and degree of malignant cell growth in affected organs. There are many clinical reports published describing the diagnosis, treatment and prognosis of cats with lymphoma; however, there has been little correlation between treatment, histologic grade and clinical outcome. Until 1999 there had only been one published study that followed treatment and outcomes for a group of cats with intestinal lymphoma.1Of 40 cats evaluated, 29 cats with low-grade lymphoma in this study had a significantly greater response (69%) to medical therapy (chlorambucil and prednisone) and underwent complete remission with a medical survival time of greater than 20.5 months.The 11 cats in the high-grade group (treated with a variety of multiple drug combinations) showed a much poorer response to therapy. A retrospective study reviewed 667 cases of feline lymphoma and identified cats suffering from low-grade lymphoma.2This study concluded that 92% of cats treated with chlorambucil and prednisone responded to treatment for more than 2.5 years and showed a disease-specific median survival time of 967 days.Both of these studies indicate that the combination of oral chlorambucil and prednisone are excellent treatment modalities for cats suffering from low-grade lymphoma. The dosage range for prednisone or prednisolone for treatment of feline lymphoma is 5-10mg daily. In spite of the success demonstrated by treatment with prednisone in the previously mentioned studies, recent pharmacokinetic work indicates that prednisolone has a much better oral bioavailability (i.e., higher levels of drug in the body) as compared to prednisone in cats.3 Veterinarians may find that providing prednisolone instead of prednisone with chlorambucil may further increase remission rates and survival times in cats with lymphoma. Both prednisolone and chlorambucil are extremely bitter drugs and many cats object strongly to the taste. By collaborating with veterinarians and pet owners, our compounding pharmacist can play an active role in providing palatable, individualized oral chemotherapeutic regimens of prednisolone and chlorambucil for cats with lymphoma. Eur J Comp Gastroenterol 1999;4:5–11.
      Feline gastrointestinal lymphoma: 67 cases (1988–1996). 
      Click here for more information. 2 J Am Vet Med Assoc. 2008 Feb 1;232(3):405-10.
      Outcome of cats with low-grade lymphocytic lymphoma: 41 cases (1995–2005)
      Click here to read the PubMed abstract of this article. 3 VetDermatology. 2004; 15 (Suppl. 1):9.
      Bioavailability and activity of prednisone and prednisolone in the feline patient. 
      Click here for more information.
        Managing Tracheal Collapse in Toy and Miniature-breed Dogs Collapsing trachea is a commonly recognized problem with toy and miniature-breed dogs (e.g., Toy Poodles, Yorkshire Terriers, Pomeranians, Maltese, Chihuahuas) that is associated with weakness of the tracheal cartilage resulting in collapse of the airway.Tracheal collapse can sometimes be helped with surgery, but medical management remains the treatment of choice. Treatment strategies involve cough suppression, and the drug therapy of choice has historically been the combination of hydrocodone and homatropine used orally three to four times daily.As long as shortages of commercially available hydrocodone/homatropine products continue, our pharmacy can play a valuable role in providing compounded hydrocodone/homatropine oral suspensions, capsules and chewable treats in canine-friendly flavors for dogs with tracheal collapse. Vet Clin North Am Small Anim Pract. 2000 Nov;30(6):1253-66, vi.
      Tracheal collapse. Diagnosis and medical and surgical treatment.
      Click here to read the PubMed abstract of this article.

        Cetirizine Pharmacokinetics in Cats While chronic dosing studies and safety and efficacy studies in allergic cats still need to be conducted, that the pharmacokinetic profile of cetirizine suggests that it is a promising alternative to glucocorticoid therapy in allergic cats. Presently, commercially available forms of cetirizine are not easily adjusted to cats. Cetrizine tablets for adult humans are 10mg tablets and could be halved to achieve an appropriate dose for a 5kg cat.Cetrizine products labeled for human children are available in 5mg chewable grape-flavored tablets or a 1mg/ml grape-flavored syrup. Because of the flavoring and the volume of liquid that would have to be administered, cetirizine products labeled for human children would be very difficult to administer to cats. Commercially-available cetirizine dosage forms are not particularly cat-friendly, and because cetirizine shows much promise for therapy of allergies in cats, veterinarians may wish to contact our compounding pharmacy to assist in preparing dosage forms of cetrizine that can be easily administered to cats. Am J Vet Res. 2008 May;69(5):670-4.
      Pharmacokinetics of cetirizine in healthy cats.
      Click here to read the PubMed abstract of this article.


      Aspirin Therapy for Cats

      A retrospective study in cats receiving high dose aspirin (> or = 40 mg/cat q72h) and cats receiving low-dose aspirin (5 mg/cat q72h) showed equally efficacious anti-platelet effect in either group but a significantly lower incidence of adverse effects in the low dose aspirin group.  Capsules containing 5mg of aspirin can be compounded in lactose, flavored with various powdered flavors. Pet owners can administer the capsules intact, or if the act of pilling is too stressful for the cat, the contents of the capsule can be sprinkled in a small amount of moist food for the cat to consume at will.




      Clinical effects and plasma concentrations of fentanyl after transmucosal administration in three species of great ape.  "fentanyl can be administered transmucosally to captive orangutans and gorillas for sedation. With further study on formulation, it may also become useful in chimpanzee protocols. The transmucosal route may also be clinically useful for acute pain management."  J Zoo Wildl Med. 2004 Jun;35(2):162-6
      Clinical effects and plasma concentrations of fentanyl after transmucosal administration in three species of great ape.  Click here to access the PubMed abstract of this article.     Emergency Emetic Kits for Canine Drug Units  Canine members of police departments are frequently trained to detect drugs and other illicit substances. Although training techniques are now being modified to avoid ingestions, most dogs were historically trained to aggressively paw, mouth, or bite any object that was suspect. This behavior greatly increases the risk of oral ingestion of these very potent, very dangerous drugs.  Veterinarians are now offering training and emergency emetics to police officers so that they may provide life-saving decontamination measures.  Compounding pharmacists can work with local police and veterinarians to provide emesis kits to ensure that these valuable public servants are afforded the best chance for survival when faced with an accidental ingestion. JAVMA, 2006 Apr 1;228(7):1028-32 Toxicologic hazards for police dogs involved in drug detection.


      Efficacy of oral supplementation with L-lysine in cats latently infected with feline herpesvirus Maggs et al. of the College of Veterinary Medicine, University of Missouri examined the effects of orally administered L-lysine on clinical signs of feline herpesvirus type 1 (FHV-1) infection and ocular shedding of FHV-1 in latently infected cats. Fewer cats and eyes were affected by conjunctivitis, and onset of clinical signs of infection was delayed on average by 7 days in cats receiving L-lysine 400 mg once daily for 30 days, compared with cats in the control group. Significantly fewer viral shedding episodes were identified in the treatment group cats, compared with the control group cats. This dose caused a significant but short-term increase in plasma L-lysine concentration without altering plasma arginine concentration or inducing adverse clinical effects. Am J Vet Res 2003 Jan;64(1):37-42
      Efficacy of oral supplementation with L-lysine in cats latently infected with feline herpesvirus.
      Click here to access the PubMed abstract of this article.   Dextromethorphan

      Of the seven major human cough suppressants, only dextromethorphanis indicated for treating cough in small animals. If after reviewing the indications and contraindications, cough suppression is desired, the available human products must be screened carefully as a very limited number contain dextromethorphan without other potentially harmful ingredients. Typically, the dose in dogs and cats is 1 to 2 mg/kg three to four times daily. Human products are not flavored to an animal�s taste, and may require administering a significant volume (typical strength is 15 mg/5 ml) to adequately dose an average size dog.

      Stool Softeners

      Docusate (DSS) can be used to assist in the passage of hard or dry feces that may occur secondary to dehydration or use of opioid analgesics or metoclopramide. While capsules hide the bitter taste, they can not be divided for appropriate dosing in smaller animals. The recommended dose in dogs and cats is 2 mg/kg once daily. For more severe cases, appropriately dosed DSS enemas may offer an alternative to phosphate-solution enemas.   Merck Veterinary Manual, 8th Edition, pp. 1691

      Ursodiol for Gallstones

      The purpose of this study, reported in Am J Health-Syst Pharm (Vol. 52) was to prepare an oral dosage form of the bile acid ursodiol (also known as ursodeoxycholic acid) from commercially available capsules and to determine the short-term stability of this formulation.  The formula used for this extemporaneous compound was found to be stable for up to 35 days.

      Ursodiol in a Dog with Chronic Hepatitis

      A dog with severe cholestasis secondary to chronic hepatitis was treated with ursodeoxycholic acid (ursodiol) orally. After 2 weeks of daily treatment, the dog was more active and had an improved appetite. Monthly serum biochemical determinations and analysis of individual bile acid profiles documented improvement in hepatobiliary tests and a marked reduction in the concentrations of potentially hepatotoxic endogenous bile acids. These effects were maintained for approximately 6 months.
      Studies have found an extemporaneously compounded ursodiol suspension to be stable for up to 35 days refrigerated. This drug is well absorbed orally and enters the liver directly from the portal system, and is then secreted into bile. Ursodiol should be administered orally as the first-pass effect is vital for effectiveness.

      J Vet Intern Med 1997 May-Jun;11(3):195-7
      Use of ursodeoxycholic acids in a dog with chronic hepatitis: effects on serum hepatic tests and endogenous bile acid composition.
      Click here to access the PubMed abstract of this article.   Aminocaproic Acid for Degenerative Myelopathy (DM) in Dogs

      DM appears with relative frequency only in the German Shepherd breed (GSD); confirmation of the diagnosis is important in other breeds before assuming that they have DM of GSD. During the past two decades, R.M. Clemmons, DVM, Ph.D., and other researchers at the University of Florida have provided important new insights into the pathoetiology of DM. Recently, they have found that when combined with the history, neurologic signs, CSF protein concentration and EMG, an elevated CSF acetylcholinesterase level helps confirm the diagnosis. It is increasingly clear that DM is caused by an autoimmune disease attacking the nervous systems of patients, leading to progressive neural tissue damage. In many respects, DM is similar to Multiple Sclerosis in human beings.  The Integrative Medical Approach to Treatment of Degenerative Myelopathy involves four basic approaches: 1) exercise, 2) dietary supplementation, 3) medication, 4) other supportive measures. Conventional medicine has little to offer patients with DM. On the other hand, use of exercise, certain vitamins and selected drugs have delayed or prevented progression of DM in many afflicted dogs. Clemmons et al have found 2 medications which appear to prevent progression or result in clinical remission of DM in up to 80% of patients - aminocaproic acid (EACA) and n-acetylcysteine (NAC). They propose that circulating immune-complexes lead to endothelial cell damage in the vessels of the CNS. Subsequently, fibrin is deposited in the perivascular spaces. When this degrades (point of action of aminocaproic acid), inflammatory cells are stimulated to migrate into the lesions. The inflammatory cells release prostaglandins and cytokines (point of action of vitamin E and C) which lead to the activation of tissue enzymes and the formation of oxygen free-radicals (point of action of acetylcysteine) which, in turn, leads to tissue damage.They recommend giving EACA as a flavored solution, 500 mg orally every 8 hours. A "source for EACA is to have a compounding pharmacy make the solution from chemical grade EACA."  The only side effects that have been attributed to EACA have been occasional gastrointestinal irritation. This has presented a problem only in a few patients, typically those with pre-existing GI problems. The only known drug interaction is with high dose estrogen compounds. N-Acetylcysteine is a potent anti-oxidant which has powerful neuroprotective effects. Clemmons et al give 75 mg/kg divided in 3 doses a day for 2 weeks; then, 3 doses every other day. The N-acetylcysteine must be diluted to a 5% solution; otherwise, it will cause stomach upset. "This new treatment is expensive unless purchased through compounding pharmacies." NAC can produce vomiting (due to the sodium content of the pharmaceutical product, which requires high concentration of base to buffer) and may increase the bleeding time. Giving fresh ginger 30 minutes before NAC or administering NAC with food (or on a full stomach) often reduces this effect. The chances of successful treatment are improved if the therapy is begun early in the course of DM rather than later. A response to the drugs should be evident within the first 7-10 days.

      Chlorpromazine for Anti-Emesis

      Chlorpromazine (Thorazine®) is a phenothiazine and works at the emetic center, the chemoreceptor trigger zone, and peripheral receptors; it is this veterinarian's "all purpose anti-emetic of choice" for cats.1 Chlorpromazine may cause extrapyramidal symptoms in cats when administered at high doses. The drug may discolor urine pink or red-brown, cause mild sedation, and may potentiate hypotension in dehydrated patients. Phenothiazines should not be given within one month of worming with an organophosphate agent. The recommended oral doses in dogs and cats is 3.3 mg/kg PO one to four times daily. Due to extensive first pass metabolism2, it may be necessary to reduce the dose in animals with liver disease. A liquid concentrate can be appropriately flavored for dogs or cats. 1Todd R. Tams, DVM, Dip ACVIM in CA VMA C/E Conf Procd, 2000
      2Veterinary Drug Handbook 3rd edition, Donald C. Plumb, ed.;  pp. 129-30

      Managing Anorexia in Uremic Dogs and Cats

      H2-receptor antagonists (cimetidine, ranitidine, and famotidine) can be useful to reduce gastric acid secretion. Increased gastrin concentrations in serum during chronic renal failure may stimulate excessive secretion of gastric acid and cause ulcer formation. Some uremic dogs and cats dramatically increase their interest in food and food intake after therapy with an H2 blocker. According to a presentation at the Atlantic Coast Veterinary Conference by Dennis J. Chew, DVM, Dip and C.A. Buffington, DVM, some uremic animals may need this medication for an extended period of time (months to rest of their lives). Much of the experience of these veterinarians has been either with cimetidine at an initial dose of 10 mg/kg, followed by 5 mg/kg PO BID or famotidine at 1 mg/kg daily. The Capsule Report, Vol. 19, No. 10, Jan. 2001

      Doxycycline for Prophylaxis and Treatment of Osteoarthritis in Dogs

      Prophylactic administration of doxycycline (a tetracycline) has markedly reduced the severity of canine osteoarthritis (OA) in weight-bearing regions of the medial femoral condyle, and therapeutic administration of oral doxycycline has been shown to reduce the severity of articular cartilage breakdown in various animal models of OA. This disease modifying effect is associated with reductions in the levels of active and total collagenase and gelatinase in articular cartilage of the involved joint. A prospective, clinical study of eighty-one dogs with OA secondary to spontaneous cranial cruciate ligament (CCL) rupture concluded that doxycycline inhibits nitric oxide production in cartilage in dogs with CCL rupture, and that doxycycline may have a role in the treatment of canine OA. Dogs with OA secondary to CCL rupture were divided into 2 groups before surgery. The Doxy-CCL group (n = 35) received 3 to 4 mg/kg doxycycline orally every 24 hours for 7 to 10 days. The CCL group (n = 46) received no treatment. Synovial fluid, articular cartilage, synovial membrane, and CCL samples were collected during surgery or immediately after euthanasia from healthy dogs (control group). Total nitric oxide concentrations measured in cartilage were significantly lower in the Doxy-CCL group than in the CCL group, but were not different from those measured in the control group. In another study, ten healthy adult mongrel dogs underwent transection of the left anterior cruciate ligament, which resulted in a marked decrease in bone mass, with increased osteoclastic activity and increased bone formation. Doxycycline treatment did not significantly affect either bone formation or bone resorption. The authors concluded that doxycycline protects against joint breakdown in this OA model via inhibition of matrix metalloproteinases in articular cartilage, rather than through an effect on subchondral bone. Vet Surg 2001 Mar-Apr;30(2):132-9
      The effects of doxycycline on nitric oxide and stromelysin production in dogs with cranial cruciate ligament rupture.
      Click here to access the PubMed abstract of this article. J Rheumatol 1996 Jan;23(1):137-42
      Effects of oral doxycycline administration on histomorphometry and dynamics of subchondral bone in a canine model of osteoarthritis.
      Click here to access the PubMed abstract of this article. J Rheumatol Suppl 1995 Feb;43:149-51
      Modification by oral doxycycline administration of articular cartilage breakdown in osteoarthritis.
      Click here to access the PubMed abstract of this article. Vet Clin North Am Small Anim Pract 1997 Jul;27(4):863-81
      Slow-acting, disease-modifying osteoarthritis agents.
      Click here to access the PubMed abstract of this article.

      Arthritis Rheum
      1992 Oct;35(10):1150-9
      Effect of stanozolol on body composition, nitrogen balance, and food consumption in castrated dogs with chronic renal failure.
      Click here to access the PubMed abstract of this article.
        Cisapride: a Prokinetic Drug Cisapride (Propulsid® - Janssen Pharmaceutica), was removed from the U.S. and Canadian markets by its manufacturer because of serious cardiac effects in humans. However, cisapride is now available as a bulk chemical for veterinary use only and can be compounded as per your prescription order. Cisapride is chemically related to metoclopramide, but unlike metoclopramide, it does not cross the blood-brain barrier or have antidopaminergic effects or cause extrapyramidal reactions. Cisapride "is more potent and has broader prokinetic activity than metoclopramide, increasing the motility of the colon, esophagus (in cats and guinea pigs), stomach, and small intestine... [Cisapride] has been used in managing gastric stasis, idiopathic constipation, gastroesophageal reflux, and postoperative ileus in dogs and cats. Practitioners found cisapride especially useful in managing chronic constipation in cats with megacolon; in many cases, it alleviated or delayed the need for subtotal colectomy. Cisapride was also used in managing cats with hairball problems."