Veterinary Medicine - February 2008 - (Page 112) Hyperadrenocorticism and trilostane PEER-REVIEWED sus suggests that a post-ACTH stimulation cortisol concentration between 1.5 and 5.5 µg/dl indicates optimal control.10-12 According to the U.K. package insert, the acceptable post-ACTH stimulation cortisol concentration range is 1.5 to 9 µg/dl,9 but clinical experience indicates that patients may manifest some signs of hyperadrenocorticism at cortisol concentrations above 5.5 µg/dl. If the cortisol concentration is below 0.7 µg/dl, withhold trilostane until signs of TABLE 5 Medical Therapy Options for Canine Hyperadrenocorticism Drug Mitotane, o,p’-DDD Mode of Action Cytotoxic Comments • Not FDA-approved for use in dogs • Close monitoring required • Variable absorption • Can cause nausea, anorexia, and weakness • Teratogenic; cytotoxic Ketoconazole Inhibits steroid synthesis • No veterinary-approved products are available • Generally low efficacy in hyperadrenocorticism • Commonly causes anorexia • Teratogenic hyperadrenocorticism recur, and closely monitor the patient for signs of hypocortisolemia.11,13 If the post-ACTH stimulation cortisol concentration is 0.7 to 1.5 µg/dl, suspend therapy for 48 hours, and then restart it with a 50% dose reduction.11,13 If the patient is inadequately controlled, dose increases of 50% to 100% are generally appropriate.11,13 Repeat the clinical evaluation and ACTH stimulation test two weeks after dose adjustment and then every three to six months (Table 7). A small number of dogs may have a post-ACTH stimulation cortisol concentration within the optimal range but still show signs of hyperadrenocorticism. In these cases, the dose should be divided and given twice daily and then adjusted based on subsequent ACTH stimulation test results. One recent report indicated that routine twice daily therapy achieved acceptable control of the hyperadrenocorticism with a lower total daily dose, but more work is needed to clarify this issue.14 Response to therapy More than 85% of dogs have shown both clinical and biochemical improvement (decreased alkaline phosphatase activity and cholesterol concentration) after a month of trilostane therapy, with substantial improvements in post-ACTH stimulation cortisol concentrations.7,11,13 Survival times for patients treated with trilostane (662 to 930 days14,15) compare favorably with those receiving mitotane (708 days).15 L-deprenyl, selegiline Monoamine oxidase inhibitor • FDA-approved for use in dogs • Low efficacy in hyperadrenocorticism • Low risk of negative effects • Undergoing FDA review • Periodic monitoring required • Good efficacy documented • Adrenal gland necrosis reported Trilostane Enzyme inhibitor U.S. importation process of trilostane from the United Kingdom Trilostane is not licensed in the United States. However, you may write to the FDA to request permission for importation on a case-by-case basis.1 • The prescribing veterinarian must contact the FDA Division of Compliance (attn. Michael Zimmerman) and complete the required 13-part letter. There must be a new letter for each request for each specific patient. • The FDA will review a request for a small, noncommercial quantity of the drug, which is generally considered to be a six-month supply or less. Approval for importation usually takes three or four weeks. • The U.K. supplier needs a faxed copy of the FDA authorization, a veterinary prescription, and credit card payment before it will ship the drug. REFERENCE 1. Dechra Veterinary Products. Vetoryl (trilostane) capsules. Available at: www.dechra-us.com/page/vetorylreg. Adverse effects Reports indicate that trilostane is generally safe and effective, but complications can occur.11 The most common is transient hypocortisolemia, which manifests as anorexia and lethargy. Clients must be instructed to discontinue trilostane if such signs occur, and an ACTH stimulation test and serum electrolyte panel should be performed. The drug should be restarted with a 50% dose reduction when the patient is again eating and active. Although trilostane seems to preferentially inhibit cortisol synthesis, aldosterone production can also be compromised.7 If this occurs, serum electrolyte 112 February 2008 VETERINARY MEDICINE http://www.dechra-us.com/page/vetorylreg
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