Mitotane is primarily used for the treatment of pituitary-dependent hyperadrenocorticism (PDH) and in the palliative care of adrenal carcinoma, primarily in canines. It works by causing severe, progressive necrosis of the zona fasciculata and zona reticularis within days of starting therapy.1 Typically, hyperadrenocorticism is most commonly seen in middle-age to older dogs (7-12 years old) with ~85% suffering from PDH. The most common clinical signs are polydipsia, polyuria, polyphagia, lethargy, panting, abdomen enlargement, and obesity.1 The most common serum abnormalities associated with elevated cortisol are increased serum alkaline phosphatases, hypercholesterolemia, hyperglycemia, and decreased BUN. Treatment with mitotane consists of an induction phase (25-50mg/kg/day) for 7-10 days and a maintenance phase (25-50mg/kg/week) often with gradual increasing dosages to maintain adequate suppression of cortisol secretion.2 Water consumption or appetite may be measured to provide an accurate endpoint for therapy with water consumption decreasing to <60ml/kg/day. Dogs on long-term treatment with mitotane should have an examination and ACTH response test every 3-4 months. Adverse effects at recommended dosages include GI irritation (vomiting and anorexia), CNS disturbance, and hypoglycemia. Because of mitotane’s potential severe toxicity, clients should be instructed to handle this drug with extreme care (gloves), wash hands after administration, and to keep out of the reach of children.
25-50mg/kg/day PO for 7-10 days, then 25-50mg/kg/weekly.
50mg PO daily for 1 week, then 50mg PO 2 to 3 times weekly.
Veterinary Drug Handbook, 4th Edition, D.C. Plumb
Helm, JR, McLaughlin G, Bode, LA, et al. A comparison of factors that influence survival in dogs with adrenal-dependent hyperadrenocorticism treated with mitotane or trilostane. J. Vet Intern Med 2011;25(2):251-260.