Mitotane (o,p'-DDD)

What is this medication for?

• Pituitary-dependent hyperadrenocorticism (PDH) — medical adrenalectomy-by-drug; adrenal tumors (cytotoxic shrinkage); palliative adrenal carcinoma

How is it given?

Give exactly as your veterinarian prescribed — never change the dose or stop on your own unless your veterinarian has told you to.

• Owner-driven induction: reduce food by ⅓ the day before (hungry dog = sensitive appetite indicator), 25 mg/kg by mouth every 12 hours WITH food, daily phone contact — appetite drop is the end-point.
• The fat depot + weeks-long half-life means toxicity can progress after stopping — one more reason prednisone must be on hand at home and given at any stress.

What if I miss a dose?

• Give it as soon as you remember — unless it is almost time for the next dose (then skip the missed one; never double up).
• Call your clinic if you miss more than one dose in a row.

Side effects — what should I watch for?

Effects listed as common in this handout

• Lethargy, wobbliness/unsteadiness, weakness, loss of appetite, vomiting, diarrhea (The stop-signals of induction)
• Relapses during maintenance (Common)

Worth a phone call to your veterinarian

• Liver changes; Coagulopathy (vWF-related bleeding tendency in Cushing dogs on mitotane — monitor) (Occasional)

⚠️ Contact your veterinarian or an emergency clinic IMMEDIATELY if you notice

• Adrenal crisis (hypocortisolism) (Over-induction — corticosterone/cortisol collapse: collapse, vomiting, unusually slow heart rate)

Before starting (or refilling), tell your veterinarian if your pet:

• has or has had: Hypersensitivity; poor appetite — "Mitotane should never be administered in animals that are not eating well" (Scott-Moncrieff)
• has or has had: Diabetes mellitus (insulin needs shift rapidly during induction), renal/hepatic disease, pregnancy

• is pregnant, nursing, or used for breeding
• is taking any other medications, supplements, or flea/tick products, including:
  • Insulin
  • Spironolactone
  • CNS depressants, warfarin (human)

Storage and handling

Room temperature. Human exposure hazard: cytotoxic — gloves handling, owners must not handle crushed tablets directly.

Good to know

• Mitotane = controlled chemical adrenalectomy vs trilostane's reversible enzyme blockade — different risk philosophy: mitotane destroys the zona fasciculata/reticularis (glucocorticoids ± some androgen), classically "sparing" glomerulosa (aldosterone usually preserved — why Addisonian crisis is rarer than with bilateral adrenalectomy).
• Owner-driven induction: reduce food by ⅓ the day before (hungry dog = sensitive appetite indicator), 25 mg/kg by mouth every 12 hours WITH food, daily phone contact — appetite drop is the end-point.
• The fat depot + weeks-long half-life means toxicity can progress after stopping — one more reason prednisone must be on hand at home and given at any stress.
• Compare-and-contrast exam pair: mitotane (cytolytic, irreversible, adrenal crisis risk, cheaper) vs trilostane (reversible 3β-HSD inhibitor, safer monitoring, now first-line in many regions).