Mitotane
Mitotane is an adrenocorticolytic drug used mainly for canine hyperadrenocorticism. It produces a longer-lasting reduction in adrenal hormone production through damage to responsive adrenal cortical cells. Its principal veterinary applications are pituitary-dependent hyperadrenocorticism and selected functional adrenal cortical tumors, including cases managed with a palliative treatment objective.
Group
Adrenocorticolytic
Mechanism of Action
Mitotane disrupts adrenal lipid handling and steroidogenic cell function. Proposed mechanisms include inhibition of sterol esterification, accumulation of toxic free cholesterol and formation of reactive metabolites. Injury is most prominent in the zona fasciculata and reticularis, reducing glucocorticoid synthesis through partial or more extensive destruction of adrenal tissue. The complete mechanism remains incompletely resolved.
Dose Rates
Dogs
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Pituitary-dependent hyperadrenocorticism induction | Reference only | PO | Total 50 mg/kg/day in divided doses for 5-10 days, then reassess clinically and with ACTH stimulation. The number of divided doses is not specified; do not prescribe the daily total as one dose. | |
| Pituitary-dependent hyperadrenocorticism maintenance — Maintenance | 50–70 mg/kg | PO | Every 168 h | Reported total weekly dose, adjusted by clinical response and ACTH stimulation. If divided across the week, allocate the total rather than repeating it each dosing day. |
| Adrenal tumour ablation | Reference only | PO | 50-75 mg/kg/day in divided doses for 10 days, then every other day for 40 days. Follow-up maintenance may be 75-100 mg/kg/week. Requires adrenal steroid replacement and a monitored multiphase protocol. | |
| Monitored PDH induction — Initial | 25 mg/kg | PO | Every 12 h | Up to 8 days; With food; stop immediately for reduced appetite, vomiting, diarrhoea, lethargy or weakness. Examine and test ACTH response at the clinical endpoint or by day 8, whichever is earlier. |
| Alternative PDH induction — Initial | 30–50 mg/kg | PO | Every 24 h | Up to 10 days; 7-10-day monitored protocol; the same daily total may instead be divided into two treatments. Stop for adverse signs and assess cortisol/electrolytes. |
| Lower weekly PDH maintenance | Reference only | PO | Total 25-50 mg/kg/week, preferably divided across the week, with ACTH-guided adjustment. A separate protocol starts at 35-50 mg/kg/week in 2-3 doses. Weekly total must not be given at each dosing day. | |
| ACTH-guided PDH maintenance alternative — Maintenance | 50 mg/kg | PO | Every 168–240 h | Every 7-10 days only after adequate adrenal suppression and clinical reassessment; monitor for hypocortisolism. |
Cats
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Historical hyperadrenocorticism treatment | Reference only | PO | 25-50 mg/kg/day for induction, then 25-50 mg/kg/week maintenance. Poor response limits use; trilostane is preferred. No induction duration or complete feline protocol is provided. |
Ferrets
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Historical adrenal-disease treatment | Reference only | PO | 50 mg/ferret daily for one week, then 50 mg two or three times weekly; variable efficacy and calendar-based maintenance require individualized reassessment. |
Indications
- Medical treatment of pituitary-dependent hyperadrenocorticism in dogs.
- Control of cortisol excess in selected dogs with functional adrenal cortical tumors.
- Palliative treatment of selected canine adrenocortical carcinomas.
Contraindications
- Inability to monitor cortisol response
- Avoid food-animal use.
- Feline response is poor; trilostane is generally preferred.
- Poor appetite or anorexia before induction; clinically suspected adrenal disease requires confirmation. Concurrent diabetes can have rapidly changing insulin requirements.
Interactions
- Adrenal steroid supplementation may be required as part of treatment.
Adverse effects
- Lethargy, anorexia, vomiting, weakness and ataxia
- Hypoadrenocorticism and possible mineralocorticoid deficiency
- Neurologic effects associated with pituitary enlargement
Toxicity
Stop mitotane if adverse effects or adrenal insufficiency occur; assess cortisol and electrolytes and supply glucocorticoid/mineralocorticoid replacement as indicated.
Preparations
| Preparation | Form | Strength | Route |
|---|---|---|---|
| Mitotane 500 mg tablet | Tablet | 500 mg / tablet | PO |
Monitoring and Administration
During induction monitor appetite, water consumption and behaviour closely; adjust using ACTH stimulation and cortisol results.
Give with food to improve absorption. Monitor electrolytes for hyperkalaemia.
Published guidance describes prednisolone/prednisone 0.2-0.25 mg/kg as replacement when needed; destructive adrenal tumour protocols generally require sustained glucocorticoid and mineralocorticoid replacement, often starting glucocorticoids around day 3.
Use cytotoxic-drug handling precautions; children and pregnant people should not be exposed. Aqueous compounded mixtures may lose potency.
Complete-ablation alternatives total 75-100 mg/kg/day in 3-4 doses for 25 days with lifelong glucocorticoid/mineralocorticoid replacement, or 100 mg/kg/day divided twice daily for 30 days with cortisone acetate 2 mg/kg/day divided twice daily, fludrocortisone 0.1 mg per 10 lb daily and sodium supplementation. These deliberately destructive protocols must remain separate from partial suppression. The printed restart “25 micrograms/kg/week” is inconsistent with the surrounding milligram regimens and is not used.
Adrenal-tumour alternative begins at total 50-75 mg/kg/day in divided doses for 10-14 days with ACTH reassessment. Nonresponse protocols escalate to 100 mg/kg/day and then by 50 mg/kg/day at 7-14-day assessments; after suppression, maintenance totals 100-200 mg/kg/week in divided doses with steroid replacement. Escalation/stop rules and endocrine monitoring are integral and cannot be replaced by a freely selectable dose range.