# Mitotane (o,p'-DDD): veterinary dose and monograph

> Mitotane (o,p'-DDD) is a veterinary drug. An adrenocorticolytic agent (a DDT relative) that selectively destroys the cortisol-producing zones of the adrenal cortex — a long-standing treatment for canine pituitary-dependent hyperadrenocorticism (Cushing's disease) and for adrenal… Indications include canine pituitary-dependent hyperadrenocorticism (Cushing's disease); adrenocortical tumour (cortisol-secreting) — medical management/cytoreduction; reduction of cortisol excess where trilostane is unsuitable/unavailable. This monograph lists 3 reference doses for dogs, each with route, frequency and source.

Source: https://vetmasterji.com/drugs/mitotane · Last reviewed: 2026-10-01

## At a glance

- **Drug class:** Veterinary drug
- **Also known as:** Lysodren, o,p-DDD
- **Species with doses:** Dogs
- **General dose range:** 25–50 mg/kg PO loading (daily) then weekly maintenance — check the species tables for the indication
- **Routes:** PO
- **Last reviewed:** 1 October 2026

## Indications

- Canine pituitary-dependent hyperadrenocorticism (Cushing's disease)
- Adrenocortical tumour (cortisol-secreting) — medical management/cytoreduction
- Reduction of cortisol excess where trilostane is unsuitable/unavailable

## Mitotane (o,p'-DDD) dose by species

Doses are per administration unless stated. mg/kg doses scale with body weight; per-animal, per-quarter and infusion-rate doses are shown as the reference writes them.

### Dogs

*Mitotane (o,p'-DDD) doses for dogs*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| PDH — induction (≈50 mg/kg per DAY) | 25 mg/kg | PO | q12h with food | until response (usually 4–9 days; ACTH test by day 8–10) |
| PDH — maintenance | 25–70 mg/kg | PO | WEEKLY total, divided into 2–4 doses | — |
| Adrenal carcinoma (higher dose) | 50–75 mg/kg | PO | per DAY, divided (10 days), then every other day | — |

- PDH — induction (≈50 mg/kg per DAY): Per-dose value shown = 25 mg/kg q12h (50 mg/kg/day). Papich 5e: 50 mg/kg/day in divided doses for 5–10 days. Plumb’s p.853: 25 mg/kg twice daily with food until water intake approaches 60 mL/kg/day, appetite falls, vomiting or listlessness — then stop and do an ACTH stimulation test (Feldman); 30–50 mg/kg/day once or divided for 7–10 days (Kintzer). Dispense prednisolone for emergencies.
- PDH — maintenance: This is a per-WEEK total — divide it through the week. Papich 5e: 50–70 mg/kg/week. Plumb’s p.853: 25–50 mg/kg/week adjusted by ACTH results (Feldman); 35–50 mg/kg/week in 2–3 doses (Kintzer); 50 mg/kg every 7–10 days (Scott-Moncrieff) — long-term requirements vary widely (26–330 mg/kg/week). Recheck ACTH at 1 month, then every 3 months.
- Adrenal carcinoma (higher dose): Daily total, divided. Papich 5e: adrenal tumour 50–75 mg/kg/day in divided doses for 10 days, then every other day for 40 days, then 75–100 mg/kg/week maintenance. Specialist supervision; glucocorticoid supplementation often required.

### Cats

*Mitotane (o,p'-DDD) doses for cats*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Not recommended | Not recommended in cats — poor response; use trilostane | — | — | — |

- Not recommended: Papich 5e: 25–50 mg/kg/day induction and 25–50 mg/kg/week maintenance have been used, but most experts do not recommend mitotane in cats because of poor response — use trilostane.

## Contraindications

Concurrent uncontrolled illness; do not start without the ability to monitor (ACTH stimulation) and to supply rescue glucocorticoids. Pregnancy. Use cautiously in diabetic Cushingoid dogs (insulin needs fall as cortisol drops). Owner unable to observe/monitor. Known hypersensitivity. Handle tablets carefully (cytotoxic-type agent).

## Species-specific warnings

> **Caution:** Dogs: Diabetic Cushingoid dogs: insulin requirements fall sharply as cortisol drops — reduce insulin and monitor glucose to avoid hypoglycaemia.

## Adverse effects

- Anorexia, vomiting, diarrhoea, lethargy (often the END-POINT signs of loading — cortisol falling)
- Iatrogenic hypoadrenocorticism (Addisonian crisis) — can be life-threatening
- Weakness, ataxia
- Rare hepatotoxicity / CNS signs at high exposure

## Drug interactions

- Insulin: requirements fall as cortisol decreases (hypoglycaemia risk) — monitor diabetics closely
- Hepatic enzyme inducers: may alter mitotane handling
- CNS depressants: additive at high mitotane exposure
- Spironolactone reportedly interferes with mitotane action

## Pregnancy and lactation

Contraindicated in pregnancy (adrenolytic/teratogenic potential).

## Monitoring

- ACTH-stimulation testing — at the end of loading and periodically during maintenance (the cornerstone of dosing)
- Appetite, water intake, demeanour (clinical end-points of loading)
- Electrolytes (Na/K) for adrenal-crisis surveillance; glucose in diabetics
- Owner education: recognise and treat a crisis (rescue prednisolone on hand)

## Toxicity and overdose

The defining toxicity is over-suppression → iatrogenic hypoadrenocorticism (Addisonian crisis: weakness, collapse, vomiting, hypovolaemia, electrolyte derangement) which can be fatal if unrecognised. GI/neurologic signs occur during loading and at high exposure. Owners must be able to recognise crisis and give rescue glucocorticoids.

Management: Stop mitotane. For iatrogenic hypoadrenocorticism: glucocorticoid replacement (prednisolone; dexamethasone in crisis), IV fluids, correct electrolytes/glucose, and mineralocorticoid support if needed — treat as an Addisonian crisis. Most cortisol-zone suppression recovers over weeks, but some dogs become permanently Addisonian.

## Clinical pearls

- Loading then weekly maintenance, dosed to ACTH-stim results — never "set and forget"; arm owners with rescue prednisolone and crisis instructions
- The clinical cue to stop loading is the dog going off its food / drinking less — test (ACTH-stim) at that point
- Trilostane is now usually first-line for PDH, but mitotane is the agent for cortisol-secreting adrenal carcinoma and remains valuable
- Iatrogenic Addison's is the big risk — recognise and treat it as an emergency
- Handle the cytotoxic-type tablets with gloves; do not crush

## Mechanism of action

Mitotane is selectively concentrated in and cytotoxic to the adrenal cortex, causing progressive necrosis/atrophy of the cortisol-producing zona fasciculata and zona reticularis (and, at higher/longer exposure, the aldosterone-producing zona glomerulosa). This lowers cortisol output to control hyperadrenocorticism; over-destruction produces iatrogenic hypoadrenocorticism — the central risk of therapy.

## Formulations and products

- 500 mg tablet (Lysodren)
- Lysodren — 500 mg tablet, Tablet (human-label)

## Storage

Tablets: 15–30 °C, dry, protect from light; handle with care (avoid crushing/skin contact — wear gloves).

## Before you use this dose

> **Caution:** Reference doses for veterinary professionals. Confirm the dose against the product label, the patient’s condition, current guidance and local regulations before use; the attending veterinarian remains responsible for every clinical decision.

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## Frequently asked questions

### What is the dose of Mitotane (o,p'-DDD) for dogs?

Reference doses for Mitotane (o,p'-DDD) in dogs: 25 mg/kg PO q12h with food for until response (usually 4–9 days; ACTH test by day 8–10) (PDH — induction (≈50 mg/kg per DAY)); 25–70 mg/kg PO WEEKLY total, divided into 2–4 doses (PDH — maintenance); 50–75 mg/kg PO per DAY, divided (10 days), then every other day (Adrenal carcinoma (higher dose)). Confirm against the label and the patient before use.

### Can Mitotane (o,p'-DDD) be given to cats?

Not recommended in cats — poor response; use trilostane (Not recommended).

### When should Mitotane (o,p'-DDD) not be used?

Concurrent uncontrolled illness; do not start without the ability to monitor (ACTH stimulation) and to supply rescue glucocorticoids. Pregnancy. Use cautiously in diabetic Cushingoid dogs (insulin needs fall as cortisol drops). Owner unable to observe/monitor. Known hypersensitivity. Handle tablets carefully (cytotoxic-type agent).

### What are the side effects of Mitotane (o,p'-DDD) in animals?

Anorexia, vomiting, diarrhoea, lethargy (often the END-POINT signs of loading — cortisol falling); Iatrogenic hypoadrenocorticism (Addisonian crisis) — can be life-threatening; Weakness, ataxia; Rare hepatotoxicity / CNS signs at high exposure.

## Sources

- Plumb's Veterinary Drug Handbook
- Merck Veterinary Manual, 11th edition
- Papich, Papich Handbook of Veterinary Drugs, 5th edition

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VetMasterJi is a clinical decision-support and education platform for veterinary professionals and students. It does not provide veterinary advice, diagnosis or treatment for specific animals. All drug doses, calculators and differentials are references that must be independently verified before clinical use; the attending registered veterinarian remains solely responsible for every clinical decision.