Mitotane
o,p'-DDD (1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene)
Also known as: Lysodren · o,p'-DDD · CB-313 · NSC-38721 · WR13045 · Lisodren
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Pituitary-dependent hyperadrenocorticism (Induction - Protocol A) | 25 mg/kg twice a day, PO with food | PO | q12h | Until clinical endpoints occur (usually 4-9 days) | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol A) | 25-50 mg/kg per week | PO | Divided in as many doses as possible weekly | Long-term | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Induction - Protocol B) | 30-50 mg/kg/day PO with a meal once daily or divided q12h | PO | q24h or q12h | 7-10 days | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol B) | 35-50 mg/kg per week in 2-3 divided doses | PO | Divided weekly | Long-term | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Induction - Protocol C) | 50 mg/kg divided q12h | PO | q12h | Until water consumption decreases to <100 mL/kg/day or adverse signs observed (usually 3-7 days) | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol C) | 50 mg/kg every 7-10 days | PO | Every 7-10 days | Long-term | 🌎 NA |
| Total adrenal ablation (Alternative Protocol D) | 75-100 mg/kg per day for 25 consecutive days, given in 3-4 doses per day with food | PO | Divided q6-8h | 25 days | 🌎 NA |
| Total adrenal ablation (Alternative Protocol E) | 100 mg/kg/day divided twice daily for 30 days | PO | q12h | 30 days | 🌎 NA |
| Palliative medical treatment of adrenal carcinomas or adenomas | 50-75 mg/kg PO in daily divided doses | PO | Divided daily | 10-14 days initially | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Induction) | 30-50 mg/kg | PO | q24h | to effect (generally 3-10 days) | 🌍 EU |
| Pituitary-dependent hyperadrenocorticism (Maintenance) | 50 mg/kg | PO | q7-14 days | Ongoing | 🌍 EU |
| Adrenal carcinomas | 50-150 mg/kg | PO | q24h | Ongoing | 🌍 EU |
- Pituitary-dependent hyperadrenocorticism (Induction - Protocol A): Reduce food by 1/3 the day before. Stop therapy if water consumption approaches 60 mL/kg/day, appetite reduces, vomiting, listlessness, or diarrhea occurs.
- Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol A): Adjust based on ACTH stimulation test results.
- Pituitary-dependent hyperadrenocorticism (Induction - Protocol B): Goal is basal and post-ACTH cortisol between 1-5 micrograms/dL.
- Pituitary-dependent hyperadrenocorticism (Induction - Protocol C): Max 5-7 days prior to ACTH stim test if water consumption cannot be monitored.
- Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol C): Dose is highly variable (26-330 mg/kg/week).
- Total adrenal ablation (Alternative Protocol D): Requires lifelong prednisone and mineralocorticoid therapy.
- Total adrenal ablation (Alternative Protocol E): Requires cortisone acetate and fludrocortisone acetate supplementation.
- Palliative medical treatment of adrenal carcinomas or adenomas: May increase to 100 mg/kg/day based on ACTH response. Maintenance is 100-200 mg/kg/week.
- Pituitary-dependent hyperadrenocorticism (Induction): Give with/after food high in fat/oil to improve absorption.
- Pituitary-dependent hyperadrenocorticism (Maintenance): Given in 2-3 divided doses as required. Give with/after food high in fat/oil.
- Adrenal carcinomas: Higher doses may become necessary. Give with/after food high in fat/oil.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Hyperadrenocorticism | 30-50 mg/kg | PO | q24h | to effect | 🌍 EU |
- Hyperadrenocorticism: Efficacy in cats is very variable, with many showing no response at non-toxic levels. Not recommended.
Ferrets
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Medical treatment of hyperadrenocorticism | 50 mg per ferret PO once daily for one week, then 50 mg PO 2-3 times per week | PO | q24h then 2-3 times/week | Long-term | 🌎 NA |
- Medical treatment of hyperadrenocorticism: Have a compounding pharmacy make 50 mg capsules. Can be coated with Nutrical.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Mitotane (also known as o,p'-DDD) is an adrenal cytotoxic agent primarily used in veterinary medicine for the medical management of pituitary-dependent hyperadrenocorticism (PDH) (Cushing's disease), principally in dogs. It is structurally related to the insecticide DDT (chlorophenothane).
Because it causes targeted necrosis of the adrenal cortex, it effectively reduces excessive cortisol production. It is also used for the palliative treatment of adrenal carcinoma in humans and dogs.
Clinical Pearl: Treatment is typically divided into two distinct phases: an induction phase (daily dosing to rapidly destroy hyperplastic adrenal tissue until clinical endpoints are reached) and a maintenance phase (weekly or biweekly dosing to prevent regrowth of the adrenal cortex). Close monitoring is mandatory, as overzealous treatment can lead to iatrogenic hypoadrenocorticism (Addison's disease).
Mechanism of action
Mitotane acts as a targeted adrenocortical cytotoxic agent.
- It causes severe, progressive necrosis and atrophy of the zona fasciculata and zona reticularis of the adrenal gland → drastically reducing the synthesis of glucocorticoids (cortisol).
- It relatively spares the zona glomerulosa, meaning mineralocorticoid (aldosterone) synthesis is usually unaffected, though clinically significant effects on aldosterone production can occasionally occur.
- The exact intracellular mechanism of cytotoxicity is not fully understood, but it is believed to involve metabolic activation within the adrenal mitochondria, leading to irreversible binding to cellular macromolecules and subsequent cell death.
Safety & warnings
Contraindications
- Known hypersensitivity to mitotane
- Pregnancy (FDA Category C in humans; Class D in veterinary medicine - embryotoxic/teratogenic)
- Patients that are not eating well (should never be administered to anorexic animals)
- Not recommended in cats (trilostane is more effective and mitotane efficacy is highly variable)
Adverse effects
- Lethargy
- Ataxia
- Weakness
- Anorexia (loss of appetite)
- Vomiting
- Diarrhea
- Neurologic signs (uncommon)
- Liver changes (congestion, centrolobular atrophy, fatty degeneration)
- Iatrogenic hypoadrenocorticism (requiring long-term glucocorticoid/mineralocorticoid replacement in ~5% of dogs)
- Diarrhoea
- Acute-onset neurological signs (2-3 weeks post-initiation)
Precautions
Warning: Mitotane should never be administered to animals that are not eating well.
- Diabetes Mellitus: Concurrent diabetes requires close monitoring as insulin requirements may rapidly decrease during initial treatment.
- Organ Dysfunction: Dogs with preexisting renal or hepatic disease should receive the drug with extreme caution and intense monitoring.
- Stress Supplementation: All dogs receiving mitotane therapy must receive additional glucocorticoid supplementation if undergoing physiological stress (e.g., surgery, trauma, acute illness).
- Human Safety: Mitotane is a cytotoxic drug. Caregivers should avoid direct skin contact (wear gloves) and wash hands after administration.
Drug interactions
Additive depressant effects may be seen if used concomitantly.
Diabetic dogs receiving insulin may have their insulin requirements rapidly decreased when mitotane therapy is instituted.
Can induce enzymes and reduce the efficacy of mitotane; conversely, mitotane can induce hepatic microsomal enzymes and increase the metabolism of phenobarbital.
Has been demonstrated to block the action of mitotane in dogs; an alternate diuretic is recommended.
Increases the hepatic metabolism of mitotane
Increases the hepatic metabolism of mitotane
Monitoring
- Physical exam and history (especially water consumption, food consumption, and weight)
- ACTH response test (crucial for dose adjustment)
- Serum electrolytes (Na+/K+)
- BUN
- CBC
- Liver enzymes
- Appetite (daily during induction)
- ACTH stimulation test (to monitor treatment efficacy)
- Blood glucose (in diabetic patients)
- Clinical signs of weakness, vomiting, or neurological changes
Pharmacokinetics
Absorption
Systemic bioavailability in dogs is poor. Oral absorption is significantly enhanced by giving the drug with food (especially food high in oil/fat content). In humans, ~40% is absorbed with peak serum levels at 3-5 hours.
Distribution
Distributes to virtually all tissues in the body. It is highly lipophilic, stored in fat, and does not accumulate in the adrenal glands. A small amount may enter the CSF.
Metabolism
Metabolized in the liver.
Elimination
Excreted as metabolites in the urine (10%) and bile (15%) within 24 hours of dosing.
Overdose
Because of the drug's toxicity and very long half-life, acute overdosage should be managed aggressively.
- Decontamination: Emptying the stomach and administering activated charcoal and a cathartic should be considered after a recent ingestion.
- Monitoring & Treatment: The patient must be closely monitored. Administer systemic glucocorticoids (e.g., dexamethasone or prednisone) and IV fluids if signs of acute hypoadrenocorticism (Addisonian crisis) develop.
Available products
Formulations
- Tablets
- 500 mg tablet
- 500 mg capsule
Human-labeled
- Mitotane Tablets (scored): 500 mg (Lysodren)
- Lysodren 500 mg tablet
Regulatory status
Available from Europe for animals that have failed trilostane therapy. POM.
POM (Prescription Only Medicine). Used under the cascade.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store at room temperature (15-30°C), in tight, light-resistant containers.
Client information
- Give with Food: Always administer this medication immediately after a meal (preferably one containing some fat or oil) to ensure proper absorption.
- Watch for Side Effects: The goal of this drug is to reduce cortisol levels, but it can sometimes reduce them too much. Watch your pet closely for signs of an "Addisonian crisis," which include lethargy, weakness, vomiting, diarrhea, or a sudden loss of appetite.
- Stop if Sick: If your pet stops eating or shows any of the above signs, stop giving the medication immediately and contact your veterinarian. You may be instructed to give a rescue dose of a steroid (like prednisone).
- Safety Precautions: Mitotane is a potent cytotoxic drug. Wear gloves when handling the tablets, or wash your hands thoroughly afterward. Keep the medication strictly out of reach of children and other pets.
- Stress: Your pet may need extra steroid medication during times of stress, such as surgery, boarding, or acute illness. Discuss this with your vet.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.