Generic Name

Mitotane

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Classification

FDA Approved Indications

• Adrenocortical carcinoma (adjuvant and palliative therapy)

Mechanism of Action

Mitotane selectively destroys adrenocortical cells and inhibits steroidogenesis by damaging mitochondria in adrenal tissue, leading to decreased production of cortisol.

Dosage and Administration

Adult: Initial dose: 3-6 g per day in divided doses; maintenance dose varies based on response, typically 2-3 g/day.

Pediatric: Not established; use is generally limited to adult patients.

Geriatric: Dose adjustments may be necessary; careful monitoring recommended.

Renal Impairment: Use caution; no specific dose adjustment provided.

Hepatic Impairment: Use with caution; monitor liver function closely.

Pharmacokinetics

Absorption: Well absorbed orally.

Distribution: Widely distributed; crosses blood-brain barrier.

Metabolism: Metabolized in the liver.

Excretion: Excreted mainly via the feces, some via urine.

Half Life: Approximately 18-24 days, allowing for gradual accumulation and clearance.

Contraindications

• Hypersensitivity to mitotane or components.
• Pregnancy and lactation due to potential teratogenic and embriotoxic effects.

Precautions

• Monitor adrenal function and steroid levels.
• Risk of adrenal insufficiency, neurology, and gastrointestinal toxicity.
• Use cautiously in patients with hepatic dysfunction.

Adverse Reactions - Common

• Gastrointestinal disturbances (nausea, vomiting, diarrhea) (Common)
• Drowsiness or dizziness (Common)
• Adrenal insufficiency signs such as weakness and fatigue (Common)

Adverse Reactions - Serious

• Adrenal crisis due to insufficiency (Serious (rare but requires urgent treatment))
• Neurological effects such as cerebellar symptoms or peripheral neuropathy (Serious)
• Hepatotoxicity including hepatitis, jaundice (Serious)

Drug-Drug Interactions

• CYP450 enzyme inducers or inhibitors may alter mitotane levels.
• Drugs affecting adrenal function, such as corticosteroids, may require dose adjustments.

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Take medication exactly as prescribed.
• Report symptoms of adrenal insufficiency (fatigue, weakness, abdominal pain).
• Avoid pregnancy and use effective contraception.
• Limit exposure to alcohol and hepatotoxic substances.

Special Considerations

Black Box Warnings:

• Potentially life-threatening adrenal insufficiency if therapy is interrupted or overdose occurs.

Genetic Factors: None specific.

Lab Test Interference: May alter cortisol and adrenal hormone levels, affecting laboratory tests.

Overdose Management

Signs/Symptoms: Severe nausea, vomiting, neurological symptoms, adrenal crisis.

Treatment: Supportive care, manage adrenal crisis with corticosteroids, maintain electrolyte balance, and provide symptomatic relief.

Storage and Handling

Storage: Store at room temperature, protected from moisture and light.

Stability: Stable through expiration date when stored properly.