No

Antineoplastic Agent, Miscellaneous

Treatment of inoperable adrenal cortical carcinoma

C

Known hypersensitivity to mitotane

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Patients should be hospitalized when mitotane therapy is initiated until a stable dose regimen is established. Discontinue temporarily following trauma or shock since the prime action of mitotane is adrenal suppression; exogenous steroids may be indicated since adrenal function may not start immediately. Administer with care to patients with severe hepatic impairment; observe patients for neurotoxicity with prolonged (2 years) use.

>10%:

Central nervous system: Vertigo, mental depression, dizziness; all are reversible with discontinuation of the drug and can occur in 15% to 26% of patients

Dermatologic: Rash (15%) which may subside without discontinuation of therapy, hyperpigmentation

Gastrointestinal: 75% to 80% will experience nausea, vomiting, and anorexia; diarrhea can occur in 20% of patients

Ocular: Diplopia, visual disturbances, blurred vision (reversible with discontinuation)

1% to 10%:

Cardiovascular: Orthostatic hypotension

Endocrine & metabolic: Flushing of skin

Genitourinary: Hemorrhagic cystitis

Neuromuscular & skeletal: Myalgia

<1%: Adrenal insufficiency may develop and may require steroid replacement; hypertension, flushing, lethargy, somnolence, mental depression, irritability, confusion, fatigue, headache, fever, hyperpyrexia, hypercholesterolemia, tremor, weakness, lens opacities, toxic retinopathy, hypouricemia, hematuria, albuminuria, shortness of breath, wheezing

Myelosuppressive:

WBC: None

Platelets: None

Symptoms of overdose include diarrhea, vomiting, numbness of limbs, weakness

Decreased effect:

Barbiturates, warfarin may be accelerated by induction of the hepatic microsomal enzyme system

Spironolactone has resulted in negation of mitotane's effect

Phenytoin may increase clearance of these drugs by microsomal enzyme stimulation by mitotane

Increased toxicity: CNS depressants may increase CNS depression

Protect from light, store at room temperature

Causes adrenal cortical atrophy; drug affects mitochondria in adrenal cortical cells and decreases production of cortisol; also alters the peripheral metabolism of steroids

Absorption: Oral: ~35% to 40%

Time to peak serum concentration: Within 3-5 hours

Distribution: Stored mainly in fat tissue but is found in all body tissues

Metabolism: Primarily in the liver by hydroxylation and oxidation and other tissues

Half-life: 18-159 days

Elimination: Metabolites excreted in urine and bile

Oral:

Adults: Start at 1-6 g/day in divided doses, then increase incrementally to 8-10 g/day in 3-4 divided doses; dose is changed on basis of side effect with aim of giving as high a dose as tolerated; maximum daily dose: 18 g

Dosing adjustment in hepatic impairment: Dose may need to be decreased in patients with liver disease

Alcohol: Additive CNS effect, avoid use

Dizziness and depression are common; may cause sedation, irritability, or confusion

May cause myelosuppression; use caution with clozapine and carbamazepine; concurrent use with psychotropics may produce additive sedation

No information available to require special precautions

No effects or complications reported

Desired effects of this drug may not be seen for 2-3 months. Wear identification that alerts medical personnel that you are taking this drug in event of shock or trauma. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) and nutrition. Avoid alcohol or OTC medications unless approved by prescriber. May cause dizziness and vertigo (avoid driving or performing tasks requiring alertness until response to drug is known); nausea, vomiting, or loss of appetite (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); orthostatic hypotension (use caution when rising from sitting or lying position or climbing stairs); muscle aches or pain (if severe, request medication from prescriber). Report severe vomiting or acute loss of appetite, muscular twitching, fever or infection, blood in urine or pain on urinating, or darkening of skin. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Patients should be warned that mitotane may impair ability to operate hazardous equipment or drive; avoid alcohol and other CNS depressants; notify physician if rash or darkening of skin, severe nausea, vomiting, depression, flushing, or fever occurs; contraceptive measures are recommended during therapy

Tablet, scored: 500 mg

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.