Drug reference

Mitotane

Corticosteroid · Antineoplastic

CorticosteroidAntineoplastic

CDSCO approvedSchedule H

EXCRETION

—

not curated

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

—

not curated

Top interactionssee all 12 →

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Mechanism

Mitotane selectively inhibits the activity of the adrenal cortex, leading to decreased steroidogenesis. This action necessitates corticosteroid replacement therapy due to the risk of precipitating acute adrenal insufficiency.

Indications

Symptomatic treatment of advanced or inoperable adrenocortical carcinomainoperable adrenocortical carcinomaPalliation of inoperable adrenocortical carcinomaHypercortisolism associated with Cushing’s Syndrome Caused by Ectopic ACTH Production

Dosing

Adult: Initially 2 –3 g daily in 2 –3 divided doses adjusted according to plasma-concentration monitoring. In severe illness, initial dose can be increased up to 6 g daily. Reduce dose or interrupt treatment if signs of toxicity. Discontinue if inadequate response after 3 months.
Max dose: Up to 6 g daily initially in severe illness (initial dose can be increased).

Pharmacokinetics

Onset

weeks to months

Half-life

Plasma concentrations of mitotane are still measurable for 6 to 9 weeks following discontinuation of therapy.

Bioavailability

Approximately 40% is absorbed after oral administration.

Protein binding

Fat is the primary site of storage.

Excretion

About 60% of an oral dose is excreted unchanged in the stool. A water-soluble metabolite found in the urine constitutes 25% of an oral or parenteral dose.

Contraindications

Acute porphyrias
Concomitant administration of spironolactone

Side effects

Common

Adrenal insufficiencyAnaemiaAppetite decreasedAstheniaCognitive impairmentConfusionDiarrhoeaDizzinessDrowsinessDyslipidaemiaGastrointestinal discomfortGynaecomastiaHeadacheHepatic disordersLeucopeniaMovement disordersMucositisMuscle weaknessNauseaParaesthesiaPolyneuropathyRashThrombocytopeniaVertigoVomitingGI disturbancesataxiaAnorexiaSomnolenceLethargyDermatitis

Serious

Acute adrenal insufficiency
Encephalopathy
Eye disorders
Flushing
Fungal infection
Generalised pain
Growth retardation
Haemorrhage
Hyperpyrexia
Hypersalivation
Hypertension
Hypothyroidism
Hypouricaemia
Lens opacity
Neuro-psychological retardation
Ovarian cyst
Postural hypotension
Proteinuria
primary adrenal insufficiency
Damage to the adrenal cortex (requires replacement doses of adrenocorticosteroids)