Aminoglutethimide

Mechanism of Action
Inhibits adrenocortical steroid synthesis by blocking the production of adrenal glucocorticoids, mineralocorticoids, estrogens, and androgens.

Indications
Suppression of adrenal function in patients with Cushing's syndrome. Unlabeled use: To cause “chemical adrenalectomy” in patients with advanced breast cancer and patients with metastatic prostate cancer.

Metabolism/Excretion
Well absorbed orally and excreted in the urine. Half-life: 11 to 16 hours.

Dosage Range
¨ Adult: Initial dose is 250 mg/day PO at 6-hour intervals. If cortisol suppression is not adequate, the dosagemay be increased in increments of 250 mg/day at 1- to 2-week intervals to a total daily dose of 2 g. If adverse side effects occur, including extreme drowsiness or a skin rash that persists for 5 days or longer or becomes severe, or if the patient develops excessively low cortisol levels, reduce the dose or discontinue the drug.
¨ Pediatric: Safety and efficacy not established.

Drug Preparation/Stability
Available in 250-mg scored tablets. Protect tablets from light and dispense from a light-resistant container. Do not store above 30°C.

Drug Administration
Per Oral

Drug Interaction
¨ Decreased effectiveness of warfarin, so dose may need to be increased.
¨ Enhanced metabolism of dexamethasone, so hydro-cortisone should be used for replacement.

Side Effects and Toxicities

• Cardiac: Orthostatic hypotension, tachycardia (rare)
• CNS: Drowsiness, headache
• Cutaneous: Morbiliform rash, pruritus (may be due to allergic or hypersensitivity reactions)
• Endocrine: Adrenal insufficiency was noted in Cush-ing's syndrome patients who were treated for at least 4 weeks. Occasional masculinization and hirsutism in women; precocious sexual development in men.
• GI: Nausea and anorexia
• Other: Fever, myalgia
• Special Considerations
• Avoid in patients who have hypersensitivity to the drug.
• Monitor adrenocortical function. If hypofunction occurs, give supplements such as hydrocortisone. Avoid dexamethasone.
• Monitor blood pressure at regular intervals because of the potential for hypotension. Advise patients to watch for signs of hypotension (e.g., weakness and dizziness) and teach the appropriate measures to be taken should they occur.
• Warn patients that drowsiness may occur and that they should not engage in activities that may be hazardous because of decreased alertness.
• Inform patients that effects may be potentiated by alcohol.