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AMINOGLUTETHIMIDE

Medical Diagnosis and Drugs, Medications
AMINOGLUTETHIMIDe
(a-mee-noe-gloo-teth'i-mide)
Cytadren
Classifications: antineoplastic aromatase inhibitor;
Therapeutic: antineoplastic
Prototype: Anastozole
Pregnancy Category: D

Availability

250 mg tablets

Action

Blocks aromatase principally in the adrenal glands, thereby preventing conversion of androgens to estrogens in peripheral tissues. Also blocks adrenal corticosteroid biosynthesis in the adrenal glands by inhibiting enzymatic conversion of cholesterol to precursors of cortisol and aldosterone.

Therapeutic Effect

Because estrogens are supplied principally by the adrenal glands in postmenopausal and oophorectomized women, aminoglutethimide-induced lowering of plasma estrogen levels (by adrenal suppression) is reportedly as effective as that produced by surgical adrenalectomy.

Uses

Temporary treatment of selected patients with Cushing's syndrome associated with adrenal carcinoma, ectopic ACTH-producing tumors, or adrenal hyperplasia.

Unlabeled Uses

To produce medical adrenalectomy in postmenopausal women with a positive estrogen receptor test, metastatic breast cancer, or who fail or relapse with tamoxifen, and for patients with prostatic carcinoma.

Contraindications

Hypothyroidism; infection. Safety during pregnancy (category D), lactation, and in children is not established.

Cautious Use

Older adults.

Route & Dosage

Cushing's Disease
Adult: PO 250 mg q6h, may be increased 250 mg/d q1–2wk if needed (max: 2 g/d)

Breast Cancer
Adult: PO 250 mg b.i.d. and hydrocortisone 60 mg h.s., 20 mg in a.m., and 20 mg at 2 p.m. daily for 2 wk, then 250 mg q.i.d. and hydrocortisone 20 mg h.s., 10 mg in a.m., and 10 mg at 2 p.m. thereafter

Administration

Oral
  • Note: For breast cancer, 40 mg of hydrocortisone daily, in divided doses is usually ordered to be given concurrently.
  • Store at 15°–30° C (59°–86° F) in tightly closed containers unless otherwise directed.

Adverse Effects (≥1%)

CNS: Lethargy, drowsiness, dizziness, uncontrolled eye movements (dose related); clumsiness, headache. CV: Hypotension, tachycardia. Endocrine: Masculinization. GI: Nausea, vomiting, anorexia, hepatotoxicity. Hematologic: (Rare) Neutropenia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis, decreased Hgb and Hct, anemia, Coombs' negative hemolytic anemia. Skin: Measles-like (morbilliform) rash, pruritus.

Interactions

Drug: Dexamethasone decreases pharmacologic effects of aminoglutethimide; decreases anticoagulant response to warfarin.

Pharmacokinetics

Onset: 3–5 d. Distribution: Crosses placenta. Metabolism: In liver. Elimination: By kidneys; recovery of adrenal responsiveness to stress occurs 36–72 h after discontinuation. Half-Life: 13 h (7 h with long-term use).

Nursing Implications

Assessment & Drug Effects

  • Monitor & report S&S of: Adrenal insufficiency or hypothyroidism (see Appendix F); in older adults, CNS effects (e.g., lethargy, ataxia, orthostatic dizziness, lightheadedness).
  • Lab tests: Baseline & periodic fasting plasma cortisol levels, periodic CBC with differential, serum electrolytes, serum alkaline phosphate, liver functions, and thyroid function.
  • Monitor BP in the recumbent and upright positions to evaluate fluid volume status and presence of orthostatic hypotension.
  • Note: Dose reduction or temporary discontinuation may be indicated by: extreme drowsiness, severe skin rash, extremely low cortisol levels.
  • Note: Patients with Cushing's syndrome may show reduced effect with continuing therapy and generally are not treated beyond 3 mo with this drug.

Patient & Family Education

  • Change positions gradually, pausing between each change. Do not stand still for prolonged periods.
  • Note: Lethargy, drowsiness, dizziness, and other adverse effects often disappear during the first few weeks of therapy. Inform physician if adverse effects persist or become bothersome.
  • Report skin rash that persists beyond 5–8 d.
  • Contact physician immediately in times of physical and emotional distress (e.g., acute illness, dental work). Steroid supplements may be indicated.
  • Do not drive or engage in potentially hazardous activities until response to drug is known.
  • Carry medical identification indicating medical diagnosis, medication(s), physician's name, address, and telephone number.
  • Notify physician immediately if pregnancy is suspected.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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