General

Pronunciation
a-meen-oh-gloo-TETH-i-mide

Trade Name(s)

• Cytadren

Pregnancy Category
Category D

Ther. class.
antineoplastics

Pharm. class.
adrenal suppressants
aromatase inhibitors

Indications

Short-term adrenal suppression in patients with Cushing's syndrome

Unlabelled Use(s):
Metastatic breast or prostate cancer

Action

Inhibits the synthesis of adrenal hormones including glucocorticoids, mineralocorticoids, estrogens, and androgens

Therapeutic Effect(s):

• Decreased production of adrenal hormones in Cushing's disease

• Decreased spread of breast or prostate cancer

Pharmacokinetics

Absorption: Rapidly and completely absorbed following oral administration

Distribution: Unknown

Protein Binding: 20–25% bound to plasma proteins

Metabolism and Excretion: 34–50% excreted unchanged by the kidneys

Half-life: 11–16 hr initially; drops to 2–9 hr after 2 wk of therapy

TIME/ACTION PROFILE (adrenal suppression)

ROUTE	ONSET	PEAK†	DURATION
PO	3–5 days	1.5 hr	72 hr‡

†Blood levels
‡Recovery of adrenal function after discontinuation of short-term therapy; may take longer (up to 1 yr) after chronic therapy

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity to glutethimide or aminoglutethimide

• Lactation: Provide alternative to breast milk

Use Cautiously in:

• Stress (trauma, surgery, or acute illness); additional mineralocorticoid and hydrocortisone may be required

• OB: Although normal pregnancies have occurred, fetal harm may result

• Pedi: Safety not established

• Geri: More susceptible to adverse CNS reactions

Adverse Reactions/Side Effects

CNS: drowsiness, dizziness, headache, weakness.

CV: hypotension, tachycardia.

GI: anorexia, nausea, hepatitis, vomiting.

Derm: measles-like rash, pruritus, urticaria.

Endo: adrenal insufficiency, hirsutism in women, hypothyroidism, masculinization in women.

Hemat: AGRANULOCYTOSIS, leukopenia, neutropenia, thrombocytopenia.

MS: myalgia.

Misc: fever.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug

• Induces (stimulates) hepatic P450 microsomal enzymes, which are responsible for metabolizing many drugs

• Increases metabolism and decreases effectiveness of dexamethasone

• May decrease the effects of warfarin, theophylline, megestrol tamoxifen, and medroxyprogesterone

• Alcohol potentiates the effects of aminoglutethimide

Route/Dosage

Cushing's Disease

• PO (Adults): 250 mg q 6 hr; may be increased in increments of 250 mg daily at 1–2 wk intervals (maximum daily dose should not exceed 2000 mg).

Breast or Prostate Cancer (unlabeled)

• PO (Adults): 250 mg twice daily for 2 wk (up to 2 g/day; with hydrocortisone) followed by increases to 250 mg qid.

Availability

• Tablets: 250 mg

Assessment

• Monitor patient for changes in signs of Cushing's syndrome (moon face, buffalo hump, hypertension, fragility, hirsutism, mood swings, increased susceptibility to infections) throughout therapy

• Monitor blood pressure with patient recumbent and upright throughout therapy to detect hypotension resulting from reduced aldosterone levels

• Assess patient for CNS side effects (clumsiness, dizziness, drowsiness, lack of energy, uncontrolled eye movements). These are dose related and require dose reduction, but usually decrease within 2–6 wk, even with continued therapy. May necessitate discontinuation of therapyGeri: Older patients are more susceptible to CNS effects; assess frequently during therapy and determine risk for falls

• Assess patient for measles-like rash and fever, which occurs within 10–15 days after start of therapy and lasts 5–7 days. May be treated with diphenhydramine and withholding of dose. After a mild to moderate rash disappears, restart therapy at 250 mg/day and gradually increase to therapeutic dose. Discontinuation of therapy may be required if severe skin rash occurs or if mild to moderate skin rash persists longer than 5–8 days

• Monitor patient closely during periods of stress (surgery, trauma, acute illness). Additional steroids may be required. Aminoglutethimide should be discontinued after shock or severe trauma

Lab Test Considerations

• Monitor 8 am plasma cortisol levels or 24-hr urinary 17-hydroxycorticosteroid concentrations periodically throughout therapy in patients with adrenal disorders to assess clinical response and determine whether mineralocorticoid/corticosteroid supplementation is necessary. Dose may be titrated according to levels that are decreased slowly in patients with adrenal hyperfunction and rapidly with breast cancer patients

» Monitor serum acid phosphatase concentrations periodically throughout therapy in patients with prostatic carcinoma. Concentrations should decrease in response to therapy

» Urinary aldosterone concentrations may be decreased, causing orthostatic hypotension and hyponatremia

» May cause increased serum concentrations of thyroid-stimulating hormone (TSH) as a reflex response to reduced serum thyroxine levels. Monitor thyroid function tests periodically during therapy

» May cause elevated AST, alkaline phosphatase, and bilirubin concentrations

» Monitor CBC and serum electrolytes (sodium, potassium, chloride) periodically during therapy. May cause leukopenia, thrombocytopenia, or agranulocytosis

Potential Nursing Diagnoses

• Risk for injury (Side Effects)

Implementation

• Therapy should be initiated in a hospital setting until a stable dosing regimen has been achieved

» Mineralocorticoid replacement (fludrocortisone) or corticosteroid replacement (hydrocortisone) may be necessary

• PO: Administer doses around the clock. Take with food to minimize nausea

Patient/Family Teaching

• Instruct patient to take medication exactly as directed and not to take more or less than prescribed. If a dose is missed, take within 2–4 hr unless almost time for next dose; do not double doses

• May cause drowsiness or dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known

• Instruct patient to notify health care professional promptly if rash, fainting, weakness, or headache becomes pronounced or if injury, infection, or other illness occurs because of risk of adrenal insufficiency

• Advise patient that nausea and loss of appetite may occur during first 2 wk of therapy. Health care professional should be notified if vomiting occurs shortly after a dose is taken or if these symptoms persist or become pronounced

• Advise patient to avoid concurrent use of alcohol

• Instruct patient to notify health care professional of medication regimen before treatment or surgery

• Emphasize importance of carrying identification describing medication regimen at all times and the need for close monitoring by health care professional

• Geri: Instruct patient and family in fall prevention strategies

Evaluation/Desired Outcomes

• Suppression of adrenal function in patients with Cushing's syndrome

• Decreased spread of malignancy in advanced postmenopausal breast or prostate cancer

aminoglutethimide is a sample topic found in Davis's Drug Guide. All other sections of this record are viewable by clicking on the index in the left column, or by clicking on "Display all Sections" in the "Content Manager".

To find other Davis's Drug Guide topics, please login or purchase a subscription.