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Trade Names:
Emcyt
- Capsules for oral use 140 mg estramustine phosphate.

Mechanism of Action

Pharmacology

Estramustine appears to act as a relatively weak alkylating agent and imparts a weak estrogenic activity. The estrogenic portion of the molecule acts as a carrier to facilitate selective uptake of the drug into estrogen receptor-positive cells. Because of the selective steroidal uptake, the alkylating effect of the nitrogen mustard is enhanced in these cells. Estramustine phosphate is readily dephosphorylated during absorption, and the major metabolites in plasma are estramustine, the estrone analog, estradiol, and estrone. Terminal half-life of estramustine phosphate is approximately 20 h and mainly excreted in the stool.

Pharmacokinetics

Metabolism

Readily dephosphorylated during absorption; major metabolites in plasma are estramustine, the estrone analog, estradiol, and estrone.

Elimination

The t _1/2 is approximately 20 h. Majority excreted in the feces.

Special Populations

May be poorly metabolized in these patients.

Indications and Usage

Palliative therapy of metastatic or progressive prostate cancer.

Unlabeled Uses

Metastatic renal cell carcinoma.

Contraindications

Hypersensitivity to estradiol or nitrogen mustard; active thrombophlebitis or thromboembolic disorders, except where the actual tumor mass is the cause of the thromboembolic phenomenon and the benefits of therapy outweigh the risks.

Dosage and Administration

PO 14 mg/kg/day (range, 10 to 16 mg/kg/day) in 3 to 4 divided doses for 30 to 90 days before assessing for continuation of therapy. Continue therapy as long as response is favorable.

General Advice

Administer PO with water 1 h or more before or 2 h after meals.

Storage/Stability

Refrigerate. Capsules may be stored at room temperature for 24 to 48 h without affecting potency. Protect from light.

Drug Interactions

Milk, milk products, and calcium-rich foods or antacids may impair the absorption of estramustine.

Laboratory Test Interactions

Abnormalities of hepatic enzymes and of bilirubin have occurred but have seldom required cessation of therapy. Perform such tests at appropriate intervals during therapy and repeat after the drug has been withdrawn for 2 mo.

Adverse Reactions

Cardiovascular

Hypertension; CHF; edema; increased risk of cerebrovascular accident; MI, thrombosis.

CNS

Lethargy; emotional lability; insomnia.

Dermatologic

Rash; pruritus; dry skin; easy bruising.

Endocrine

Decreased glucose tolerance; breast tenderness or enlargement.

GI

Nausea; vomiting; diarrhea; anorexia; flatulence; elevated LFTs.

Genitourinary

Decreased glucose tolerance; gonadal suppression; breast tenderness; breast enlargement.

Hematologic

Leukopenia and thrombocytopenia have been reported in a small number of patients.

Musculoskeletal

Leg cramps.

Respiratory

Dyspnea.

Precautions

Children

Safety and efficacy not established.

Hepatic Function

Estramustine may be poorly metabolized in patients with impaired liver function.

Mutagenesis

Both estradiol and nitrogen mustard are mutagenic. Advise use of contraceptive measures.

Thrombosis

The risk of thrombosis including nonfatal MI, increases in men receiving estrogens for prostate cancer. Use with caution in patients with a history of thrombophlebitis, thrombosis, or thromboembolic disorders, especially if associated with estrogen therapy. Use with caution in patients with cerebral vascular or coronary artery disease.

Glucose tolerance

Tolerance to glucose may be decreased. Monitor blood sugar in diabetic patient when therapy is started. Report significant changes to health care provider.

Elevated BP

BP elevation may occur. Monitor BP periodically while on estramustine.

Fluid retention

Exacerbation of preexisting or incipient peripheral edema or CHD may occur.

Calcium/Phosphorus metabolism

Calcium/phosphorus metabolism may be influenced. Use with caution in patients with metabolic bone disease associated with hypercalcemia or in patients with renal function impairment.

Patient Information

• Use contraceptive measures during therapy because of the possibility of mutagenic effects.
• Milk, milk products, and calcium-rich foods or antacids may impair the absorption of estramustine.
• Take with water at least 1 h before or 2 h after meals.