No

Antineoplastic Agent, Alkylating Agent

Palliative treatment of prostatic carcinoma (progressive or metastatic)

C

Active thrombophlebitis or thromboembolic disorders, hypersensitivity to estramustine or any component, estradiol or nitrogen mustard

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Glucose tolerance may be decreased; elevated blood pressure may occur; exacerbation of peripheral edema or congestive heart disease may occur; use with caution in patients with impaired liver function, renal insufficiency, or metabolic bone diseases.

>10%:

Cardiovascular: Edema

Gastrointestinal: Diarrhea, nausea, mild increases in AST (SGOT) or LDH

Endocrine & metabolic: Decreased libido, breast tenderness, breast enlargement

Respiratory: Dyspnea

1% to 10%:

Cardiovascular: Myocardial infarction

Central nervous system: Insomnia, lethargy

Gastrointestinal: Anorexia, flatulence

Hematologic: Leukopenia

Local: Thrombophlebitis

Neuromuscular & skeletal: Leg cramps

Respiratory: Pulmonary embolism

<1%: Cardiac arrest, depression, pigment changes, hypercalcemia, hot flashes, tinnitus, night sweats

Symptoms of overdose include nausea, vomiting, myelosuppression

There are no known antidotes, treatment is primarily symptomatic and supportive

Decreased effect: Milk products and calcium-rich foods/drugs may impair the oral absorption of estramustine phosphate sodium

Refrigerate at 2°C to 8°C (36°F to 46°F); capsules may be stored outside of refrigerator for up to 24-48 hours without affecting potency

Mechanism is not completely clear, thought to act as an alkylating agent and as estrogen

Absorption: Oral: Well absorbed (75%)

Metabolism: Dephosphorylated in the intestines and eventually oxidized and hydrolyzed to estramustine, estrone, estradiol, and nitrogen mustard

Half-life: 20 hours

Time to peak serum concentration: Within 2-3 hours

Elimination: In feces via bile

Adults: Oral: 14 mg/kg/day (range: 10-16 mg/kg/day) in 3-4 divided doses for 30-90 days; some patients have been maintained for >3 years on therapy

Administer at least 1 hour before or 2 hours after eating

May cause sedation or insomnia; rarely may cause depression

None reported

No information available to require special precautions

No effects or complications reported

It may take several weeks to manifest effects of this medication. Store capsules in refrigerator. Do not take with milk or milk products. Preferable to take on empty stomach (1 hour before or 2 hours after meals). Small frequent meals, frequent mouth care may reduce incidence of nausea or vomiting. You may experience flatulence, diarrhea, decreased libido (reversible), breast tenderness or enlargement. Report sudden acute pain or cramping in legs or calves, chest pain, shortness of breath, weakness or numbness of arms or legs, difficulty breathing, or edema (increased weight, swelling of legs or feet). Pregnancy precautions: Inform prescriber if you are pregnant. Do not get pregnant during or for 1 month following therapy. Male: Do not cause a female to become pregnant. Male/female: Consult prescriber for instruction on appropriate barrier contraceptive measures. This drug may cause severe fetal defects.

Administer on an empty stomach, particularly avoid taking with milk

Capsule, as phosphate sodium: 140 mg

Benson R and Hartley-Asp B, "Mechanisms of Action and Clinical Uses of Estramustine," Cancer Invest, 1990, 8(3-4):375-80.

Gunnarsson PO and Forshell GP, "Clinical Pharmacokinetics of Estramustine Phosphate," Urology, 1984, 23(6 Suppl):22-7.

Hudes GR, "Estramustine-Based Chemotherapy," Semin Urol Oncol, 1997, 15(1):13-9.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Kreis W, "Estramustine Revisited," Cancer Treat Res, 1995, 78:163-84.

Perry CM and McTavish D, "Estramustine Phosphate Sodium. A Review of Its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Efficacy in Prostate Cancer," Drugs Aging, 1995, 7(1):49-74.