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Pronunciation
(es tra MUS teen)
Generic Available (U.S.)
No
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Palliative treatment of progressive or metastatic prostate cancer
Pregnancy Considerations
Estramustine is not indicated for use in women. Men who were impotent on estrogen therapy have regained potency while taking estramustine; effective contraception should be used for male patients with partners of childbearing potential.
Breast-Feeding Considerations
Estramustine is not indicated for use in women.
Contraindications
Hypersensitivity to estramustine, estradiol, nitrogen mustard, or any component of the formulation; active thrombophlebitis or thromboembolic disorders (except where tumor mass is the cause of thromboembolic disorder and the benefit may outweigh the risk)
Canadian labeling: Additional contraindications (not in the U.S. labeling): Severe hepatic or cardiac disease
Warnings/Precautions
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Allergic reaction: Allergic reactions and angioedema, including airway involvement, have been reported.
• Cardiovascular effects: Elevated blood pressure or congestive heart disease may occur. Estrogen treatment for prostate cancer is associated with an increased risk of thrombosis or MI.
• Estrogenic effects: Estrogen use may cause gynecomastia and/or impotence.
• Fluid retention: Peripheral edema (new onset or exacerbation) or congestive heart disease may occur. Use with caution in patients where fluid accumulation may be poorly tolerated, including cardiovascular disease (HF or hypertension), migraine, seizure disorder or renal dysfunction.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with a history of cardiovascular disease (eg, thrombophlebitis, thrombosis, or thromboembolic disease) and cerebrovascular or coronary artery disease.
• Diabetes: Use with caution in patients with diabetes mellitus; may decrease glucose tolerance.
• Hepatic impairment: Use with caution in patients with hepatic impairment (may be metabolized poorly).
• Metabolic bone disease: Use with caution in patients with metabolic bone diseases due to the effects on calcium and phosphorus homeostasis.
• Osteoblastic metastases: Patients with osteoblastic metastases should have their calcium monitored regularly.
• Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues:
• Immunization: Avoid vaccination with live vaccines during treatment (risk of infection may be increased due to immunosuppression). Although the response to vaccines may be diminished, inactivated vaccines may be administered during treatment.
Other warnings/precautions:
• Monitoring: Patients with prostate cancer should have their calcium monitored regularly.
Adverse Reactions
>10%:
Cardiovascular: Edema (20%)
Endocrine & metabolic: Gynecomastia (75%), breast tenderness (71%), libido decreased
Gastrointestinal: Nausea (16%), diarrhea (13%), gastrointestinal upset (12%)
Hepatic: LDH increased (2% to 33%), AST increased (2% to 33%)
Respiratory: Dyspnea (12%)
1% to 10%:
Cardiovascular: CHF (3%), MI (3%), cerebrovascular accident (2%), chest pain (1%), flushing (1%)
Central nervous system: Lethargy (4%), insomnia (3%), emotional lability (2%), anxiety (1%), headache (1%)
Dermatologic: Bruising (3%), dry skin (2%), pruritus (2%), hair thinning (1%), rash (1%), skin peeling (1%)
Gastrointestinal: Anorexia (4%), flatulence (2%), burning throat (1%), gastrointestinal bleeding (1%), thirst (1%), vomiting (1%)
Hematologic: Leukopenia (4%), thrombocytopenia (1%)
Hepatic: Bilirubin increased (1% to 2%)
Local: Thrombophlebitis (3%)
Neuromuscular & skeletal: Leg cramps (9%)
Ocular: Tearing (1%)
Respiratory: Pulmonary embolism (2%), upper respiratory discharge (1%), hoarseness (1%)
<1%, postmarketing, and/or case reports: Allergic reactions, anemia, angina, angioedema, cerebrovascular ischemia, confusion, coronary ischemia, depression, glucose tolerance decreased, hyper-/hypocalcemia, hypertension, impotence, muscle weakness, venous thrombosis
Drug Interactions
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Calcium Salts: May decrease the absorption of Estramustine. Exceptions: Calcium Chloride. Risk D: Consider therapy modification
Clodronate: May increase the serum concentration of Estramustine. Risk C: Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Food: Estramustine serum levels may be decreased if taken with milk and other dairy products, calcium supplements, and vitamins containing calcium.
Storage
Refrigerate at 2°C to 8°C (36°F to 46°F).
Mechanism of Action
Combines the effects of estradiol and nitrogen mustard. It appears to bind to microtubule proteins, preventing normal tubulin function. The antitumor effect may be due solely to an estrogenic effect. Estramustine causes a marked decrease in plasma testosterone and an increase in estrogen levels.
Pharmacodynamics/Kinetics
Absorption: Oral: 75%
Metabolism:
GI tract: Initial dephosphorylation
Hepatic: Oxidation and hydrolysis; metabolites include estramustine, estrone analog, estrone, and estradiol
Half-life elimination: Terminal: 15-24 hours
Time to peak, serum: 2-3 hours
Excretion: Feces (2.9% to 4.8% as unchanged drug)
Dosage
Details concerning dosing in combination regimens should also be consulted.
Oral: Adults: Males: Prostate cancer: 14 mg/kg/day (range: 10-16 mg/kg/day) in 3 or 4 divided doses
Combination therapy with docetaxel (unlabeled dose): 280 mg 3 times/day for 5 days (days 1 through 5) of a 21-day treatment cycle for up to 12 cycles (Petrylak, 2004)
Dosage: Combination Regimens
Prostate cancer:
Doxorubicin + Ketoconazole/Estramustine + Vinblastine
Estramustine + Docetaxel
Estramustine + Docetaxel + Calcitriol
Estramustine + Docetaxel + Carboplatin
Estramustine + Docetaxel + Hydrocortisone
Estramustine + Docetaxel + Prednisone
Estramustine + Etoposide
Estramustine-Paclitaxel
Estramustine-Vinblastine
Estramustine + Vinorelbine
Paclitaxel + Estramustine + Carboplatin
Paclitaxel + Estramustine + Etoposide
Administration: Oral
Administer on an empty stomach, at least 1 hour before or 2 hours after eating.
Monitoring Parameters
Serum calcium, liver function tests; blood pressure
Dietary Considerations
Should be taken at least 1 hour before or 2 hours after eating. Milk products and calcium-rich foods or supplements may impair the oral absorption of estramustine phosphate sodium.
Patient Education
It may take several weeks to manifest effects of this medication. Take on empty stomach, 1 hour before or 2 hours after meals or any supplements containing calcium; do not take with milk or milk products. Patients with diabetes should use caution and monitor glucose carefully; glucose tolerance may be decreased. May cause nausea, vomiting, flatulence, diarrhea, decreased libido (reversible), or breast tenderness or enlargement. Report sudden acute pain or cramping in legs or calves, unusual swelling in legs or feet, chest pain, shortness of breath, weakness or numbness of arms or legs, or respiratory difficulty.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause sedation or insomnia; rarely may cause depression
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Use caution in presence of renal or hepatic impairment, metabolic disease, seizure disorders, or migraine history. Assess serum calcium levels and LFTs. Monitor for hypertension, CNS changes, and thromboembolism on a regular basis. Caution patients with diabetes to monitor glucose carefully; glucose tolerance may be decreased.
Oncology: Emetic Potential
Moderate (30% to 90%)
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral, as phosphate sodium:
Emcyt®: 140 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Emcyt)
140 mg (150): $892.00
References
Benson R and Hartley-Asp B, “Mechanisms of Action and Clinical Uses of Estramustine,” Cancer Invest, 1990, 8(3-4):375-80.
Bergenheim AT and Henriksson R, “Pharmacokinetics and Pharmacodynamics of Estramustine Phosphate,” Clin Pharmacokinet, 1998, 34(2):163-72.
Floyd JD, Nguyen DT, Lobins RL, et al, “Cardiotoxicity of Cancer Therapy,” J Clin Oncol, 2005, 23(30):7685-96.
Hudes GR, “Estramustine-Based Chemotherapy,” Semin Urol Oncol, 1997, 15(1):13-9.
Kreis W, “Estramustine Revisited,” Cancer Treat Res, 1995, 78:163-84.
Lubiniecki GM, Berlin JA, Weinstein RB, et al, “Thromboembolic Events With Estramustine Phosphate-Based Chemotherapy in Patients With Hormone-Refractory Prostate Carcinoma: Results of a Meta-Analysis,” Cancer, 2004, 101(12):2755-9.
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.
Petrylak DP, Tangen CM, Hussain MH, et al, “Docetaxel and Estramustine Compared With Mitoxantrone and Prednisone for Advanced Refractory Prostate Cancer,” N Engl J Med, 2004, 351(15):1513-20.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
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