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Estramustine

Medically reviewed by Drugs.com. Last updated on Aug 7, 2020.

Pronunciation

(es tra MUS teen)

Index Terms

  • Estramustine Phosphate
  • Estramustine Phosphate Sodium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as phosphate sodium:

Emcyt: 140 mg

Brand Names: U.S.

  • Emcyt

Pharmacologic Category

  • Antineoplastic Agent, Alkylating Agent
  • Antineoplastic Agent, Antimicrotubular
  • Antineoplastic Agent, Hormone (Estrogen/Nitrogen Mustard)

Pharmacology

Estramustine is an estradiol and nornitrogen mustard carbamate-linked combination which has antiandrogen effects (due to estradiol) and antimicrotubule effects (due to nornitrogen mustard); it causes a marked decrease in plasma testosterone and an increase in estrogen levels.

Absorption

Incomplete (Bergenheim 1998)

Metabolism

Initially dephosphorylated in the GI tract, then hepatically oxidated and hydrolyzed to estramustine, estromustine (oxidized isomer of estramustine), estrone, and estradiol.

Excretion

Feces (primarily); urine (trace amounts) (Bergenheim 1998)

Time to Peak

2 to 3 hours (Bergenheim 1998)

Half-Life Elimination

Estromustine: 13.6 hours (range: 9 to 23 hours); Estrone: 16.5 hours (Bergenheim 1998)

Special Populations: Hepatic Function Impairment

Estramustine may be poorly metabolized in patients with hepatic impairment.

Use: Labeled Indications

See Use: Unsupported.

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 US labeling): Severe hepatic or cardiac disease

Documentation of allergenic cross-reactivity for estrogens is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

Estramustine is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting.

Oral: Administer on an empty stomach, at least 1 hour before or 2 hours after eating. Administer with water; do not administer with milk, milk-based products, or calcium products.

Dietary Considerations

Milk products and calcium-rich foods or supplements may impair the oral absorption of estramustine phosphate sodium.

Storage

Store at 2°C to 8°C (36°F to 46°F).

Drug Interactions

Calcium Salts: May decrease the absorption of Estramustine. Management: Administer estramustine on an empty stomach, at least 1 hour before or 2 hours after the dose of an oral calcium supplement. If coadministered with calcium salts, monitor for decreased estramustine therapeutic effects. Exceptions: Calcium Chloride. Consider therapy modification

Clodronate: May increase the serum concentration of Estramustine. Monitor therapy

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification

Adverse Reactions

Frequency not always defined.

>10%:

Cardiovascular: Edema (20%)

Endocrine & metabolic: Gynecomastia (75%), increased lactate dehydrogenase (2% to 33%), decreased libido

Gastrointestinal: Nausea (16%), diarrhea (13%), gastrointestinal irritation (12%)

Genitourinary: Breast tenderness (71%)

Hepatic: Increased serum AST (2% to 33%)

Respiratory: Dyspnea (12%)

1% to 10%:

Cardiovascular: Cardiac failure (3%), local thrombophlebitis (3%), myocardial infarction (3%), cerebrovascular accident (2%), pulmonary embolism (2%), chest pain (1%), flushing (1%)

Central nervous system: Lethargy (4%), insomnia (3%), emotional lability (2%), anxiety (1%), headache (1%)

Dermatologic: Pruritus (2%), xeroderma (2%), exfoliation of skin (1%), skin rash (1%), thinning hair (1%)

Endocrine & metabolic: Increased thirst (1%)

Gastrointestinal: Anorexia (4%), flatulence (2%), gastrointestinal hemorrhage (1%), sore throat (1%), vomiting (1%)

Hematologic & oncologic: Leukopenia (4%), bruise (3%), thrombocytopenia (1%)

Hepatic: Increased serum bilirubin (1% to 2%)

Neuromuscular & skeletal: Leg cramps (9%)

Ophthalmic: Lacrimation (1%)

Respiratory: Hoarseness (1%), rhinorrhea (1%)

<1%, postmarketing, and/or case reports: Anemia, angina pectoris, angioedema, cerebral ischemia, confusion, depression, decreased glucose tolerance, hypercalcemia, hypocalcemia, hypersensitivity reaction, hypertension, impotence, ischemic heart disease, myasthenia, venous thrombosis

Warnings/Precautions

Concerns related to adverse effects:

• 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 (including fatalities). Use with caution in patients with a history of thrombophlebitis, thrombosis, or thromboembolic disease, especially if associated with estrogen therapy. Use with caution in patients with cerebrovascular disease or coronary artery disease.

• Endocrine effects: Estrogenic effects may decrease testosterone levels; may cause gynecomastia and/or impotence.

• Fluid retention: Peripheral edema (new onset or exacerbation) or congestive heart disease has been observed. Use with caution in patients where fluid accumulation may be poorly tolerated, including cardiovascular disease (HF or hypertension), migraine, seizure disorder or renal dysfunction.

• Gastrointestinal toxicity: Estramustine is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting.

• Glucose tolerance: Glucose tolerance may be decreased; use with caution in patients with diabetes mellitus.

• Hepatic effects: Liver enzyme and bilirubin abnormalities may occur; monitor during and for 2 months after treatment.

• Hypersensitivity: Allergic reactions and angioedema, including airway involvement, have been reported.

• Hypertension: May cause hypertension; monitor blood pressure periodically.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment (estramustine 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 are at risk for hypocalcemia; monitor calcium regularly.

• Renal impairment: Use with caution in patients with renal impairment.

Other warnings/precautions:

• Limitation of use: A clinical practice guideline from the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario recommends that estramustine not be offered to men with metastatic castration-resistant prostate cancer due to a lack of benefit in survival or quality of life (ASCO [Basch 2014]).

Monitoring Parameters

Monitor serum calcium, liver function tests (during and for 2 months following treatment), and serum glucose (in diabetic patients). Monitor blood pressure and fluid status. Monitor adherence.

Reproductive Considerations

Some 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.

Pregnancy Considerations

Estramustine is not indicated for use in women.

Patient Education

What is this drug used for?

• It is used to treat prostate cancer. It may be given for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Diarrhea

• Tender breasts

• Leg cramps

• Enlarged breasts

• Sexual dysfunction

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit

• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting

• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight

• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood

• Severe dizziness

• Passing out

• Weight gain

• Swelling

• Trouble breathing

• Severe headache

• Vision changes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.