Usage
Estramustine phosphate sodium is prescribed for the palliative treatment of metastatic and/or progressive prostate carcinoma. It is classified as an antineoplastic agent, specifically an antimicrotubule agent. Its mechanism of action involves interfering with the growth of cancer cells by blocking DNA replication and decreasing serum testosterone levels. The exact mechanism of its antineoplastic action is not fully understood.
Alternate Names
Estramustine phosphate sodium is also known as estramustine phosphate. Brand names include Emcyt and Estracyt.
How It Works
Pharmacodynamics: Estramustine combines estradiol (an estrogen) and mechlorethamine (a nitrogen mustard derivative). Its antineoplastic activity likely stems from the combined effects of both components, although the precise interplay isn’t completely elucidated. Estramustine interferes with cancer cell growth by disrupting DNA replication and lowering serum testosterone.
Pharmacokinetics: Estramustine is administered orally and is dephosphorylated in the intestines before being oxidized in the liver. Approximately 14-21% is excreted in feces and 22-36% in urine. Absorption can be affected by food, especially dairy products and calcium-rich foods. Patients with hepatic or renal impairment require careful monitoring and potential dose adjustment. The terminal half-life is approximately 20 days.
Dosage
Standard Dosage
Adults:
The recommended dose is 14 mg/kg/day orally, divided into three or four doses. Alternatively, dosing may begin at 560-840 mg daily in divided doses, adjusted up to 140-1400 mg daily based on response and gastrointestinal tolerance. Therapy should be continued as long as a favorable response persists (some patients have continued treatment for over three years). It’s crucial to assess potential benefits after 30-90 days of treatment.
Children:
Estramustine is not recommended for pediatric use.
Special Cases:
- Elderly Patients: While no specific geriatric dosing guidelines exist, caution is advised due to potential age-related decline in organ function.
- Patients with Renal Impairment: Estramustine should be used cautiously in patients with renal impairment. Dose adjustments may be necessary. Close monitoring of renal function is crucial.
- Patients with Hepatic Dysfunction: Caution is warranted in patients with hepatic impairment, and dose adjustments might be required based on the severity of dysfunction.
- Patients with Comorbid Conditions: Particular caution is required for patients with pre-existing conditions such as diabetes, cardiovascular disease, thrombophlebitis, thromboembolic disorders, and conditions that may worsen fluid retention.
Clinical Use Cases
Estramustine’s primary use is in managing metastatic or progressive prostate cancer. It is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments should be considered based on individual patient response, gastrointestinal tolerance, renal function, and hepatic function.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, breast tenderness/enlargement, fluid retention, hot flashes, decreased libido, impotence, insomnia, lethargy, anorexia, flatulence, leg cramps, headache, dyspnea, gynecomastia.
Rare but Serious Side Effects:
Thromboembolism, myocardial infarction, stroke, angioedema, hypersensitivity reactions, blood pressure elevation, heart failure, hepatic dysfunction (liver enzyme and bilirubin abnormalities), decreased glucose tolerance, anemia, leukopenia, thrombocytopenia, and secondary malignancies.
Long-Term Effects:
Chronic complications from prolonged use may include cardiovascular issues, secondary malignancies, and metabolic bone diseases.
Adverse Drug Reactions (ADR):
Angioedema, thromboembolism, myocardial infarction, stroke, and severe hypersensitivity reactions.
Contraindications
- Hypersensitivity to estramustine, estradiol, or nitrogen mustard.
- Active thrombophlebitis or thromboembolic disorders (except when the tumor is the cause).
Drug Interactions
Estramustine may interact with various medications, including:
- Tricyclic antidepressants (TCAs): May increase both therapeutic effect and toxicity.
- Calcium-, magnesium-, or aluminum-containing drugs (e.g., antacids): May decrease estramustine absorption.
- Anticoagulants: Increased risk of bleeding.
- Antidiabetic agents: Altered glucose control.
- Medications affecting estrogen levels: Potential additive or antagonistic effects.
Pregnancy and Breastfeeding
Estramustine is contraindicated in women, especially during pregnancy and breastfeeding, due to the risk of fetal harm and potential excretion in breast milk. Effective contraception is mandatory if a male patient’s partner could become pregnant.
Drug Profile Summary
- Mechanism of Action: Interferes with cancer cell growth, blocks DNA replication, and decreases serum testosterone levels.
- Side Effects: Nausea, vomiting, diarrhea, breast tenderness, fluid retention, thromboembolism (rare).
- Contraindications: Hypersensitivity, active thrombophlebitis or thromboembolic disorders.
- Drug Interactions: TCAs, antacids, anticoagulants, antidiabetics, medications affecting estrogen levels.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 14 mg/kg/day orally divided TID-QID or 560 - 1400 mg daily adjusted based on response and tolerance.
- Monitoring Parameters: Liver function tests (LFTs), endocrine function tests (testosterone levels), serum calcium, fluid status, blood pressure, serum glucose.
Popular Combinations
Estramustine is sometimes used in combination with other chemotherapeutic agents for advanced prostate cancer, but there are no universally established “popular combinations.” Clinical trials are ongoing to evaluate the efficacy and safety of different combinations.
Precautions
Pre-screening for allergies, cardiovascular conditions, history of blood clots, diabetes, metabolic disorders, liver and kidney function, and fluid retention problems is crucial. Precautions related to pregnancy, breastfeeding, and use in children are as stated above. Driving may be impaired due to potential dizziness and lethargy. Avoid alcohol, as it may exacerbate some side effects. Smoking is discouraged due to general health risks, especially in cancer patients.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Estramustine?
A: The recommended dose is 14 mg/kg/day orally, divided into three or four doses or 560-840 mg daily in divided doses titrated up to 1400 mg daily, administered at least one hour before or two hours after meals.
Q2: What are the most common side effects?
A: Nausea, vomiting, diarrhea, breast tenderness or enlargement, fluid retention (edema), and hot flashes are common side effects.
A: Myocardial infarction, stroke, thromboembolic events (such as deep vein thrombosis or pulmonary embolism), angioedema and severe hypersensitivity reactions require immediate medical intervention.
Q4: Can Estramustine be used in women?
A: No, Estramustine is not indicated for use in women, especially during pregnancy or breastfeeding. It can cause fetal harm.
Q5: What are the key drug interactions to be aware of?
A: Significant interactions can occur with tricyclic antidepressants, antacids, anticoagulants, antidiabetic medications, and drugs that influence estrogen levels. Consult a comprehensive drug interaction database for detailed information.
Q6: How should Estramustine be administered?
A: Estramustine capsules should be taken orally with water, at least one hour before or two hours after meals. Avoid administering with milk or other dairy products.
Q7: What should I advise patients regarding birth control while taking Estramustine?
A: Male patients whose partners are of childbearing potential must use effective contraception during treatment and for a period after discontinuation as advised by their physician. Estramustine can cause fetal harm.
Q8: Are there any specific monitoring requirements for patients on Estramustine?
A: Monitor liver function tests, endocrine function tests (including testosterone levels), serum calcium, fluid status, blood pressure, and serum glucose regularly. Monitor closely for signs and symptoms of hypersensitivity, cardiovascular complications, thromboembolism, and endocrine adverse effects.
Q9: What is the mechanism of action of Estramustine?
A: Estramustine works by blocking the replication of DNA in cancer cells, thus inhibiting their growth and spread. It also decreases serum testosterone levels, which further contributes to its anti-cancer effects in prostate cancer.
Q10: What are the contraindications to using Estramustine?
A: Estramustine is contraindicated in patients with known hypersensitivity to the drug or its components (estramustine, estradiol, or nitrogen mustard). It is also contraindicated in patients with active thrombophlebitis or thromboembolic disorders, except in cases where the tumor itself is the cause and the physician deems the benefits outweigh the risks.
