Estramustine Sodium Phosphate

What it is and how it works

Estramustine phosphate is a conjugate of estradiol and normustine that is dephosphorylated to estramustine and estromustine. Its main cytotoxic action is antimitotic, binding microtubule-associated proteins and tubulin and disrupting the mitotic spindle; the released oestrogen also has an anti-androgenic effect through suppression of testosterone.

Indications

Palliative treatment of advanced prostate cancer, particularly hormone-refractory (castration-resistant) disease.

Dosage and administration (summary)

Oral, usually about 14 mg/kg daily (commonly 560 mg–1.4 g daily) in 2–3 divided doses, taken at least 1 hour before or 2 hours after meals and not with milk, dairy products or calcium-containing medicines, which impair absorption.

Contraindications

Severe hepatic impairment, severe cardiovascular disease (including active thromboembolic disorders and severe ischaemic or congestive heart disease), peptic ulcer, and hypersensitivity to estradiol or nitrogen mustards.

Warnings and precautions

Thromboembolic events, fluid retention, heart failure and hypertension may occur; caution is required in patients with cardiovascular disease, diabetes, hypertension or hepatic impairment. Liver function, blood pressure and blood glucose should be monitored, and gynaecomastia and gastrointestinal upset are common.

Pregnancy

Not applicable to its indication; it is genotoxic, and effective contraception is advised for male patients with partners of child-bearing potential.

Source: reference summary prepared from the EU SmPC/EPAR, BNF and WHO Model Formulary. The approved product information in Iran governs.