EMCYT- estramustine phosphate sodium capsule
Pharmacia and Upjohn Company
DESCRIPTION
Estramustine phosphate sodium, an antineoplastic agent, is an off-white powder readily soluble in water. EMCYT Capsules are white and opaque, each containing estramustine phosphate sodium as the disodium salt monohydrate equivalent to 140 mg estramustine phosphate, for oral administration. Each capsule also contains magnesium stearate, silicon dioxide, sodium lauryl sulfate, and talc. Gelatin capsule shells contain the following pigment: titanium dioxide.
Chemically, estramustine phosphate sodium is estra-1,3,5(10)-triene-3,17-diol(17?)-,3-[bis(2-chloroethyl)carbamate] 17-(dihydrogen phosphate), disodium salt, monohydrate. It is also referred to as estradiol 3-[bis(2-chloroethyl)carbamate] 17-(dihydrogen phosphate), disodium salt, monohydrate. Estramustine phosphate sodium has an empiric formula of C23 H30 Cl2 NNa2 O6 P�H2 O, a calculated molecular weight of 582.4, and the following structural formula:
Chemical Structure
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CLINICAL PHARMACOLOGY
Estramustine phosphate (Figure 1) is a molecule combining estradiol and nornitrogen mustard by a carbamate link. The molecule is phosphorylated to make it water soluble.
Chemical Structure
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Estramustine phosphate taken orally is readily dephosphorylated during absorption, and the major metabolites in plasma are estramustine (Figure 2), the estrone analog (Figure 3), estradiol, and estrone.
Chemical StructureChemical Structure
Prolonged treatment with estramustine phosphate produces elevated total plasma concentrations of estradiol that fall within ranges similar to the elevated estradiol levels found in prostatic cancer patients given conventional estradiol therapy. Estrogenic effects, as demonstrated by changes in circulating levels of steroids and pituitary hormones, are similar in patients treated with either estramustine phosphate or conventional estradiol.
The metabolic urinary patterns of the estradiol moiety of estramustine phosphate and estradiol itself are very similar, although the metabolites derived from estramustine phosphate are excreted at a slower rate.
Emcyt Indications and Usage
EMCYT Capsules are indicated in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate.
CONTRAINDICATIONS
EMCYT Capsules should not be used in patients with any of the following conditions:
1)
Known hypersensitivity to either estradiol or to nitrogen mustard.
2)
Active thrombophlebitis or thromboembolic disorders, except in those cases where the actual tumor mass is the cause of the thromboembolic phenomenon and the physician feels the benefits of therapy may outweigh the risks.
