Emcyt Information
Emcyt (Estramustine phosphate sodium) Description
Estramustine phosphate sodium, an antineoplastic agent, is an off-white powder readily soluble in water. Emcyt (Estramustine phosphate sodium) 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(17β)-,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 CHClNNaOP•HO, a calculated molecular weight of 582.4, and the following structural formula:
Emcyt (Estramustine phosphate sodium) 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.
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.
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 (Estramustine phosphate sodium) Indications And Usage
Emcyt (Estramustine phosphate sodium) Capsules are indicated in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate.
Emcyt (Estramustine phosphate sodium) Contraindications
Emcyt (Estramustine phosphate sodium) Capsules should not be used in patients with any of the following conditions:
Emcyt (Estramustine phosphate sodium) Warnings
It has been shown that there is an increased risk of thrombosis, including fatal and nonfatal myocardial infarction, in men receiving estrogens for prostatic cancer. Emcyt (Estramustine phosphate sodium) Capsules should be used with caution in patients with a history of thrombophlebitis, thrombosis, or thromboembolic disorders, especially if they were associated with estrogen therapy. Caution should also be used in patients with cerebral vascular or coronary artery disease.
Glucose Tolerance—Because glucose tolerance may be decreased, diabetic patients should be carefully observed while receiving Emcyt (Estramustine phosphate sodium) .
Elevated Blood Pressure—Because hypertension may occur, blood pressure should be monitored periodically.
Emcyt (Estramustine phosphate sodium) Precautions
Fluid Retention. Exacerbation of preexisting or incipient peripheral edema or congestive heart disease has been seen in some patients receiving therapy with Emcyt (Estramustine phosphate sodium) Capsules. Other conditions which might be influenced by fluid retention, such as epilepsy, migraine, or renal dysfunction, require careful observation.
Emcyt (Estramustine phosphate sodium) may be poorly metabolized in patients with impaired liver function and should be administered with caution in such patients.
Because Emcyt (Estramustine phosphate sodium) may influence the metabolism of calcium and phosphorus, it should be used with caution in patients with metabolic bone diseases that are associated with hypercalcemia or in patients with renal insufficiency. Patients with prostate cancer and osteoblastic metastases are at risk for hypocalcemia and should have calcium levels closely monitored.
Gynecomastia and impotence are known estrogenic effects.
Allergic reactions and angioedema at times involving the airway have been reported.
Emcyt (Estramustine phosphate sodium) Adverse Reactions
In a randomized, double-blind trial comparing therapy with Emcyt (Estramustine phosphate sodium) Capsules in 93 patients (11.5 to 15.9 mg/kg/day) or diethylstilbestrol (DES) in 93 patients (3.0 mg/day), the following adverse effects were reported:
Emcyt (Estramustine phosphate sodium) Overdosage
Although there has been no experience with overdosage to date, it is reasonable to expect that such episodes may produce pronounced manifestations of the known adverse reactions. In the event of overdosage, the gastric contents should be evacuated by gastric lavage and symptomatic therapy should be initiated. Hematologic and hepatic parameters should be monitored for at least 6 weeks after overdosage of Emcyt (Estramustine phosphate sodium) Capsules.
Emcyt (Estramustine phosphate sodium) Dosage And Administration
The recommended daily dose is 14 mg per kg of body weight (ie, one 140 mg capsule for each 10 kg or 22 lb of body weight), given in 3 or 4 divided doses. Most patients in studies in the United States have been treated at a dosage range of 10 to 16 mg per kg per day.
Patients should be instructed to take Emcyt (Estramustine phosphate sodium) Capsules at least 1 hour before or 2 hours after meals. Emcyt (Estramustine phosphate sodium) should be swallowed with water. Milk, milk products, and calcium-rich foods or drugs (such as calcium-containing antacids) must not be taken simultaneously with Emcyt (Estramustine phosphate sodium) .
Patients should be treated for 30 to 90 days before the physician determines the possible benefits of continued therapy. Therapy should be continued as long as the favorable response lasts. Some patients have been maintained on therapy for more than 3 years at doses ranging from 10 to 16 mg per kg of body weight per day.
Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
Emcyt (Estramustine phosphate sodium) How Supplied
White opaque capsules, each containing estramustine phosphate sodium as the disodium salt monohydrate equivalent to 140 mg estramustine phosphate—bottle of 100 (NDC 0013-0132-02).
Emcyt (Estramustine phosphate sodium) Capsules should be stored in the refrigerator at 36° to 46°F (2° to 8°C).
Emcyt (Estramustine phosphate sodium)
Emcyt (Estramustine phosphate sodium) Principal Display Panel - Mg Capsule Bottle Label
