DRUG INTERACTIONS
Data from a single-dose drug-drug interaction study involving conjugated estrogens and medroxyprogesterone acetate indicate that the pharmacokinetic disposition of both drugs is not altered when the drugs are coadministered. No other clinical drug-drug interaction studies have been conducted with conjugated estrogens.
In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4 such as St. John's Wort preparations (Hypericum perforatum), phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects.
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CONTRAINDICATIONS
Estrogens/progestins combined should not be used in women with any of the following conditions:
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Undiagnosed abnormal genital bleeding.
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Known, suspected, or history of cancer of the breast.
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Known or suspected estrogen-dependent neoplasia.
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Active deep vein thrombosis, pulmonary embolism or a history of these conditions.
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Active or recent (e.g., within past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction).
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Liver dysfunction or disease.
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PREMPRO or PREMPHASE therapy should not be used in patients with known hypersensitivity to their ingredients.
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Known or suspected pregnancy. There is no indication for PREMPRO or PREMPHASE in pregnancy. There appears to be little or no increased risk of birth defects in children born to women who have used estrogen and progestins from oral contraceptives inadvertently during pregnancy. (See PRECAUTIONS.)
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