DRUG INTERACTIONS F. Drug Interactions
Data from a single-dose drug-drug interaction study involving conjugated estrogens and medroxyprogesterone acetate indicate that the pharmacokinetic dispositions of both drugs are 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.
|
OVERDOSAGE
Overdosage of estrogen may cause nausea and vomiting, breast tenderness, abdominal pain, drowsiness/fatigue and withdrawal bleeding may occur in females. Treatment of overdose consists of discontinuation of Premarin together with institution of appropriate symptomatic care.
|
CONTRAINDICATIONS
Premarin therapy should not be used in individuals with any of the following conditions:
- Undiagnosed abnormal genital bleeding.
- Known, suspected, or history of cancer of the breast except in appropriately selected patients being treated for metastatic disease.
- Known or suspected estrogen-dependent neoplasia.
- Active deep vein thrombosis, pulmonary embolism or a history of these conditions.
- Active or recent (within the past year) arterial thromboembolic disease (for example, stroke, myocardial infarction).
- Liver dysfunction or disease.
- Known hypersensitivity to any of the ingredients in Premarin.
- Known or suspected pregnancy.
|
