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Drug-Drug interaction: Drug interactions have not been assessed for estradiol gel. Nevertheless, with transdermal administration, the first-pass effect in the liver is avoided and, thus, transdermally applied estrogens might be less affected than oral hormones by enzyme inducers.
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, efavirenz and rifampicin 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 undesirable effects.
