Data from a drug-drug interaction study involving conjugated estrogens and medroxyprogesterone acetate (MPA) indicate that the pharmacokinetic disposition of both drugs is not altered when the drugs are coadministered. Other clinical drug-drug interaction studies have not 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 (Hypericum perforatum) preparations, phenobarbital, phenytoin, carbamazepine, rifampicin and dexamethasone 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 cimetidine, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice, may increase plasma concentrations of estrogens and may result in side effects.
Interference with Laboratory and Other Diagnostic Tests: Laboratory Test Interactions: Increased platelet count; decreased levels of antithrombin III, and increased plasminogen antigen and activity.
Estrogens increase thyroid-binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 levels by column or by radioimmunoassay or T3 levels by radioimmunoassay. T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered.
Other binding proteins may be elevated in serum, i.e., corticosteroid binding globulin (CBG), sex hormone-binding globulin (SHBG) leading to increased circulating corticosteroid and sex steroids, respectively. Free or biologically active hormone concentrations may be decreased.
Increased plasma HDL and HDL2 cholesterol subfraction concentrations, reduced LDL cholesterol concentrations, increased triglyceride levels.
Impaired glucose tolerance.
The response to metyrapone may be reduced.