DRUG INTERACTIONS
Potent CYP3A4 Inhibitors
Following the administration of 10 mg of VESIcare in the presence of 400 mg of ketoconazole, a potent inhibitor of CYP3A4, the mean Cmax and AUC of solifenacin increased by 1.5 and 2.7-fold, respectively. Therefore, it is recommended not to exceed a 5 mg daily dose of VESIcare when administered with therapeutic doses of ketoconazole or other potent CYP3A4 inhibitors [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)]. The effects of weak or moderate CYP3A4 inhibitors were not examined.
CYP3A4 Inducers
There were no in vivo studies conducted to evaluate the effect of CYP3A4 inducers on VESIcare. In vitro drug metabolism studies have shown that solifenacin is a substrate of CYP3A4. Therefore, inducers of CYP3A4 may decrease the concentration of solifenacin.
Drugs Metabolized by Cytochrome P450
At therapeutic concentrations, solifenacin does not inhibit CYP1A1/2, 2C9, 2C19, 2D6, or 3A4 derived from human liver microsomes.
Warfarin
Solifenacin has no significant effect on the pharmacokinetics of R-warfarin or S-warfarin [see Clinical Pharmacology (12.3)].
Oral Contraceptives
In the presence of solifenacin there are no significant changes in the plasma concentrations of combined oral contraceptives (ethinyl estradiol/levonorgestrel) [see Clinical Pharmacology (12.3)].
Digoxin
Solifenacin had no significant effect on the pharmacokinetics of digoxin (0.125 mg/day) in healthy subjects [see Clinical Pharmacology (12.3)].
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