Multiple doses of the antimuscarinic agent solifenacin do not affect the pharmacodynamics or pharmacokinetics of warfarin or the steady‐state pharmacokinetics of digoxin in healthy subjects

Abstract

Solifenacin succinate is used for the treatment of overactive bladder (OAB). The potential for pharmacokinetic and/or pharmacodynamic interactions between solifenacin and warfarin or digoxin was investigated. The solifenacin-warfarin study was a two-period crossover trial conducted in healthy males. Subjects received warfarin on the 10th day of 16 days of dosing with either solifenacin or placebo. The solifenacin-digoxin study was an one-sequence crossover trial conducted in healthy males and females. Following a phase-in period for digoxin, solifenacin was administered concomitantly with the drug on days 9-18. The AUC(PT; 0-168 h) following a single dose of warfarin was unchanged in the presence of solifenacin [point estimate = 1.005; 90% confidence interval (CI) 0.98, 1.02)]. The AUC(0-infinity) values for both warfarin enantiomers were also unchanged. A small increase in the C(max) of digoxin was observed during treatment with solifenacin, but for AUC(ss,tau) and C(max) the 90% CI fell within the prespecified interval of 0.80-1.25. Combined administration of solifenacin and warfarin or digoxin was well tolerated. Since the pharmacokinetics and pharmacodynamics of a single dose of warfarin and the steady-state pharmacokinetics of digoxin were not affected by coadministration of solifenacin in healthy subjects, the need for dosing adjustments for digoxin and/or warfarin does not seem warranted.