Objective: This study investigated the effect of varenicline on the multiple-dose pharmacokinetics of digoxin.
Methods: Eighteen smokers were randomized to receive digoxin (Lanoxicaps 0.2 mg QD) with varenicline 1 mg BID or placebo for 14 days.
Results: Varenicline had no clinically relevant effect on the digoxin steady-state exposure, as evidenced by the 90% confidence intervals for the ratios of AUC(0-24) (87.5-108%) and C(min) (83.8-116%) wholly contained within 80-125%. Digoxin C(max) and T(max) remained unchanged in the presence of varenicline, consistent with no apparent alteration in digoxin bioavailability. A minimal 11.3% increase in digoxin renal clearance was noted during varenicline treatment while having no impact on its systemic exposure. Results are supported by mechanistic evidence in Caco-2 cell monolayers that varenicline is neither a P-gp substrate nor an inhibitor of P-gp-mediated efflux of digoxin. Co-administration of varenicline and digoxin was well tolerated.
Conclusion: The results suggest that digoxin can be safely administered with varenicline without the need for dose adjustment.