Evaluation of Effects of Terbinafine on Single Oral Dose Pharmacokinetics and Anticoagulant Actions of Warfarin in Healthy Volunteers

Study Objective . To evaluate the potential effects of oral terbinafine, a new synthetic antifungal agent of the allylamine class, on the pharmacokinetics and pharmacodynamics of racemic warfarin. Design . Randomized, double‐blind, placebo‐controlled, crossover study. Subjects . Sixteen healthy men. Interventions . Placebo or terbinafine 250 mg was administered once/day for 14 consecutive days, separated by a washout period lasting at least 2 weeks. A single oral dose of racemic warfarin 30 mg was coadministered with placebo or terbinafine on day 8 of each treatment period. Blood samples were collected for 168 hours after administration of warfarin to determine the drug's pharmacokinetics and anticoagulant effects. Measurements and Main Results . No major differences were seen in the plasma concentration‐time profiles of a single dose of warfarin administered with terbinafine or with placebo. Conclusions . Because of the lack of clinically significant interactions between terbinafine and warfarin during multiple‐dose administration of terbinafine, no adjustment of warfarin dosage during concomitant therapy appears to be necessary.