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


DMPK Department, Novartis Pharmaceuticals, 2-4 rue Lionel Terray, 92500 Rueil-Malmaison, France


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.