Evaluation of pharmacokinetic and pharmacodynamic interactions when lenalidomide is co-administered with warfarin in a randomized clinical trial setting.

Abstract

Lenalidomide is an oral immunomodulatory drug used to treat multiple myeloma and some other hematological malignancies. Warfarin is often used concomitantly as prophylaxis against potential venous thromboembolism associated with lenalidomide treatment. The objective of this study was to evaluate the pharmacokinetic and pharmacodynamic drug interactions between lenalidomide and warfarin in healthy volunteers. This was a double-blind, placebo-controlled, randomized, two-period crossover study. Eighteen healthy male and female subjects were treated with 10 mg/day lenalidomide or placebo for 9 days. A single oral 25 mg dose of warfarin was administered on Day 4 of each treatment period. Blood was sampled to determine international normalized ratio (INR), prothrombin time (PT), and area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C max) warfarin and lenalidomide. The 90 % confidence intervals (CI) for the ratio of AUC or Cmax geometric means between co-administration with lenalidomide and placebo were within the 80-125 % bioequivalence bounds for R-warfarin and S-warfarin. The 90 % CI for the ratio of area under the INR curve from time zero until 144 hours after dosing (AUCINR, 0-144) or the peak INR geometric means between co-administration with lenalidomide versus placebo was also within the 85-125 % bounds. Additionally, the AUC and C max values of lenalidomide were not altered by co-administration with warfarin. Co-administration of lenalidomide with warfarin did not alter the plasma exposure or anticoagulant effect to warfarin or the plasma exposure to lenalidomide, indicating that no dose adjustment of either drug is needed when these two drugs are co-administered.