Absence of a pharmacokinetic interaction between etanercept and warfarin

Etanercept, a soluble recombinant human tumor necrosis factor receptor (TNFr) fusion protein, is effective and well tolerated in the treatment of rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). The primary objective of this study was to investigate the potential pharmacokinetic and pharmacodynamic interaction between a single dose of R- and S-enantiomers of warfarin and multiple doses of etanercept after administration of warfarin and etanercept alone and together. In a nonrandomized, three-period study, 12 healthy male subjects received a single oral 25-mg dose of warfarin after an overnight fast, followed by twice-weekly 25-mg subcutaneous doses of etanercept for seven doses. The last dose of etanercept was administered concurrently with a second dose of warfarin. Serial blood samples for plasma warfarin concentration measurement and international normalized ratio (INR) assessment were collected before and up to 144 hours after dose administration. Serial blood samples for serum etanercept concentration measurement were collected before and up to 60 hours after the sixth dose and 264 hours after the seventh dose. Etanercept did not affect the pharmacokinetics and pharmacodynamics of warfarin. All ratios of maximum serum concentration (C(max)) and area under the serum concentration versus time curve (AUC) for pharmacokinetics (R- and S-enantiomers of warfarin) and INR fell within the confidence interval of 0.8 to 1.25. Warfarin also did not cause a clinically significant alteration in the pharmacokinetics of etanercept. In conclusion, coadministration of etanercept and warfarin would not be expected to change the pharmacokinetics of either medication; therefore, no dosage adjustment is needed in cases in which warfarin and etanercept are coadministered.