Failure of Indomethacin and Warfarin to Interact in Normal Human Volunteers

In young, normal, male Caucasian volunteers, two different double-blind, placebo-controlled, randomized studies were performed to determine whether indomethacin interacts in a clinically significant fashion with warfarin. In the first study, stabilized hypoprothrombinemia was achieved by daily oral warfarin administration for at least 11 days; then indomethacin was administered concurrently with warfarin for five more days. During this five-day period failure of indomethacin to alter the degree of hypoprothhrombinemia induced by warfarin indicated that indomethacin does not interact with warfarin in vivo in a clinically significant fashion. A similar conclusion was drawn from results of the second experiment, in which plasma warfarin concentrations and prothrombin times were measured after a single oral dose of warfarin administered both before and after ten consecutive days of oral indomethacin administration. Thus, these studies suggest that warfarin may be given to patients receiving indomethacin and indomethacin may be administered to patients on warfarin without intensification or diminution of the normally expected hypoprothrombinemie effects of the dose of warfarin in that individual.