Celecoxib Does Not Significantly Alter the Pharmacokinetics or Hypoprothrombinemic Effect of Warfarin in Healthy Subjects

Abstract

The objective of this study was to determine the effects of celecoxib, an anti-inflammatory/analgesic agent that primarily inhibits COX-2 and not COX-1 at therapeutic doses, on the steady-state pharmacokinetic profile and hypoprothrombinemic effect of racemic warfarin in healthy volunteers. Twenty-four healthy adult volunteers on maintenance doses of racemic warfarin (2-5 mg daily), stabilized to prothrombin times (PT) 1.2 to 1.7 times pretreatment PT values for 3 consecutive days, were randomized to receive concomitant celecoxib (200 mg bid) or placebo for 7 days in an open-label, multiple-dose, randomized, placebo-controlled, parallel-group study of warfarin pharmacokinetics and PT. Steady-state exposure of S- and R-warfarin (area under the curve [AUC]) and maximum plasma concentration (Cmax) in subjects receiving celecoxib were within 2% to 8% of the warfarin AUC and Cmax in subjects receiving placebo during the concomitant treatment period. In addition, PT values were not significantly different in subjects receiving warfarin and celecoxib concomitantly compared with subjects receiving warfarin and placebo. In conclusion, concomitant administration of celecoxib has no significant effect on PT or steady-state pharmacokinetics of S- or R-warfarin in healthy volunteers.

The Potential Inhibitory Effect of Revaprazan, an Acid Pump Antagonist, on Anticoagulation with Warfarin

“…The typical example is the celecoxib-warfarin interaction. The manufacturer had concluded no interaction with warfarin by performing open-label, multi-dose, placebo-controlled randomized study performed on 24 healthy volunteers (Karim et al 2000). However, after its introduction to market, a few case reports began to emerge about clinically significant delays in INR (Mersfelder and Stewart 1997;Haase et al 2000).…”

Revisiting the Significance of Warfarin Protein-Binding Displacement Interactions

“…Celecoxib and rofecoxib are recently marketed NSAIDs that are reported 19,20 to have no significant effects on bleeding time or platelet aggregation. Initial product labeling 21 for celecoxib reported that a drug interaction study in healthy volunteers showed that the drug did not alter the anticoagulant effects of warfarin.…”

Neuroimmune Interaction

“…This observation should represent a possible mechanism for how a drug interaction may be elicited in the drug metabolizing system. However, in this particular observation this has to be further elucidated, since the warfarin-celecoxib interaction was not seen in healthy volunteers (Karim et al 2000).…”