Interaction of rofecoxib with warfarin

ADRAC has previously published a report on the interaction between celecoxib and warfarin¹; it appears that rofecoxib (Vioxx) and warfarin may also sometimes interact to a clinically significant extent.

ADRAC has received 416 reports of suspected adverse reactions to rofecoxib since its marketing in Australia in late 2000. Of these, 8 described an increase in the INR in patients taking warfarin. In 6 of those reports, INR values were given, ranging from 3.8 to 11.8. In half of the reports, the timing of the reaction relative to the date of commencing rofecoxib was accurately described; this varied from 1 to 6 weeks. Five of the 8 reports did not describe haemorrhagic complications, however bleeding was reported in 2 cases (epistaxis and rectal haemorrhage) and anaemia (haemoglobin 87 g/L) in one case. Five patients were hospitalised, and 2 received treatment with intravenous vitamin K.

A further report described a patient taking both rofecoxib and warfarin, who died after a cerebral haemorrhage, although in this case the INR was stable (1.7 - 2.5) throughout.

A recently-published study showed that rofecoxib 25 mg daily for 21 days added to a stable warfarin regime increased INR by an average of 8%.² Celecoxib and warfarin are both metabolised by the enzyme CYP2C9, which may provide an explanation for the interaction of those two drugs. A mechanism for the interaction of rofecoxib and warfarin is unknown.

ADRAC recommends that, in patients taking warfarin, increased monitoring of INR should be conducted when rofecoxib treatment is started, stopped or the dose changed.

Reference

1. ADRAC. Interaction of celecoxib and warfarin. Aust Adv Drug React Bull 2001; 20: 2.
2. Schwartz JI, Bugianesi KJ, Ebel DL et al. The effect of rofecoxib on the pharmacodynamics and pharmacokinetics of warfarin. Clin Pharmacol Ther 2000; 68: 626-36.