Published: September 2001
Prescriber Update 22: 16-18
Medsafe Editorial Team
The selective COX-2 inhibitors, celecoxib (Celebrex™) and rofecoxib (Vioxx™), may interact with warfarin causing an increase in the international normalised ratio (INR) and putting the patient at risk of a haemorrhagic event. If a COX-2 inhibitor is considered necessary for a patient taking warfarin, the INR should be checked a few days after introduction of the COX-2 inhibitor and monitored closely for the first two weeks. If the INR increases, the dose of warfarin should be reduced or the COX-2 inhibitor withdrawn. Monitor the INR with either option.
The New Zealand Centre for Adverse Reactions Monitoring (CARM) has received one report of a possible interaction between celecoxib and warfarin. A 59-year-old man, stablised on warfarin, developed haematuria after three doses of celecoxib; his international normalised ratio (INR) had risen to 3.1.
Up to the middle of May 2001, the Australian Adverse Drug Reactions Advisory Committee (ADRAC) had received 37 reports of possible interaction between celecoxib and warfarin. Twenty of these reports described an increase in INR and 17 a bleeding event with or without a recorded increase in INR. In two cases the INR was more than 10. In most cases there was evidence of the interaction within two weeks of starting celecoxib. None of the patients died. Most of the patients were more than 60 years old.
The ADRAC database also holds four reports of possible interaction between rofecoxib and warfarin. Two cases were of raised INR and two of bleeding events, including a fatal cerebral haemorrhage.
The mechanism of the interaction is unknown, but it is possible that celecoxib inhibits the metabolism of warfarin by CYP2C9.1,2 Less is known about the interaction with rofecoxib.
If celecoxib or rofecoxib are considered necessary for a patient taking warfarin, the INR should be checked a few days after introduction of the COX-2 inhibitor and monitored closely for the first two weeks. The INR should be checked again if the dose of either agent is changed. Particular care should be taken if the patient is elderly, and/or is taking multiple medicines or suffers from multiple diseases. If the INR increases, it may be possible to continue the selective COX-2 inhibitor by reducing the dose of warfarin.2,3 Otherwise the COX-2 inhibitor should be discontinued to avoid a haemorrhagic event. The INR should be checked and restabilised following any dose reduction of warfarin or cessation of the COX-2 inhibitor.
The interaction between COX-2 inhibitors and warfarin has now been included in the list of adverse reactions of current concern in order to encourage reporting of these adverse events and to gather more data about them.
Competing interests (authors): none declared