warfarin and sulfasalazine

Sulfasalazine and its metabolite sulfapyridine may inhibit the metabolism of warfarin via CYP2C9, and may also displace warfarin from plasma protein binding sites. These actions increase the plasma concentration of warfarin, enhancing its anticoagulant effect.

Patients receiving warfarin may develop an elevated INR, prolongation of prothrombin time, and an increased risk of bleeding, including gastrointestinal bleeding and haemorrhage. The onset of interaction is variable, and significant bleeding may occur.

If co-prescription is necessary, monitor INR frequently, especially after starting or stopping sulfasalazine. Consider reducing the warfarin dose to maintain the target INR. Advise the patient to report signs of bleeding such as bruising, black stools, or blood in urine. Alternative therapy with less interaction potential may be considered.

Case reports and small studies support an increase in anticoagulant effect when sulfasalazine is added to warfarin. Although not extensively studied in large trials, the interaction is considered well documented clinically. The risk is likely higher at higher doses of sulfasalazine.