In pharmacological studies,sulindac did not significantly alterthe anticoagulant effect of warfarin or phenprocoumon. Isolatedcases of a modest to marked increase in anticoagulant effectsof warfarin have been reported with sulindac. Note that all NSAIDs increase risk of gastrointestinal bleeding, and anincreased risk is seen when they are combined with anticoagulants.
In a study in healthy subjects stabilised on warfarin, sulindac 200mg twice daily for 7 days did not significantly alter prothrombin time, when compared with placebo, although prothrombin time was slightly higher in sulindac group (See reference number 1). Similarly,in 20 patients stabilised on phenprocoumon, sulindac 200 to 400mg daily for 4 weeks did not alter measures of coagulation or bleeding time (See reference number 2).
However,a patient stabilised on warfarin, ferrous sulfate, phenobarbital and sulfasalazine had a marked increase in his prothrombin time ratio from about 3.2 to 10 after taking sulindac 100mg twice daily for 5 days (See reference number 3-5). There are 4 similar cases of this interaction on record (See reference number 1,5-7). One of patients had a gastrointestinal bleed after taking only three 100mg doses of sulindac, although this patient was also taking flurbiprofen (See reference number 5). Another patient was stabilised on about a 40 % lower dose of warfarin with continuation of sulindac (See reference number 6). Another patient had a potassium-losing renal tubular defect, which was thought to contribute to interaction (See reference number 1).
Not understood. In one patient,renal impairment may have caused sulindac accumulation, which in turn may have affected warfarin pharmacokinetics (See reference number 1). See also Coumarins and related drugs + NSAIDs interaction.
The pharmacological studies cited suggest that usually no coumarin dose adjustment would be needed in patients given sulindac. However, isolated cases of an interaction suggest that, rarely, some patients may be affected. Also note that all NSAIDs, can irritate gastric mucosa, affect platelet activity and cause gastrointestinal bleeding, which will be more severe in anticoagulated patients.
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