Drug interactions between dicumarol and Flagyl

MONITOR CLOSELY: Coadministration with metronidazole may increase the plasma concentrations and hypoprothrombinemic effect of warfarin. The proposed mechanism is metronidazole inhibition of CYP450 2C9, the isoenzyme responsible for the metabolic clearance of the more active S(-) enantiomer of warfarin. The interaction was associated with significant bleeding and elevation of prothrombin time in two case reports. No data are available for other oral anticoagulants, although at least one other coumarin derivative is known to be metabolized by CYP450 2C9. MANAGEMENT: Given the potential for interaction and the high degree of interpatient variability with respect to warfarin metabolism, patients should be closely monitored during concomitant therapy with metronidazole. The INR should be checked frequently and warfarin dosage adjusted accordingly, particularly following initiation or discontinuation of metronidazole in patients who are stabilized on their warfarin regimen. The same precaution may be applicable during therapy with other oral anticoagulants, although clinical data are lacking. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.