Drug interactions between MetroLotion and warfarin

MONITOR: Coadministration with vaginal metronidazole may enhance the hypoprothrombinemic effect of warfarin and other oral anticoagulants. 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 has been reported with systemically administered metronidazole and warfarin. Significant bleeding and elevation of prothrombin time have been observed. No data are available for vaginally administered metronidazole. Although peak serum levels and systemic exposure are substantially lower than in systemic administration, the possibility of an interaction cannot be excluded.

MANAGEMENT: The potential for interaction with warfarin and other oral anticoagulants should be considered during coadministration with vaginal preparations of metronidazole. The INR should be checked frequently and anticoagulant dosage adjusted accordingly, particularly following initiation and discontinuation of metronidazole therapy in patients who are stabilized on their anticoagulant regimen. 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.