MONITOR: Isoniazid may increase the anticoagulant effect of warfarin, perhaps by inhibition of warfarin metabolism. This effect has been reported with an isoniazid dose of 600 mg per day. Other oral anticoagulants may interact with isoniazid in a similar fashion. The proposed mechanism is inhibition of CYP450 2C9 hepatic metabolism by isoniazid.
MANAGEMENT: The patient's INR should be monitored, and the anticoagulant dosage should be adjusted if necessary, whenever isoniazid is initiated, discontinued or the dosage is changed. 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 bruising, red or brown urine, or red or black stools.
GENERALLY AVOID: Rifampin may decrease the anticoagulant effect of warfarin by enhancing CYP450 hepatic microsomal enzyme metabolism of warfarin.
MANAGEMENT: Concurrent use should be avoided unless no alternatives are available. The INR or prothrombin time should be monitored closely during concomitant therapy and after rifampin is discontinued. Adjustments in warfarin dosage may be needed when rifampin dosage is added, discontinued, or changed. This interaction may occur with other oral anticoagulants and with rifabutin.
