Drug interactions between warfarin and Xenical

MONITOR: Coadministration with orlistat may potentiate the hypoprothrombinemic effect of oral anticoagulants. The proposed mechanism is orlistat reduction of the absorption of vitamin K, a fat-soluble vitamin and cofactor in the synthesis of blood clotting factors that are inhibited by oral anticoagulants. In addition, dietary changes often prompted by orlistat use may also alter vitamin K intake and contribute to the interaction. A case report describes a 66-year-old patient stabilized on warfarin who was found to have an increased INR during a follow-up visit 18 days after starting orlistat. A significant reduction in warfarin dosage was subsequently required to maintain INR in the therapeutic range while receiving orlistat.

MANAGEMENT: Patients should be closely monitored during concomitant therapy with oral anticoagulants and orlistat. The INR should be checked frequently and anticoagulant dosage adjusted accordingly, particularly following initiation or discontinuation of orlistat 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.