Drug interactions between Coumadin and modafinil

MONITOR: Theoretically, coadministration with modafinil (the racemate) or armodafinil (the R-enantiomer) may increase the plasma concentrations of warfarin and other coumarin anticoagulants. Exposure of human hepatocytes to modafinil in vitro has produced concentration-dependent suppression of CYP450 2C9, the isoenzyme that metabolizes warfarin, but no indication of CYP450 2C9 suppression has been observed clinically. In a study in which 28 healthy subjects received warfarin (5 mg single dose) alone and after treatment with either modafinil (200 mg for 7 days followed by 400 mg for 21 days) or placebo, the pharmacokinetics of warfarin were not significantly altered following modafinil compared to placebo. However, the potential for more subtle interactions after chronic warfarin administration cannot be ruled out.

MANAGEMENT: Given the potential for interaction and the high degree of interpatient variability with respect to anticoagulant metabolism, patients should be closely monitored during concomitant therapy with modafinil or armodafinil. The INR should be checked regularly for the first several months of coadministration and thereafter whenever modafinil or armodafinil dosing is changed or stopped. Patients should be advised to promptly report any signs of bleeding to their doctor, 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.