Drug interactions between Coumadin and rabeprazole

MONITOR: Coadministration with proton pump inhibitors (PPIs) has occasionally been associated with enhanced hypoprothrombinemic effect of warfarin. The exact mechanism is unknown but may involve PPI inhibition of CYP450 2C19 and/or 3A4, the isoenzymes partially responsible for the metabolic clearance of the biologically less active R(+) enantiomer of warfarin. There have been reports of increased INR and prothrombin time in patients receiving warfarin with various commercially available proton pump inhibitors. However, a significant pharmacokinetic interaction has not been reported. In one study, coadministration of omeprazole 20 mg/day and warfarin (individualized dosage) in 21 healthy, young men for 2 weeks resulted in a 12% increase in the mean plasma concentration of R(+) warfarin compared to coadministration with placebo. Plasma concentrations of the S(-) enantiomer were unaffected, and no clinically significant alterations in coagulation times were noted. Similar results were reported in a group of 28 patients on continuous therapy with warfarin given omeprazole 20 mg/day for 3 weeks. Additionally, other studies reported no pharmacokinetic interaction between warfarin and pantoprazole or dexlansoprazole.

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 PPIs. The INR should be checked frequently and warfarin dosage adjusted accordingly, particularly following initiation, discontinuation or change of dosage of PPI in patients who are stabilized on their warfarin regimen. The same precaution may be applicable during therapy with other oral anticoagulants. 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.