Moderate
Probable
Description
Ranitidine can modestly increase warfarin plasma levels and INR by inhibiting CYP2C9-mediated warfarin metabolism, though the magnitude is smaller than with cimetidine.
Mechanism
Ranitidine weakly inhibits CYP2C9, the primary enzyme responsible for S-warfarin hydroxylation; reduced clearance leads to higher warfarin concentrations and elevated INR.
Clinical Significance
Case reports and pharmacokinetic studies show modest but clinically relevant INR elevations; the interaction is less pronounced than the well-established cimetidine-warfarin interaction.
Management
Monitor INR when starting or stopping ranitidine in patients on warfarin; adjust warfarin dose if INR rises above therapeutic range; consider switching to a PPI with less CYP interaction (e.g., pantoprazole).