proton pump inhibitors (PPIs) and warfarin

Last edited 06/2022 and last reviewed 07/2022

Proton pump inhibitors (PPIs) and warfarin

A clinically significant interaction between warfarin and Proton Pump Inhibitors (PPIs) is not expected (1)

• however, case reports of PPIs increasing the INR resulting in bleeding have been documented in the literature and in post-marketing surveillance
  
  
  
• combined use of warfarin with omeprazole or esomeprazole can potentially enhance the anticoagulant effect of warfarin possibly as a result of CYP2C19 enzyme inhibition
• combined use of warfarin with lansoprazole, pantoprazole and rabeprazole has led to cases of increased INR and bleeding
  • mechanism for this is unknown
    
    
• evidence relating to interaction between warfarin and PPIs
• case reports of PPIs increasing the International Normalised Ratio (INR) resulting in bleeding have been documented in the literature and in post-marketing surveillance
• two studies found that omeprazole increased the plasma concentration of an isomer of warfarin but the increases were not considered clinically significant
• studies with esomeprazole, lansoprazole, pantoprazole and rabeprazole found no significant changes in warfarin plasma concentration or coagulation times
• monitoring:
  • when starting a PPI in a patient on warfarin
    • SPCs for esomeprazole, lansoprazole and pantoprazole recommend monitoring when starting or stopping in patients taking warfarin
    • it is advised to monitor INR in patients (especially the elderly) who are started on a PPI
  • when stopping a PPI in a patient on warfarin
    • warfarin monitoring is recommended when stopping PPIs in patients stabilised on warfarin

Reference:

• NHS Specialist Pharmacy Service (June 2022). Using Proton Pump Inhibitors (PPIs) alongside warfarin - clinical considerations