Complications for using PPIs with warfarin

A clinically significant interaction between warfarin and Proton Pump Inhibitors (PPIs) is not expected.  However, case reports of PPIs increasing the INR resulting in bleeding have been documented in the literature and in post-marketing surveillance.

Interaction

Evidence

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.

Mechanism

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. The mechanism for this is unknown.

Licensing information

The Summary of Product Characteristics (SPC) for warfarin lists omeprazole as a medication that can enhance the anticoagulant effect of warfarin. Similarly, the SPC for omeprazole states that use can increase the overall exposure to warfarin.

The SPCs for esomeprazole, lansoprazole and pantoprazole note that, although an interaction with warfarin is not expected, there have been post-marketing reports of increased INR.

The SPC for rabeprazole does not list an interaction with warfarin.

Initiating a PPI

Choosing a suitable PPI

Before initiating PPIs in a patient who is stabilised on warfarin consider

• Whether a PPI is required or whether another agent can be used
• Which PPI is least likely to have an effect on the patients INR
• What monitoring may be required post initiation of a PPI

Monitoring

SPCs for esomeprazole, lansoprazole and pantoprazole recommend monitoring when starting or stopping in patients taking warfarin.

The NICE Clinical Knowledge Summary prescribing information for warfarin advises to monitor INR in patients (especially the elderly) who are started on a PPI. Patients who are prescribed a drug that may interact with warfarin should have an INR test performed after 3–5 days.

Further guidance on monitoring patients on warfarin is available on the SPS medicines monitoring page for warfarin

Counselling

Advise warfarin patients that newly initiated PPI may increase INR levels, and it is important to attend monitoring appointments to assess this.

Advise patients to seek medical advice if signs of over-anticoagulation occur. These include:

• Spontaneous bleeding that does not stop. This includes bruising, bleeding gums, nosebleeds, prolonged bleeding from cuts, blood in the urine or stools, coughing up blood, a subconjunctival haemorrhage, and vaginal bleeding in a postmenopausal woman
• Sudden severe back pain

Stopping a PPI

Monitoring

Warfarin monitoring is recommended when stopping PPIs in patients stabilised on warfarin.

Further guidance on monitoring patients on warfarin is available on the SPS medicines monitoring page for warfarin

Initiating warfarin

Patients started on warfarin do not need any additional monitoring based on their PPI usage.

Update history