Case study

Metronidazole causes an unexpected rise in INR in anticoagulated patients even after warfarin has been stopped

By Antonella P. Tonna, MSc, MRPharmS, David Scott, PhD, MRPharmS, David Keeling, MD, FRCP, and Ivan Tonna , MSc, MRCP

Interaction between metronidazole and warfarin is thought to potentiate the anticoagulant effect of warfarin. In this article, the authors propose mechanisms for this interaction, based on three case studies

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Antonella Tonna is a PhD student and ad hoc lecturer at The Robert Gordon University, Aberdeen. At the time of writing she was surgical admission and discharge pharmacist at the Oxford Radcliffe Hospitals.

David Scott is regional clinical training pharmacist and David Keeling is consultant haematologist, both at the Oxford Radcliffe Hospitals.

Ivan Tonna is specialist registrar, infectious diseases at Aberdeen Royal Infirmary. At the time of writing he was based at the Oxford Radcliffe Hospitals.

SUMMARY

In the 1970s an interaction between metronidazole and warfarin was described in healthy volunteers. Subsequently, there have been few reports describing the interaction during the concurrent administration of warfarin and metronidazole. A critical analysis of warfarin interactions concluded that the metronidazole-warfarin interaction is “highly probable”, with metronidazole potentiating the anticoagulant effect of warfarin.

We propose mechanisms for this interaction, based on three patients in a surgical emergency unit whose international normalised ratios (INR) rose despite the cessation of warfarin some days previously.

Informed patient consent has been obtained for publication of these studies.