The prevalence of warfarin-related adverse drug interactions has been examined using information from a Finnish post-mortem toxicology database, and from the related death certificates. The concomitant use of warfarin and NSAIDs/ paracetamol/ tramadol was a focus of the study.

Over 6000 post-mortem cases were included in the study,  representing over 10% of all deaths during a 1-year period. All warfarin-positive cases and cases containing interacting drugs were included. For controls, all cases containing paracetamol or tramadol were also included, and for each warfarin-positive case, an age-, sex- and alcohol-matched control case was sourced.

The following findings were reported:

• In 33% of the 328 warfarin-positive cases, at least one interacting drug was present, and paracetamol was the most abundant, accounting for 49% (n = 53).

• When paracetamol and warfarin were detected simultaneously, the number of fatal bleeds was 4.6 and 2.7 times higher compared to paracetamol or warfarin use alone respectively.

• The presence of an NSAID in combination with warfarin was rare, as only six cases were identified.

• A majority (66%) of the post-mortem blood samples had a warfarin concentration <0.5mg/l, and for the rest of the cases, the mean concentration was 0.70mg/l.

The researchers note that their findings suggest “a significantly elevated risk for an adverse outcome in the simultaneous use of warfarin and paracetamol compared to warfarin alone” and though the mechanism of the interaction is not clear, the safety of paracetamol use among patients on warfarin should be given more serious consideration. The safety of concomitant use of warfarin and tramadol remained unclear due to the small number of cases.