warfarin and flucloxacillin

Flucloxacillin may increase the anticoagulant effect of warfarin. The mechanism is not fully established but is thought to involve reduction in vitamin K production by gut flora, leading to decreased synthesis of clotting factors. Some evidence also suggests interference with warfarin metabolism or displacement from protein binding, though these are less consistent.

An increase in INR and prothrombin time can occur, potentially leading to clinically significant bleeding. The effect may become apparent within days of starting flucloxacillin and can persist for several weeks after stopping. Patients may present with bruising, epistaxis, or other bleeding manifestations.

Monitor INR closely before, during, and after co-prescribing flucloxacillin. Consider a reduced warfarin dose or more frequent INR checks, particularly in the first week. Advise patients to report any signs of bleeding. If flucloxacillin is stopped, INR may fall, requiring dose adjustment.

Evidence from case reports and observational studies. The interaction is well recognised in clinical practice and is listed in major drug interaction databases, although mechanisms remain incompletely understood.