The Australian Drug Evaluation Committee (ADRAC) has received reports of interactions between warfarin and all four macrolide antibiotics (azithromycin, clarithromycin, erythromycin, and roxithromycin) (see table below) (1). Although most cases were asymptomatic, some reports documented substantial increases in INR. The haemorrhagic complications reported included haematoma, haemoptysis, haematuria, melaena, and retroperitoneal haemorrhage.

Close attention should be paid to INR monitoring in patients taking warfarin who are commenced on a macrolide antibiotic. Consideration could also be given to the use of an alternative antibiotic if possible. Azithromycin has a particularly long half-life (around 68 hours), so that an interaction with warfarin may theoretically persist for some days after azithromycin has been ceased.

Extracted from Australian Adverse Drug Reactions Bulletin, Volume 23, Number 2, April 2004

Reference

1. Australian Adverse Drug Reactions Bulletin, 14: 11 (1995).