Australia. The Australian Adverse Drug Reactions Advisory Committee (ADRAC) has received a number of reports of interactions between warfarin and the macrolide antibacterials, azithromycin, clarithromycin, erythromycin and roxithromycin. Substantial increases in the International Normalized Ratio (INR) for blood coagulation time were observed in a number of these cases, although most patients were asymptomatic (see Table 4). Almost all reactions occurred within one week of starting the antibacterial; haemorrhagic complications included haemoptysis, haematoma, malaena, haematuria and retroperitoneal haemorrhage. There was one fatal case in a 79-year-old woman whose INR rose to 11.6 within 8 days of initiating warfarin and roxithromycin simultaneously. She died from widespread bleeding that included haemopericardium and subdural haemorrhage. ADRAC warns that the INR should be monitored closely in patients receiving warfarin who are started on a macrolide antibacterial, and that, if possible, an alternative antibacterial could be considered.

Reference:

Australian Adverse Drug Reactions Bulletin Vol. 23, No. 2, April 2004.

Table 4. ADRAC warfarin-macrolide interactions

* two cases also involved a potential interaction with metronidazole
** onset was >365 days in one patient