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 Adverse Cases


Back Reported Adverse Drug Reaction Cases
Macrolides and warfarin interaction
ADRAC has received reports of interactions between warfarin and all four macrolide antibiotics (azithromycin, clarithromycin, erythromycin, and roxithromycin) (see Table).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
The one fatality reported involved a 79 year old woman who was started on warfarin and roxithromycin simultaneously. By day 8 of treatment, her INR had risen to 11.6. She subsequently died from widespread bleeding, including subdural haemorrhage and haemopericardium.
Nearly all reactions occurred in the first week after starting the antibiotic; reactions reported later than this may reflect the frequency of INR monitoring.

Table: ADRAC reports of macrolide-warfarin interaction

 

Drug

reports
(no. symptomatic)

onset in days (median; range)

INR (median)

azithromycin

3 (0)

3; 2-5

9.6

clarithromycin

6 (2)

7; 0-9

7.6

erythromycin*

19 (4)

5; 0-18

9.7

roxithromycin

56 (27)

6; 0-36#

8.8

 

* metronidazole was another potentially interacting agent in 2 cases.
# onset > 1 year in a further patient.

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.

References:
Interaction of warfarin with macrolide antibiotics. Aust Adv Drug Reactions Bull 1995;14:11.
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