Enhanced hypoprothrombinemia with warfarin due to azithromycin.
OBJECTIVE
To report a case of probable azithromycin-warfarin drug interaction with enhanced hypoprothrombinemic effect of warfarin.


METHODS
An 83-year-old African American man stabilized on warfarin therapy (10 mg on Wednesdays, 7.5 mg on other days) developed a prolonged prothrombin time one day after starting azithromycin 500 mg. The elevated prothrombin time normalized 3 days after azithromycin was discontinued. After the initial increase in the international normalized ratio, the absence of any significant confounding factors affecting the anticoagulant effect of warfarin in our patient and the numerous reports of such interactions indicate that an interaction between azithromycin and warfarin may have been responsible for the elevated prothrombin time seen in this patient. An objective causality assessment revealed that the adverse event was probably related to the combination of these drugs.


CONCLUSIONS
Azithromycin, unlike erythromycin and clarithromycin, is not known to inhibit the cytochrome P450 enzyme system and is presumed to be the macrolide of choice in patients already on warfarin. However, previously reported cases of azithromycin-warfarin interactions support the possibility that azithromycin does interact with warfarin, although the exact mechanism is not understood.


CONCLUSIONS
Azithromycin may interact with warfarin and enhance its hypoprothrombinemic effects. This effect may be delayed for 4-8 days after a course of azithromycin has been completed. Periodic monitoring of the prothrombin time is recommended when using azithromycin in patients taking warfarin.
Rao
Krishnamoorthy B
KB
Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Pallaki
Muralidhar
M
Tolbert
Sandra R
SR
Hornick
Thomas R
TR
D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D000925:Anticoagulants / Q000009:adverse effects*; D017963:Azithromycin / Q000009:adverse effects*; D004347:Drug Interactions; D006801:Humans; D007020:Hypoprothrombinemias / Q000139:chemically induced*; D008297:Male; D014859:Warfarin / Q000009:adverse effects*
D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D014859:Warfarin; D017963:Azithromycin