Potential interaction between clarithromycin and warfarin

To report a possible drug interaction between clarithromycin and warfarin in a patient with chronic atrial fibrillation.

A patient with chronic atrial fibrillation was placed on warfarin therapy. International normalized ratios (INRs) ranged from 1.61 to 3.99 while the dosage was being adjusted during the first 5 months of warfarin therapy. The dosage was titrated to 20 mg/wk; laboratory tests obtained 2 weeks after this dosage was started indicated an INR of 2.1. The same dosage was continued. Clarithromycin 500 mg bid was started for an acute exacerbation of bronchitis 10 days after the last INR was obtained and was continued for 14 days of therapy. An INR obtained 3 days after completion of the clarithromycin therapy was 16.8. The warfarin was withheld and vitamin K 20 mg im was administered. The INR obtained the next day was 1.52. The warfarin was restarted and the dosage was titrated to between 22.5 and 25 mg/wk, with INRs ranging from 0.85 to 3.14.

Many factors influence the metabolism of warfarin, including disease states, medications, age, and diet. Data collected in this case suggested clarithromycin may have contributed to the increase in the effect of warfarin. Inhibition of the cytochrome P450 oxidizing system appears to be the reason for the increase. Numerous drugs and disease states affect the rate at which this system metabolizes drugs.

The potential interaction between clarithromycin and warfarin warrants prudent monitoring of the INR during concurrent administration of these drugs. Warfarin dosages may need to be reduced during concurrent clarithromycin therapy to prevent bleeding complications. Further controlled clinical trials are needed to substantiate the interaction between clarithromycin and warfarin.