The Food and Drug Administration (FDA) has revised the labeling for clarithromycin (Biaxin) to include a warning of a potential increased risk of cardiovascular (CV) morbidity or death in patients with heart disease who receive the drug. The risk can extend for several years after treatment. The label now also includes results from the study on which this revision is based. Exactly how clarithromycin increases the risk of CV morbidity or death isn't known at this time. The long-term safety outcomes of clarithromycin in patients without heart disease have not been studied.

The FDA's decision to add this new warning follows the analysis of a long-term (10-year) follow-up study of patients with coronary heart disease who received clarithromycin for two weeks as part of an earlier clinical trial: the CLARICOR (clarithromycin for patients with stable coronary heart disease) trial.1, 2 The FDA also considered findings from six observational studies, which were mixed. The FDA felt that all the studies had design limitations, but the long-term follow-up study provided the strongest evidence of CV risk.

CLARICOR was a randomized, placebo-controlled trial of 4,373 patients with stable coronary heart disease which sought to determine if clarithromycin could decrease CV death or events by decreasing inflammation.1 Study participants received clarithromycin 500 mg/day or placebo for two weeks. Initial results indicated that patients taking clarithromycin had an increased risk of all-cause mortality for up to three years after initiating treatment. In December 2005, the FDA issued an alert to providers regarding these data, but did not make prescribing recommendations or labeling changes at that time.

Analysis of the 10-year follow-up study confirmed an increased risk of all-cause mortality and cerebrovascular morbidity with clarithromycin use in patients not on a statin at the start of the trial.2 Long-term analysis showed that CV death outside the hospital was increased in patients during the first three years after receiving clarithromycin, but was lower for the last four years of the analysis. This is attributed to the likelihood that the most frail of the trial participants died early in the review period.

NPs should consider the risk-to-benefit ratio of clarithromycin use in their patients and consider prescribing a different antibiotic to patients with heart disease. Adverse effects should be reported to MedWatch at http://www.fda.gov/Safety/MedWatch/default.htm. To read the Drug Safety Communication regarding clarithromycin, go to http://www.fda.gov/downloads/Drugs/DrugSafety/UCM597723.pdf.

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