FDA warns clarithromycin could cause death in patients with heart disease

The U.S. FDA is warning physicians against prescribing the antibiotic clarithromycin to patients with coronary artery disease. In long-term follow up of a randomized controlled trial, there was an unexpectedly higher rate of death in patients who received a two-week treatment course of clarithromycin, compared to placebo.

FDA has added a new warning to clarithromycin's label, advising prescribers to choose other antibiotics in patients with coronary artery disease.

The new warning is based on long-term follow-up of patients enrolled in the CLARICOR trial, originally completed in 2002. Clarithromycin or placebo were given for 14 days to about 4,300 patients, with the rationale that Chlamydia pneumoniae found in atherosclerotic plaques could contribute to plaque instability, and that eradication of the bacteria would prevent heart attacks.

It did not: CLARICOR found patients in the clarithromycin arm died more often, with a statistically significant 27% increased relative risk for cardiovascular death at three years' follow-up. The FDA issued a safety alert at that time.

FDA's new warning is based on 10-year follow-up of the same patients. Significantly more patients who had taken clarithromycin in the trial died over the following decade, compared to those who had taken placebo. The increased risk for death associated with clarithromycin was attenuated in patients who were taking statins at the time of enrollment in CLARICOR. FDA also considered data from observational studies comparing patients taking clarithromycin with or without coronary artery disease.

It's unclear exactly why or how all patients died, or how clarithromycin could have caused their deaths years after a short course of treatment. Clarithromycin (a macrolide antibiotic) has been hypothesized as being pro-arrhythmogenic, as well as a potential cause of myocardial infarction, the latter through unknown mechanisms. However, these risks were presumed to be limited to the treatment period, or perhaps for a short period after. There has been no previously recognized long-term cardiac risk from clarithromycin or any other antimicrobial agent.

The FDA announcement did not go so far as to warn against clarithromycin use in patients with risk factors for coronary artery disease:

Because we currently do not have study information in these patients, and observational studies have shown different results, we cannot determine whether results of the CLARICOR trial can be applied to patients who do not have heart disease."

The warning probably affects primary care physicians the most. Clarithromycin is commonly prescribed as a treatment for strep throat, pneumonia, H. pylori infection, and Lyme disease.

Infectious disease physicians and pulmonologists prescribe clarithromycin as a first-line antimicrobial for treatment of Mycobacterium avium complex (MAC) infection. Azithromycin, an alternative to clarithromycin and the most commonly used macrolide, received its own FDA drug safety communication for risk of sudden cardiac death in 2013.

Source: FDA