FDA: Clarithromycin Risks Persist in Patients With CAD

The US Food and Drug Administration (FDA) is alerting clinicians to the possibility of greater risks of cardiovascular morbidity and mortality in patients with heart disease who are prescribed clarithromycin, an issue that first popped up on the radar more than a decade ago.

“Healthcare professionals should be aware of these significant risks and weigh the benefits and risks of clarithromycin before prescribing it to any patient, particularly in patients with heart disease and even for short periods, and consider using other available antibiotics,” the agency wrote in a drug safety communication released last week. “Advise patients with heart disease of the signs and symptoms of cardiovascular problems, regardless of the medical condition for which you are treating them with clarithromycin.”

The FDA first warned of the issue back in December 2005, after results of the placebo-controlled CLARICOR trial, which enrolled patients with stable coronary heart disease, showed that 2 weeks of treatment with clarithromycin increased mortality in patients followed for at least a year.

The updated drug safety communication comes following a review of 10-year follow-up data from the trial showing that adverse events accrue even beyond 1 year after drug exposure. The long-term results show that clarithromycin treatment increased risks of all-cause mortality and cerebrovascular disease throughout the study period, with the relationships confined to patients not taking statins at the beginning of the study. The increase in cardiovascular mortality was seen in the first 3 years of follow-up, whereas in the last 4 years of follow-up, cardiovascular death outside the hospital was lower in the clarithromycin group.

Evidence from observational studies is mixed. The CLARICOR trial results “provide the strongest evidence of the increase in risk compared to the observational study results,” the FDA stated in its alert last week. “Based on these studies, FDA is unable to determine why the risk of death is greater for patients with heart disease.”

The agency has added a new warning and the CLARICOR results to the drug’s label, and said that it is continuing to monitor the situation. Generic versions of the drug, commonly sold as Biaxin, are also affected.