Statin-Antibiotic Combination May Cause Toxic Reaction

A new study suggests that coprescription of clarithromycin or erythromycin with a statin could increase the risk for statin toxicity.

Researchers from the London Health Sciences Center (Canada), the University of Western Ontario (UWO; London, Canada), and the University of Toronto (Canada) conducted a population-based cohort study to measure the frequency of statin toxicity after coprescription of a statin with clarithromycin or erythromycin, which inhibit cytochrome P450 isoenzyme 3A4 (CYP3A4), resulting in increased blood levels of statins metabolized by CYP3A4. The study involved continuous statin users older than 65 years who were prescribed clarithromycin (72,591 patients) or erythromycin (3,267 patients) between 2003 and 2010, compared with those prescribed azithromycin (68,478 patients) which does not inhibit CYP3A4.

The results showed that compared with azithromycin, coprescription of a statin with clarithromycin or erythromycin was associated with a slightly higher risk for hospitalization with rhabdomyolysis (muscle damage), and a 26% increased risk of acute kidney injury. All-cause mortality was also increased by 25%. The most prescribed statin was atorvastatin (73%) followed by simvastatin and lovastatin. The study was published in the June 18, 2013, issue of Annals of Internal Medicine.

“These drugs do interact and cause difficulties for patients, but adverse reactions are rare,” said senior author professor Amit Garg, MD, PhD, of the department of epidemiology and biostatistics at the UWO. “Most people will be fine, but at a population level, hundreds of events are preventable.”

“It is well documented that certain medications that inhibit the liver enzyme cytochrome P450 isoenzyme 3A4 can increase the drug level of statin medications,” commented professor of cardiology Gregg Fonarow, MD, a spokesman for the American Heart Association (AHA). “Nevertheless, large-scale randomized clinical trials and clinical effectiveness studies have demonstrated [that] the benefits of statin therapy in reducing fatal and nonfatal cardiovascular events outweigh the potential risks.”

Related Links:
London Health Sciences Center
University of Western Ontario
University of Toronto