June 18th, 2013

Statin Toxicity Associated with CYP3A4-Inhibiting Antibiotics

Higher rates of hospitalization for rhabdomyolysis occur among patients on statins who also start taking clarithromycin or erythromycin, which inhibit statin metabolism, according to an Annals of Internal Medicine study.

Using provincial databases, researchers examined 30-day outcomes among some 140,000 Ontario residents who were taking a statin metabolized by the cytochrome P450 isoenzyme 3A4 (CYP3A4). All participants were aged 66 or older. Roughly half were starting a prescription for the CYP3A4-inhibiting antibiotics clarithromycin or erythromycin, and the other half were starting azithromycin.

CYP3A4-inhibiting antibiotics were associated with a 0.02% increase in absolute risk for hospitalization with rhabdomyolysis, the study’s primary outcome, compared with azithromycin (relative risk, 2.17). Increased risks for acute kidney injury and all-cause mortality were also noted.

The authors recommend that coprescribing a CYP3A4-metabolized statin (atorvastatin, simvastatin, or lovastatin) and a CYP3A4-inhibiting antibiotic (clarithromycin or erythromycin) “be avoided when possible.”

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