Some antibiotics taken with statins by older patients may cause more hospitalizations, all-cause mortality

Older people taking statins who were prescribed clarithromycin or erythromycin were hospitalized more frequently for rhabdomyolysis and acute kidney injury and had higher all-cause mortality than people who were prescribed azithromycin, a Canadian study found.

Researchers conducted a population-based cohort study in Ontario, Canada, from 2003 to 2010, among statin users older than 65 who were prescribed clarithromycin (n=72,591) or erythromycin (n=3,267) compared with azithromycin (n=68,478).

Results appeared in the June 18 Annals of Internal Medicine.

The median daily dose was 1,000 mg each for clarithromycin and erythromycin and 300 mg for azithromycin. The median duration of antibiotic therapy was 10 days for clarithromycin or erythromycin and 5 days for azithromycin.

Coprescription of clarithromycin or erythromycin with a CYP3A4-metabolized statin was associated with a higher risk for hospitalization with rhabdomyolysis (relative risk [RR], 2.17; 95% CI, 1.04 to 4.53) and acute kidney injury (RR, 1.78; 95% CI, 1.49 to 2.14) compared to azithromycin. The risk for hospitalization with hyperkalemia was not statistically different (RR, 1.31; 95% CI, 0.89 to 1.94). The risk for all-cause 30-day mortality was higher with clarithromycin or erythromycin (RR, 1.56; 95% CI, 1.36 to 1.80).

Compared to azithromycin, clarithromycin or erythromycin was associated with a 0.02% (95% CI, 0.01% to 0.03%) absolute increase in hospitalization with rhabdomyolysis and a 0.25% (95% CI, 0.17% to 0.33%) increase in all-cause mortality, with corresponding numbers needed to harm of 5,870 (95% CI, 3,068 to 67,758) and 399 (95% CI, 304 to 577), respectively.

The researchers wrote, “Given the frequency at which statins are prescribed (atorvastatin is currently the most commonly prescribed drug in Canada), and the high rate of coprescription seen in our study and in other jurisdictions, this preventable drug–drug interaction remains clinically important. The results suggest that many deaths and hospitalizations with acute kidney injury in Ontario may have been attributable to this interaction.”