Cardiac death risk 5x greater with concurrent oral erythromycin and CYP3A inhibitors

Concurrent use of oral erythromycin and strong inhibitors of CYP3A should be avoided, according to research published in TheNew England Journal of Medicine.

Researchers found that the rate of sudden death from cardiac causes was 5 times as high (incidence-rate ratio, 5.35; 95% CI, 1.72–16.64; P=.004) among patients who concurrently used erythromycin and CYP3A inhibitors (nitroimidazole antifungal agents, diltiazem, verapamil, troleandomycin), compared to those who had not used CYP3A inhibitors or the study antibiotic medications. The rate of sudden death from cardiac causes was twice as high (incidence-rate ratio, 2.01; 95% CI, 1.08–3.75; P=.03) among patients currently using erythromycin (n=5,305 person-years) as those who had not used any of the study antibiotic medications. There was no significant increase in the risk of sudden death among former users of erythromycin (n=111,779 person-years) (incidence-rate ratio, 0.89; 95% CI, 0.72–1.09; P=.26) or among those who were currently using amoxicillin (n=6,846 person-years) (incidence-rate ratio, 1.18; 95% CI, 0.59–2.36; P=.65).

The population-based study included 1,476 cases of sudden death from cardiac causes and 1,249,943 person-years of follow-up among a Tennessee Medicaid cohort between January 1, 1988, and December 31, 1993. Participants were aged 15 to 84 years (mean age 45; 70% female), not residing in a long-term care facility, and had no life-threatening noncardiac illness. Sudden death was defined as a sudden fatal condition caused by ventricular tachyarrhythmia in the absence of a known noncardiac condition.

SOURCE Ray WA, Murray KT, Meredith S, Narashimhulu SS, Hall K, Stein CM. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med. 2004;351:1089–1096.