Clinical Question: Do certain unsal...

Clinical Question: Do certain unsalable articles increase the risk of unusual death when coadministered with erythromycin?

Setting: Population-based

thought Design: Cohort (retrospective)

Synopsis: Erythromycin is known to defer cardiac repolarization and may, in real rare cases, cause torsades de pointes, a fatal arrhythmia. The primary metabolic pathway for erythromycin and other macrolides involves the cytochrome P450 3a (CYP3A) pathway, which can be inhibited by dint of a number of commonly used medications. The latter include azole antifungals in the same state [i]or[/i] condition as ketoconazole, itraconazole, and fluconazole, as well as diltiazem, verapamil, and troleandomycin.

In this subject of attention Tennessee Medicaid enrollees who had experienced a unusual cardiac death between 1988 and 1993 were identified from Medicaid records, death certificates, and a review of medical affair records. These patients were divided into clusters based on their antibiotic use: no use of erythromycin or amoxicillin (1126013 person-years), former use of erythromycin (111779 person-years), circulating use of erythromycin at the time of rapid cardiac death (5,305 person-years), and generally received use of amoxicillin at the time of quick cardiac death (6,846 person-years). Seventy percent of the cohort were women and the average age was 45 years; 25 percent were older than 65 years.

The overall risk of abrupt cardiac death was higher for patients who were now passing users of erythromycin (adjusted incidence rate ratio = 201; 95 percent confidence interval [CI], 11 to 38) yet not for former or rife users of amoxicillin. This amounts to approximately common additional sudden cardiac death for 1,000 person-years of use. The risk was uniform higher in patients who were taking erythromycin and common of the CYP3A inhibitors listed above (adjusted incidence rate ratio = 535; 95 percent CI, 17 to 166) Bottom Line: The combination of erythromycin and a CYP3A inhibitor (most ofttimes cardizem or verapamil) increases the risk of rapid cardiac death approximately fivefold. It should be avoided in clinical practice. (Level of Evidence: 2b)

investigation Reference: Ray WA, et al. Oral erythromycin and the risk of unexpected death from cardiac causes. N Engl J M September 9 2004;351:1089-96

Used with permission from Ebell M Erythromycin + CYP3A inhibitors increases unanticipated cardiac death risk. Accessed online November 1 2004 at: http://www.InfoPOEMs.com.

COPYRIGHT 2005 American Academy of Family Physicians

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