QT prolongation clinically relevant when antibiotic and CYP 3A inhibitors are combined, New England journal of Medicine shows.

Pharmacists do need to intervene when patients are prescribed erethromycin and strong inhibitors of the cytochrome P450 3A (CYP 3A) isoenzymes, according to an analysis of Tennessee Medicaid data reported in today New England journal of Medicine. Written by Vanderbilt University professer Wayne A. Ray,PhD, and colleagues, the article shows that erythromycin alone doubles the risk of sudden cardiac death, and patients odds of suffering this outcome are increased 5-fold when drugs such as ketoconazole are added to the mix.
The drug interaction, which can prolong the QT interval and thereby lead to sudden cardiac death, was assessed by reviewing 1.2 million person-years of treatment and 1,476 cases of sudden cardiac death among members of a previously identified cohort. In comoarison with the marked elevation in risk of sudden cardiac death with erythromycin alone or in combination with inhibitor, patients who concurrently used amoxicillin and CYP 3A inhibitors had no increase in risk. CYP 3A inhibitors included in the study were azole antifungal drugs(ketoconazole, itraconazole, and fluconazole, all administered systemically), diltiazem, verapamil, and troleandomycin.Clarithromycin (Biaxin-Abbott) was considered separately, while other potent CYP 3A inhibitors such as the protease inhibitors and recently marketed medications were not included in the study.
In an accompanying perspectives article, Barbara A. Liu, MD, and David N. Juurlink, MD, PhD, of the University of Toronto, review drugs effects on the QT interval and problems in learning more about this interaction: "Most of what is known about drug-induced QT-interval prolongation derives from spontaneous reporting mechanisms. Though instructive, these reports tell us little about what happens in the real world. ?How many people who are exposed to these drugs have no sequelae? How many avoidable sudden deaths might actually be misattributed to coronary disease? How do multiple risk factors act together in an individual patient? As illustrated by the study reported by Ray and colleagues…, the discipline of pharmacoepidemiology has much to teach us about the consequences of drug interaction in clinical practice. As more of this information comes to light, a few short lists and an element of caution with the prescription pad will probably go a long way toward preventing torsades de pointes and other serious adverse effects of drug interactions."