A viewpoint on drugs that prolong the QTc interval.
Insufficient evidence exists to suggest that prolongation of the QT interval corrected for heart rate (QTc) is necessarily beneficial. In all but life-threatening situations, QTc prolongation resulting from pharmacologic agents must be considered a risk. Because dose-response relations for torsades de pointes cannot be established and because prolongation of the QTc interval is thought to precede the development of torsades, it is reasonable to assume that the QTc prolongation itself constitutes the marker of risk. An assessment of the relation between the dose of a given drug and its effect on the QTc interval will aid in making the judgment that the potential benefit outweighs the risk. Ideally, a drug should demonstrate as wide a safety margin as possible, as reflected in a large separation between the ED50 value associated with therapeutic benefit and that associated with QTc prolongation.
Lipicky
R J
RJ
Division of Cardio-Renal Drug Products, U.S. Food and Drug Administration, Rockville, Maryland 20857.
D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D004562:Electrocardiography / Q000187:drug effects*; D006801:Humans; D016171:Torsades de Pointes / Q000139:chemically induced*