%0 Journal Article
%T Risk of QT prolongation and torsade de pointes associated with exposure to hydroxyzine: re©\evaluation of an established drug
%A Anne©\Fran£¿oise Schlit
%A Annie Delaunois
%A Aurore Colomar
%A Branderley Claudio
%A Christopher Peters
%A Jean©\Pierre Valentin
%A J¨¹rgen W. G. Bentz
%A Luca Cariolato
%A Rossen Boev
%A Victor S. Sloan
%J Archive of "Pharmacology Research & Perspectives".
%D 2017
%R 10.1002/prp2.309
%X Several noncardiac drugs have been linked to cardiac safety concerns, highlighting the importance of post©\marketing surveillance and continued evaluation of the benefit©\risk of long©\established drugs. Here, we examine the risk of QT prolongation and/or torsade de pointes (TdP) associated with the use of hydroxyzine, a first generation sedating antihistamine. We have used a combined methodological approach to re©\evaluate the cardiac safety profile of hydroxyzine, including: (1) a full review of the sponsor pharmacovigilance safety database to examine real©\world data on the risk of QT prolongation and/or TdP associated with hydroxyzine use and (2) nonclinical electrophysiological studies to examine concentration©\dependent effects of hydroxyzine on a range of human cardiac ion channels. Based on a review of pharmacovigilance data between 14th December 1955 and 1st August 2016, we identified 59 reports of QT prolongation and/or TdP potentially linked to hydroxyzine use. Aside from intentional overdose, all cases involved underlying medical conditions or concomitant medications that constituted at least 1 additional risk factor for such events. The combination of cardiovascular disorders plus concomitant treatment of drugs known to induce arrhythmia was identified as the greatest combined risk factor. Parallel patch©\clamp studies demonstrated hydroxyzine concentration©\dependent inhibition of several human cardiac ion channels, including the ether©\a©\go©\go©\related gene (hERG) potassium ion channels. Results from this analysis support the listing of hydroxyzine as a drug with ¡°conditional risk of TdP¡± and are in line with recommendations to limit hydroxyzine use in patients with known underlying risk factors for QT prolongation and/or TdP
%K Hydroxyzine
%K minimization
%K QT prolongation
%K risk
%K torsade de pointes
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415947/