How to Prescribe Drugs With an Identified Proarrhythmic Liability

Abstract

This is an article in the Journal of Clinical Pharmacology's Core Entrustable Professional Activities in Clinical Pharmacology series that discusses druginduced proarrhythmia and is offered as a teaching aid for medical students and residents. Drugs from diverse pharmacological classes can lead to multiple types of arrhythmias including the polymorphic ventricular tachycardia torsades de pointes (TdP). Although typically occurring in selflimiting bursts with or without associated symptoms, which can range from mild lightheadedness and palpitations to syncope and seizures, TdP can also occasionally progress to ventricular fibrillation and sudden cardiac death. To provide patients with the optimal therapeutic benefits of potentially proarrhythmic drugs, prescribers are responsible for obtaining a good understanding of the compound's benefit-risk properties and perform a judicious assessment of the patient's clinical characteristics and individual risk factors. Dose adjustments and/or additional monitoring of electrocardiograms and electrolyte balances may be appropriate in some cases. This article explains the pharmacological mechanism of action of drug-induced proarrhythmia associated with compounds that prolong the repolarization period, illustrates how this liability is conveyed in a drug's prescribing information (label), details the clinical characteristics of patients most susceptible to this type of proarrhythmia, and describes interventions that can be made if TdP occurs. Three clinical vignettes are provided at the end of the article to highlight the relevance of the preceding discussions.

Identification of Risk of QT Prolongation by Pharmacists When Conducting Medication Reviews in Residential Aged Care Settings: A Missed Opportunity?

“…Our study adds to a growing body of research showing that there is a need for greater awareness amongst pharmacists and other health professionals regarding the risk factors—both pharmacological and non-pharmacological—associated with QT prolongation, and hence identification of patients at greatest risk of TdP [23,24,25]. Several educational review papers are now available and suitable for this purpose [4,26,27,28].…”

“…For example, in academic institutions that have more than one healthcare professional school, joint workshops and/or symposia provide the opportunity for initial didactic teaching followed by interprofessional discussions involving students and faculty from each professional school on campus. The papers by Thind and colleagues [27] and Klotzbaugh [28] may be particularly useful for generating such interprofessional discussions, as they include clinical vignettes specifically designed for this purpose. Each of the vignettes addresses how an individual patient was prescribed certain drug(s), and highlights the effects of these prescriptions.…”

Covid-19 treatment update: follow the scientific evidence

“…The clinical community to include emergency room physicians, nurse practitioners, physician assistants and pharmacists, as well as others employing a tele-health platform must adopt a well-informed and consistent approach to safely prescribe drugs with QTc prolonging or proarrhythmic potential [34]. A management algorithm must include a comprehensive understanding of drug pharmacology, risk-benefit relationships and a track record of safety.…”

Effect of 3 Single Doses of Trazodone on QTc Interval in Healthy Subjects

“…QT‐interval prolongation, which according to European Society of Cardiology guidelines is defined as a QT interval >470 ms in women and >450 ms in men, 31 is associated with a higher risk of polymorphic ventricular tachycardia or torsade de pointes (TdP), which may ultimately lead to sudden cardiac death 32 . As also reported by Thind et al, the degree of QT prolongation of a single drug should be considered in the larger picture of other proarrhythmic factors 33 . Several risk factors are associated with an increased risk for QT‐interval prolongation, eg, hypopotassemia, renal impairment, use of diuretics, other QTc‐prolonging drugs including several classes of antidepressants, and unmodifiable risk factors such as age >65 years and female gender.…”