Drug-induced proarrhythmia: Discussion and considerations for clinical practice

The clinical practice of pharmaceutical medicine includes contributions from physicians, pharmacists, nurse practitioners, and physician assistants. Drug safety considerations are of considerable importance. This article discusses drug-induced proarrhythmia, with a specific focus on Torsade de Pointes (Torsade), a polymorphic ventricular tachycardia that typically occurs in self-limiting bursts that can lead to dizziness, palpitations, syncope, and seizures, but on rare occasions can progress to ventricular fibrillation and sudden cardiac death. A dedicated clinical pharmacology study conducted during a drug's clinical development program has assessed its propensity to induce Torsade using prolongation of the QT interval as seen on the surface electrocardiogram (ECG) as a biomarker. Identification of QT-interval prolongation does not necessarily prevent a drug from receiving marketing approval if its overall benefit-risk balance is favorable, but, if approved, a warning is placed in its Prescribing Information. This article explains why drugs can have a proarrhythmic propensity and concludes with a case presentation.