“Late” proarrhythmia due to quinidine

Torsades de Pointes Associated with Chlorpromazine: Case Report and Review of Associated Ventricular Arrhythmias

“…In three cases 43,45,46 chlorpromazine was the only drug the patient was receiving. In agreement with recent observations of "late" drug-induced proarrhythmia 54 and similar to our patient, six subjects [43][44][45][46][47]51 were receiving chlorpromazine for more than 1 year before presentation with the arrhythmia. Electrolyte abnormalities may have contributed to onset of arrhythmia in five cases, [43][44][45][46]51 like our patient.…”

“…57,67 However, it is increasingly recognized that proarrhythmia can occur late in the course of therapy, even after years of receiving a potentially proarrhythmic drug (as was observed in our patient). 54,68 In one study, 54 the authors identified potential initiating factors that could explain the occurrence of "late" proarrhythmia in patients receiving longterm quinidine therapy. These temporally related factors included the addition of other drugs that prolonged ventricular repolarization, new onset bradycardia, and hypokalemia.…”

QT Prolongation Associated with Azithromycin/Amiodarone Combination

“…9 While the early incidence of torsades de pointes is considered an idiosyncratic reaction to the antiarrhythmic drugs, the late occurrence is thought to be related to the introduction of a second risk factor such as hypokalemia, bradycardia, or change in the dose of antiarrhythmic medication. 10 In the present case the patient was at no time hypokalemic or hypomagnesemic nor was there a change in her usual amiodarone dose. Therefore, it seems unlikely that amiodarone was responsible for the symptoms or increased QTc and QT dispersion from the baseline in this patient.…”

The International Serious Adverse Events Consortium (iSAEC) phenotype standardization project for drug-induced torsades de pointes

“…15 The temporal relationship is particularly important if TdP occurs after the initiation of drug therapy although delayed or 'late proarrhythmia' has been described with quinidine and non-cardiac drugs. 16,17 A causal association can also be strengthened by the presence of QT prolongation during drug exposure, and at least partial resolution of QT prolongation, as well as THE cessation of TdP with drug withdrawal. The time course will, however, be dependent on the pharmacokinetic behaviour of the drug and its pharmacology including the interactions with multiple ion channels.…”