Donepezil-induced torsades de pointes without QT prolongation

Abstract

We report a case of torsades de pointes (TdP) induced by donepezil without QT prolongation. An 86year-old woman was admitted to our hospital because of a syncopal attack. She had been treated for Alzheimer's disease with donepezil. Initial 12-lead electrocardiogram showed atrial fibrillation and normal corrected QT interval. After admission, atrial fibrillation spontaneously recovered to normal sinus rhythm on electrocardiographic monitoring. On the second day, electrocardiographic monitoring documented TdP. We discontinued donepezil immediately. After washout of donepezil, TdP was not observed again. Corrected QT interval was normal throughout hospitalization. This case suggests that donepezil may cause life-threatening ventricular arrhythmias without QT prolongation. Even if corrected QT interval is normal in patients taking donepezil and experiencing symptoms associated with TdP, electrocardiographic monitoring is recommended. <Learning objective: Donepezil may cause life-threatening ventricular arrhythmias without QT prolongation. Even if corrected QT interval is normal in patients taking donepezil and experiencing symptoms associated with torsades de pointes, electrocardiographic monitoring is recommended.>

Effect of QT Prolongation in Patients Taking Cholinesterase Inhibitors (Donepezil) for Alzheimer’s Disease

“…In all these case reports, discontinuation of donepezil improved QTc prolongation, and no recurrence of arrhythmias was reported. Even in the case of TdP without QTc prolongation, 9 the arrhythmia did not recur with donepezil discontinuation. Based on these case reports and the results of the present study, it is difficult to predict the occurrence of QTc prolongation and arrhythmias in patients taking donepezil.…”

Correlation Between Donepezil and QTc Prolongation and Torsades de Pointes: A Very Rare Phenomenon

“…The patient was commenced on bisoprolol and metildigoxin for paroxysmal AF (PAF) with medical outpatient follow-up. The patient was discharged home without donepezil with normal discharge ECG (normal QTc) [18].…”

“…Following discontinuation of donepezil, QTc gradually reduced to 0.446 seconds on the 18th day [21]. [16][17][18][19][20][21]…”

“…One of the logical conclusions of AChE inhibition will be the increased level of calcium within the intracellular space. Increased intracellular calcium levels can lead to prolongation of phase 2 of the cardiac action potential cycle, which in turn can lead to an enhanced risk of ventricular arrhythmias [18]. Figure 1 describes the proposed mechanism of donepezil leading to ventricular arrhythmias.…”

“…It is also important to note some of the risk factors identified to act synergistically in this scenario, which are IHD, electrolyte disturbances (hypocalcaemia, hypokalaemia or hypomagnesaemia), female sex, old age, congestive heart failure, atrial flutter, AF, bradycardia, drug overdoses, rapid IV drug administration, polymorphism of genes coding ion channels or enzymes involved in drug metabolism, use of drugs that prolong the QTc, congenital long QT syndrome, and family history of sudden death [18]. In some of the case reports described in the literature, an association has been found between donepezil and ventricular arrhythmias, especially TdP, QTc prolongation, bradycardia, and heart blocks [17].…”