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

Malik, Bilal Haider; Hamid, Pousette; Khan, Safeera; Gupta, Deepti; Islam, Muhammad

doi:10.7759/cureus.6451

Cited by 8 publications

(12 citation statements)

References 34 publications

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“…48,93 Two additional cases from this series (not previously described by us, by Gurbuz et al, or by Vogel et al) occurred in female patients over the age of 80 who were on multiple medications and had hypertension. 48 One of these cases is of exceptional significance as the patient developed asymptomatic TdP multiple times without a finding of prolonged QT C . 48,94 Findings of TdP in the absence of prolonged QT C have also occurred in other patients; for example, a 72 year old female patient on sotalol and dofetilide.…”

Section: A Review Of Case Reportsmentioning

confidence: 51%

“…will open voltage-gated calcium channels; this in turn leads to the conclusion that intracellular calcium levels increase, prolonging the cardiac action potential cycle, and hence increasing risk of ventricular arrhythmias. 48 However, it is unlikely that differences in risk of arrhythmia would occur on the basis of ACh activation of cardiac ACh receptors -as all AChEIs increase ACh levels. As well, there is no evidence that one AChEI results in drastically different levels of ACh in comparison to other AChEIs; otherwise, significant efficacy or safety differences should be seen.…”

Section: It Has Also Been Found That Activation Of Cardiac Ach Receptorsmentioning

confidence: 99%

“…We reviewed this case series in detail as it was a more in-depth description of cases (relative to aforementioned case reports which only provided short summaries of other cases), it was more recent (published in December 2019), and only one case was previously reviewed by us (Takaya et al). 48 This case series focused on donepezil and did not examine galantamine or rivastigmine. 48,93 Two additional cases from this series (not previously described by us, by Gurbuz et al, or by Vogel et al) occurred in female patients over the age of 80 who were on multiple medications and had hypertension.…”

Section: A Review Of Case Reportsmentioning

confidence: 99%

“…48 This case series focused on donepezil and did not examine galantamine or rivastigmine. 48,93 Two additional cases from this series (not previously described by us, by Gurbuz et al, or by Vogel et al) occurred in female patients over the age of 80 who were on multiple medications and had hypertension. 48 One of these cases is of exceptional significance as the patient developed asymptomatic TdP multiple times without a finding of prolonged QT C .…”

Section: A Review Of Case Reportsmentioning

confidence: 99%

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Comparative risk of cardiac arrhythmias associated with acetylcholinesterase inhibitors used in treatment of dementias – A narrative review

Huang

Alsabbagh

2020

Pharmacology Res & Perspec

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Donepezil, galantamine, and rivastigmine are the three acetylcholinesterase inhibitors (AChEIs), out of a total of only four medications prescribed in the treatment of Alzheimer's Disease (AD) and related dementias. These medications are known to be associated with bradycardia given their mechanism of action of increasing acetylcholine (ACh). However, in March 2015, donepezil was added to the CredibleMeds “known‐risk” category, a list where medications have a documented risk for acquired long‐QT syndrome (ALQTS) and torsades de pointes (TdP) – a malignant ventricular arrhythmia that is a different adverse event than bradycardia (and is not necessarily associated with ACh action). The purpose of this article is to review the three AChEIs, especially with regards to mechanistic differences that may explain why only donepezil poses this risk; several pharmacological mechanisms may explain why. However, from an empirical point‐of‐view, aside from some case‐reports, only a limited number of studies have generated relevant information regarding AChEIs' and electrocardiogram findings; none have specifically compared donepezil against galantamine or rivastigmine for malignant arrhythmias such as TdP. Currently, the choice of one of the three AChEIs for treatment of AD symptoms is primarily dependent upon clinician and patient preference. However, clinicians should be aware of the potential increased risk associated with donepezil. There is a need to examine the comparative risk of malignant arrhythmias among AChEIs users in real‐world practice; this may have important implications with regards to changes in AChEI prescribing patterns.

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Section: A Review Of Case Reportsmentioning

confidence: 51%

Section: It Has Also Been Found That Activation Of Cardiac Ach Receptorsmentioning

confidence: 99%

Section: A Review Of Case Reportsmentioning

confidence: 99%

Section: A Review Of Case Reportsmentioning

confidence: 99%

See 2 more Smart Citations

Comparative risk of cardiac arrhythmias associated with acetylcholinesterase inhibitors used in treatment of dementias – A narrative review

Huang

Alsabbagh

2020

Pharmacology Res & Perspec

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“…The duration of the repolarized ventricles is reflected by QTc interval, and the activity of class III antiarrhythmic is indicated by QTc prolongation [13,14]. However, administration of ibutilide causes prolongation of the (QTc) interval and high risk for ventricular tachycardia TdP [15].…”

Section: Discussionmentioning

confidence: 99%

Ibutilide is efficacy but not safe in cardioversion of atrial fibrillation for patients aged over 75 years

Zhang

2020

Preprint

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Background: Atrial fibrillation (AF) is the common arrhythmia resulting in high morbidity and mortality. Ibutilide is used to convert AF to sinus rhythm pharmacologically. We aimed to evaluate the clinical efficacy and safety of ibutilide for patients over 75 years old with recent onset AF.Methods: 81 patients over 75 years old with recent onset AF less than 72 hours, range from 75 to 85 years, were analyzed retrospectively from January 2015 to January 2019. 40 patients received ibutilide, and another 41 patients received propafenone as the control group. In ibutilide group, patients weighing over 60 kg were received 1 mg of ibutilide, and ibutilide at 0.01 mg / kg were administrated when the patient’s body weight was less than 60 kg. If cardioversion failed, 1 mg or 0.01 mg/kg of ibutilide would be given after 10 minutes. In control group, patients were received propafenone at 75mg. If there was no effect on cardioversion, 35 mg of propafenone would be given after 10 minutes.Results: In control group 26 patients (63.4%) converted to sinus rhythm, and in ibutilide group, 35(87.5%) converted to sinus rhythm (p<0.05, vs control group). The converting time of ibutilide group was shorter than control group(13.5±9.27s vs 43.72±10.27s,P<0.05 ). The corrected QT (QTc) intervals was significantly prolonged in patients after the administration of ibutilide(P<0.05). In ibutilide group, five patients (12.5%) appeared torsades de pointes (TdP) and converted to sinus rhythm via electrical cardioversion. Six patients (14.6%) developed severe bradycardia in control group, and the bradycardia alleviated after discontinuation of propafenone. Nine patients (21.9%) who failed in cardioversion with 24 hours by propafenone converted to sinus rhythm via electrical cardioversion.Conclusion: Ibutilide could effectively convert recent onset (<72 hours) AF in patients aged over 75 years. However, it was worth noting that the high rate of TdP emerged in these elderly patients after the treatment of ibutilide.

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Heart Activity and Cognition

Vercesi

2020

Brain and Heart Dynamics

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

Cited by 8 publications

References 34 publications

Comparative risk of cardiac arrhythmias associated with acetylcholinesterase inhibitors used in treatment of dementias – A narrative review

Comparative risk of cardiac arrhythmias associated with acetylcholinesterase inhibitors used in treatment of dementias – A narrative review

Ibutilide is efficacy but not safe in cardioversion of atrial fibrillation for patients aged over 75 years

Heart Activity and Cognition

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