From the Guidelines
Donepezil can have significant effects on the heart, particularly in patients with pre-existing cardiac conditions, and its use should be carefully monitored. The medication works by inhibiting acetylcholinesterase, which increases acetylcholine levels in the brain but can also affect the heart, leading to potential cardiac side effects such as bradycardia, heart block, QT interval prolongation, and syncope 1. These effects are thought to occur because acetylcholine naturally slows heart rate, and increasing its levels can exacerbate this effect. Patients with pre-existing cardiac conditions, particularly those with sick sinus syndrome, heart block, or other arrhythmias, should use donepezil with caution or avoid it altogether. The standard starting dose is 5 mg daily, which may be increased to 10 mg daily after 4-6 weeks if tolerated, as indicated in guidelines for managing Alzheimer's disease 1. Cardiac side effects typically appear within the first few weeks of treatment or after dose increases. Regular monitoring of heart rate and rhythm is recommended, especially in elderly patients or those with cardiovascular risk factors. If significant bradycardia (heart rate below 50 beats per minute) or new arrhythmias develop, the medication may need to be discontinued or the dose reduced, as suggested by studies evaluating the treatment of dementia 1. Some key points to consider when prescribing donepezil include:
- Starting with a low dose and gradually increasing as needed and tolerated
- Monitoring for cardiac side effects, particularly in patients with pre-existing cardiac conditions
- Regularly assessing heart rate and rhythm in elderly patients or those with cardiovascular risk factors
- Advising patients to report symptoms such as dizziness, lightheadedness, fainting, or palpitations promptly to their healthcare provider. Overall, while donepezil can be an effective treatment for Alzheimer's disease, its potential effects on the heart must be carefully considered and monitored to minimize risks and ensure the best possible outcomes for patients.
From the FDA Drug Label
Because of their pharmacological action, cholinesterase inhibitors may have vagotonic effects on the sinoatrial and atrioventricular nodes. This effect may manifest as bradycardia or heart block in patients both with and without known underlying cardiac conduction abnormalities. Syncopal episodes have been reported in association with the use of donepezil hydrochloride.
Donepezil may have effects on the heart, including:
- Vagotonic effects on the sinoatrial and atrioventricular nodes
- Bradycardia (slow heart rate)
- Heart block
- Syncopal episodes (fainting spells) These effects may occur in patients with or without pre-existing cardiac conduction abnormalities 2, 2, 2.
From the Research
Donepezil Effects on the Heart
- Donepezil, an acetylcholinesterase inhibitor, has been reported to have cardiovascular side effects, including bradycardia and atrioventricular block 3, 4, 5, 6, 7
- Studies have shown that donepezil can decrease heart rate and prolong the PR interval in patients with Alzheimer's disease 4, 5, 7
- The risk of bradycardia has been found to be higher in patients taking donepezil compared to those taking other medications for Alzheimer's disease treatment 6
- Donepezil administration has been shown to improve parasympathetic function, as indicated by decreased low/high frequency ratio and high frequency components and oscillation of RR intervals 7
- However, donepezil has not been found to have significant effects on QRS duration and QT intervals in elderly patients with ischemic heart disease 7
Patient-Specific Factors
- Age and dosage of donepezil have not been found to be significantly associated with the risk of bradycardia 6
- Males have been found to be more likely than females to report bradycardia as an adverse event 6
- Patients with a history of conduction defects or sick sinus syndrome may be at higher risk of cardiovascular side effects from donepezil 3