Published: 6 September 2013


Donepezil: Syncope, Heart Block and Beta-adrenergic Blockade

Prescriber Update 34(3):30
September 2013

The Centre for Adverse Reactions Monitoring (CARM) has received two reports of bradycardia and syncope occurring in patients taking donepezil and metoprolol.

One of these patients developed recurrent syncope with initially normal telemetry. Syncopal episodes persisted for two months. On further telemetry, heart block was observed requiring a temporary pacemaker. The second patient did not have telemetry. Both patients recovered when donepezil and metoprolol were discontinued.

CARM has also received one report of symptomatic bradycardia and first degree heart block. This occurred when donepezil was added to long-term treatment with metoprolol and diltiazem. The patient showed subsequent improvement when all three medicines were discontinued. There was no relapse when metoprolol was reintroduced.

Donepezil is a cholinesterase inhibitor indicated for Alzheimer's disease and vascular dementia1. Donepezil affects parasympathetic innervation of the myocardium. The main effect is suppression of atrioventricular node conduction.

Beta-adrenergic blocking agents, such as metoprolol, block catecholamine-induced increases in heart rate, myocardial contractility and blood pressure2.

Donepezil alone can therefore cause bradycardia, heart block and syncope and this is a possibility in all three case reports1,3. However, where there is an enhanced parasympathetic effect on the myocardium due to donepezil, and metoprolol has blocked the usual sympathetic response of increasing blood pressure then the possibility of postural syncope of central cardiac origin is increased.

The combination of donepezil and a beta-blocker is not contraindicated but, if there is new-onset syncope, whichever of the two medicines was added most recently should be discontinued. A synergistic effect on cardiac conduction is also possible1.

All patients taking donepezil, with or without a beta-blocker, should be monitored for syncope, clinically important bradycardia or heart block. The possibility of these being accentuated by concomitant beta blockade should be considered. Particular watchfulness is needed for patients with pre-existing conduction abnormalities1.

Dr Ruth Savage
New Zealand Pharmacovigilance Centre

  1. Pfizer New Zealand Ltd. 2012. Aricept Data Sheet. 25 October 2012. URL: (accessed 2 August 2013).
  2. AFT Pharmaceuticals Ltd. 2009. AFT-Metoprolol CR Data Sheet. 1 December 2009. URL: (accessed 2 August 2013).
  3. Bordier P, Garrigue S, Barold SS, et al. 2003. Significance of syncope in patients with Alzheimer's disease treated with cholinesterase inhibitors. Europace 5(4): 429–31.
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