Bradycardia donepezil

Donepezil is primarily a reversible inhibitor of acetylcholinesterase with a long elimination half-life. It lacks the hepatotoxicity of tacrine but frequently causes nausea, vomiting and diarrhoea. These side effects, together with occasional bradycardia, sycope and changes in the sleep architecture, are directly associated with a central and peripheral enhancement of cholinergic function. At the present time, donepezil is the most widely prescribed anticholinesterase in the United States and Europe. 

Seven elderly patients with psychotic or non-psychotic behavioral symptoms in Lewy body dementia had some benefit from donepezil (24). Donepezil was withdrawn prematurely in three patients owing to poor response and/or adverse events. The adverse events were sedation, somnolence, worsening of chronic obstructive pulmonary disease, syncope, sweating, and bradycardia. These results have to be confirmed in controlled trials. 

Symptomatic sinus bradycardia is a possible adverse effect of treatment with donepezil in Alzheimer s disease (51). 

An 84-year-old patient with hypertensive cardiomyopathy developed bradycardia, fainting, and left-sided heart failure 3 weeks after starting treatment with donepezil. When donepezil was withdrawn, the sinus bradycardia disappeared 24-hour electrocardiography showed no signs of sinus node disease, and no episodes of this type recurred during the next 6 months. 

A 79-year-old nursing home patient was given donepezil 50 mg in error. She developed nausea, vomiting, and persistent bradycardia—typical cholinergic adverse effects. She was treated with atropine, 0.2 mg as needed, for bradycardia (total dose 3 mg over 18 hours) and was discharged on the second day. 

Calvo-Romero JM, Ramos-Salado JL. Bradycardia sinusal sintomatica associada a donepecilo. [Symptomatic sinus bradycardia associated with donepezil.] Rev Neurol 1999 28(ll) 1070-2. 

Adverse effects inevitably include cholinergic symptoms with nausea, diarrhoea and abdominal cramps appearing commonly. There may also be bradycardia, sinoatrial or atrioventricular block. Urinary incontinence, syncope, convulsions, and psychiatric disturbances also occur. Rapid dose increase appears to make symptoms more pronounced. Hepatotoxicity is a rare association with donepezil. 

In another retrospective analysis of data in the French Pharmacovigilance Database, the most frequent adverse drug reactions with donepezil alone and memantine alone were respectively bradycardia (10% versus 7%), weakness (5% versus 6%), and convulsions (4% versus 3%) [102. ... 

---