Cholinesterase inhibitors and cardiac arrhythmias

Cholinesterase inhibitors such as donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl) are being used increasingly in the treatment of Alzheimer's disease. The product information for all three drugs notes that increased cholinergic activity may have vagal effects on heart rate such as bradycardia.

The Table shows reports of cardiac arrhythmias and other effects, like syncope, which may be indicative of such problems. The larger number of reports with donepezil is almost certainly due to greater usage of this drug. Most patients recovered after the cholinesterase inhibitor was stopped or in some cases, reduced in dose. Many patients were hospitalised and in 4 cases a pacemaker was required. Four elderly patients died from suspected myocardial infarction; it is unclear whether their medication had any role in these events.

Table: Cardiac arrhythmias with cholinesterase inhibitors

	Donepezil	Rivastigmine	Galantamine
Bradycardia	14	7	6
Bundle branch block	1	-	1
AV block	5	-	1
Syncope	10	8	4
Unspecified arrhythmia	2	-	1
Myocardial infarction/cardiac arrest	7	1	-
Total number of all reports	235	82	54
PBS prescriptions (to December 2003)	439,000	78,000	67,000

Prescribers need to be aware of the potential for cardiac arrhythmias, particularly bradycardia, with cholinesterase inhibitors. Patients with sick sinus syndrome or other supraventricular cardiac conduction conditions may be at particular risk. A pharmacodynamic interaction can also be predicted with the concomitant use of beta-blockers or calcium channel blockers.

Reference
Australian Adverse Drug Reactions Bulletin, Vol.23, no.5 (Oct 2004)