Published: 13 December 2017

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Interactions with Donepezil

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Prescriber Update 38(4): 51
December 2017

Donepezil is a specific and reversible acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease and vascular dementia^1,2. Alzheimer's disease is the most common form of dementia and the number of people affected is expected to increase as the population ages.

When patients taking donepezil require treatment with other medicines, consideration should be given to potential interactions. This is particularly important when preparing patients for surgery. For example, donepezil can considerably prolong the depolarising action of suxamethonium and may shorten the duration and diminish the magnitude of neuromuscular blockade with atracurium^3,4.

Medicines that are known to interact with donepezil are shown in Table 1. Check the medicine data sheets (www.medsafe.govt.nz/Medicines/infoSearch.asp) or use the interactions search bar in the New Zealand Formulary (http://nzf.org.nz/nzf_6272) for more information.

Table 1: Summary of medicines that may interact with donepezil^1,2,5

Interaction Type	Medicine Group	Medicine Examples	Effect
Pharmacodynamic interactions	Non-depolarising neuromuscular blocking agents	pancuronium, rocuronium, vecuronium, atracurium, mivacurium	Donepezil may reduce the effects of these agents.
	Depolarising neuromuscular blocking agents	suxamethonium	Donepezil may prolong the effects of these agents.
	Anticholinesterase agents	neostigmine, pyridostigmine	Synergistic effects with donepezil.
	Beta blockers	atenolol, carvedilol, metoprolol, propranolol	Donepezil may increase the risk of bradycardia.
Pharmacokinetic interactions	CYP3A4 inhibitors CYP2D6 inhibitors	itraconazole, erythromycin, ketoconazole, fluoxetine, quinidine	Could inhibit metabolism of donepezil. Clinical effects not known.
	CYP3A4 inducers CYP2D6 inducers	rifampicin, phenytoin, carbamazepine, dexamethasone	May reduce levels of donepezil.

The Centre for Adverse Reactions Monitoring (CARM) has received four reports describing a drug interaction with donepezil. Three of these reports describe an interaction with metoprolol resulting in bradycardia. Please continue to report any adverse reactions, including medicine interactions, with donepezil to CARM. Reports can be submitted on paper or electronically (https://nzphvc.otago.ac.nz/).

References

1. Pfizer New Zealand Ltd. 2012. Aricept New Zealand Data Sheet 25 October 2012. URL: medsafe.govt.nz/profs/Datasheet/a/AricepttabAriceptDtab.pdf (accessed 29 September 2017).
2. REX Medical Limited. 2014. Donepezil New Zealand Data Sheet 8 January 2014. URL: medsafe.govt.nz/profs/Datasheet/d/donepeziltab.pdf (accessed 29 September 2017).
3. AstraZeneca Limited. 2014. Suxamethonium Chloride BP New Zealand Data Sheet 9 December 2014. URL: medsafe.govt.nz/profs/Datasheet/s/SuxamethoniumChlorideinj.pdf (accessed 8 November 2017).
4. GlaxoSmithKline NZ Ltd. 2013. Tracrium Data Sheet 20 November 2013. URL: medsafe.govt.nz/profs/Datasheet/t/Tracriuminj.pdf (assessed 29 November 2017).
5. New Zealand Formulary. 2017. New Zealand Formulary v64 1 October 2017. URL: http://nzf.org.nz/ (accessed 4 October 2017).