Issues for surgery
Potentially irreversible decline in cognitive function if stopped (see Further information).
Interaction with neuromuscular blocking drugs (NMBDs) if continued (see Interactions with common anaesthetic agents).
Advice in the perioperative period
Elective and emergency surgery
Continue.
Ensure anaesthetist is aware of drug interactions.
Consider the following:
- If possible, avoid NMBDs
- If NMBDs are required – monitor blockade
- Consider use of rocuronium / sugammadex
- Consider use of remifentanil infusion
Post-operative advice
Restart as soon as possible post-operatively.
Interactions with common anaesthetic agents
Neuromuscular blocking drugs (NMBDs)
Non-depolarising NMBDs
Donepezil potentially antagonises the effect of non-depolarising NMBDs; larger doses may be required to achieve satisfactory paralysis.
Neostigmine may be ineffective as a reversal agent due to the pre-existing level of cholinesterase inhibition; furthermore, administration of neostigmine could potentiate the effect through a phase II depolarising block with suxamethonium. Neostigmine should be used with caution in patients taking donepezil.
Case reports provide support for these interactions.
Suxamethonium
Donepezil is expected to prolong the effects of suxamethonium through the inhibition of acetylcholine metabolism.
Bradycardia
Donepezil can increase the risk of bradycardia when used concomitantly with the following:
- alfentanil, fentanyl or remifentanil
- neostigmine
- propofol
- suxamethonium (see also Neuromuscular blocking drugs above).
Interactions with other common medicines used in the perioperative period
None.
Further information
Rationale for continuing pre-operatively
Manufacturer’s advice is to stop donepezil 2-3 weeks pre-operatively in view of its 70 hour elimination half-life. However, clinical trials have shown that a treatment gap of 3 weeks resulted in loss of cognitive function which was only partially regained when treatment restarted thus reducing the long term beneficial effects of treatment. In view of this potentially irreversible decline in cognitive function the withdrawal of donepezil 2-3 weeks before an operation cannot be supported.
Delirium
Patients with dementia are at increased risk of developing post-operative delirium. Avoiding medications with anticholinergic side effects (e.g. cyclizine) can minimise this risk.
References
Alcorn, S and Foo, I. Perioperative management of patients with dementia. BJA Education. 2017; 17(3):94-98
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 13th May 2019]
Summary of Product Characteristics – Aricept® (donepezil). Eisai Ltd. Accessed via www.medicines.org.uk 13/05/2019 [date of revision of the text May 2018]
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 13th May 2019]
Aronson, J. (2016) Suxamethonium. Chapter in Meyler’s Side Effects of Drugs, 16th edition, Elsevier
Baruah J, Easby J, Kessell G: Effects of acetylcholinesterase inhibitor therapy for Alzheimer’s disease on neuromuscular block. Br J Anaesth. 2008;100(3):420
Seltzer, B. Cholinesterase Inhibitors in the Clinical Management of Alzheimer’s Disease: Importance of Early and Persistent Treatment. The Journal of International Medical Research. 2006; 34:339-347