Donepezil

  Issues for Surgery

Potentially irreversible decline in cognitive function if stopped (see Further Information).

Interaction with neuromuscular blocking drugs (NMBDs) if continued (see Interaction(s) 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 / sugammadex¹
• Consider use of remifentanil infusion

Post-operative advice

Restart as soon as possible post-operatively.

  Interaction(s) with Common Anaesthetic Agents

Neuromuscular Blocking Drugs (NMBDs)

Non-depolarising NMBDs
Donepezil potentially antagonises the effect of non-depolarising NMBDs^{1, 2, 3, 4}; larger doses may be required to achieve satisfactory paralysis¹.

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^1,4,5. Neostigmine should be used with caution in patients taking donepezil⁵.

Case reports provide support for these interactions^{4, 5, 6}.

Suxamethonium
Donepezil is expected to prolong the effects of suxamethonium through the inhibition of acetylcholine metabolism^{1, 2, 3, 4}.

Bradycardia

Donepezil can increase the risk of bradycardia when used concomitantly with the following²: -

• alfentanil, fentanyl or remifentanil
• neostigmine
• propofol
• suxamethonium (see also Neuromuscular Blocking Drugs above)

  Interaction(s) with other Common Medicines used in the Perioperative Period

None^{2, 3, 4}.

  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-life¹. 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 treatment⁷. In view of this potentially irreversible decline in cognitive function the withdrawal of donepezil 2-3 weeks before an operation cannot be supported⁵.

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 risk¹.

  References

1. Alcorn, S and Foo, I. Perioperative management of patients with dementia. BJA Education. 2017; 17(3):94-98
2. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 13^th May 2019]
3. 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]
4. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com  [Accessed on 13^th May 2019]
5. Aronson, J. (2016) Suxamethonium. Chapter in Meyler’s Side Effects of Drugs, 16^th edition, Elsevier
6. 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
7. 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