Issues for surgery
For insomnia – loss of symptom control if omitted.
Risk of withdrawal symptoms if omitted (see Further information).
Increased sedative effect and risk of cumulative central nervous system depression if continued.
Potential for post-operative delirium for elderly patients or those on long-term treatment, if continued (see Further information).
Advice in the perioperative period
Elective and emergency surgery
Continue.
Inform anaesthetist on day of admission of type and dose of zopiclone the patient usually takes so anaesthesia can be adjusted accordingly if necessary.
Post-operative advice
Restart post-operatively if appropriate.
Bear in mind the potential for post-operative confusion and delirium (POD), especially in those patients who are elderly and / or have been taking long-term zopiclone (see Further information).
Patients who are discharged on the day of surgery after having received an anaesthetic and who usually take zopiclone should be advised of the potential of enhanced drowsiness and psychomotor effects and counsel against undertaking skilled tasks (e.g. driving).
Interactions with common anaesthetic agents
Central Nervous System (CNS) depression
Also see Interactions with other common medicines used in the perioperative period.
Zopiclone has CNS depressant effects which may be additive with other medicines that also have CNS depressant effects such as:
- inhalational and intravenous anaesthetics
- local anaesthetics
- opioids
- other benzodiazepines
Opioids
Giving zopiclone with opioids during anaesthesia may reduce the dose required of both drugs. The patient should be monitored and adjustments made according to the effect.
If zopiclone is used concomitantly with opioids, possible euphoria may be enhanced; this may lead to increased psychological dependence.
The current recommendation from manufacturers for the prescribing of zopiclone with opioids is that concurrent use should be reserved for patients in whom alternative treatment options are not possible or are inadequate. If the decision is made to prescribe zopiclone with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible.
Interactions with other common medicines used in the perioperative period
CNS depression
Also see Interactions with common anaesthetic agents for information on opioids.
Zopiclone has CNS depressant effects which may be additive with antiemetics that also have CNS depressant effects such as:
- cyclizine
- droperidol
- prochlorperazine
Antimicrobials
Macrolide antibiotics
Compounds that inhibit hepatic enzymes may increase the concentration of zopiclone and enhance its activity. Hence, caution is recommended when zopiclone is co-administered with macrolide antimicrobials (e.g. erythromycin, clarithromycin). Monitor the patient for increased sedative effects and adjust the benzodiazepine dose as necessary.
Further information
Withdrawal
Sudden discontinuation of zopiclone is associated with withdrawal symptoms including confusion, toxic psychosis, convulsions, delirium and rebound effects. Doses should be reduced gradually.
Withdrawal symptoms from zopiclone are unlikely if treatment duration has been less than 4 weeks.
Post-operative delirium (POD)
POD has been shown to be a predictor of death, increased mortality, and longer duration of stay especially in ventilated patients. Zopiclone has been found to increase the frequency of POD. The frequency may be higher in elderly patients. In addition, if a patient develops POD, consideration should be given to not using benzodiazepines as the first-line agents for treatment.
References
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 29th August 2019
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 10th July 2019]
Kudoh A, Takase H, Takahira Y. Postoperative confusion increases in elderly long-term benzodiazepine users. Anesthesia & Analgesia. 2004; 99(6):1674
Lepouse C, Lautner CA, Liu A et al. Emergence delirium in adults on the post-anaesthesia care unit. British Journal of Anaesthesia. 2006; 96(6):747-753
Perks A, Cheema S, Mohanraj R. Anaesthesia and epilepsy. BJA: British Journal of Anaesthesia. 2012; 108(4):562-571
Summary of Product Characteristics – Zopiclone 7.5mg Tablets. Accord-UK Ltd. Accessed via www.medicines.org.uk 11/09/2019 [date of revision of the text June 2019]
Zhang Y, Tany Y, Yang J et al. Perioperative Use of Benzodiazepines: A Reconsideration of Risks and Benefits. J Anaesth Perioper Med. 2018; 5(1):34-40