UK Clinical Pharmacy Association


Issues for surgery

For insomnia – exacerbation of symptoms 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


Inform anaesthetist on day of admission of type and dose of benzodiazepine 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 zolpidem (see Further information).

Patients who are discharged on the day of surgery after having received an anaesthetic and who usually take zolpidem 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.

Zolpidem 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


Giving zolpidem 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 zolpidem drugs are 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 zolpidem 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 zolpidem 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.

Zolpidem has CNS depressant effects which may be additive with antiemetics that also have CNS depressant effects such as:

  • cyclizine, droperidol and prochlorperazine.
  • droperidol
  • prochlorperazine



Concomitant use of ciprofloxacin may slightly increase blood levels of zolpidem. Concurrent use of ciprofloxacin and zolpidem is not recommended by the manufacturer; however, evidence for this interaction is limited. It is unlikely that any clinically significant increases in zolpidem effects will occur.

Whilst single surgical prophylactic doses should not pose a problem, continued post-operative treatment may require close monitoring for zolpidem adverse effects.

Further information


Sudden discontinuation of zolpidem is associated with withdrawal symptoms including confusion, toxic psychosis, convulsions, delirium and rebound effects. Doses should be reduced gradually.

Withdrawal symptoms from zolpidem 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. Zolpidem has been found to increase the frequency of POD. The frequency may be higher in elderly patients and those on long-term zolpidem. In addition, if a patient develops POD, consideration should be given to not using benzodiazepines as the first-line agents for treatment.


Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. [Accessed on 29th August 2019

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. [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 – Zolpidem Tartrate 10mg Tablets. Zentiva. Accessed via 11/09/2019 [date of revision of the text January 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