Issues for surgery
For treatment of epilepsy – loss of seizure control if omitted.
For panic disorder in psychiatric patients – 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
Continue.
Inform anaesthetist on day of admission of the patient's usual dose of clonazepam so anaesthesia can be adjusted accordingly if necessary.
Epilepsy
Patients should be advised to take their regular medications on the day of surgery.
Abrupt withdrawal of any anticonvulsant drug should be avoided.
Confirm with the patient if they need to be maintained on a specific manufacturer’s product (see Further information).
Anxiolysis
Discontinuation of clonazepam in psychiatric patients with panic disorders should be avoided. Seek advice from Mental Health Team if necessary.
Post-operative advice
For patients with epilepsy
Clonazepam is only available as oral preparations. If patients cannot resume their usual oral medication post-operatively, the advice of a Neurologist should be sought to determine the most appropriate antiepileptic preparation, dose and frequency to be used.
For patients taking clonazepam for other indications
Restart post-operatively if appropriate.
If patient cannot resume their usual oral medication post-operatively and is at risk of withdrawal, consider using a suitable intravenous preparation. Consult with a psychiatrist if necessary.
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 benzodiazepines (see Further information).
Patients who are discharged on the day of surgery after having received an anaesthetic and who usually take benzodiazepines 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
For general information regarding the use of anaesthetic agents in patients with epilepsy see Antiepileptics overview.
Central Nervous System (CNS) depression
Also see Interactions with other common medicines used in the perioperative period.
Benzodiazepines have 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 benzodiazepines 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 benzodiazepines 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 benzodiazepines 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 benzodiazepines with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible.
Neuromuscular Blocking Drugs (NMBDs)
There are conflicting reports of the effect of diazepam on NMBDs; potentiation, or antagonism of neuromuscular block, and lack of interaction have all been reported.
Interactions with other common medicines used in the perioperative period
CNS depression
Also see Interactions with common anaesthetic agents for information on opioids.
Benzodiazepines have 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 benzodiazepines and enhance their activity. Hence, caution is recommended when benzodiazepines are co-administered with macrolide antimicrobials (e.g. erythromycin, clarithromycin). Monitor the patient for increased sedative effects and adjust the benzodiazepine dose as necessary.
Proton Pump Inhibitors (PPIs)
Esomeprazole and omeprazole might increase the serum concentrations of benzodiazepines (via CYP2C19 inhibition) leading to increased adverse effects such as drowsiness, although the clinical relevance is low in most patients – monitor the patient for adverse effects (e.g. drowsiness, sedation, ataxia) and adjust the dose of benzodiazepine as necessary. Alternatively, consider changing to a non-interacting PPI (e.g. lansoprazole).
Further information
Withdrawal
Sudden discontinuation of benzodiazepines is associated with withdrawal symptoms including confusion, toxic psychosis, convulsions, delirium and rebound effects. Doses should be reduced gradually.
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. Benzodiazepines have been found to increase the frequency of POD. The frequency may be higher in elderly patients and those on long-term benzodiazepines. In addition, if a patient develops POD, consideration should be given to not using benzodiazepines as the first-line agents for treatment.
MHRA/CHM Advice: Antiepileptic Drugs: updated advice on switching between different manufacturer’s products for a particular drug (November 2017)
Epilepsy
Clonazepam is a category 2 antiepileptics, hence the need for continued supply of a particular manufacturer’s product should be based on clinical judgement and consultation with the patient and/or carer taking into account factors such as seizure frequency treatment history, and potential implications to the patient having a breakthrough seizure. Non-clinical factors such as patient anxiety, confusion, potential for dosing errors should also be considered (for more information see Antiepileptics overview).
Other indications
There is no specific advice available for maintaining patients on a specific manufacturer’s product for indications other than epilepsy.
References
Atracurium Besilate. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 29th August 2019]
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 29th August 2019
Carter EL, Adapa RM. Adult epilepsy and anaesthesia. BJA Education. 2015; 15(3):111-117
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 – Clonazepam Auden 2mg Tablets. TEVA UK Limited. Accessed via www.mhra.gov.uk 11/09/2019 [date of revision of the text September 2018]
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