Issues for surgery
Risk of central nervous system (CNS) depression if continued (see Interactions with common anaesthetic agents and Interactions with other common medicines used in the perioperative period).
Advice in the perioperative period
Elective and emergency surgery
Continue.
For patients who may decide to quit smoking during the perioperative period see Further Information.
Consider checking liver function tests (LFTs) pre-operatively as agomelatine has been associated with hepatoxicity (see Further Information).
Post-operative advice
If a long nil by mouth (NBM) period is anticipated, or if there are concerns with enteral absorption, advice on alternative preparations/routes should be sought from a psychiatrist.
Interactions with common anaesthetic agents
Central Nervous System (CNS) depression (also see Interactions with other common medicines used in the perioperative period)
Agomelatine has CNS depressant effects which may be additive with other medicines that also have CNS depressant effects such as:
- benzodiazepines
- inhalational anaesthetics and intravenous anaesthetics
- local anaesthetics
- opioids
Consult British National Formulary for available drugs in each class.
Interactions with other common medicines used in the perioperative period
CNS depression (also see under Interactions with common anaesthetic agents for information on opioids)
Agomelatine has CNS depressant effects which may be additive with antiemetics that also have CNS depressant effects such as cyclizine, droperidol and prochlorperazine.
Ciprofloxacin
Ciprofloxacin is predicted to increase the exposure to agomelatine through inhibition of CYP1A2, the manufacturer advises concomitant use is contraindicated.
Further information
Smoking cessation
Quitting smoking pre-operatively improves surgical outcomes through reducing risk of post-operative complications4. Smoking induces CYP1A2, decreasing the bioavailability of agomelatine, especially in those smoking at least 15 cigarettes a day. If a patient decides to quit smoking during the perioperative period it must be remembered that smoking cessation can reduce agomelatine clearance (potential for increased plasma agomelatine levels) – dosage adjustments might be necessary, although the manufacturer doesn’t give any specific advice.
Hepatotoxicity
Agomelatine has been associated with hepatotoxicity. LFTs should be monitored after 3, 6, 12 and 24 weeks of treatment and then regularly thereafter when clinically indicated3. If recent LFTs are not available, consider checking pre-operatively.
Manufacturer advises treatment should be discontinued immediately if alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) exceed 3 times the upper limit of normal or if signs and symptoms of liver disorder (dark urine, light coloured stools, jaundice, bruising, fatigue, abdominal pain or pruritus) develop. No withdrawal symptoms would be expected with abrupt withdrawal.
References
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 20th July 2019]
Faculty of Public Health, The Royal College of Surgeons of Edinburgh, The Royal College of Anaesthetists, ash (action on smoking and health). Joint Briefing: Smoking and surgery. April 2016. Available at www.rcoa.ac.uk [Accessed 20th July 2019]
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 20th July 2019]
Summary of Product Characteristics – Valdoxan® (agomelatine) 25mg film-coated tablets. Servier Laboratories Limited. Accessed via www.medicines.org.uk 20/07/2019 [date of revision of the text December 2018]