Agomelatine


  Issues for Surgery


Risk of central nervous system (CNS) depression if continued (see Interaction(s) with Common Anaesthetic Agents and Interaction(s) 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 hepatoxicity1 (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.


  Interaction(s) with Common Anaesthetic Agents


Central Nervous System (CNS) Depression (also see under Interaction(s) 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 as1, 2: -

  • benzodiazepines
  • inhalational anaesthetics and intravenous anaesthetics
  • local anaesthetics
  • opioids
    (Consult British National Formulary for available drugs in each class)


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


CNS Depression (also see under Interaction(s) 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 prochlorperazine1, 2.

Ciprofloxacin

Ciprofloxacin is predicted to increase the exposure to agomelatine through inhibition of CYP1A2, the manufacturer advises concomitant use is contraindicated1, 2, 3.


  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 day2, 3. 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 advice1, 2.

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 withdrawal3.


  References


  1. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 20th July 2019]
  2. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 20th July 2019] 
  3. 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]
  4. 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]