Moclobemide


  Issues for Surgery


Risk of withdrawal symptoms and risk of relapse if omitted (see Further Information).

Risk of serotonin syndrome if continued (see Interaction(s) with Common Anaesthetic Agents and Interaction(s) with other Common Medicines used in the Perioperative Period).

Risk of hypertensive crisis if continued (see Interaction(s) with Common Anaesthetic Agents).


  Advice in the Perioperative period


Elective Surgery

Stop moclobemide on the day before surgery, i.e. last dose to be taken 24 hours before surgery1.

Emergency Surgery

Inform Anaesthetist if patient has taken dose(s) of moclobemide in previous 24 hours. Monoamine oxidase inhibitor (MAOI)-safe anaesthesia will need to be used if the operation cannot be delayed1 (see Interaction(s) with Common Anaesthetic Agents).

For MAOI safe anaesthesia avoid1: -

  • indirect-acting sympathomimetics (e.g. ephedrine, metaraminol)
  • pethidine

Post-operative Advice

Restart moclobemide after the operation, once there is no longer a risk of interactions.

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


Sympathomimetics

Indirectly-acting sympathomimetics can lead to potentially fatal hypertensive crisis in patients taking irreversible MAOIs. The evidence suggests the interaction is much weaker with moclobemide, a reversible inhibitor of monoamine oxidase A (RIMA), but it is still possible1, 2 and the manufacturer advises to avoid concurrent use3, 4.

Directly-acting sympathomimetics (e.g. adrenaline / epinephrine, isoprenaline, noradrenaline / norepinephrine) can be used safely in patients taking moclobemide1, however, the effect is likely to be intensified and prolonged due to receptor hypersensitivity in those patients who have a hypotensive response to MAOIs1, 2.

It is recommended that lower doses of phenylephrine are used in patients taking moclobemide and the dose titrated carefully against clinical response1, 2.

Opiates

CNS Excitation (Serotonin Syndrome)
Serotonin syndrome has been reported in a patient given pethidine in addition to their usual moclobemide; they were also taking nortriptyline and lithium, which may have contributed to the interaction2. Further reports of an interaction are limited, however, the manufacturer advises avoid concomitant use of moclobemide with pethidine due to risk of serotonin syndrome3.

Fentanyl may also increase the risk of serotonin syndrome4.

Manufacturer also advises avoid concomitant use of moclobemide with tramadol due to risk of serotonin syndrome2, 3.

CNS Depression (Opioid Toxicity)
Moclobemide does not inhibit hepatic microsomal enzymes so accumulation of opioids is unlikely1, however, opioid potentiation has been noted in animal studies3. Morphine, fentanyl and codeine should be used with caution and doses titrated to response3.


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


Opiates (see Interaction(s) with Common Anaesthetic Agents)

Non-opioid Medications associated with CNS Excitation (Serotonin Syndrome)

Manufacturer advises avoid concomitant use of moclobemide with linezolid due to risk of serotonin syndrome3. Increased side effects would also be expected4.

There is also an increased risk of developing serotonin syndrome when moclobemide is used concurrently with the following3, 4:

  • granisetron
  • ondansetron
  • methylthioninium chloride (methylene blue)

Monitor patients for symptoms of serotonin syndrome such as fever, tremors, diarrhoea, and agitation. Concurrent treatment should be stopped if serotonin syndrome occurs4.


  Further Information


Risk of Interaction

Moclobemide is a reversible inhibitor of monoamine oxidase type A (RIMA)2 with an elimination half-life of between 2 and 4 hours1, 3. Interactions are unlikely to occur 24 hours after it has been stopped as MAO activity will have returned to normal1, 2.

Withdrawal

Withdrawal effects may occur within 5 days of stopping antidepressant treatment; they are usually mild and self-limiting, but in some cases may be severe4. The risk of withdrawal symptoms is increased if the antidepressant is stopped suddenly after regular administration for more than 8 weeks4. Despite reducing the moclobemide dose over 3 days a case report describes withdrawal symptoms such as muscle cramps, shivering, headache, nausea and hot flushes5; the dose should preferably be reduced gradually over about 4 weeks4.


  References


  1. Luck JF, Wildsmith JAW & Christmas DMB. Monoamine Oxidase Inhibitors and Anaesthesia. The Royal College of Anaesthetists 2003; Bulletin 21:1029-1034
  2. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 19th June 2019]
  3. Summary of Product Characteristics – Manerix® (moclobemide) 300mg. Mylan. Accessed via www.medicines.org.uk 19/06/2019 [date of revision of the text February 2018]
  4. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 19th June 2019]
  5. Moclobemide. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. Electronic version. Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com. [Accessed 19th June 2019]