Monoamine-oxidase B (MAO-B) Inhibitors


Rasagiline, Safinamide, Selegiline

 

  Issues for Surgery


Risk of exacerbation of Parkinson’s Disease (PD) and akinesia if omitted1.

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 and Emergency Surgery

Continue2.

To minimise disruption to the patient’s usual medication regime Parkinson’s medication can be given with a sip of water up until anaesthetic induction2.

Post-operative Advice

Resume post-operatively at patient’s usual dose.

If a long nil by mouth (NBM) period is anticipated or if there are concerns regarding enteral absorption alternative routes / medications should be considered2, 3 (see Further Information).


  Interaction(s) with Common Anaesthetic Agents


For general information regarding the use of anaesthetic agents in PD – see Parkinson’s Disease – A General Overview’.

Hypertensive Crisis

MAO-B inhibitors are predicted to increase the risk of hypertensive crisis when given with adrenaline / epinephrine, dobutamine, dopamine, ephedrine, metaraminol, noradrenaline / norepinephrine, phenylephrine and pseudoephedrine4.

A hypertensive reaction occurred with concurrent use of dopamine and selegiline. This exaggerated vasopressor response was thought to be due to inhibition of dopamine metabolism by selegiline. Caution is advised if dopamine is to be used in patients who are currently taking selegiline or have taken any doses in the previous 2 weeks5, 6.

CNS Excitation (Serotonin Syndrome)

Some opioids act as weak serotonin reuptake inhibitors (SRIs) and can precipitate serotonin syndrome in conjunction with MAOIs. This is most likely in patients taking irreversible or non-selective MAOIs; however, it may also occur with selective MAO-B inhibitors, particularly at higher doses when selectivity can be lost7.

Symptoms of serotonin syndrome have been reported when pethidine was given to a patient taking selegiline; rasagiline and safinamide are expected to interact similarly6, 7. Opioids that have serotonergic effects (pethidine, fentanyl, tramadol, methadone, tapentadol and dextromethorphan) should be avoided in patients taking MAO-B inhibitors or have taken any doses of MAO-B inhibitors in the previous 14 days7.

Morphine, codeine, oxycodone and buprenorphine are not thought to be inhibitors of serotonin reuptake so are preferred opioids for patients taking MAOIs, however caution is advised7.

Hypotension

MAOB inhibitors can increase the risk of hypotension when used concomitantly with inhalational and intravenous anaesthetics4.

Bradycardia

Selegiline can increase the risk of bradycardia when used concomitantly with the following4: -

  • alfentanil, fentanyl or remifentanil
  • cisatracurium
  • neostigmine


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


Antiemetics

MAOB inhibitors can increase the risk of hypotension when used concomitantly with droperidol or prochlorperazine4. However, these medications should be avoided in patients with PD as they exacerbate symptoms4.

For general information regarding the use of antiemetics in PD – see ‘Parkinson’s Disease – A General Overview’.

CNS Excitation (Serotonin Syndrome)

For a discussion of opioids see under Interaction(s) with Common Anaesthetic Agents above.

There is also an increased risk of developing serotonin syndrome when MAOIs are used concurrently with the following4: -

  • granisetron
  • ondansetron
  • linezolid
  • 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.

Ciprofloxacin

Ciprofloxacin inhibits the metabolism of rasagiline and increases plasma levels by 83%, the clinical significance of this increase has not been assessed but the manufacturer advises caution. Be alert for rasagiline adverse effects e.g. headache, dyspepsia6, 8.


  Further Information

 

Loss of Selectivity

At licensed doses selegiline is a selective MAO-B inhibitor; however, at higher doses this selectivity will be lost. At doses greater than 10mg daily there is a theoretical risk of hypertension after ingestion of tyramine-rich food. This would suggest greater potential for interactions with other medications in line with the irreversible monoamine oxidase inhibitors5.

NBM Period and Alternative Routes

If there is significant post-operative nausea and vomiting, post-operative ileus or concerns about enteral absorption, the oral route is likely to be unreliable and may lead to suboptimal treatment. Alternative routes / medications should be considered – see ‘Parkinson’s Disease – A General Overview’.

Patients who do not rapidly regain the ability to take their usual PD medication should be seen by a PD Specialist Nurse or Movement Disorder Consultant at the earliest opportunity3.

Prescribing and Administration

Access to the correct medication / formulation at the correct time remains a problem for people with PD whilst they are in hospital3. Delayed doses can have serious implications (see PHS above). PD patients often have complex medication regimes; prescribers should take care to confirm the correct dose, formulation and time of administration with the patient or carer. The time of administration should be documented on the prescription chart and nursing staff should ensure that PD medications are given promptly.


  References


  1. National Institute of Health and Clinical Excellence (2017). NG71 Parkinson’s disease in adults. https://www.nice.org.uk/guidance/ng71 [Accessed on 6th June 2019]
  2. Chambers DJ. Sebastian J. and Ahearn DJ. Parkinson’s disease. BJA Education. 2017; 17:145-149
  3. Brennan KA & Genever RW. Managing Parkinson’s disease during surgery. BMJ. 2010; 341:c5718
  4. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 9th June 2019]
  5. Summary of Product Characteristics – Eldepryl® (selegiline) 10mg Tablets. Orion Pharma (UK) Limited. Accessed via www.medicines.org.uk 09/06/2019 [date of revision of the text March 2015]
  6. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 9th June 2019]
  7. Specialist Pharmacy Service. What is the risk of interaction between opioids and monoamine oxidase inhibitors (MAOIs)? (2017). Available at: www.sps.nhs.uk [Accessed on 22nd June 2019]
  8. Summary of Product Characteristics – Azilect® (rasagiline) 1mg Tablets. Teva Pharmaceuticals Ltd. Accessed via www.medicines.org.uk 09/06/2019 [date of revision of the text June 2018]