Amantadine


  Issues for Surgery


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

Risk of withdrawal, potentially resembling parkinsonism-hyperpyrexia syndrome (PHS) if omitted (see Further Information).


  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 postoperatively at patient’s usual dose.

If a long nil by mouth (NBM) period is anticipated or if there are concerns regarding absorption see Further Information3.


  Interaction(s) with Common Anaesthetic Agents

 

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

Hypotension

Amantadine can increase the risk of hypotension when used concomitantly with inhalational or intravenous anaesthetics4.

Seizure Threshold

Amantadine lowers the seizure threshold; concurrent use with medications that also lower the seizure threshold (e.g. anaesthetic agents, tramadol) may have an additive effect on the risk of seizure5.


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

 

Antiemetics

Amantadine can increase the risk of hypotension when used concomitantly with droperidol or prochlorperazine4. However, these antiemetics 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’.

Seizure Threshold (see Interaction(s) with Common Anaesthetic Agents above)

Co-trimoxazole

Case reports describe acute confusion (in an elderly man) and amantadine toxicity (in a patient with end stage renal failure) with concomitant administration of amantadine and co-trimoxazole. It is suggested that the trimethoprim component of co-trimoxazole competes with amantadine for renal secretion, leading to toxicity. The clinical significance of this interaction is unclear - bear in mind if an unexpected reaction occurs5.

Antimuscarinics

Amantadine may enhance the adverse effects of antimuscarinics; dose reduction should be considered with concomitant use5, 6.


  Further Information


Withdrawal

Abrupt discontinuation of amantadine may exacerbate Parkinson’s symptoms. Isolated reports suggest abrupt discontinuation may also precipitate or aggravate neuroleptic malignant syndrome in individuals taking antipsychotics and a similar syndrome in individuals not taking concurrent psychoactive medication6, 7. Acute delirium after gradual withdrawal of long-term amantadine has been noted in 3 patients, this resolved when amantadine was restarted6. However, specialists do not consider these isolated reports to be clinically significant in the event a patient is unable to take their usual dose of amantadine.

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. There is no clinical alternative to amantadine; providing alternative routes / medications are considered for any other PD medications the patient may be taking there is unlikely to be any detrimental effect from withholding amantadine in these circumstances – 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. 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 9th 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 21st June 2019]
  5. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 21st June 2019]
  6. Amantadine. 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 21st June 2019]
  7. Summary of Product Characteristics – Trilasym® (amantadine) 50mg/5ml Oral Solution. Fontus Health Ltd. Accessed via www.medicines.org.uk 21/06/2019 [date of revision of the text May 2019]