Levodopa with Dopa-Decarboxylase Inhibitor (DDI)


Co-beneldopa: Levodopa with Benserazide, Co-careldopa: Levodopa with Carbidopa

 

  Issues for Surgery


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

Risk of Parkinsonism-Hyperpyrexia Syndrome (PHS) if omitted (see Further Information).

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


  Advice in the Perioperative period


Elective and Emergency Surgery

Continue (including combination products) 2, 3, 4, 5, 6.

Combination Products: -

  • Stalevo® contains levodopa + carbidopa + entacapone (also see Catechol-O-methyltranseferase (COMT) Inhibitors monograph)

To minimise disruption to the patient’s usual medication regime, oral levodopa with DDI medications can be given with a sip of water up until anaesthetic induction2. Duodopa® intestinal gel can be continued for as long as the patient is permitted to take fluids by mouth5.

Due to the short half-life of levodopa it may be necessary to site a naso-gastric tube (NGT) during prolonged procedures to enable administration of further doses (of soluble co-beneldopa)7 – for advice on equivalent doses see http://parkinsonscalculator.com/ or refer to in-house guidelines where appropriate.

If a long nil by mouth (NBM) period is anticipated post-operatively the patient’s specialist should be contacted pre-operatively for advice on alternative routes / medications7.

Post-operative Advice

Oral levodopa and Duodopa® intestinal gel should be restarted post-operatively, at the patient’s usual dose, as soon as oral intake of fluid is allowed3, 4, 5.

If a long NBM period is anticipated or if there are concerns regarding enteral absorption, alternative routes / medications should be considered2, 7 (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’.

Hypotension

Levodopa preparations can increase the risk of hypotension when used concomitantly with inhalational or intravenous anaesthetics8.

Sympathomimetics

The manufacturers advise caution with concomitant administration of co-beneldopa and sympathomimetics e.g. epinephrine / adrenaline, norepinephrine / noradrenaline as their action may be potentiated4. Dose reduction and monitoring of cardiovascular adverse effects is advised4. No recommendation is made regarding other sympathomimetics e.g. ephedrine, metaraminol, phenylephrine.


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


Antiemetics

Cyclizine may decrease the absorption of levodopa8; however, this is unlikely to be clinically significant, as cyclizine is generally considered useful in patients with PD2, 9.

Levodopa preparations can increase the risk of hypotension when used concomitantly with droperidol or prochlorperazine8. However, these medications should be avoided in patients with PD as they exacerbate symptoms8.

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

Iron Supplements

Iron forms chelation complexes with levodopa and carbidopa leading to a reduced bioavailability and possible worsening of symptoms3, 4, 9; this appears to be clinically significant in some patients4, 9. Iron and levodopa administration should be separated as much as possible and the patient monitored for deterioration in symptoms10.


  Further Information

 

Parkinsonism – Hyperpyrexia Syndrome (PHS)

Abrupt withdrawal of levodopa can result in PHS1, 2, 7, 10. It is most common in individuals with severe Parkinson’s symptoms or on larger doses of levodopa6. Symptoms mimic those of neuroleptic malignant syndrome and include muscle rigidity, fever, cardiovascular instability, profuse sweating and altered mental status (agitation, delirium, and coma)2, 10. PHS carries a significant mortality, up to 20% in untreated cases2.

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 and potentially PHS. 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 opportunity7.

Prescribing and Administration

Access to the correct medication / formulation at the correct time remains a problem for people with PD whilst they are in hospital7. Delayed doses can have serious implications. 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. Summary of Product Characteristics – Sinemet Plus® (levodopa with carbidopa) 25mg/100mg Tablets. Merck Sharp & Dohme Limited. Accessed via www.medicines.org.uk 06/06/2019 [date of revision of the text May 2019]
  4. Summary of Product Characteristics – Madopar® (levodopa with benserazide) 100mg/25mg Hard Capsules. Roche Products Limited. Accessed via www.medicines.org.uk 06/06/2019 [date of revision of the text March 2016]
  5. Summary of Product Characteristics – Duodopa® (levodopa with carbidopa) intestinal gel. AbbVie Ltd. Accessed via www.medicines.org.uk 06/06/2019 [date of revision of the text November 2017]
  6. Summary of Product Characteristics – Stalevo® (entacapone, levodopa and carbidopa) 100/25/200mg. Orion Pharma (UK) Limited. Accessed via www.medicines.org.uk 22/06/2019 [date of revision of the text February 2018]
  7. Brennan KA & Genever RW. Managing Parkinson’s disease during surgery. BMJ. 2010; 341:c5718
  8. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 6th June 2019]
  9. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com Accessed on 6th June 2019]
  10. Levodopa. 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 18th June 2019]