Entacapone, Opicapone, Tolcapone
Issues for Surgery
Risk of exacerbation of Parkinson’s Disease (PD) and akinesia if omitted1.
Reduced effectiveness of levodopa preparations if omitted.
Risk of parkinsonism-hyperpyrexia syndrome (PHS) if omitted, especially with combination products containing levodopa (see Further Information).
Increased sensitivity to inotropes and vasopressors if continued (see Interaction(s) with Common Anaesthetic Agents).
Advice in the Perioperative period
Elective and Emergency Surgery
Combination product: -
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.
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 / medications4.
Resume post-operatively at patient’s usual dose3.
If a long nil by mouth (NBM) period is anticipated or if there are concerns regarding enteral absorption alternative routes / medications should be considered2, 4 (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’.
Inotropes and Vasopressors
COMT inhibitors inhibit the enzyme which is involved in the metabolism of inotropes and vasopressors therefore it is predicted that their action may be potentiated2, 3, 5, 6, 7, 8, 9, 10, 11. Entacapone potentiated the increase in heart rate and arrhythmogenic effects of epinephrine / adrenaline and isoproterenol / isoprenaline in a study confirming this theory; similar effects are anticipated with other inotropes and vasopressors and other COMT inhibitors are predicted to interact similarly9.
The manufacturers advise caution when drugs known to be metabolised by COMT are given to patients taking COMT inhibitors – they specifically name epinephrine / adrenaline, dobutamine, dopamine, isoproterenol / isoprenaline and norepinephrine / noradrenaline5, 6, 7, 8, 9. Dose reduction and careful monitoring for increased inotrope or vasopressor adverse effects is advised9.
Interaction(s) with other Common Medicines used in the Perioperative Period
For general information regarding the use of antiemetics in PD – see ‘Parkinson’s Disease – A General Overview’.
Entacapone formed chelates with iron in vitro. The clinical relevance of this is not known but it is recommended that entacapone and iron compounds should be administered at least 2 to 3 hours apart3, 5, 8, 9, 10. For combination products containing levodopa see also Levodopa with Dopa-Decarboxylase Inhibitor (DDI) monograph.
Tolcapone and Hepatotoxicity
Tolcapone has been associated with hepatotoxicity and acute liver failure. Liver function tests (LFTs) should be monitored every 2 weeks for the first year of treatment with tolcapone, every 4 weeks for the next 6 months and every 8 weeks thereafter. If recent LFTs are not available consider checking pre-operatively7, 8, 11.
Manufacturer advises treatment should be discontinued immediately if alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST) exceed the upper limit of normal or if signs and symptoms of hepatic failure (persistent nausea, fatigue, lethargy, anorexia, jaundice, dark urine, pruritus, right upper quadrant tenderness) develop7. COMT inhibitors prevent peripheral breakdown of levodopa increasing the amount reaching the brain8. If tolcapone is discontinued due to abnormal LFTs consult patient’s specialist as an increase in levodopa dose may be necessary7, 8.
Parkinsonism-Hyperpyrexia Syndrome (PHS)
Risk of PHS with combination products containing levodopa – see Levodopa with Dopa-Decarboxylase Inhibitor (DDI) monograph.
Symptoms associated with PHS were not reported in controlled trials in which entacapone was discontinued abruptly, however, isolated cases have been reported in practice following abrupt reduction or discontinuation of entacapone and other concomitant dopaminergic medications. Ideally withdrawal of COMT inhibitors should be slow; if symptoms still develop an increase in levodopa dose may be necessary3, 5, 11.
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 opportunity4.
Prescribing and Administration
Access to the correct medication / formulation at the correct time remains a problem for people with PD whilst they are in hospital4. 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.