Adult: As adjunct to standard preparation of levodopa/benserazide or levodopa/carbidopa in patients with "end of dose" motor fluctuations: 200 mg with each levodopa/dopa decarboxylase inhibitor dose. Max: 200 mg 10 times daily. Alternatively, Max: 200 mg 8 times daily. Gradually reduce the dose of levodopa by approx 10-30% or increase dosing interval within the first few weeks of starting treatment. Dosage recommendations may vary between countries (refer to specific country guidelines).
Hepatic Impairment
Contraindicated.
Administration
May be taken with or without food.
Contraindications
Phaeochromocytoma, history of neuroleptic malignant syndrome (NMS) and/or non-traumatic rhabdomyolysis, major psychotic disorder. Hepatic impairment. Concomitant use with non-selective monoamine oxidase (MAO-A and MAO-B) inhibitors. Concomitant use with both selective MAO-A and selective MAO-B inhibitors.
Special Precautions
Patient with CV disease, history of MI and arrhythmias. Avoid abrupt withdrawal. Pregnancy and lactation.
Adverse Reactions
Significant: Abnormal thinking, behavioural changes, hallucinations, aggressive behaviour, agitation, confusion, disorientation, delusions, paranoid ideation, psychotic-like behaviours, impulse control disorders, somnolence, dyskinesia, melanoma, orthostatic hypotension, syncope, severe rhabdomyolysis, diarrhoea. Cardiac disorders: Ischaemic heart disease, MI. Gastrointestinal disorders: Nausea, vomiting, abdominal pain, dry mouth, constipation, colitis. Rarely, anorexia. General disorders and administration site conditions: Fatigue, increased sweating. Hepatobiliary disorders: Cholestatic hepatitis. Injury, poisoning and procedural complications: Fall. Investigations: Weight decrease, abnormal LFTs. Musculoskeletal and connective tissue disorders: Back pain. Nervous system disorders: Parkinsonism aggravated, dizziness, dystonia, hyperkinesia, hypokinesia. Psychiatric disorders: Insomnia, nightmares, agitation. Renal and urinary disorders: Urine discolouration. Respiratory, thoracic and mediastinal disorders: Dyspnoea. Skin and subcutaneous tissue disorders: Skin, hair, beard, nail discolouration. Rarely, erythematous or maculopapular rash, urticaria. Potentially Fatal: NMS-like syndrome (e.g. hyperpyrexia, confusion).
This drug may cause dizziness, orthostatic hypotension, somnolence and episodes of sudden sleep onset, if affected, do not drive or operate machinery. May cause reddish-brown discolouration of urine.
Monitoring Parameters
Monitor liver function, blood pressure, mental status and impulse control disorders; daytime sleepiness; weight loss (patients with diarrhoea); dermatologic examination (regularly). Monitor for signs and symptoms of neuroleptic malignant syndrome (if abrupt discontinuation is required).
May enhance the adverse/toxic effect of non-selective MAOIs (e.g. phenelzine, tranylcypromine). May interfere with metabolism of drugs metabolised by COMT and potentiate their action (e.g. isoprenaline, epinephrine, norepinephrine, dopamine, dobutamine, apomorphine, methyldopa). May aggravate levodopa-induced orthostatic hypotension. May potentiate dopaminergic effects with dopamine agonists (e.g. bromocriptine), selegiline, amantadine. May form chelates with Fe preparations in the gastrointestinal tract.
Food Interaction
May potentiate the sedative effect of alcohol.
Action
Description: Mechanism of Action: Entacapone is a selective, reversible inhibitor of catechol-O-methyltransferase (COMT), an enzyme involved in the metabolism of levodopa and dopamine. It prevents the peripheral breakdown of levodopa resulting in increased concentration available for absorption in the blood-brain barrier, thereby leading to increased CNS levels of dopamine, the active metabolite of levodopa. Pharmacokinetics: Absorption: Rapidly absorbed from the gastrointestinal tract. Bioavailability: Approx 35%. Time to peak plasma concentration: Approx 1 hour. Distribution: Plasma protein binding: 98%, mainly to albumin. Metabolism: Metabolised via isomerisation to the cis-isomer, followed by direct glucuronidation of the parent and cis-isomer; undergoes extensive first-pass metabolism. Excretion: Mainly via faeces (90%); urine (10-20%, as glucuronide conjugates). Elimination half-life: β phase: 0.4-0.7 hour; γ phase: 2.4 hours.
Chemical Structure
Entacapone Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5281081, Entacapone. https://pubchem.ncbi.nlm.nih.gov/compound/Entacapone. Accessed Apr. 26, 2024.
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