COMT Inhibitor — Parkinson's Disease Pregnancy: No overt teratogenic or primary foetotoxic effects were seen in animal studies at exposures markedly higher than therapeutic levels, but as there is no experience in pregnant women entacapone should not be used during pregnancy. Entacapone was excreted in milk in animal studies and safety in infants is unknown, so women should not breast-feed during treatment (eMC §4.6).

Entacapone

Brand names: Comtess, Stalevo (combined with levodopa/carbidopa)

Entacapone is a COMT inhibitor given together with levodopa to reduce end-of-dose 'wearing off' in Parkinson's disease. It has no antiparkinsonian effect on its own.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 200 mg (one tablet) with each levodopa/dopa-decarboxylase inhibitor dose

Route: Oral — administered simultaneously with each levodopa/carbidopa or levodopa/benserazide dose; may be taken with or without food

Frequency: With every levodopa/dopa-decarboxylase inhibitor dose (up to ten times daily)

Max: 200 mg ten times daily, i.e. 2,000 mg entacapone per day (eMC §4.2). The US labelling gives a lower maximum of 200 mg eight times daily (1,600 mg per day), stating that clinical experience above 1,600 mg daily is limited.

eMC §4.2 (Entacapone Mylan 200 mg film-coated tablets). Entacapone should ONLY be used in combination with levodopa/benserazide or levodopa/carbidopa — it has no antiparkinsonian effect of its own, and the prescribing information for the levodopa preparation applies to concomitant use. LEVODOPA DOSE ADJUSTMENT: entacapone enhances the effects of levodopa, so to reduce levodopa-related dopaminergic adverse reactions (dyskinesias, nausea, vomiting, hallucinations) it is often necessary to adjust the levodopa dose within the first days to first weeks after starting entacapone — the daily levodopa dose should be reduced by about 10-30% by extending dosing intervals and/or reducing the amount of levodopa per dose, according to clinical condition. Entacapone increases levodopa bioavailability from standard levodopa/benserazide preparations slightly (5-10%) more than from standard levodopa/carbidopa preparations, so patients on levodopa/benserazide may need a larger levodopa reduction. DISCONTINUATION: if entacapone is stopped, the dosing of other anti-Parkinsonian treatments, especially levodopa, must be adjusted to maintain sufficient symptom control; the US labelling adds that rapid withdrawal or abrupt dose reduction could cause emergence of Parkinson's disease signs and symptoms and may lead to hyperpyrexia and confusion resembling neuroleptic malignant syndrome, so withdrawing slowly with close monitoring is prudent. HEPATIC IMPAIRMENT: contraindicated (see §4.3). ELDERLY: no dosage adjustment required. PAEDIATRIC: safety and efficacy in children below 18 years of age have not been established and no data are available — verify any under-18 use against a children's formulary.

Dose adjustments

Renal

Renal insufficiency does not affect the pharmacokinetics of entacapone and there is no need for dose adjustment; however, for patients receiving dialysis therapy a longer dosing interval may be considered (eMC §4.2).

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

US labelling (FDA)

Reference — US labelling, may differ from UK

DOSAGE AND ADMINISTRATION The recommended dose of entacapone is one 200 mg tablet administered concomitantly with each levodopa and carbidopa dose to a maximum of 8 times daily (200 mg × 8 = 1,600 mg per day). Clinical experience with daily doses above 1,600 mg is limited. Entacapone should always be administered in association with levodopa and carbidopa. Entacapone has no antiparkinsonian effect of its own. In clinical studies, the majority of patients required a decrease in daily levodopa dose if their daily dose of levodopa had been greater than or equal to 800 mg or if patients had moderate or severe dyskinesia before beginning treatment. To optimize an individual patient's response, …

Source: US FDA prescribing information (openFDA / DailyMed), label dated 2023-10-07. Accessed 2026-06-12. US dosing and indications can differ from UK practice — use UK sources for prescribing decisions.

Contraindications

Hypersensitivity to the active substance or to any of the excipients
Hepatic impairment
Phaeochromocytoma
Concomitant use of entacapone with non-selective monoamine oxidase (MAO-A and MAO-B) inhibitors, e.g. phenelzine, tranylcypromine
Concomitant use of a selective MAO-A inhibitor plus a selective MAO-B inhibitor together with entacapone
A previous history of neuroleptic malignant syndrome (NMS) and/or non-traumatic rhabdomyolysis

Side effects

Dyskinesia (very common; 27% in pooled clinical study data) and aggravated parkinsonism, dizziness, dystonia and hyperkinesia (common)
Nausea (very common; 11%), diarrhoea (8%), abdominal pain (7%), dry mouth (4.2%), constipation and vomiting
Urine discoloration (very common) — urine may be discoloured reddish-brown, which is a harmless phenomenon
Insomnia, hallucinations, confusion and paroniria (common); agitation (very rare)
Ischaemic heart disease events other than myocardial infarction, e.g. angina pectoris (common); myocardial infarction (uncommon); abnormal hepatic function tests (rare) and hepatitis with mainly cholestatic features (frequency not known); fatigue, increased sweating and falls (common)

Interactions

Non-selective MAO inhibitors (e.g. phenelzine, tranylcypromine) — concomitant use is contraindicated (eMC §4.3)
A selective MAO-A inhibitor given together with a selective MAO-B inhibitor — concomitant use with entacapone is contraindicated (eMC §4.3)
Levodopa — entacapone enhances the effects of levodopa and increases its bioavailability; the daily levodopa dose usually needs reducing by about 10-30% when entacapone is started, with a larger reduction likely for levodopa/benserazide preparations (eMC §4.2)
The eMC §4.5 interaction section was not captured in this bundle — clinician to review it in the SPC

Clinical monograph

How it works

It inhibits catechol-O-methyltransferase peripherally, slowing the breakdown of levodopa and prolonging and smoothing its delivery to the brain.

Prescribing in practice

It is effective only when given with levodopa and can increase levodopa-related dyskinesia and nausea — the levodopa dose may need reducing when entacapone is started.
Diarrhoea is common and can occasionally be severe and prolonged, sometimes requiring discontinuation.
It harmlessly discolours the urine red-brown, which should be explained so patients are not alarmed.

Monitoring

Review motor fluctuations and dyskinesia after starting, adjusting levodopa as needed; monitor for diarrhoea, nausea and unintended weight loss.

Counselling the patient

Your urine may turn a harmless red-brown colour.
Tell your prescriber if you develop persistent or troublesome diarrhoea.
Increased involuntary movements or nausea can occur — your levodopa dose may need adjusting.

Evidence & guidelines

Recognised option for end-of-dose motor fluctuations in Parkinson's disease (NICE NG71).

Reference: NICE NG71 (Parkinson's Disease); Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways