[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [COMT inhibitors](https://durgical.com/en/pharmacology/classes/comt-inhibitors/) › Entacapone

[Pharmacology](https://durgical.com/en/pharmacology/) · [COMT inhibitors](https://durgical.com/en/pharmacology/classes/comt-inhibitors/)

# Entacapone

A COMT inhibitor given with every levodopa + carbidopa dose to make it last longer. Colours urine brownish-orange.

Updated 2026-11-01

- Class: [COMT inhibitors](https://durgical.com/en/pharmacology/classes/comt-inhibitors/)
- Enzyme: Catechol-O-methyltransferase (COMT)
- ATC code: N04BX02

✂**Catechol-O-methyltransferase (COMT)**Entacapone

ⓘ The figure shows tolcapone in rat COMT; entacapone is a related nitrocatechol that occupies the same catechol site.

**Target in 3D:** Catechol-O-methyltransferase (COMT). PDB structure 3S68 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/3S68) · Drag to rotate · pinch to zoom

## Mechanism of action

Entacapone reversibly inhibits catechol-O-methyltransferase, mostly outside the brain. With DOPA decarboxylase blocked by carbidopa, COMT becomes the main route that destroys levodopa; blocking it raises levodopa exposure and prolongs its half-life, so each dose lasts longer.

- Carbidopa blocks decarboxylation of levodopa
- Entacapone blocks COMT, the next breakdown route
- Levodopa stays longer in the blood
- On time lasts longer; wearing-off is reduced

## Pharmacokinetics

**Metabolism**
Almost completely metabolized before excretion; very little unchanged in urine

**Elimination**
Mainly through the bile

**Onset and duration**
From the first dose; it raises levodopa exposure and prolongs levodopa's half-life

## Indications

- Adjunct to levodopa + carbidopa for end-of-dose wearing-off in Parkinson disease [Parkinson disease →](https://durgical.com/en/conditions/parkinson-disease/)

## Adverse effects

### Common

- Dyskinesia (levodopa effect increased)
- Nausea and abdominal pain
- Diarrhoea
- Brownish-orange urine (harmless)

### Serious (rare, important)

- Hallucinations and orthostatic hypotension
- Persistent diarrhoea and colitis
- Rhabdomyolysis and hyperpyrexia with confusion (rare)
- Sudden sleep and impulse-control disorders, as with other dopaminergic therapy

## Contraindications

- Hypersensitivity to entacapone
- Nonselective MAO inhibitors (combination avoided)

## Key interactions

**Nonselective MAO inhibitors (phenelzine, tranylcypromine)**
Would block most catecholamine metabolism; avoided

**Drugs metabolized by COMT (isoproterenol, epinephrine, dobutamine)**
Greater rise in heart rate and possible arrhythmias

## What is monitored

- Dyskinesia (levodopa dose may need lowering)
- Bowel habit and weight (diarrhoea)
- Blood pressure and hallucinations

## Administration and safety

- Always given together with each levodopa + carbidopa dose
- Also exists in a fixed tablet with levodopa and carbidopa
- Not stopped abruptly: withdrawal can worsen parkinsonism

## Nursing care

- Explain the urine colour change in advance
- Record dyskinesias and off periods after starting
- Ask about diarrhoea, which can appear weeks or months later
- Teach to rise slowly

## Pregnancy and breastfeeding

Human data are lacking; animal studies at high doses showed fetal variations.

## Memory aid

«EntaCAPONE puts a CAP ON levodopa breakdown» – and the urine turns orange.

## Test yourself

Think of the answer, then tap the question to see it.

## Why does entacapone only work when levodopa is given with carbidopa?

With decarboxylase blocked, COMT is the main route destroying levodopa; entacapone has no effect of its own.

## Which harmless change should patients be warned about?

Brownish-orange discolouration of the urine.

## Why can dyskinesia increase after adding entacapone?

It raises and prolongs levodopa levels, so the levodopa dose may need to be lowered.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/entacapone/)

## Related drugs

- [Tolcapone](https://durgical.com/en/pharmacology/tolcapone/)
- [Levodopa + carbidopa](https://durgical.com/en/pharmacology/levodopa-carbidopa/)

## Related conditions

- [Parkinson disease](https://durgical.com/en/conditions/parkinson-disease/)

[← Back to the class: COMT inhibitors](https://durgical.com/en/pharmacology/classes/comt-inhibitors/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - ENTACAPONE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=56327e32-3b06-4144-91a0-bb1908842e33) (DailyMed (U.S. National Library of Medicine), 2026); [Entacapone: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a601236.html) (MedlinePlus (U.S. National Library of Medicine), 2024); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 21 (McGraw Hill, 2023).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/pharmacology/entacapone/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/entacapone/