[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/) › Tolcapone

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

# Tolcapone

A COMT inhibitor that extends levodopa, reserved for selected patients because it can cause fatal liver failure.

Updated 2026-11-01

- Class: [COMT inhibitors](https://durgical.com/en/pharmacology/classes/comt-inhibitors/)
- Enzyme: Catechol-O-methyltransferase (COMT)
- ATC code: N04BX01

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

ⓘ The figure shows tolcapone bound to rat COMT with its methyl donor SAM; the human enzyme has 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

Tolcapone inhibits catechol-O-methyltransferase in the periphery and, to a small extent, in the brain. With carbidopa blocking decarboxylation, this keeps levodopa levels up for longer and increases its effect, including its adverse effects.

- Tolcapone blocks COMT in blood and, partly, in brain
- Levodopa is not methylated to 3-O-methyldopa
- Levodopa levels last longer; off time shortens

## Pharmacokinetics

**Distribution**
Enters the brain only to a small extent

**Metabolism**
Extensively metabolized in the liver

## Indications

- Adjunct to levodopa + carbidopa in Parkinson disease with motor fluctuations, when other add-on treatments have failed or are unsuitable [Parkinson disease →](https://durgical.com/en/conditions/parkinson-disease/)

## Adverse effects

### Common

- Dyskinesia and nausea
- Diarrhoea
- Sleep disorders and somnolence
- Urine discoloration

### Serious (rare, important)

- Acute fulminant liver failure, sometimes fatal (boxed warning)
- Rhabdomyolysis and hyperpyrexia with confusion
- Hallucinations and orthostatic hypotension

## Contraindications

- Liver disease, or raised liver enzymes before starting
- Previous tolcapone-induced liver injury
- History of non-traumatic rhabdomyolysis or hyperpyrexia and confusion related to medication
- Hypersensitivity to tolcapone

## Key interactions

**Nonselective MAO inhibitors**
Would block most catecholamine metabolism; avoided

**Other liver-toxic drugs**
Added risk of liver injury

**Drugs metabolized by COMT (isoproterenol, epinephrine, dobutamine)**
Stronger cardiovascular effects

## What is monitored

- Liver tests (ALT, AST) before starting and regularly during treatment
- Symptoms of liver injury: nausea, fatigue, anorexia, jaundice, dark urine, itching, right upper abdominal pain
- Clinical benefit early on: it is stopped if no clear benefit appears within about three weeks

## Administration and safety

- Used only with levodopa + carbidopa and after informed discussion of the liver risk
- Not stopped abruptly; levodopa may need adjusting

## Nursing care

- Check that liver tests are done on schedule
- Teach the warning signs of liver injury and to report them at once
- Watch for dyskinesia and hallucinations

## Pregnancy and breastfeeding

Human data are lacking; it is used only if clearly needed.

## Memory aid

«TOLcapone takes its TOLL on the liver».

## Test yourself

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

## What is the main safety concern with tolcapone?

Fulminant, potentially fatal liver failure.

## When is tolcapone stopped for lack of effect?

If no substantial clinical benefit appears within about three weeks.

## How does tolcapone differ from entacapone in distribution?

Tolcapone also inhibits COMT in the brain to some extent; entacapone acts almost only peripherally.

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

## Related drugs

- [Entacapone](https://durgical.com/en/pharmacology/entacapone/)
- [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 - TOLCAPONE tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dd367eec-359a-4065-b5c3-7c0107c823fe) (DailyMed (U.S. National Library of Medicine), 2021); [Tolcapone: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a698036.html) (MedlinePlus (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 21 (McGraw Hill, 2023).

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Representative model, for educational purposes only.

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