A COMT inhibitor for Parkinson's
Tolcapone
A COMT inhibitor that extends the effect of levodopa in Parkinson's, used with liver monitoring because of a risk of liver harm.
What is Tolcapone?
Tolcapone is a COMT inhibitor used alongside co-careldopa (levodopa) to make each levodopa dose last longer and reduce the "wearing-off" that can develop with long-term Parkinson's treatment. Because it carries a risk of serious liver injury, it is used when other options have not worked, and liver-function blood tests are needed before and during treatment. It can cause diarrhoea and harmless discolouration of the urine. It is stopped if it does not clearly help.
Education and reference only. This is a plain-language guide to Tolcapone — it deliberately contains no doses. Doses depend on the person, the brand and the reason for treatment, and belong with your prescriber. Always check the BNF, the product labelling (SmPC) and follow medical advice.
What it is
Tolcapone is a medicine called a COMT inhibitor, used together with levodopa (as co-careldopa) in Parkinson's disease. It helps each dose of levodopa last longer, which is useful when the effect of levodopa starts to wear off before the next dose. Because of a risk of serious liver injury, it is generally reserved for people who have not done well with another COMT inhibitor, and it is used with regular liver monitoring.
How it works
Levodopa is broken down in the body partly by an enzyme called COMT. Tolcapone blocks COMT, so less levodopa is broken down before it reaches the brain and more is available for longer. This smooths and extends the effect of each levodopa dose, helping to reduce the wearing-off that can develop over time.
Company & origin
Originated / developed by: Roche (originator).
A COMT inhibitor used in the UK to extend the effect of levodopa in Parkinson's disease, with liver-function monitoring.
What it treats
Conditions Tolcapone is used for
Practical use
How to take Tolcapone
General, dose-free guidance — always follow your prescriber's and the leaflet's specific instructions.
- Take it together with your levodopa (co-careldopa) exactly as prescribed; it is an add-on, not a replacement.
- Attend for the liver blood tests your team arranges before and during treatment, as these are essential for safety.
- Report yellowing of the skin or eyes, dark urine, persistent nausea, tiredness or tummy pain straight away.
- Expect that your levodopa dose may be reduced, and tell your team if you develop diarrhoea or more involuntary movements.
- If you miss a dose, take your next dose at the usual time; do not double up, and do not stop suddenly without advice.
Weighing it up
Advantages & disadvantages of Tolcapone
Advantages
- Extends the effect of each levodopa dose and reduces wearing-off.
- Can be useful when another COMT inhibitor has not given enough benefit.
- Taken by mouth alongside existing levodopa treatment.
Disadvantages
- Carries a risk of serious liver injury, so liver blood tests are needed.
- Commonly causes diarrhoea, sometimes after several weeks.
- May increase involuntary movements, so the levodopa dose often needs lowering.
Practical use
Good to know
The most important point with tolcapone is the risk of serious liver injury, which is why liver-function blood tests are carried out before starting and regularly during treatment, and why it is treated as a reserve option. It is stopped if there is no clear benefit after a reasonable trial, or if liver tests become abnormal. Report any yellowing of the skin or eyes, dark urine, persistent nausea, unusual tiredness or right-sided tummy pain straight away. It commonly causes diarrhoea, sometimes appearing after a few weeks, and it can harmlessly discolour the urine. Because it boosts levodopa, the levodopa dose may need lowering to manage involuntary movements.
Who should not take it / use with caution
- People with liver disease or abnormal liver blood tests should not take it.
- Anyone who has previously had liver problems with tolcapone must not take it again.
- It should not be taken with, or close to, certain older antidepressants known as non-selective MAO inhibitors.
Monitoring
- Liver-function blood tests before treatment and regularly during it.
- Review of whether wearing-off is improving, balanced against involuntary movements.
- Watching for signs of liver harm such as jaundice, dark urine or persistent nausea.
Side effects
- Diarrhoea, sometimes appearing after a few weeks, and nausea.
- Increased involuntary movements (dyskinesias) and dizziness on standing.
- Less commonly but importantly, liver injury — report jaundice, dark urine or persistent sickness urgently.
Key interactions
- Non-selective MAO inhibitor antidepressants must be avoided or carefully separated.
- Other medicines that can affect the liver may add to the risk of liver harm.
- Tell your team about all medicines, as some need dose changes when used with it.
Available as: Tablets taken by mouth.
Answers
Tolcapone: frequently asked questions
Why do I need liver blood tests?
Tolcapone can cause serious liver injury, so liver function is checked before and regularly during treatment, and it is stopped if tests become abnormal.
What should make me seek urgent advice?
Yellowing of the skin or eyes, dark urine, persistent nausea, unusual tiredness or right-sided tummy pain should be reported promptly as they can signal liver trouble.
Why might my levodopa dose be lowered?
Tolcapone makes levodopa last longer, which can increase involuntary movements, so the levodopa dose is often reduced to balance this.
Will it discolour my urine?
It can give the urine a harmless yellow-orange colour; this does not mean anything is wrong.
What happens if it does not help?
If there is no clear benefit after a reasonable trial, it is stopped, because the liver risk means it is only continued when it is clearly working.
The wider class
About COMT inhibitors
Tolcapone belongs to the comt inhibitors class. For how the class as a whole works, its shared safety principles and monitoring, see the full guide.
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Authoritative sources
- BNF
- NICE CKS
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