Neurology
COMT inhibitors
Entacapone, opicapone (Parkinson's) — Add-on tablets that make each dose of levodopa last longer in Parkinson's disease.
Education and reference only. This is a plain-language class overview — it deliberately contains no doses. Always check the current Summary of Product Characteristics (SmPC), the BNF and your local formulary before prescribing or administering any medicine.
Quick answer
What is COMT inhibitors?
COMT inhibitors are add-on tablets for Parkinson's disease that extend how long each dose of levodopa works. They are always used with levodopa — never alone — to reduce the return of symptoms between doses.
- How it works: Levodopa is broken down in the body partly by an enzyme called catechol-O-methyltransferase (COMT) before it can reach the brain.
- In practice: In practice COMT inhibitors (entacapone and opicapone, and the rarely used tolcapone) are used only alongside levodopa in Parkinson's disease, where their job is to make each levodopa dose last longer and reduce "wearing off".
What it is
COMT inhibitors are add-on tablets for Parkinson's disease that extend how long each dose of levodopa works. They are always used with levodopa — never alone — to reduce the return of symptoms between doses.
How it works
Levodopa is broken down in the body partly by an enzyme called catechol-O-methyltransferase (COMT) before it can reach the brain. COMT inhibitors block that enzyme, so more levodopa survives and crosses into the brain, and each dose lasts longer. This smooths out "wearing off" — but because it effectively increases levodopa exposure, it also amplifies levodopa's side effects.
In practice
In practice COMT inhibitors (entacapone and opicapone, and the rarely used tolcapone) are used only alongside levodopa in Parkinson's disease, where their job is to make each levodopa dose last longer and reduce "wearing off". They have no useful effect on their own — they work purely by protecting levodopa from being broken down before it reaches the brain. Entacapone is taken with each levodopa dose (and is also available as a combined tablet with levodopa and carbidopa), while opicapone is taken once daily at bedtime. The practical themes follow from boosting levodopa: they often increase levodopa's effects and side effects, especially involuntary movements (dyskinesia), nausea, dizziness on standing and hallucinations, so the levodopa dose is frequently reduced when they are started. Entacapone commonly turns the urine a harmless brownish-orange and can cause diarrhoea, which is occasionally troublesome and delayed. Tolcapone can rarely cause serious liver injury, so it is restricted and needs liver monitoring — entacapone and opicapone do not share this to the same degree. They are introduced and adjusted as part of fine-tuning a levodopa regimen, not as a stand-alone treatment.
Examples
Practical use
How to take it & use it well
- Take it only alongside your levodopa, as it works purely by making each levodopa dose last longer and has no useful effect on its own.
- If you take entacapone, take it with each levodopa dose, or as the combined levodopa tablet if you have been given that, exactly as your team has set out.
- If you take opicapone, take it once daily, usually at bedtime, and follow any advice about leaving a gap from your levodopa around that time.
- Do not be alarmed if your urine turns a harmless brownish-orange colour with entacapone, as this is expected and not a sign of harm.
- Tell your team about new or worsening involuntary movements, nausea, dizziness on standing or hallucinations, as your levodopa dose may need reducing.
- Report persistent diarrhoea, which can come on after some weeks with entacapone, as it is occasionally troublesome and may need the medicine reviewed.
Common uses
- Add-on to levodopa for "wearing off"
- Reducing "off" time and smoothing motor fluctuations
- Available combined with levodopa/carbidopa (entacapone)
Monitoring
- "Off" time, motor fluctuations and dyskinesia after starting
- Blood pressure (postural), nausea, hallucinations; bowel habit (diarrhoea)
- Liver function if tolcapone is used
Weighing it up
Advantages & disadvantages
Advantages
- It makes each dose of levodopa last longer, smoothing out symptoms and reducing 'wearing off' between doses.
- Entacapone is available as a combined tablet with levodopa, which can simplify the number of tablets you take.
- Opicapone is taken just once a day, which is convenient compared with dosing alongside every levodopa dose.
- It can let some people get more steady benefit from their existing levodopa without large increases in levodopa itself.
- Entacapone and opicapone do not carry the liver risk of the older, restricted drug in this group, so they are the usual choices.
Disadvantages
- It does nothing on its own, so it is only ever useful taken together with levodopa.
- By boosting levodopa it often increases its side effects, especially involuntary movements, nausea, dizziness on standing and hallucinations.
- The levodopa dose frequently has to be reduced when it is started, which takes some adjusting.
- Entacapone commonly turns the urine brownish-orange and can cause diarrhoea that is sometimes delayed and hard to settle.
- The older drug tolcapone in this group can rarely cause serious liver injury, so it is restricted and needs liver monitoring.
Key safety principles
What to watch for
- Used only with levodopa — they have no benefit alone; the levodopa dose is often reduced when starting to avoid extra involuntary movements, nausea or hallucinations.
- Entacapone harmlessly discolours urine brownish-orange and can cause diarrhoea (sometimes delayed and troublesome).
- Tolcapone can rarely cause serious liver injury, so it is restricted and needs liver monitoring; entacapone/opicapone are the usual choices.
Key interactions
What to avoid or check alongside
- It is used only with levodopa, so the two are managed together, and the levodopa dose is often reduced when it is started to avoid extra side effects.
- By making levodopa last longer it can increase involuntary movements, nausea and hallucinations, which is why the combination is fine-tuned carefully.
- Tolcapone, the restricted member of this group, can rarely harm the liver and needs liver monitoring, whereas entacapone and opicapone do not to the same degree.
- Entacapone can reduce the absorption of iron, so iron tablets are usually spaced apart from it; tell your team if you take iron.
- Tell your team about all your medicines, as some other treatments are used cautiously alongside it, and your full Parkinson's regimen is balanced as a whole.
Patient & carer advice
- Always take it with your levodopa — on its own it does nothing
- Your urine may turn a harmless brownish-orange colour
- Tell your team about new or worsening involuntary movements, or persistent diarrhoea, as the dose may need adjusting
Answers
COMT inhibitors: frequently asked questions
What do COMT inhibitors do?
They protect levodopa from being broken down before it reaches the brain, which makes each levodopa dose last longer and reduces 'wearing off'. They are used only alongside levodopa and have no benefit taken on their own. Entacapone is taken with each levodopa dose, while opicapone is taken once a day, usually at bedtime.
Why has my urine turned orange?
Entacapone harmlessly turns the urine a brownish-orange colour in many people. It looks dramatic but is completely expected and is not a sign that anything is wrong with your kidneys or bladder. It is simply the colour of the medicine passing through. There is no need to worry or to stop the tablets because of it.
Why might my levodopa dose be lowered when I start this?
Because COMT inhibitors make levodopa last longer, they effectively increase how much levodopa effect you get. This can bring on more involuntary movements, nausea, dizziness on standing or hallucinations. To keep the balance right, your team often reduces the levodopa dose when this is started. Tell them about any new effects so it can be fine-tuned.
Is diarrhoea common with these medicines?
Entacapone can cause diarrhoea, and it is worth knowing this can come on after some weeks rather than straight away. For most people it is mild, but occasionally it is troublesome and persistent. If it does not settle or is affecting you, tell your team, as the medicine may need reviewing rather than just putting up with it.
Are they safe for my liver?
Entacapone and opicapone, the two usual choices, do not carry a notable liver risk. The older drug in this group, tolcapone, can rarely cause serious liver injury, so it is restricted and used only with regular liver monitoring. Your team will tell you which you are on and arrange any blood tests that are needed.
Authoritative sources
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