Opicapone
COMT inhibitors
COMT inhibitors
Once-daily peripheral COMT inhibitor added to levodopa with carbidopa to treat end-of-dose «wearing-off» in Parkinson disease.
Quick facts
- Group
- COMT inhibitors
- Target
- Catechol-O-methyltransferase (COMT)
- Used for
- Adjunct to levodopa
- Key effects
- Dyskinesia · Constipation and dry mouth · Insomnia
- Monitor
- «On» and «off» time and dyskinesia · Hallucinations
- ATC
- N04BX04
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows opicapone bound to rat COMT with S-adenosylhomocysteine and magnesium; the catechol site is the same in the human enzyme.
When carbidopa blocks peripheral DOPA decarboxylase, COMT becomes the main enzyme that degrades levodopa outside the brain, to 3-O-methyldopa. Opicapone inhibits peripheral COMT, so more levodopa reaches the brain and each dose lasts longer. Although its plasma half-life is short, it leaves the enzyme very slowly, which allows a single daily dose.
- Inhibits COMT in peripheral tissues
- Less levodopa is converted to 3-O-methyldopa
- More levodopa reaches the brain for longer
- «On» time is extended and wearing-off is reduced
Indications
- Adjunct to levodopa with carbidopa for end-of-dose «wearing-off» in Parkinson disease Parkinson disease →
Adverse effects
Common
- Dyskinesia
- Constipation and dry mouth
- Insomnia
- Dizziness and orthostatic hypotension
- Weight loss
Contraindications
- Use with non-selective MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid), or within two weeks of stopping them
- Pheochromocytoma or paraganglioma
Key interactions
- Non-selective MAO inhibitors
- Combined block of both catecholamine-degrading enzymes; the combination is avoided.
- Alcohol
- Adds to the drowsiness.
- Levodopa
- Intended potentiation; dyskinesia may increase and the levodopa dose may need adjusting.
What is monitored
- «On» and «off» time and dyskinesia
- Blood pressure lying and standing
- Daytime sleepiness and sudden sleep episodes
- Hallucinations and impulse-control behaviours
Administration and safety
- Oral capsule, usually once a day at bedtime, at least an hour before or after eating.
- It is not stopped suddenly; withdrawal is gradual.
- The surgical or dental team is told the patient takes it.
Pregnancy and breastfeeding
Information is limited; a pregnancy during treatment is reported to the treating doctor.
Nursing care
- Ask about MAO inhibitors and about pheochromocytoma before starting.
- Teach to rise slowly from bed and to report fainting.
- Warn about sudden sleep and avoid driving until the effect is known.
- Ask patient and family about hallucinations and compulsive behaviours.
Pharmacokinetics
- Absorption
- Oral capsule, once daily at bedtime, away from meals.
- Half-life
- Short in plasma, but its tight, slowly reversible binding to COMT keeps the enzyme inhibited through the day.
Test yourself
Think of the answer, then tap the question to see it.
Why does opicapone prolong the effect of levodopa?
It inhibits peripheral COMT, so less levodopa becomes 3-O-methyldopa and more reaches the brain.
How can opicapone be given once daily despite a short plasma half-life?
It dissociates very slowly from COMT, so inhibition lasts long after plasma levels fall.
Which two conditions or drugs rule out opicapone?
Non-selective MAO inhibitors and pheochromocytoma or paraganglioma.
Connections
← Back to the class: 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: Opicapone: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2020); RCSB PDB - 7XGI: COMT SAH Mg opicapone complex (RCSB Protein Data Bank, 2023); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.