Section 03 · Monograph

Opicapone

Reviewed Nov 2026FDA label

OngentysCOMT inhibitor

Indications

Adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease experiencing 'off' episodesFDA-labeled

Selective, reversible, peripherally-acting catechol-O-methyltransferase (COMT) inhibitor with a long-acting binding profile allowing once-daily dosing
Reduces peripheral metabolism of levodopa to 3-O-methyldopa, increasing levodopa peak exposure by approximately 43–44% and overall exposure (AUC) by approximately 62–94%, extending levodopa's clinical effect and reducing 'off' time

50 mg administered orally once daily at bedtime
Patients should not eat for at least 1 hour before and at least 1 hour after dosing

End-stage renal disease: avoid use
No dose adjustment required for mild-to-moderate renal impairment or in elderly patients

Moderate hepatic impairment (Child-Pugh B): reduce to 25 mg once daily at bedtime
Severe hepatic impairment (Child-Pugh C): avoid use

Concomitant use of non-selective monoamine oxidase (MAO) inhibitors
History of pheochromocytoma, paraganglioma, or other catecholamine-secreting neoplasms

Contraindicated with non-selective MAO inhibitors — risk of arrhythmias and hypertensive crisis; selective MAO-B inhibitors (e.g., selegiline, rasagiline) are permitted
Use caution with catecholamine-metabolized drugs (epinephrine, norepinephrine, dopamine, dobutamine, isoproterenol) — monitor heart rate, rhythm, and blood pressure
No clinically significant pharmacokinetic interaction with carbidopa/levodopa itself beyond the intended COMT effect

Dyskinesia — most common adverse reaction, 20% vs. 6% placebo; leading cause of discontinuation (3%)
Constipation (6% vs. 2% placebo)
Blood creatine kinase elevation (5% vs. 2% placebo)
Hypotension/syncope (5% vs. 1% placebo) — consider discontinuation if symptomatic
Weight decrease (4% vs. 0% placebo)
Hallucinations (3% vs. 1% placebo); insomnia (3% vs. 2% placebo); impulse control disorders (1% vs. 0%)
Discoloration of urine (brownish-orange), a class effect shared with entacapone due to COMT-inhibitor/catechol metabolite excretion
Somnolence/sudden sleep onset — patients may not perceive warning signs and may feel alert immediately beforehand

Blood pressure and heart rate, particularly with concomitant catecholamine-metabolized drugs
Symptomatic hypotension or syncope
Dyskinesia severity; consider levodopa dose reduction if it worsens
New or worsening hallucinations, delusions, aggression, or other psychotic behaviors — warrants dose reduction or discontinuation
Impulse control/compulsive behaviors (gambling, hypersexuality, spending, binge eating) via direct questioning
Liver function; avoid use in severe hepatic impairment
Signs of NMS-like syndrome with abrupt discontinuation; taper and adjust dopaminergic therapy gradually
Counsel patients regarding urine discoloration to prevent unnecessary alarm

No adequate human data on use in pregnancy; animal studies in rabbits showed fetal abnormalities at clinically relevant exposures, indicating potential risk of fetal harm
Use in pregnancy only if the potential benefit justifies the potential risk to the fetus
No human lactation data available; opicapone was detected in animal milk at concentrations comparable to maternal plasma
Weigh the developmental and health benefits of breastfeeding against the mother's clinical need for opicapone and any potential adverse effects on the breastfed infant