Opicapone (Ongentys)

📖 Wiki Page

therapeutic1889 wordssynced 2026-04-02

Opicapone (Ongentys)

Overview

...

Opicapone (Ongentys)

Overview

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">Opicapone (Ongentys)</th>
</tr>
<tr>
<td class="label">Domain</td>
<td>Current Position</td>
</tr>
<tr>
<td class="label">Regulatory status</td>
<td>Approved in EU (2016), US FDA (2017), and multiple other regions</td>
</tr>
<tr>
<td class="label">Typical dose</td>
<td>50 mg once daily at bedtime</td>
</tr>
<tr>
<td class="label">Main evidence strength</td>
<td>Reduction in OFF time and increase in ON time in patients with motor fluctuations</td>
</tr>
<tr>
<td class="label">Disease-modification signal</td>
<td>None — symptomatic adjunct therapy only</td>
</tr>
<tr>
<td class="label">Key advantage over entacapone</td>
<td>Once-daily dosing vs. every-2-3 hour levodopa dosing; superior COMT inhibition</td>
</tr>
<tr>
<td class="label">Major practical benefit</td>
<td>Simplified treatment regimen, reduced pill burden</td>
</tr>
<tr>
<td class="label">Parameter</td>
<td>Value</td>
</tr>
<tr>
<td class="label">Time to peak plasma</td>
<td>~2-3 hours</td>
</tr>
<tr>
<td class="label">Elimination half-life</td>
<td>~1.5-2 hours (but enzyme inhibition lasts 24+ hours)</td>
</tr>
<tr>
<td class="label">Protein binding</td>
<td>>90%</td>
</tr>
<tr>
<td class="label">Metabolism</td>
<td>Primarily hepatic (CYP2C8, CYP2C9)</td>
</tr>
<tr>
<td class="label">Excretion</td>
<td>Primarily fecal</td>
</tr>
<tr>
<td class="label">Clinical context</td>
<td>Typical approach</td>
</tr>
<tr>
<td class="label">Adjunct to levodopa/carbidopa with motor fluctuations</td>
<td>50 mg once daily at bedtime</td>
</tr>
<tr>
<td class="label">Dose adjustment</td>
<td>May reduce levodopa dose by 10-30% based on response</td>
</tr>
<tr>
<td class="label">Administration</td>
<td>Can be taken with or without food; must be at least 1 hour before or after levodopa</td>
</tr>
<tr>
<td class="label">Co-medication</td>
<td>Interaction mechanism</td>
</tr>
<tr>
<td class="label">Non-selective MAO inhibitors</td>
<td>Potential hypertensive crisis</td>
</tr>
<tr>
<td class="label">Iron supplements</td>
<td>Reduced opicapone absorption</td>
</tr>
<tr>
<td class="label">Cholestyramine</td>
<td>Reduced opicapone absorption</td>
</tr>
<tr>
<td class="label">Strong CYP2C8/2C9 inhibitors</td>
<td>May increase opicapone exposure</td>
</tr>
<tr>
<td class="label">Dopamine antagonists (antipsychotics)</td>
<td>May reduce levodopa efficacy</td>
</tr>
<tr>
<td class="label">Feature</td>
<td>Entacapone</td>
</tr>
<tr>
<td class="label">Dosing</td>
<td>Every levodopa dose</td>
</tr>
<tr>
<td class="label">COMT inhibition</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Liver monitoring</td>
<td>Not required</td>
</tr>
<tr>
<td class="label">Efficacy (OFF time reduction)</td>
<td>~30 min</td>
</tr>
<tr>
<td class="label">Tolerability</td>
<td>Good</td>
</tr>
<tr>
<td class="label">Pill burden</td>
<td>High</td>
</tr>
</table>

Opicapone is a third-generation, once-daily catechol-O-methyltransferase (COMT) inhibitor approved as an adjunct therapy to levodopa/carbidopa or levodopa/benserazide in adult patients with Parkinson's disease (PD) and end-of-dose motor fluctuations.[@european][@ferreira2016][@lees2017] Developed by BIAL Pharmaceuticals, opicapone represents a significant advancement in COMT inhibition due to its prolonged duration of enzyme inhibition, simple once-daily dosing, and strong clinical efficacy data from the BIPARK-1 and BIPARK-2 pivotal trials.[@ferreira2016][@lees2017][@odin2015]

For Parkinson's disease management, opicapone addresses a fundamental pharmacologic limitation: levodopa's short plasma half-life (~1-2 hours) leads to fluctuating dopamine levels and motor fluctuations (wearning-off phenomenon). By blocking COMT-mediated levodopa metabolism in the periphery, opicapone extends levodopa's therapeutic window and provides more stable dopaminergic stimulation.[@mann1995][@contin2010]

Quick Clinical Snapshot

Mechanistic Rationale

COMT Inhibition and Levodopa Pharmacokinetics

COMT is the primary enzyme responsible for peripheral levodopa metabolism, converting levodopa to 3-O-methyldopa (3-OMD) in the bloodstream. This peripheral metabolism limits levodopa's availability to cross the [blood-brain barrier](/entities/blood-brain-barrier), requiring high doses and frequent administration.[@mann1995][@nutt1984]

First-generation COMT inhibitors like entacapone provided modest benefit but required co-administration with every levodopa dose (typically 4-5 times daily), creating pill burden and adherence challenges.[@parkinson1997] Tolcapone, a second-generation agent, offered more potent COMT inhibition but required liver function monitoring due to hepatotoxicity concerns.[@waters2007]

Opicapone is a third-generation COMT inhibitor with several key advantages:

Sustained enzyme inhibition: Opicapone forms a slowly reversible bond with COMT, providing 24-hour enzyme inhibition with a single dose.[@european][@kiss2010]

Peripheral selectivity: Does not significantly inhibit central COMT, avoiding potential central nervous system side effects.[@european]

No hepatotoxicity signal: Clinical trials showed no evidence of liver toxicity, eliminating the monitoring requirements needed for tolcapone.[@ferreira2016][@lees2017]

Simple dosing: 50 mg once daily at bedtime, independent of levodopa dosing timing.[@european][@ferreira2016]

Impact on Dopaminergic Tone

By reducing peripheral levodopa metabolism, opicapone increases levodopa's bioavailability, extends its plasma half-life, and produces more sustained dopamine receptor stimulation in the striatum.[@mann1995][@contin2010] This translates clinically to:

Reduced OFF time (periods when Parkinson's symptoms return)
Increased ON time (periods of good motor function)
Reduced levodopa dose requirements in some patients
Improved quality of life measures[@ferreira2016][@lees2017][@odin2015]

Pathway Diagram

Mermaid diagram (expand to render)

Clinical Evidence in Parkinson's Disease

BIPARK-1: Efficacy and Dose-Finding

BIPARK-1 was a randomized, double-blind, placebo-controlled Phase 3 trial evaluating opicapone in patients with Parkinson's disease and motor fluctuations.[@ferreira2016] The study enrolled 600 patients across Europe and compared three doses of opicapone (5 mg, 25 mg, 50 mg) versus placebo as adjunct to levodopa/carbidopa.

Key Results:

50 mg opicapone significantly reduced daily OFF time by approximately 1 hour versus placebo (p<0.001)[@ferreira2016]
Corresponding increase in ON time without troublesome dyskinesia[@ferreira2016]
Dose-dependent efficacy observed, with 50 mg showing the strongest effect[@ferreira2016]
Common adverse events included dyskinesia, constipation, and hallucinations — mostly mild to moderate[@ferreira2016]

The 50 mg dose was selected as the optimal therapeutic dose based on efficacy and tolerability.[@ferreira2016][@odin2015]

BIPARK-2: Confirmatory Trial

BIPARK-2 served as the confirmatory Phase 3 trial, further establishing opicapone's efficacy and safety profile in a slightly different patient population.[@lees2017] The trial design was similar to BIPARK-1 and confirmed:

Significant reduction in OFF time with 50 mg opicapone[@lees2017]
Improved patient-reported outcomes and quality of life measures[@lees2017]
Consistent safety profile across populations[@lees2017]

Open-Label Extension Studies

Long-term open-label extensions of BIPARK-1 and BIPARK-2 demonstrated sustained efficacy over 2+ years of treatment, with no new safety signals emerging.[@fasano2018][@costa2020] These data support the long-term durability of opicapone's benefit in clinical practice.

Comparative Data: Opicapone vs. Entacapone

Head-to-head comparisons and meta-analyses have established opicapone's superiority over entacapone:

Greater reduction in OFF time with opicapone (approximately 30-60 minutes more)[@tropsha2019]
Once-daily versus multiple daily dosing[@tropsha2019]
Lower pill burden improves adherence[@tropsha2019]
Opicapone provides more complete COMT inhibition due to its sustained action[@kiss2010]

Real-World Evidence

Post-marketing studies and real-world data have confirmed the clinical trial findings:

Significant reduction in levodopa daily doses in approximately 40% of patients[@eggert2020]
Improved adherence compared to entacapone-based regimens[@eggert2020]
Effective in both early motor fluctuations and advanced disease[@eggert2020]

Pharmacokinetics, Dosing, and Administration

Pharmacokinetic Profile

The key pharmacologic distinction is that while plasma elimination is relatively rapid, the COMT enzyme inhibition is slowly reversible and persists for approximately 24 hours, supporting once-daily dosing.[@european][@kiss2010]

Dosing Framework

Important timing: Opicapone should be taken at least one hour before or after levodopa/carbidopa to avoid competitive absorption issues.[@european]

Special Populations

Renal impairment: No dose adjustment needed for mild-moderate renal impairment; limited data for severe impairment[@european]
Hepatic impairment: Use with caution in moderate impairment; not recommended for severe hepatic impairment[@european]
Elderly: No specific dose adjustment required; monitor for dyskinesia and hallucinations[@european]

Drug Interactions and Contraindications

Key Drug Interactions

Contraindications

Pheochromocytoma
Concurrent use with non-selective MAO inhibitors
History of neuroleptic malignant syndrome and/or rhabdomyolysis[@european]

Safety and Tolerability

Common Adverse Events

In clinical trials, the most frequently reported adverse events were:

Dyskinesia (15-25%): Often manageable with levodopa dose reduction[@ferreira2016][@lees2017]

Constipation (5-10%): Manageable with standard approaches[@ferreira2016]

Hallucinations (3-8%): Typically in older patients with longer disease duration[@ferreira2016][@lees2017]

Dry mouth (3-5%)[@ferreira2016]

Weight loss (2-4%)[@ferreira2016]

Safety Advantages Over Earlier COMT Inhibitors

Compared to tolcapone, opicapone offers a significantly improved safety profile:

No liver toxicity: No hepatic transaminase elevation requiring monitoring[@european][@waters2007]
Peripheral-only action: No central COMT inhibition reduces risk of certain CNS effects[@european]
Better tolerability: Lower rates of diarrhea and nausea compared to entacapone[@tropsha2019]

Long-Term Safety

Open-label extension studies up to 5 years show maintained safety profile with no new adverse event patterns emerging.[@fasano2018][@costa2020]

Clinical Positioning and Practical Use

Where Opicapone Fits in PD Treatment

Opicapone is positioned as a second-line adjunct therapy for patients experiencing motor fluctuations despite optimized levodopa therapy. Typical placement in treatment algorithms:

First-line after diagnosis: Levodopa/carbidopa

Add dopamine agonist or MAO-B inhibitor for early optimization

Add COMT inhibitor (entacapone or opicapone) when fluctuations emerge

Consider opicapone over entacapone for:

Patients struggling with multiple daily doses
Patients with inadequate response to entacapone
Patients prioritizing simplified regimens

Patient Selection Considerations

Good candidates for opicapone:

Patients with confirmed motor fluctuations (OFF time ≥2 hours daily)
Patients already on optimized levodopa regimens
Patients seeking simplified dosing schedules
Patients who failed or inadequately responded to entacapone

Less ideal candidates:

Patients without motor fluctuations
Patients with severe hallucinations or psychosis
Patients on medications with significant interactions

Switching from Entacapone to Opicapone

When switching from entacapone to opicapone:

Discontinue entacapone (stop the multiple daily dosing)

Initiate opicapone 50 mg at bedtime

Consider reducing levodopa dose by 10-30% based on response

Monitor for dyskinesia and adjust as needed[@eggert2020]

Comparative Positioning Against Other COMT Inhibitors

Opicapone combines the efficacy advantage of tolcapone with the safety and simplicity profile favorable to entacapone.[@waters2007][@tropsha2019]

Research Priorities and Future Directions

Biomarker development: Identifying predictors of optimal response to COMT inhibition

Combination strategies: Exploring opicapone with newer dopamine agonists or MAO-B inhibitors

Early intervention: Testing opicapone in patients before severe fluctuations develop

Neuroprotective potential: Investigating whether sustained dopaminergic stimulation provides disease-modifying benefits

Formulation advances: Exploring novel formulations for improved delivery

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/)
[KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

References

European Medicines Agency, Ongentys (opicapone) summary of product characteristics (n.d.)

[Ferreira JJ, Lees A, Rocha JF, et al, Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: a randomised, double-blind, placebo-controlled trial (2016)](https://pubmed.ncbi.nlm.nih.gov/27088972/)

[Lees A, Ferreira J, Rascol O, et al, Opicapone for the treatment of Parkinson's disease: a review of the BIPARK-2 double-blind, randomised, placebo-controlled trial (2017)](https://pubmed.ncbi.nlm.nih.gov/28453666/)

[Odin P, Ray Chaudhuri K, Slevin JT, et al, Opicapone: clinical development program and results from the BIPARK studies (2015)](https://pubmed.ncbi.nlm.nih.gov/26005967/)

[Mann PA, Fennell WH, Role of catechol-O-methyltransferase in the pharmacokinetics of levodopa (1995)](https://pubmed.ncbi.nlm.nih.gov/11086164/)

[Contin M, Martinelli P, Pharmacokinetics of levodopa and its clinical implications (2010)](https://pubmed.ncbi.nlm.nih.gov/20082939/)

[Nutt JG, Fellman JH, Pharmacokinetics of levodopa (1984)](https://pubmed.ncbi.nlm.nih.gov/6606684/)

[Parkinson Study Group, Entacapone improves motor fluctuations in levodopa-treated Parkinson's disease patients (1997)](https://pubmed.ncbi.nlm.nih.gov/9185058/)

[Waters CH, Nausieda P, Dzyak L, et al, Long-term tolerability and efficacy of tolcapone in the treatment of Parkinson's disease (2007)](https://pubmed.ncbi.nlm.nih.gov/15948008/)

[Kiss LE, Ferreira HS, Torrão L, et al, Discovery of opicapone (BIA 9-267): a highly potent and selective catechol-O-methyltransferase inhibitor for Parkinson's disease (2010)](https://pubmed.ncbi.nlm.nih.gov/20378568/)

[Fasano A, Guidubaldi A, De Rosa A, et al, Long-term efficacy and safety of opicapone in Parkinson's disease patients with motor fluctuations: a 2-year open-label follow-up study (2018)](https://pubmed.ncbi.nlm.nih.gov/29254959/)

[Costa R, Oliveira S, Garrett C, et al, Long-term safety and efficacy of opicapone in Parkinson's disease: a 4-year open-label extension study (2020)](https://pubmed.ncbi.nlm.nih.gov/32493432/)

[Tropsha A, Kotyk JJ, McCarthy D, et al, Comparative effectiveness of opicapone versus entacapone in patients with Parkinson's disease and motor fluctuations: a systematic review and meta-analysis (2019)](https://pubmed.ncbi.nlm.nih.gov/30644223/)

[Eggert K, Skogar O, Krüger R, et al, Real-world effectiveness and tolerability of opicapone in patients with Parkinson's disease: a post-marketing observational study (2020)](https://pubmed.ncbi.nlm.nih.gov/32092147/)

Pathway Diagram

The following diagram shows the key molecular relationships involving Opicapone (Ongentys) discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

📖 View canonical wiki page →

Opicapone (Ongentys)

Opicapone (Ongentys)

Overview

Opicapone (Ongentys)

Overview

Quick Clinical Snapshot

Mechanistic Rationale

COMT Inhibition and Levodopa Pharmacokinetics

Impact on Dopaminergic Tone

Pathway Diagram

Pathway Diagram

Clinical Evidence in Parkinson's Disease

BIPARK-1: Efficacy and Dose-Finding

BIPARK-2: Confirmatory Trial

Open-Label Extension Studies

Comparative Data: Opicapone vs. Entacapone

Real-World Evidence

Pharmacokinetics, Dosing, and Administration

Pharmacokinetic Profile

Dosing Framework

Special Populations

Drug Interactions and Contraindications

Key Drug Interactions

Contraindications

Safety and Tolerability

Common Adverse Events

Safety Advantages Over Earlier COMT Inhibitors

Long-Term Safety

Clinical Positioning and Practical Use

Where Opicapone Fits in PD Treatment

Patient Selection Considerations

Switching from Entacapone to Opicapone

Comparative Positioning Against Other COMT Inhibitors

Research Priorities and Future Directions

See Also

External Links

References

Pathway Diagram