Introduction
Ongentys (opicapone) is a novel, once-daily catechol-O-methyltransferase (COMT) inhibitor approved as an adjunct therapy to levodopa/carbidopa in the treatment of Parkinson's disease. It addresses the wearing-off phenomenon that commonly develops in patients with Parkinson's disease after prolonged levodopa therapy.
Mechanism of Action
Ongentys acts as a reversible, peripherally-selective COMT inhibitor. By inhibiting the COMT enzyme in peripheral tissues, it reduces the conversion of levodopa to 3-O-methyldopa, thereby increasing levodopa bioavailability and prolonging its duration of action. This results in more stable plasma levodopa concentrations and enhanced dopamine delivery to the central nervous system.
Indications
Ongentys is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease experiencing "off" episodes. It is approved for use in adults and is specifically designed to address end-of-dose motor fluctuations.
Dosage and Administration
- Standard dosage: 50 mg once daily, taken orally at bedtime
- Administration: Should be taken at least one hour before or after meals
- Special populations:
- Renal impairment: No dosage adjustment necessary - Hepatic impairment: Not recommended in patients with moderate to severe hepatic impairment - Elderly: No dosage adjustment necessary - Pediatrics: Safety and effectiveness not established
Pharmacokinetics
- Absorption: Rapidly absorbed with peak plasma concentrations achieved within 2-4 hours
- Distribution: Extensive plasma protein binding (>99.9%)
- Metabolism: Primarily metabolized via glucuronidation; not a substrate of CYP enzymes
- Elimination: Primarily eliminated in feces (90%) with minimal renal excretion
- Half-life: Approximately 1-2 hours, but COMT inhibition persists for up to 24 hours
Contraindications
- Hypersensitivity to opicapone or any component of the formulation
- Concomitant use with non-selective monoamine oxidase (MAO) inhibitors
- History of neuroleptic malignant syndrome and/or nontraumatic rhabdomyolysis
Warnings and Precautions
- Dopaminergic effects: May cause or exacerbate dyskinesia
- Impulse control disorders: May cause compulsive behaviors including gambling, sexual, spending, or eating behaviors
- Hallucinations/psychosis: May exacerbate psychotic disorders
- Withdrawal symptoms: Abrupt discontinuation may lead to hyperpyrexia and confusion
- Hepatic effects: Monitor liver function tests periodically
- Melanoma: Patients with Parkinson's disease have higher risk of melanoma; regular dermatological examinations recommended
Drug Interactions
- Non-selective MAO inhibitors: Contraindicated due to risk of hypertensive crisis
- Other COMT inhibitors: Avoid concomitant use
- Dopamine D2 receptor antagonists: May diminish effectiveness
- Drugs affecting catecholamines: Use caution with sympathomimetics
- Alcohol: May increase sedation
Adverse Effects
Common (≥5%):- Dyskinesia (20%)
- Constipation (8%)
- Blood creatine phosphokinase increased (7%)
- Hypotension (6%)
- Weight loss (5%)
- Dry mouth (5%)
- Hallucinations
- Impulse control disorders
- Neuroleptic malignant syndrome
- Rhabdomyolysis
- Hepatotoxicity
Monitoring Parameters
- Motor function and "on"/"off" time patterns
- Development or worsening of dyskinesia
- Mental status changes, hallucinations, or psychotic behavior
- Signs of impulse control disorders
- Liver function tests at baseline and periodically
- Blood pressure (orthostatic changes)
- Weight changes
- Skin examinations for melanoma detection
Patient Education
- Take medication once daily at bedtime, consistently with regard to food
- Do not abruptly discontinue medication without medical supervision
- Report any new or worsening involuntary movements
- Be aware of potential impulse control changes and report compulsive behaviors
- Rise slowly from sitting/lying position to prevent dizziness
- Avoid alcohol consumption
- Regular skin examinations recommended
- Inform all healthcare providers about all medications being taken
- Report any signs of liver problems (yellowing skin/eyes, dark urine, abdominal pain)
References
1. Ferreira JJ, et al. Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Lancet Neurol. 2016;15(2):154-165. 2. US Food and Drug Administration. Ongentys (opicapone) prescribing information. 2020. 3. Lees AJ, et al. Opicapone for the treatment of Parkinson's disease: A review of a new licensed medicine. Mov Disord. 2018;33(10):1528-1539. 4. Rocha JF, et al. Opicapone: A short lived and very long acting catechol-O-methyltransferase inhibitor. J Clin Pharmacol. 2018;58(4):436-449. 5. European Medicines Agency. Ongentys assessment report. 2016.