Ongentys (opicapone)

Opicapone is a selective and reversible catechol-O-methyltransferase (COMT) inhibitor. Concomitant administration of opicapone with levodopa and a decarboxylase inhibitor (e.g., carbidopa) results in increased and more sustained plasma levodopa concentrations compared with administration of levodopa and a decarboxylase inhibitor.

Opicapone is a peripheral, selective, and reversible third-generation COMT inhibitor. Opicapone binds with high affinity to COMT, resulting in a slow complex dissociation rate conferring its long duration of action. The COMT enzyme catalyzes the metabolism of substrates containing a catechol structure including dihydroxyphenylalanine (DOPA), catecholamines (dopamine, norepinephrine, and epinephrine), and their metabolites.

Decarboxylation is normally the major metabolic pathway for levodopa; however, when decarboxylation is prevented by carbidopa, COMT becomes the major metabolic pathway. Opicapone inhibits the metabolism of levodopa in peripheral tissues, thereby increasing its elimination half-life and delivery to the brain.

The high binding affinity of opicapone results in sustained COMT inhibition and a long duration of action, allowing for once-daily administration. Administration of opicapone 50 mg daily inhibited COMT activity in erythrocytes with more than 65% of inhibitory activity maintained over the 24-hour dosing interval in patients with parkinson disease. Enzyme activity slowly returns to baseline after opicapone is discontinued.

COMT inhibition of more than 35% is still seen 5 days following the last dose. Concomitant administration of opicapone with levodopa and a decarboxylase inhibitor (e.g., carbidopa) results in increased plasma levodopa concentrations compared with administration of levodopa and carbidopa alone. Opicapone increased peak plasma concentrations of levodopa by 43-44% and AUC by 62-94% compared with administration of levodopa/carbidopa alone.

The pharmacokinetics of opicapone are dose proportional over the dose range of 25-50 mg. Peak plasma concentrations of the drug are reached approximately 2 hours after oral administration. Administration of opicapone with a moderate fat/moderate calorie meal decreases peak plasma concentrations by 62%, decreases AUC by 31%, and delays time to peak concentration by 4 hours.

In one of the principal efficacy studies, opicapone was administered without regard to food, while in the other study, administration of opicapone was separated from food intake by 1 hour. (See Administration under Dosage and Administration.) Opicapone distributes peripherally and does not cross the blood-brain barrier. The drug is highly protein bound (more than 99%). Opicapone is primarily metabolized through sulfation; glucuronidation, methylation by COMT, reduction, and glutathione conjugation also are involved.

The mean elimination half-life of opicapone is 1-2 hours. The primary route of excretion is fecal with 70% of a dose recovered in feces (22% as unchanged drug); 20% of the dose is expired in air, and 5% is excreted in urine (less than 1% as unchanged drug). Age, sex, and race/ethnicity do not have clinically important effects on the pharmacokinetics of opicapone.

USES: This medication is used with other medications (levodopa/carbidopa) to treat Parkinson's disease. Opicapone belongs to a class of drugs known as COMT inhibitors. Many people taking levodopa for Parkinson's disease have problems with the effects of levodopa wearing off between scheduled doses, which causes symptoms to return or get worse.

Opicapone blocks a certain natural substance (COMT) that breaks down levodopa in the body. This effect helps levodopa to work better and for a longer time.

Generic name: opicapone
Pronunciation: (oh-PIK-a-pone)

The following indications are listed for Ongentys:

• Idiopathic Parkinsonism

Also known as: Paralysis Agitans, Primary Parkinson's Disease.

No ICD codes are available for this drug.