Opicapona
Opicapona Uses, Dosage, Side Effects, Food Interaction and all others data.
Opicapona is a potent, reversible, and peripherally-acting third-generation inhibitor of catechol-o-methyltransferase (COMT), an enzyme involved in the breakdown of various catecholamines including dopamine. Many patients with Parkinson’s disease treated with levodopa plus a dopa decarboxylase (DDC) inhibitor (eg carbidopa) experience motor complications over time, which calls for the management of these symptoms through the use of a dopamine agonist, a monoamine oxidase B inhibitor (selegiline, rasagiline), a catechol-O-methyl transferase (COMT) inhibitor, or amantadine, or using a modified-release formulation of levodopa.
Opicapona is used for adjunct therapy to levodopa and carbidopa in adult patients with Parkinson's disease and end-of-dose motor fluctuations. Opicapona was approved for use by the European Commission in June 2016 and the FDA in April 2020. It is marketed under the brand name Ongentys as once-daily oral capsules. Exhibiting a long duration of action that exceeds 24 hours, opicapone can be administered once-daily and demonstrates the lowest risk for cytotoxicity compared to other catechol-O-methyltransferase inhibitors.
Opicapona is a COMT inhibitor that serves to improve the availability and duration of action of levodopa (L-Dopa), a standard pharmacological treatment for Parkinson's Disease. Opicapona works by blocking the peripheral degradation of L-Dopa mediated by COMT. Opicapona has a long duration of action: following administration of a 50 mg dose, COMT inhibition lasted for more than 24 hours. In clinical trials, opicapone as adjunct therapy to L-Dopa plus a dopa decarboxylase inhibitor significantly improved motor fluctuations than placebo, and the effects were comparable to entacapone.
| Trade Name | Opicapona |
| Availability | Prescription only |
| Generic | Opicapone |
| Opicapone Other Names | Opicapona, Opicapone |
| Related Drugs | Neupro, Azilect, Duopa, Apokyn, Xadago, Ongentys, Gocovri, Rytary, Sinemet, Sinemet CR |
| Type | |
| Formula | C15H10Cl2N4O6 |
| Weight | Average: 413.17 Monoisotopic: 411.9977395 |
| Protein binding | Opicapone is >99% bound to plasma proteins, which is independent of the drug concentration. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Opicapona is a catechol-O-methyltransferase inhibitor used as an adjunct treatment for Parkinson's Disease in adults currently receiving levodopa and a dopa decarboxylase inhibitor.
Opicapona is indicated as adjunctive therapy in adults with Parkinson’s disease and end-of-dose motor fluctuations or “off” episodes whose symptoms cannot be stabilized on the combination therapy of levodopa and DOPA decarboxylase inhibitor (e.g., carbidopa).
Opicapona is also used to associated treatment for these conditions: Parkinson's Disease (PD)
How Opicapona works
Levodopa (L-Dopa) is the gold standard for managing motor and some non-motor symptoms associated with Parkinson's Disease; however, only a small fraction of administered L-Dopa actually crosses the blood-brain barrier to exert its therapeutic action and patients face the risk of developing end-of-dose motor fluctuations, which reflects the rapid peripheral metabolism of L-dopa by aromatic L-amino acid decarboxylase and catechol-O-methyltransferase (COMT).
Opicapona is a peripheral, selective, and reversible catechol-O-methyltransferase (COMT) inhibitor. It displays a high binding affinity that is in sub-picomolar ranges, resulting in a slow complex dissociation rate constant and long duration of action in vivo. When opicapone is added to the treatment regimen that contains L-Dopa and DOPA decarboxylase inhibitor, opicapone helps to increase the plasma levels and enhance the therapeutic efficacy of L-Dopa.
Toxicity
There is no reported LD50 data of opicapone. As there is no known antidote for opicapone overdose, overdosage should be managed with symptomatic and supportive treatment. Removal of the drug through gastric lavage and/or inactivation by administering activated charcoal should be considered.
Food Interaction
- Take separate from meals. Take opicapone at least one hour before or after eating, as a moderate calorie meal decreases Cmax and overall plasma exposure to the drug, and delays Tmax.
[Moderate] ADJUST DOSING INTERVAL: Food may reduce the rate and extent of absorption of opicapone.
When opicapone was administered following a moderate fat
MANAGEMENT: Patients should avoid eating 1 to 2 hours before and after taking opicapone.
Opicapona Alcohol interaction
[Moderate] GENERALLY AVOID:
Alcohol may potentiate some of the pharmacologic effects of central nervous system (CNS)-active agents.
Use in combination may result in additive CNS depression and/or impairment of judgment, thinking, and psychomotor skills.
Patients receiving CNS-active agents should be advised to avoid or limit consumption of alcohol.
Ambulatory patients should be counseled against driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
Opicapona Disease Interaction
Major: pheochromocytoma, psychosisModerate: end stage renal disease, hypotension, liver impairment, lactose intolerance
Volume of Distribution
Following oral administration, the apparent Vd of opicapone at a dose of 50 mg was 29 L with an inter-subject variability of 36%. One study showed small systemic accumulation after multiple-dosing.
Elimination Route
Orally administered opicapone demonstrates a linear, dose-dependent absorption profile. Opicapona is rapidly absorbed, with an oral bioavailability of about 20%. Following administration of a single 50 mg dose of opicapone, the median Tmax was two hours, ranging from one to four hours. A moderate fat or moderate calorie meal was shown to decrease the Cmax by 62%, the mean overall plasma exposure (AUC) by 31%, and the Tmax by 4 hours.
Half Life
The mean elimination half-life of opicapone is one to two hours. Despite the short half-life, the observed half-life of opicapone-induced COMT inhibition in human red blood cells was 61.6 hours with a standard deviation of 37.6 hours.
Clearance
Following oral administration of 50 mg opicapone, the apparent total body clearance was 22 L/h, with an inter-subject variability of 45%.
Elimination Route
Following administration of a single 100 mg dose of radiolabeled opicapone in healthy subjects, about 70% of the total dose was recovered in feces, where 22% of the recovered dose was excreted as an unchanged parent drug. About 20% of the total dose was recovered in exhaled air and about 5% was recovered in the urine, where less than 1% of the recovered dose was in an unchanged form. The primary detectable metabolite in the urine was the glucuronide metabolite.
Innovators Monograph
You find simplified version here Opicapona
