Parkinson disease: Oral: 50 mg once daily at bedtime.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution in severe impairment. Avoid use in patients with end-stage renal disease (CrCl <15 mL/minute).
Mild (Child-Pugh class A): There are no dosage adjustments provided in the manufacturer's labeling.
Moderate (Child-Pugh class B): 25 mg once daily at bedtime.
Severe (Child-Pugh class C): Avoid use (has not been studied).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Ongentys: 25 mg, 50 mg [contains fd&c blue #2 (indigotine)]
No
Oral: Administer at bedtime; do not eat for 1 hour before and at least 1 hour after dose.
Parkinson disease: Adjunctive treatment to levodopa/carbidopa in patients with Parkinson disease experiencing “off” episodes.
Opicapone may be confused with entacapone or tolcapone.
Ongentys (brand name for opicapone) may be confused with Onglyza (brand name for saxagliptin).
New-onset or exacerbation of preexisting dyskinesia was the most common adverse effect of opicapone, in combination with levodopa, as well as the most common adverse event leading to discontinuation in clinical trials; most of the dyskinesia events occurred in patients already experiencing dyskinesia at baseline during clinical trials (Ref). During clinical trials, most of the gain of on-time with opicapone was without troublesome dyskinesia; in addition, there was no significant difference between placebo and opicapone with regards to the increase in on-time with troublesome dyskinesia (Ref).
Mechanism: Dose-related; related to the pharmacologic action (ie, potentiation of dopaminergic effects) (Ref).
Onset: Varied; most dyskinetic events occurred within the first 4 weeks of treatment in clinical trials (Ref).
Risk factors:
• Higher doses of levodopa
• Concomitant use of other dopaminergic drugs
• Preexisting dyskinesia (Ref)
Impulse control disorder (ICD) and/or compulsive behaviors, which may manifest as pathological gambling, hypersexuality, intense urges to spend money uncontrollably, and other intense urges, have been reported (Ref). In some cases, the behavior will subside with a dose reduction or discontinuation.
Mechanism: Dose-related; related to the pharmacologic action (ie, potentiation of dopaminergic effects) (Ref). The impact of the disease process and concurrent medications must be considered (Ref).
Onset: Variable; based on clinical experience, onset of dopaminergic adverse effects often occurs within the first several weeks following initiation of catechol-O-methyltransferase inhibitor therapy; onset may be dependent on the presence of patient risk factors and concomitant medications.
Risk factors:
• In general, the following are potentially associated with Parkinson disease-impulse control behaviors (Ref):
- Concomitant use of dopamine agonists
- Concomitant use of levodopa use; Note: Some studies have failed to find an association or strong association with the use of levodopa and the risk of ICD (Ref)
- Duration of treatment (Ref)
- Younger age
- Male patients
- Comorbid depression
- Comorbid anxiety
• Suspected or diagnosed dopamine dysregulation syndrome
Opicapone, in combination with levodopa, may cause orthostatic hypotension; orthostatic hypotension has resulted in treatment discontinuation (Ref). In addition, nonorthostatic hypotension, presyncope, and syncope have been reported.
Mechanism: Dose-related; related to the pharmacologic action (ie, potentiation of dopaminergic effects) (Ref).
Risk factors:
• Concomitant use of other hypotensive agents
• In general, the following risk factors may increase the likelihood of orthostatic hypotension in Parkinson disease (Ref)
- Age >68 years
- Polypharmacy (use of >5 medications)
- Concomitant use of amantadine or diuretics
Note: Concomitant use of entacapone, another catechol-O-methyltransferase inhibitor, appeared to reduce the risk of orthostatic hypotension in this study.
Use of opicapone, in combination with levodopa, may result in hallucinations, including auditory hallucinations, visual hallucinations, or mixed hallucinations; may also cause aggressive behavior, agitation, or delusions. During one clinical trial, visual hallucinations resulted in treatment discontinuation in several patients (Ref).
Mechanism: Dose-related; related to the pharmacologic action (ie, potentiation of dopaminergic effects) (Ref)
Onset: Variable; based on clinical experience, onset of dopaminergic adverse effects often occurs within the first several weeks following initiation of catechol-O-methyltransferase inhibitor therapy; onset may be dependent on the presence of patient risk factors and concomitant medications.
Risk factors:
• Prior history of a major psychotic disorder
• Age ≥70 years (Ref)
• Concomitant use of other agents known to cause psychiatric effects (eg, dopaminergic agonists, anticholinergic agents)
Opicapone, when added to levodopa, may result in a sudden onset of sleep while engaging in activities of daily living, including sleep driving; events have been reported to occur without significant warning signs and may result in accidents. Patients may report feeling alert immediately prior to events.
Mechanism: Dose-related; related to the pharmacologic action (ie, potentiation of dopaminergic effects).
Onset: Varied; based on clinical experience, onset may occur within the first several weeks of treatment with catechol-O-methyltransferase (COMT) inhibitors but may also develop years later in some patients. One case report described onset of irresistible sleep episodes 3 days following initiation of entacapone, another COMT inhibitor (Ref).
Risk factors:
• Preexisting sleep disorder
• Concomitant use of other sedating agents
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Neuromuscular & skeletal: Dyskinesia (20%; severe dyskinesia: 1% [Lees 2019]) (table 1)
|
Drug (Opicapone) |
Placebo |
Dose |
Number of Patients (Opicapone) |
Number of Patients (Placebo) |
Comments |
Source |
|---|---|---|---|---|---|---|
|
20% |
6% |
50 mg/day |
265 |
257 |
N/A |
Ongentys PI 2020.04 |
|
1% |
0.8% |
N/A |
322 |
147 |
Severe |
Lees 2019 |
1% to 10%:
Cardiovascular: Hypertension (3%), hypotension (including orthostatic hypotension, presyncope, syncope: 5%) (table 2), increased serum creatine kinase (5%)
|
Drug (Opicapone) |
Placebo |
Dose |
Number of Patients (Opicapone) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
5% |
1% |
50 mg/day |
265 |
257 |
Including orthostatic hypotension, presyncope, syncope |
Endocrine & metabolic: Weight loss (4%)
Gastrointestinal: Constipation (6%), xerostomia (3%)
Nervous system: Dizziness (3%), hallucination (including auditory hallucinations, visual hallucinations: 3% (table 3)), impulse control disorder (1%) (table 4), insomnia (3%), psychosis (including aggressive behavior, agitation, delusion: 1%) (table 5)
|
Drug (Opicapone) |
Placebo |
Dose |
Number of Patients (Opicapone) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
3% |
1% |
50 mg/day |
265 |
257 |
Including auditory hallucination, visual hallucination, mixed hallucination |
|
Drug (Opicapone) |
Placebo |
Dose |
Number of Patients (Opicapone) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
1% |
0% |
50 mg/day |
265 |
257 |
|
Drug (Opicapone) |
Placebo |
Dose |
Number of Patients (Opicapone) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
1% |
0% |
50 mg/day |
265 |
257 |
Including aggressive behavior, agitation, delusion |
Frequency not defined: Nervous system: Sleep driving, sudden onset of sleep
Concomitant use of nonselective monoamine oxidase inhibitors; pheochromocytoma, paraganglioma, or other catecholamine secreting neoplasms.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with mild to moderate hepatic impairment; avoid use in severe impairment.
• Renal impairment: Use caution in patients with severe renal impairment; discontinue opicapone if tolerability issues arise. Avoid use in patients with end-stage renal disease (CrCl <15 mL/minute).
Other warnings/precautions:
• Discontinuation of therapy: Dopaminergic agents have been associated with a syndrome resembling neuroleptic malignant syndrome upon withdrawal or abrupt dosage reduction; patients should be monitored closely if therapy is discontinued.
Substrate of BCRP/ABCG2, MRP2, OATP1B1/1B3 (SLCO1B1/1B3), OATP2B1/SLCO2B1, P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits COMT
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
COMT Substrates: COMT Inhibitors may increase the serum concentration of COMT Substrates. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: Opicapone may enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Pipamperone [INT]: COMT Inhibitors may diminish the therapeutic effect of Pipamperone [INT]. Pipamperone [INT] may diminish the therapeutic effect of COMT Inhibitors. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Food decreases the rate and extent of absorption of opicapone. Management: Do not eat for 1 hour before and at least 1 hour after opicapone.
Based on data from animal reproduction studies, in utero exposure to opicapone may cause fetal harm. Opicapone is used in combination with levodopa/carbidopa. Also refer to the Levodopa/Carbidopa monographs for additional information.
It is not known if opicapone is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Opicapone is used in combination with levodopa/carbidopa. Also refer to the Levodopa/Carbidopa monographs for additional information.
Liver and renal function tests (baseline and as clinically indicated); BP (baseline and as clinically indicated); mental alertness, daytime somnolence, preexisting sleep disorder.
Opicapone is a reversible and selective inhibitor of catechol-O-methyltransferase (COMT); COMT is the major degradation pathway for levodopa. When opicapone is taken with levodopa, the pharmacokinetics are altered, resulting in more sustained levodopa serum levels compared to levodopa taken alone. The resulting levels of levodopa provide for increased concentrations available for absorption across the blood-brain barrier, thereby providing for increased CNS levels of dopamine, the active metabolite of levodopa.
Absorption: With a moderate-fat/moderate-calorie meal, the mean Cmax decreased 62%, AUC decreased 31%, and the Tmax was delayed by 4 hours.
Protein binding: >99%.
Metabolism: Via sulphation (primarily), glucuronidation, methylation, reduction, and glutathione concentration.
Half-life elimination: 1 to 2 hours.
Time to peak: 2 hours (range: 1 to 4 hours).
Excretion: Feces: ~70% (22% as unchanged drug); expired air: 20%; urine: 5% (<1% as unchanged drug).
Hepatic function impairment: AUC increased by 35% in mild impairment (Child-Pugh class A) and 84% in moderate impairment (Child-Pugh class B).
Capsules (Ongentys Oral)
25 mg (per each): $26.81
50 mg (per each): $26.81
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
