Opicapone (Monograph)

Brand name: Ongentys
Drug class: Catechol-O-Methyltransferase (COMT) Inhibitors
Chemical name: 5-[3-(2,5-dichloro-4,6-dimethyl-1-oxidopyridin-1-ium-3-yl)-1,2,4-oxadiazol-5-yl]-3-nitrobenzene-1,2-diol
Molecular formula: C₁₅H₁₀Cl₂N₄O₆
CAS number: 923287-50-7

Medically reviewed by Drugs.com on Jul 31, 2023. Written by ASHP.

Introduction

Selective, reversible inhibitor of catechol-O-methyltransferase (COMT).

Uses for Opicapone

Parkinsonian Syndrome

Adjunct to levodopa-carbidopa in patients with parkinson disease experiencing “off” episodes.

Shown to be noninferior to entacapone when used as adjunctive treatment to levodopa/carbidopa in patients with advanced parkinson disease experiencing motor fluctuations.

Opicapone Dosage and Administration

Administration

Oral Administration

Administer once daily at bedtime. Avoid consuming food for 1 hour before and for ≥1 hour after the drug is administered. (See Food under Pharmacokinetics.)

If a dose is missed, administer next dose at the usually scheduled time the next day.

Dosage

Adults

Parkinsonian Syndrome

Oral

50 mg once daily at bedtime.

Discontinuance of Therapy

Oral

Manufacturer makes no specific recommendations for tapering opicapone when discontinuing therapy. Some clinicians recommend tapering dosage prior to discontinuing therapy. (See Withdrawal-Emergent Hyperpyrexia and Confusion under Cautions.)

Switching from Entacapone to Opicapone Therapy

Oral

Manufacturer makes no specific recommendations for transitioning patients from entacapone to opicapone.

In clinical studies, patients were permitted to switch from entacapone to opicapone. Patients who were receiving entacapone (200 mg with each levodopa/carbidopa dose) were switched to opicapone 25 mg once daily at bedtime for 1 week, after which opicapone dosage could be increased to 50 mg daily if needed.

Special Populations

Dosage in Hepatic Impairment

Mild hepatic impairment (Child-Pugh class A): No dosage adjustment needed.

Moderate hepatic impairment (Child-Pugh class B): Reduce dosage to 25 mg once daily at bedtime.

Severe hepatic impairment (Child-Pugh class C): Avoid use. (See Hepatic Impairment under Cautions.)

Dosage in Renal Impairment

Mild, moderate, or severe renal impairment (Cl_cr 15–89 mL/minute): No dosage adjustment needed.

End-stage renal disease (Cl_cr <15 mL/minute): Avoid use. (See Renal Impairment under Cautions.)

Geriatric Patients

No dosage adjustment needed.

Cautions for Opicapone

Contraindications

• Concomitant use of nonselective MAO inhibitors. (See MAO Inhibitors under Interactions.)

• History of pheochromocytoma, paraganglioma, or other catecholamine-secreting neoplasms.

Warnings/Precautions

Concomitant Use with Drugs Metabolized by COMT

Concomitant use with certain drugs metabolized by COMT (e.g., dobutamine, dopamine, epinephrine, isoproterenol, norepinephrine) may result in arrhythmias, increased heart rate, and excessive changes in BP regardless of the administration route (including inhalation). (See Interactions.)

Monitor for these effects in patients receiving such concomitant therapy.

Falling Asleep During Daily Activities and Somnolence

Falling asleep during daily activities reported with no preceding warning signs. Cases included falling asleep while operating a motor vehicle, sometimes resulting in accidents.

Prior to initiating therapy, consider other factors that may increase risk of somnolence (e.g. concomitant use of other sedating drugs, presence of a sleep disorder).

If a patient develops daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, driving a motor vehicle), consider adjusting other dopaminergic agents or sedative drugs, or discontinuing opicapone. If opicapone is continued, advise patients to avoid driving and other activities that require full attention.

Hypotension and Syncope

Hypotension (both orthostatic and non-orthostatic), syncope, and presyncope reported.

Monitor for hypotension.

Consider adjusting dosage of other drugs that can lower BP or discontinuing opicapone if these effects occur.

Dyskinesia

May cause dyskinesia or worsen pre-existing dyskinesia.

Consider reducing daily levodopa dose or dose of other dopaminergic drugs to manage dyskinesia.

Hallucinations and Psychosis

Hallucinations (including auditory, visual, and mixed hallucinations) reported.

Consider discontinuing opicapone if hallucinations or other psychotic-like behaviors occur.

Generally should not be used in patients with major psychotic disorders due to risk of exacerbating psychoses.

Impulse Control and Compulsive Disorders

Impulse control disorders, including intense urges (e.g., urges to gamble, uncontrolled spending, binge eating, increased sexual urges) and inability to control these urges may occur. In some cases, urges ceased when opicapone dosage was reduced or the drug discontinued. (See Advice to Patients.)

If such disorders occur, reassess patient’s current antiparkinsonian therapies and consider discontinuing opicapone.

Use opicapone with caution in patients with suspected or confirmed dopamine dysregulation syndrome.

Withdrawal-Emergent Hyperpyrexia and Confusion

Patients undergoing rapid dose reduction, withdrawal of, or changes in drugs that increase central dopaminergic tone can develop a symptom complex resembling neuroleptic malignant syndrome (e.g., elevated temperature, muscle rigidity, altered consciousness, autonomic instability) with no other apparent etiology.

Patients discontinued opicapone without tapering in the pivotal trials; no cases of neuroleptic malignant syndrome were reported. Some clinicians recommend tapering opicapone dosage when discontinuing the drug.

Monitor patients when discontinuing opicapone and consider adjusting other dopaminergic therapies if needed.

Specific Populations

Pregnancy

Insufficient data in pregnant women. Animal data suggest potential for fetal harm (i.e., structural abnormalities).

Lactation

Not known whether opicapone or its metabolites distribute into human milk or if the drug has any effect on milk production or the nursing infant. Opicapone distributes into rat milk at concentrations similar to maternal plasma concentrations.

Consider known benefits of breast-feeding along with potential risks on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

No overall differences in safety or efficacy between geriatric patients ≥65 years of age and younger patients, but increased sensitivity in some older individuals cannot be ruled out.

Increased rates of hallucinations and weight loss reported in patients ≥70 years of age compared with younger patients.

Hepatic Impairment

Opicapone exposure is increased in patients with hepatic impairment. (See Special Populations under Pharmacokinetics.)

Dosage adjustment needed in patients with moderate hepatic impairment (Child-Pugh class B). (See Hepatic Impairment under Dosage and Administration.)

Avoid use in patients with severe hepatic impairment (Child-Pugh class C).

Renal Impairment

Renal elimination has a minor role in the clearance of opicapone. (See Special Populations under Pharmacokinetics.)

Because of potential for increased exposure, monitor for adverse effects and discontinue opicapone if needed in patients with severe renal impairment (Cl_cr 15–30 mL/minute).

Avoid use in patients with end-stage renal disease (Cl_cr <15 mL/minute).

Common Adverse Effects

Dyskinesia, constipation, increased blood creatine kinase, hypotension/syncope, weight loss.

Drug Interactions

Does not inhibit or induce major CYP enzymes. Substrate of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance protein (MRP) 2, and organic anion transport proteins (OATP) 1B3, and OATP2B1.

Does not inhibit P-gp, BCRP, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, OCT2, OATP1B3, bile salt export pump (BSEP), multidrug and toxin extrusion transporter (MATE) 1, or MATE2-K.

Drugs Affecting or Affected by Hepatic Microsomal Enzymes

Did not alter the pharmacokinetics of CYP2C9, CYP1A2, CYP3A4, and CYP2C8 substrates in clinical studies.

Drugs Affecting or Affected by Transport Systems

Interactions not expected with drugs affecting or affected by transport systems. Opicapone did not alter the pharmacokinetics of OATP1B1 substrates in clinical studies.

MAO Inhibitors

Concomitant use with nonselective MAO inhibitors may increase catecholamine concentrations and increase risk of arrhythmias, increased heart rate, and excessive BP. (See Specific Drugs under Interactions.) Concomitant use contraindicated.

Drugs Metabolized by COMT

May alter the pharmacokinetics of drugs metabolized by COMT and cause increased heart rate, arrhythmias, and changes in BP. (See Specific Drugs under Interactions.)

Protein-bound Drugs

In vitro studies indicate that opicapone does not alter protein binding of other highly protein-bound drugs (e.g., warfarin, diazepam, digoxin, tolbutamide).

Specific Drugs

Opicapone Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations attained approximately 2 hours after oral administration.

Dose proportional pharmacokinetics over dose range of 25–50 mg daily.

Food

Administration with a moderate fat/moderate calorie meal decreased peak plasma concentrations by 62%, decreased AUC by 31%, and delayed time to peak concentrations by 4 hours. (See Administration under Dosage and Administration.)

Special Populations

Mild hepatic impairment (Child-Pugh class A): Increased peak plasma concentrations by 34% and AUC by 35%; not considered clinically relevant.

Moderate hepatic impairment (Child-Pugh class B): Increased peak plasma concentrations by 89% and systemic exposure by 84%. (See Hepatic Impairment under Dosage and Administration.)

Severe hepatic impairment (Child-Pugh class C): Effect on pharmacokinetics not known.

Mild or moderate renal impairment (Cl_cr 30–89 mL/minute): Clinically relevant changes in pharmacokinetics not observed in population pharmacokinetic analysis.

Severe renal impairment or end-stage renal disease (Cl_cr <30 mL/minute): Effect on pharmacokinetics not known.

Clinically important differences in pharmacokinetics not observed based on age, sex, and race/ethnicity.

Distribution

Extent

Peripheral distribution only; does not cross blood-brain barrier.

Not known whether opicapone is distributed into human milk.

Plasma Protein Binding

>99%.

Elimination

Metabolism

Metabolized primarily by sulfation in the liver with minor contributions from glucuronidation, methylation by COMT, reduction, and glutathione conjugation.

Elimination Route

Hepatobiliary elimination in feces (approximately 70%; 22% as unchanged drug); also eliminated in expired air (20%) and urine (5%; <1% as unchanged drug).

Half-life

Approximately 1–2 hours.

Stability

Storage

Oral

Capsules

<30°C.

Actions

• Reversibly and selectively inhibits COMT in peripheral tissues.

• Administered with levodopa/carbidopa to inhibit peripheral metabolism of levodopa and increase its elimination half-life and delivery to the brain. When decarboxylation of levodopa is inhibited by carbidopa, COMT becomes the major metabolizing enzyme for levodopa.

• High binding affinity to COMT results in slow complex dissociation rate, which confers a long duration of action despite a relatively short elimination half-life.

• When used as adjunct to levodopa/carbidopa, increased plasma levodopa concentrations are obtained compared with administration of levodopa/carbidopa alone.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling.

• Instruct patients and/or caregivers that opicapone capsules should be taken at bedtime. Inform patients to not eat food for 1 hour before and for at least 1 hour after intake of opicapone.

• Advise patients and/or caregivers that somnolence has been reported with opicapone. Patients treated with dopaminergic medications have reported falling asleep while engaged in activities of daily living. These adverse reactions may affect the ability to drive and operate machinery safely.

• Advise patients that opicapone may cause hypotension or syncope.

• Advise patients that opicapone may cause dyskinesia or exacerbate pre-existing dyskinesia.

• Advise patients that opicapone may cause hallucinations, delusions, or aggressive behavior, and to report any of these adverse reactions to their healthcare provider.

• Importance of asking patients whether they have developed any new or increased gambling urges, sexual urges, or other urges while receiving opicapone and of advising them of the importance of reporting such urges.

• Advise patients to contact their healthcare provider before stopping opicapone, and to inform their clinician if any symptoms such as fever, confusion, or severe muscle stiffness develop after the drug is discontinued.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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