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
Opicapone is a catechol-O-methyltransferase (COMT) inhibitor.
Uses for Opicapone
Opicapone has the following uses:
Opicapone is a catechol-O-methyltransferase (COMT) inhibitor indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease (PD) experiencing “off” episodes.
Opicapone Dosage and Administration
Opicapone is available in the following dosage form(s) and strength(s):
Capsules: 25 mg and 50 mg.
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Dosage and Administration
The recommended dosage is 50 mg administered orally once daily at bedtime.
Patients should not eat food for 1 hour before and for at least 1 hour after intake of opicapone.
The recommended dosage in patients with moderate hepatic impairment is 25 mg orally once daily at bedtime; avoid use in patients with severe hepatic impairment.
Cautions for Opicapone
Concomitant use of non-selective monoamine oxidase (MAO) inhibitors.
History of pheochromocytoma, paraganglioma, or other catecholamine secreting neoplasms.
Cardiovascular Effects with Concomitant Use of Drugs Metabolized by Catechol-O-methyltransferase (COMT)
Possible arrhythmias, increased heart rate, and excessive changes in blood pressure may occur with concomitant use of opicapone and drugs metabolized by COMT (e.g., isoproterenol, epinephrine, norepinephrine, dopamine, and dobutamine), regardless of the route of administration (including inhalation). Monitor patients treated concomitantly with opicapone and drugs metabolized by COMT).
Falling Asleep During Activities of Daily Living and Somnolence
Patients treated with dopaminergic medications and medications that increase levodopa exposure, including opicapone, have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes has resulted in accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event.
Before initiating treatment with opicapone, advise patients of the potential to develop drowsiness and specifically ask about factors that may increase the risk for somnolence with dopaminergic therapy, such as concomitant sedating medications or the presence of a sleep disorder. If a patient develops daytime sleepiness or episodes of falling asleep during activities that require full attention (e.g., driving a motor vehicle, conversations, eating), consider discontinuing opicapone or adjusting other dopaminergic or sedating medications. If a decision is made to continue opicapone, patients should be advised not to drive and to avoid other potentially dangerous activities.
In Study 1 and Study 2, hypotension (orthostatic and non-orthostatic), syncope, and presyncope occurred in 5% of patients treated with opicapone 50 mg compared to 1% of patients who received placebo. Monitor patients for hypotension (orthostatic and non-orthostatic) and advise patients about the risk for syncope and presyncope. If these adverse reactions occur, consider discontinuing opicapone or adjusting the dosage of other medications that can lower blood pressure.
Opicapone potentiates the effects of levodopa and may cause dyskinesia or exacerbate pre-existing dyskinesia.
In controlled clinical trials (Study 1 and Study 2), dyskinesia occurred in 20% of patients treated with opicapone 50 mg compared to 6% of patients who received placebo. Dyskinesia was also the most common adverse reaction leading to discontinuation of opicapone.
Reducing the patient’s daily levodopa dosage or the dosage of another dopaminergic drug may mitigate dyskinesia that occurs during treatment with opicapone.
Hallucinations and Psychosis
In Study 1 and Study 2, hallucinations (hallucinations, auditory hallucinations, visual hallucinations, mixed hallucinations) occurred in 3% of patients treated with opicapone 50 mg compared to 1% of patients who received placebo. Delusions, agitation, or aggressive behavior occurred in 1% of patients treated with opicapone 50 mg, and in no patient who received placebo. Consider stopping opicapone if hallucinations or psychotic-like behaviors occur.
Patients with a major psychotic disorder should ordinarily not be treated with opicapone because of the risk of exacerbating the psychosis with an increase in central dopaminergic tone. In addition, treatments for psychosis that antagonize the effects of dopaminergic medications may exacerbate the symptoms of PD.
Impulse Control/Compulsive Disorders
Patients treated with opicapone can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges while taking one or more dopaminergic therapies that increase central dopaminergic tone. In some cases, these urges were reported to have stopped when the dose was reduced, or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending, or other urges while being treated with opicapone.
In Study 1 and Study 2, impulse control disorders occurred in 1% of patients treated with opicapone 50 mg, and in no patient who received placebo. Re-evaluate the patient’s current therapy(ies) for Parkinson’s disease and consider stopping opicapone if a patient develops such urges while taking opicapone.
Use with caution in Parkinson’s patients with suspected or diagnosed dopamine dysregulation syndrome.
Withdrawal-Emergent Hyperpyrexia and Confusion
A symptom complex resembling neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in drugs that increase central dopaminergic tone. In the controlled clinical studies of opicapone, patients discontinued opicapone treatment without dose tapering or gradual withdrawal. There were no reports of neuroleptic malignant syndrome in opicapone controlled clinical studies. When discontinuing opicapone, monitor patients and consider adjustment of other dopaminergic therapies as needed.
Risk Summary: There are no adequate data on the developmental risk associated with use of opicapone in pregnant women. In animal studies, oral administration of opicapone during pregnancy resulted in adverse effects on embryofetal development (increased incidence of fetal abnormalities) at clinically relevant plasma exposures in one of two species tested. In addition, opicapone is always given concomitantly with levodopa/carbidopa, which is known to cause developmental toxicity in rabbits.
The background risk of major birth defects and miscarriage in the U.S. general population is 2-4% and 15-20% of clinically recognized pregnancies, respectively. The background risk for major birth defects and miscarriage in patients with Parkinson’s disease is unknown.
Animal Data: Oral administration of opicapone (0, 150, 375, or 1000 mg/kg/day) to pregnant rats throughout gestation resulted in no adverse effects on embryofetal development. Plasma exposure (AUC) at the highest dose tested (1000 mg/kg/day) was approximately 40 times that in humans at the recommended human dose (RHD) (50 mg/day).
In pregnant rabbits, oral administration of opicapone (0, 100, 175, or 225 mg/kg/day) during the period of organogenesis resulted in increased incidence of structural abnormalities at all doses tested; maternal toxicity was observed at all but the lowest dose tested. A no-effect dose for adverse effects on embryofetal development was not identified. Plasma exposure (AUC) at the low-effect dose (100 mg/kg/day) was less than that in humans at the RHD.
Oral administration of opicapone (0, 150, 375, or 1000 mg/kg/day) throughout gestation and lactation resulted in no adverse effects on pre- and postnatal development; however, effects on neurobehavioral development in the offspring were not rigorously assessed. Plasma exposure (AUC) at the highest dose tested (1000 mg/kg/day) was approximately 40 times that in humans at the RHD.
Opicapone is always given concomitantly with levodopa/carbidopa, which is known to cause visceral and skeletal malformations in rabbits. The developmental toxicity of opicapone in combination with levodopa/carbidopa was not assessed in animals.
Risk Summary: There are no data on the presence of opicapone in human milk, the effects on the breastfed infant, or the effects on milk production. In lactating rats, oral administration of opicapone resulted in levels of opicapone or metabolites in milk similar to those in maternal plasma. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for opicapone and any potential adverse effects on the breastfed infant from opicapone or from the underlying maternal condition.
Safety and effectiveness in pediatric patients have not been established.
No dose adjustment is required for elderly patients. Of the total number of patients who received opicapone 50 mg in Study 1 and Study 2, 52% of patients were 65 years and older. No overall differences in safety and effectiveness were observed between these patients and younger patients, but greater sensitivity to adverse reactions of some older individuals cannot be ruled out.
The renal route of elimination plays a minor role in the clearance of opicapone. Avoid use of opicapone in patients with end-stage renal disease (ESRD) (CLcr <15 mL/min). No dosage adjustment is required for patients with mild, moderate, or severe renal impairment. However, because of a potential for increased exposure, monitor patients with severe renal impairment for adverse reactions and discontinue opicapone if tolerability issues arise.
Opicapone exposure is increased in patients with hepatic impairment. Avoid use of opicapone in patients with severe (Child-Pugh C) hepatic impairment. Dosage adjustment is recommended for patients with moderate (Child-Pugh B) hepatic impairment. No dosage adjustment is required in patients with mild (Child-Pugh A) hepatic impairment.
Common Adverse Effects
Most common adverse reactions (≥4% and > placebo): dyskinesia, constipation, blood creatine kinase increased, hypotension/syncope, and weight decreased.
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Please see product labeling for drug interaction information.
Mechanism of Action
Opicapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT).
COMT catalyzes the transfer of the methyl group of S-adenosyl-l-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include DOPA, catecholamines (dopamine, norepinephrine, and epinephrine), and their hydroxylated metabolites. When decarboxylation of levodopa is prevented by carbidopa, COMT becomes the major metabolizing enzyme for levodopa, catalyzing its metabolism to 3-methoxy-4-hydroxy-l-phenylalanine (3-OMD).
Advice to Patients
Patient Counseling Information
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.
Certain medications can cause an interaction with opicapone. Advise patients and/or caregivers to inform their healthcare provider of all the medicines the patient is taking, including over-the-counter medicines, dietary supplements, and herbal products.
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 some patients’ 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 they should report any of these adverse reactions to their healthcare provider.
Inform patients of the potential for experiencing intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and other intense urges and the inability to control these urges while taking opicapone and one or more medications that increase central dopaminergic tone that are generally used for the treatment of PD. Advise patients that they should report any of these adverse reactions to their healthcare provider.
Advise patients to contact their healthcare provider before stopping opicapone. Tell patients to inform their healthcare provider if they develop symptoms such as fever, confusion, or severe muscle stiffness after stopping opicapone.
For further information on opicapone, call 1-833-ONGENTYS (833-664-3689) or visit www.ongentys.com.
AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
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.
Neurocrine Biosciences Inc.
Neurocrine Biosciences Inc.
AHFS Drug Information. © Copyright 2021, Selected Revisions May 25, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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