Ongentys (opicapone)

No dosing information is available for this tab.

Opicapone is administered orally once daily at bedtime.

Because presence of food in the GI tract may decrease exposure of opicapone, patients should not consume any food for 1 hour before and for at least 1 hour after taking the drug. (See Description.)

If a dose of opicapone is missed, the next dose should be taken at the usually scheduled time the next day.

No dosing information is available for this tab.

Opicapone does not inhibit nor induce major cytochrome P-450 (CYP) isoenzymes.

Opicapone is a 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. The drug 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.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Comt Inhibitors/Selected Maois

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Since MAOI's and COMT are the two major enzymes responsible for the metabolism of catecholamines, the combination of entacapone, tolcapone, or opicapone and a non-selective MAOI may inhibit the majority of catecholamine metabolism pathways.(1-3)

CLINICAL EFFECTS: Concurrent administration of entacapone, tolcapone, or opicapone with a non-selective MAOI may result in elevated levels of catecholamines, which may result in elevated heart rate and blood pressure.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The Canadian(4) and UK(1) manufacturers of entacapone state that concomitant use of either a non-selective MAOI or a selective MAO-A inhibitor with a selective MAO-B inhibitor with entacapone is contraindicated. Nonselective MAOI should be discontinued at least 2 weeks prior to initiating entacapone therapy.(4) The UK manufacturer of tolcapone states that tolcapone should not be coadministered with either a non-selective MAOI or a selective MAO-A inhibitor with a selective MAO-B inhibitor. (5) The US manufacturer of tolcapone states that patients should not ordinarily be treated concomitantly with tolcapone and a non-selective MAOI. Tolcapone may be concurrently administered with a selective MAO-B inhibitor.(2) The Middle East and US manufacturers of opicapone state that concomitant use of opicapone with MAO inhibitors other than those for the treatment of Parkinson's disease is contraindicated.(10,11)

DISCUSSION: Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the two major enzymes systems involved in the metabolism of catecholamines. Therefore, theoretically, the combination of either entacapone, tolcapone, or opicapone with a non-selective MAO inhibitor will result in inhibition of the majority of catecholamine metabolism pathways.(1,2) At daily oral doses of 10 mg, selegiline is primarily a selective MAO-B inhibitor; however, at higher doses, selegiline is capable of inhibiting MAO-A.(6) At dosages administered transdermally for the treatment of depression, selegiline is not selective for MAO-B.(7) Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(8,9) Metaxalone is a weak inhibitor of MAO.(12,13)

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Comt Inhibitors/Rasagiline; Oral Selegiline

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Since MAOIs and COMT are the two major enzymes responsible for the metabolism of catecholamines, the combination of entacapone, tolcapone, or opicapone and a non-selective MAOI may inhibit the majority of catecholamine metabolism pathways.(1-3)

CLINICAL EFFECTS: Concurrent administration of entacapone, tolcapone, or opicapone with a non-selective MAOI may result in elevated levels of catecholamines, which may result in elevated heart rate and blood pressure.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Entacapone(1,4), tolcapone(5), and opicapone(9,10) should not be used with either a non-selective MAOI or the combination of a selective MAO-A inhibitor and a selective MAO-B inhibitor. Nonselective MAOIs should be discontinued at least 2 weeks prior to initiating COMT inhibitor therapy. Entacapone, tolcapone, or opicapone may be used with oral selegiline, provided that the daily dose of selegiline does not exceed 10 mg, and with rasagiline, provided that the daily dose of rasagiline does not exceed 1 mg, and that patients are not also receiving a selective MAO-A inhibitor.

DISCUSSION: Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the two major enzymes systems involved in the metabolism of catecholamines. Therefore, theoretically, the combination of either entacapone or tolcapone with a non-selective MAO inhibitor will result in inhibition of the majority of catecholamine metabolism pathways.(1,2) Rasagiline is selective for MAO-B in humans at recommended dosages of 1 mg per day or less.(6) Rasagiline has been used with entacapone in clinical trials with no reports of adverse effects.(6) Concurrent administration of rasagiline and entacapone increased rasagiline oral clearance by 28%.(7) At daily doses of 10 mg, selegiline is primarily a selective MAO-B inhibitor; however, at higher doses, selegiline is capable of inhibiting MAO-A.(8)

Entacapone; Opicapone/Comt-Metabolized Agents

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Entacapone and opicapone are selective and reversible inhibitors of catechol-O-methyltransferase (COMT) and drugs that are metabolized by COMT can not be fully metabolized when given with entacapone or opicapone.(1)

CLINICAL EFFECTS: COMT-metabolized agents can interact with entacapone or opicapone and may result in an increased heart rates, arrhythmias, or an excessive change in blood pressure.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturers of entacapone and opicapone recommend using caution when administering entacapone or opicapone and a COMT-metabolized agent regardless of the route of administration (including inhalation).(1-3)

DISCUSSION: In an interaction study, ventricular tachycardia was observed after epinephrine and entacapone administration.(1) Another study on the effect of entacapone given with isoproterenol and epinephrine concluded that entacapone may potentiate the chronotropic and arrhythmogenic effects of isoproterenol and epinephrine.(4)

*Concomitant use of nonselective monoamine oxidase (MAO) inhibitors. (See MAO Inhibitors under Drug Interactions.)

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

• Paraganglioma
• Pheochromocytoma

• Child-pugh class B hepatic impairment

• Hypotension

Adverse effects reported in 4% or more of patients receiving opicapone in clinical studies and at a frequency greater than placebo include dyskinesia, constipation, increased blood creatine kinase, hypotension/syncope, and weight loss.

More Frequent

• Hypotension

Less Frequent

• Hallucinations
• Hypertension
• Orthostatic hypotension

More Frequent

• Constipation
• Dyskinesia
• Syncope
• Weight loss

Less Frequent

• Aggressive behavior
• Agitation
• Delusional disorder
• Impulse control disorder
• Increased creatine kinase level
• Insomnia
• Xerostomia

Rare or Very Rare

• Accidental fall
• Acute cognitive impairment
• Dizziness
• Sudden onset of sleep

No enhanced messaging available.

The safety and efficacy of opicapone have not been established in pediatric patients.

There are no adequate data on the developmental risk associated with use of opicapone in pregnant women. However, there is a possibility of fetal risk based on animal studies. Animal data showed some evidence of adverse embryofetal development at clinically relevant plasma concentrations. Structural abnormalities were seen when opicapone was administered to pregnant rabbits during organogenesis.

It is not known whether opicapone distributes into human milk or whether the drug has any effects on the breast-fed infant or on milk production. Opicapone distributes into milk in rats at concentrations similar to those in maternal plasma.

The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for opicapone, and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition .

The manufacturer states that dosage adjustment is not necessary in geriatric patients.

Among patients who received opicapone 50 mg daily in the principal efficacy studies, 52% were 65 years of age and older. No overall differences in safety or efficacy were identified between these geriatric patients and younger patients, but increased sensitivity in some older individuals cannot be ruled out. A subgroup analysis of these studies found that rates of hallucinations and weight loss were more common in patients 70 years of age and older compared with younger patients.