catechol o methyltransferase comt inhibitors
Parkinson's disease in patients experiencing "off" episodes (as adjunctive therapy to levodopa/carbidopa).
Acts as a selective and reversible inhibitor of the enzyme, catechol-O-methyltransferase (COMT), which prevents the metabolism of levodopa, increasing its availability to the CNS.
Reduction in "off" episodes.
Absorption: Moderate fat/calorie meal delays and reduces extent of absorption.
Protein Binding: >99%.
Metabolism and Excretion: Primarily metabolized via sulfation, and to a lesser extent by glucuronidation, methylation, reduction, and glutathione conjugation; primarily excreted in feces (77%; 22% as unchanged drug), with 20% in expired air, and 5% in urine (<1% as unchanged drug).
Half-life: 1–2 hr.
TIME/ACTION PROFILE (plasma concentrations)
- Concurrent use of nonselective MAO inhibitors;
- Pheochromocytoma, paraganglioma, or other catecholamine secreting neoplasms
- Major psychotic disorders
- End-stage renal disease (CCr <15 mL/min)
- Severe hepatic impairment.
Use Cautiously in:
- Severe renal impairment
- Moderate hepatic impairment (↓ dose)
- OB: Safety not established in pregnancy;
- Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
- Pedi: Safety and effectiveness not established in children;
- Geri: Older adults may have ↑ risk of adverse reactions.
Adverse Reactions/Side Effects
CV: hypertension, hypotension, presyncope, syncope
GI: constipation, dry mouth
Metabolic: ↓ weight
MS: ↑ creatine kinase
Neuro: dyskinesia, aggressive behavior, agitation, delusions, dizziness, hallucinations, impulse control disorders (gambling, sexual, uncontrolled spending, binge/compulsive eating), insomnia, psychosis, somnolence
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Nonselective MAO inhibitors, including isocarboxazid, phenelzine, or tranylcypromine may significantly ↑ risk of arrhythmias, tachycardia, and ↑ BP; concurrent use contraindicated (can concomitantly use selective MAO-B inhibitors with opicapone).
- Concurrent use of drugs that are metabolized by COMT, including dopamine, dobutamine, epinephrine, isoproterenol, and norepinephrine, may ↑ risk of arrhythmias, tachycardia, and ↑ BP; closely monitor.
PO (Adults): 50 mg once daily at bedtime.
PO (Adults): Moderate hepatic impairment– 25 mg once daily at bedtime.
Capsules: 25 mg, 50 mg
- Assess patient for signs and symptoms of Parkinson's disease (tremor, muscle weakness and rigidity, ataxic gait) prior to and throughout therapy. Opicapone may cause or exacerbate pre-existing dyskinesia. May require reduction in dose of levodopa or other dopaminergic drugs.
- Assess BP periodically during therapy.
- PO Administer once daily at bedtime on an empty stomach. Avoid eating for 1 hr before and at least 1 hr after dose.
- Instruct patient to take opicapone as directed on an empty stomach. Omit missed doses and take next scheduled dose next day. Caution patient not to discontinue opicapone without consulting health care professional. Abrupt discontinuation or rapid dose reduction may result in neuroleptic malignant syndrome (fever, muscular rigidity, altered consciousness, autonomic instability). Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
- Caution patient to make position changes slowly to minimize orthostatic hypotension, especially at start of therapy. Notify health care professional if orthostatic hypotension occurs.
- May cause sudden onset of sleep, drowsiness, or dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Advise patient to avoid taking alcohol or other CNS depressants concurrently with opicapone.
- Inform patient and caregiver that hallucinations, nausea, dyskinesia, or dystonia may occur during opicapone therapy. Notify health care professional if hallucinations occur; may need to discontinue therapy.
- Advise patient to notify health care professional if new or increased gambling, sexual, or other intense urges or hallucinations occur. Dose reduction may be required.
- Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Reduction in "off" episodes.