Encapon 200

MECHANISM OF ACTION: Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT).
COMT is responsible for catalyzing O-methylation of levodopa to 3-O-methyldopa.
Concurrent administration of COMT inhibitors with levodopa/carbidopa is directed at enhancing levodopa bioavailability (via blockade of 3-O-methyldopa formation), increasing the amount of levodopa brain penetration (by reducing 3-O-methyldopa plasma levels), increasing the elimination half-life of levodopa, and ultimately prolonging and stabilizing its therapeutic effect in Parkinson's disease.
Entacapone provided comparable benefits in Parkinson's disease patients with wearing-off symptoms using either levodopa/benserazide or levodopa/carbidopa.
Pharmacokinetics: Absorption: Systemic: Bioavailability: 35%; food effects: none.
Distribution: Systemic: Vd: 20 L.
Excretion: Systemic: Fecal: 90%; Renal: 10%, 0.2% unchanged.

Entacapone is indicated as an adjunct to levodopa and carbidopa to treat end-of-dose "wearing-off" in patients with Parkinson disease. The effectiveness in patients with Parkinson disease who do not experience end-of-dose "wearing off" has not been evaluated.

Entacapone should only be used in combination with levodopa/benserazide or levodopa/carbidopa. The prescribing information for these levodopa preparations is applicable to their concomitant use with entacapone.
Parkinson's disease; Adjunct: Adult: Usual dosage: 200 mg orally with each dose of levodopa and carbidopa; reductions in daily levodopa dose or extension of levodopa dosing intervals may be necessary to optimize patient's response.
The maximum recommended dose is 200 mg ten times daily, i.e. 2,000 mg of entacapone.
Entacapone enhances the effects of levodopa. Hence, to reduce levodopa-related dopaminergic adverse reactions, e.g. dyskinesias, nausea, vomiting and hallucinations, it is often necessary to adjust levodopa dosage within the first days to first weeks after initiating entacapone treatment. The daily dose of levodopa should be reduced by about 10 to 30% by extending the dosing intervals and/or by reducing the amount of levodopa per dose, according to the clinical condition of the patient.
Pediatric Dosing: Normal Dosage: General Dosage Information: Safety and efficacy have not been established in pediatric patients.
Renal Impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, renal function was not found to significantly affect the pharmacokinetics of entacapone.

MANAGEMENT OF MILD TO MODERATE TOXICITY: Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea and/or vomiting. Manage mild hypotension with IV fluids.
MANAGEMENT OF SEVERE TOXICITY: Treatment is symptomatic and supportive. Treat hypotension with IV fluids, dopamine, or norepinephrine.
Manage dystonic reactions with anticholinergic agents (diphenhydramine, benztropine) or benzodiazepines.
Antidote: None.

Hypersensitivity to entacapone or any component of the product.

Cardiovascular: Orthostatic hypotension and syncope may occur.
Concomitant Use: Use of non-selective MAOI inhibitors (eg, phenelzine, tranylcypromine) should generally be avoided.
Dermatologic: Increased risk of developing melanoma; monitoring recommended.
Gastrointestinal: Diarrhea and colitis (primarily lymphocytic) have occurred; discontinue use and institute appropriate therapy with prolonged diarrhea.
Musculoskeletal: Severe rhabdomyolysis has been reported.
Neurologic: Falling asleep during activities of daily living, with or without somnolence, has been reported; discontinuation recommended.
Neurologic: Abrupt discontinuation or dose reduction may result in a symptom complex similar to neuroleptic malignant syndrome.
Neurologic: New onset or exacerbation of dyskinesia may occur.
Psychiatric: Compulsive behaviors and impaired impulse control have been reported; monitoring recommended and dose reduction or discontinuation may be necessary.
Psychiatric: New or worsening changes in mental status or behaviour, which may be severe and include psychotic behavior, have been reported.
Psychiatric: Avoid use in patients with major psychotic disorder.
Renal: Retroperitoneal fibrosis has been reported with ergot-derived dopaminergic therapy; may resolve with discontinuation.
Respiratory: Pulmonary fibrosis has occurred with entacapone, and other fibrotic complications (including retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, and pleural thickening) have been reported with ergot-derived dopaminergic therapies; may resolve with discontinuation.
Concurrent levodopa dose may need to be reduced by about 10-30% · ischaemic heart disease.
HEPATIC IMPAIRMENT: Manufacturer advises avoid.
TREATMENT CESSATION: Avoid abrupt withdrawal.

Teratogenicity/Effects in Pregnancy: Available evidence is inconclusive or is inadequate for determining fetal risk when used in pregnant women or women of childbearing potential. Weigh the potential benefits of drug treatment against potential risks before prescribing this drug during pregnancy.
Breastfeeding: Available evidence and/or expert consensus is inconclusive or is inadequate for determining infant risk when used during breastfeeding. Weigh the potential benefits of drug treatment against potential risks before prescribing this drug during breastfeeding.

Common: Gastrointestinal: Abdominal pain (8%), Diarrhea (10%), Nausea (14%), Vomiting (4%), Xerostomia (3%).
Musculoskeletal: Backache (2% to 4%).
Neurologic: Behavior showing reduced motor activity (9%), Dyskinesia (25%), Hyperactive behavior (10%).
Renal: Discolored urine (10%).
Other: Fatigue (6%).
Serious: Cardiovascular: Syncope (1.2%).
Musculoskeletal: Rhabdomyolysis.
Neurologic: Asleep, Sudden onset, Neuroleptic malignant syndrome.
Psychiatric: Hallucinations.

See table.

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Antiparkinsonian Drugs

N04BX02 - entacapone ; Belongs to the class of other dopaminergic agents used in the management of Parkinson's disease.

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