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Entacapone (INN) ( or ) is a drug commonly used in combination with other medications for the treatment of Parkinson's disease. It is known as a selective and reversible inhibitor of the catechol-O-methyltransferase (COMT) enzyme. When taken together with levodopa (L-DOPA) and carbidopa, entacapone stops the catechol-O-methyltransferase enzyme from breaking down and metabolizing levodopa, resulting in an overall increase of levodopa remaining in the brain and body.

Entacapone together with levodopa and carbidopa allows levodopa to have a longer effect in the brain and reduces Parkinson’s disease signs and symptoms for a greater length of time than levodopa and carbidopa therapy alone.

Entacapone is developed by Orion Pharma and marketed by Novartis under the trade name Comtan. Stalevo, another medication developed by Orion Pharma and marketed by Novartis, is a single tablet formulation that contains levodopa, carbidopa, and entacapone.

Medical use
Entacapone is used as adjunct therapy with levodopa and carbidopa for people with Parkinson's disease to treat the signs and symptoms of end-of-dose “wearing-off." “Wearing-off” is characterized by the re-appearance of both motor and non-motor symptoms of Parkinson’s disease occurring towards the end of a previous levodopa and carbidopa dose.

Entacapone is an orally active drug that can be taken with or without food.

A doctor’s prescription is required to use entacapone. Potential limiting conditions to consider before starting entacapone include: Entacapone does not cure Parkinson’s disease.
 * History of allergic reaction to entacapone
 * History of liver disease, liver dysfunction, or alcoholism
 * Current or planned pregnancy
 * Current or planned surgeries

Adverse effects
The following adverse effects have been reported by people with Parkinson's disease treated with entacapone:

Dyskinesia
Entacapone may cause or worsen dyskinesia for people with Parkinson's disease treated together with levodopa and carbidopa. In particular, “peak-dose dyskinesias” may occur when levodopa levels are at its peak concentration in the serum plasma.

Sudden sleep onset
People have reported sudden sleep onset while engaging in daily activities without prior warning of drowsiness. In controlled studies, patients on entacapone had a 2.0% increased risk of somnolence compared to placebo.

Orthostatic hypotension and syncope
Episodes of hypotension have been shown to be more common at the start of entacapone use.

Hallucinations and psychotic-like behavior
Post-marketing data shows that entacapone may change or worsen mental status, leading to behaviors such as delusions, agitation, confusion, and delirium.

Compulsive behavior
People using entacapone may experience increased urges to participate in gambling, sexual activities, money spending, and other stimulating reward behaviors.

Diarrhea
Diarrhea may occur within 4-12 weeks of initial entacapone use but resolves after discontinuation of the drug. Use of entacapone in the presence of diarrhea can also be associated with weight loss, low potassium levels, and dehydration. In clinical studies, severe diarrhea was the most common reason for discontinuation of entacapone.

Urine discoloration
A common side-effect due to entacapone's metabolites which cause a person's urine to turn orange, red, brown, or black in color.

Contraindications
There is a high risk for allergic reactions for people who are hypersensitive to entacapone.

Mechanism of action
Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). COMT eliminates biologically active catechols present in catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. When administered with a decarboxylase inhibitor, COMT acts as the major metabolizing enzyme for levodopa and metabolizes it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and in the periphery.

For the treatment of Parkinson’s disease, entacapone is given as an adjunct to levodopa and an aromatic amino acid decarboxylase inhibitor, carbidopa. Entacapone inhibits COMT and the metabolism of levodopa, thus increasing plasma levels of levodopa and causing more constant dopaminergic stimulation in order to reduce the signs and symptoms presented in the disease.

Absorption
The transport maximum (Tmax) is approximately 1 hour. Absolute oral bioavailability (F) is 35.0%.

Distribution
The volume of distribution (VD) after intravenous injection approximately 20.0 liters. Entacapone has high binding activity to serum albumin that limits its distribution into tissues.

Metabolism and Elimination
Entacapone has a half-life of approximately 0.3-0.7 hours. It is primarily metabolized by the liver with 0.2% of the medication unchanged in urine.

Pregnancy and Breastfeeding
Pregnancy Category C: risk is not ruled out. Although there have been animal studies that showed that entacapone was excreted into maternal rat milk, there have been no studies with human breast milk. Mothers should speak with their physician before using entacapone while breastfeeding or during pregnancy.

Pediatrics
Entacapone safety and efficacy have not been assessed in infants or children.

Liver Impairment
Biliary excretion is the major route of excretion for entacapone. Entacapone may require additional caution when given to people with liver dysfunction. Kidney Impairment No clinically significant considerations for people with poor kidney function.