Entacapone

Entacapone is a prescription drug used to treat Parkinson Disease in combination with the standard levodopa/carbidopa therapy. The symptoms of Parkinson disease are caused by degeneration of neurons that release the neurotransmitter dopamine, resulting in insufficient levels. Neurotransmitters are chemicals that carry messages from one neuron to another, or from a neuron to a muscle. Levodopa is used to supplement dopamine levels in the brain. Entacapone increases the amount of levodopa entering the brain by preventing its deactivation by an enzyme called catechol-O-methyltransferase (COMT). Another COMT inhibitor used to treat Parkinson disease is tolcapone (Tasmar). The Food and Drug Administration approved entacapone in October 1999.

Two schematic drawings of sections of the human brain. Parkinson disease is caused by a degeneration of neurons in the basal ganglia (colored areas in the drawings)that release dopamine. The goal of treatment is to supplement dopamine in the brain. The areas that make up the basal ganglia include striatum (blue), globus pallidus (green), subthalamic nucleus (yellow), substantia nigra (red). The right section is the deeper one, closer to the back of the head. Source: Wikimedia Commons

Other Names

Entacapone is marketed as Comtan by Novartis.

Uses

Entacapone is indicated to treat people with Parkinson disease taking the standard levodopa/carbidopa therapy who experience end-of-dose “wearing-off” symptoms. “Wearing off” symptoms occur approximately one to two hours after taking levodopa as its concentration in the brain decreases. The symptoms include a return of the rigidity and immobility associated with the disease.

How Entacapone is Taken

Entacapone is available in 200-mg oral tablets. The recommended dose is 200 mg taken concurrently with each levodopa/carbidopa dose up to a maximum of eight times daily.

How Entacapone Works

Levodopa is the standard treatment of Parkinson disease. It is converted into dopamine in the body. However, enzymes outside the central nervous system (brain and spinal cord) convert the majority of levodopa into dopamine before it can enter the brain. This drastically limits levodopa passage into the brain. Carbidopa in conjunction with levodopa increases the amount of levodopa entering the brain. The levodopa/carbidopa combination is effective in early-stage Parkinson disease, but the disease progresses and eventually the combination becomes less effective.

In later stages of Parkinson disease the “wearing off” symptoms of rigidity and immobility appear despite treatment with levodopa/carbidopa. These symptoms appear because the concentration of dopamine (from levodopa) fluctuate. The concentration of levodopa can be increased to compensate, but often this causes uncontrolled, jerky, and sometimes painful limb movements (dyskinesias).

COMT is an enzyme that transfers a molecule (called methyl) to levodopa, thus limiting its ability to cross into the brain. Entacapone inhibits COMT and increases the amount of levodopa available to the brain. When entacapone is given in combination with levodopa/carbidopa, circulating levels of levodopa are increased and sustained. As a result, dopamine’s effects in the brain are elevated and the symptoms of Parkinson disease are reduced.

How the Body Affects Entacapone

Entacapone is rapidly absorbed, reaching peak circulating levels in approximately one hour. It is extensively metabolized and approximately 90% is excreted in the feces.

Side Effects

The most common side effects of entacapone, occurring in more than 5% of patients, include the following:

• Dyskinesia/hyperkinesia (abnormal muscular activity)
• Nausea
• Urine discoloration
• Diarrhea
• Abdominal pain
• Confusion
• Hallucinations

Risks and Precautions

Entacapone could hinder daily activities, such as driving a car, or performance of some jobs, such as operating heavy machinery, because the drug may cause drowsiness. However, not everyone experiences these effects.

Drug Interactions

Since entacapone inhibits COMT, it could elevate blood concentrations of other drugs that are metabolized by the enzyme. Some drugs metabolized by COMT include the following:

• Norepinephrine (noradrenaline)
• Epinephrine (adrenaline)
• Dopamine
• Dobutamine (Dobutrex)
• Alpha-methyldopa
• Apomorphine (Apokyn)
• Bitolterol (Tornalate)

Entacapone is contraindicated in people taking nonselective MAO inhibitors, such as paragyline and nialamide.

Alternatives

Entacapone is available with levodopa and carbidopa in a formulation called Stalevo.

Tolcapone is another COMT inhibitor available to treat Parkinson disease. It has a longer duration of action than does entacapone but has also been associated with liver damage in some people.

Research

One study of over 170 patients demonstrated that entacapone provided additional anti-Parkinsonian benefits to levodopa-treated patients with Parkinson disease experiencing "wearing-off" despite treatment with drugs that enhance dopamine levels.^[1] The benefits included a reduction in the dose of medications and improvements in symptoms.

References

1. ↑ Fénelon G, Giménez-Roldán S, Montastruc JL, et al. Efficacy and tolerability of entacapone in patients with Parkinson's disease treated with levodopa plus a dopamine agonist and experiencing wearing-off motor fluctuations. A randomized, double-blind, multicentre study. J Neural Transm. 2003 Mar;110(3):239-51. Abstract

External Links

FDA: Patient Information Sheet