Comtan (entacapone) is a therapy to treat the motor symptoms experienced by Parkinson’s disease patients, produced by Orion and marketed by Novartis in the U.S.

Outside of the U.S. Comtan is marketed as Comtess.

How Comtan works

Parkinson’s disease results in a progressive loss of control in movement, along with various other non-motor symptoms. This is caused by the death of nerve cells in the brain that produce a chemical called dopamine. Dopamine is a messenger that sends signals between brain cells and is essential for the correct coordination of movement.

Comtan is a catechol-O-methyltransferase (COMT) inhibitor. COMT is an enzyme (a biological catalyst that triggers particular reactions) that normally breaks down excess dopamine in the brain. As Parkinson’s disease patients have a reduction in dopamine, blocking the action of this enzyme can result in dopamine levels to increase.

Comtan is normally taken alongside a levodopa treatment. Levodopa is a substance that the body can convert into dopamine. It is generally the first line of treatment in Parkinson’s disease once the symptoms worsen. However, extended use of high doses of levodopa results in adverse side effects such as dyskinesia (involuntary movements) and motor fluctuations meaning that the patient experiences “off” periods when the symptoms of Parkinson’s disease such as tremor start to come back long before another dose of levodopa can be taken.

Comtan can be prescribed initially instead of increased the dose of levodopa, therefore extending the period of time until levodopa-induced side effects occur. It can also be used to reduce the level of motor fluctuations the patient experiences.

Comtan in clinical trials

Comtan was approved by the U.S. Food and Drug Administration (FDA) in October 1999. The safety and efficacy of the drug were confirmed through three randomized, double-blind, placebo-controlled trials, which led to its approval.

In two studies (one in North America and one in Nordic countries), Comtan was specifically assessed for its ability to reduce the level of motor fluctuations (“off” periods). Over 24 weeks, patients who had documented levodopa-induced motor fluctuations were prescribed either 200 mg of Comtan or a placebo alongside levodopa treatment.

Both studies showed a significant increase in the amount of “on” hours (when they can function relatively well with fewer symptoms) in the Comtan group compared to the placebo group. In the Nordic group there was an increase of 1.5 hours (compared to 0.1 hours in the placebo), and an increase of 1 hour (compared to 0.4 hours in the placebo) in the North American group. There was also a significant improvement in Unified Parkinson’s Disease Rating Scale (UPDRS) scores, which assesses the change in the general movement ability of the patients and the ability to perform “activities of daily life” such as dressing and walking.

A third study, in Germany and Austria, assessed a range of patients with or without motor fluctuations. A similar significant and positive impact on UPDRS scores was observed compared to the placebo.

Other information

Abruptly ending Comtan treatment can result in withdrawal symptoms where motor fluctuations became much worse than before.

The most common side effects experienced by patients taking Comtan are dyskinesia (involuntary movements), urine discoloration, diarrhea, nausea, muscle spasms, abdominal pain, vomiting, and dry mouth.

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