COMT inhibitors for Parkinson's disease


Generic Name Brand Name
entacapone Comtan
entacapone/levodopa/carbidopa Stalevo
tolcapone Tasmar

How It Works

Normally when a person takes a dose of levodopa, only a very small portion of the dose actually enters the brain and is changed into dopamine inside the brain. The rest is absorbed by the body or changed into dopamine outside the brain. (Dopamine cannot pass freely into and out of the brain.)

Catechol O-methyltransferase (COMT) inhibitors allow a larger amount of levodopa to reach the brain, which raises dopamine levels there. They help provide a more stable, constant supply of levodopa, which makes its beneficial effects last longer.

Why It Is Used

COMT inhibitors are used in combination with levodopa to treat people with Parkinson's disease who have:1

  • Times between doses of levodopa where the medicine stops working (called wearing-off).
  • Unpredictable "off" periods. This does not have to happen between doses of levodopa, but can happen anytime.
  • A stable response to levodopa (no “off” periods or wearing-off effect) but want greater relief from their symptoms without increasing their levodopa dosage.
  • Sudden and uncontrollable movements (dyskinesias). COMT inhibitors will allow the dose of levodopa to be decreased, which can reduce the severity of dyskinesias.

Doctors are also now starting to prescribe entacapone and levodopa more often at the beginning of drug therapy.

Note: The use of tolcapone (Tasmar) has been limited to only those situations in which all other treatment options have failed. Tolcapone has been linked to several cases of fatal liver failure. By law, a doctor must obtain formal informed consent from the patient before prescribing this medicine. A person taking tolcapone will have frequent blood tests to monitor liver function.

This warning and legal requirement does not apply to entacapone (Comtan) or Stalevo. They are considered very safe drugs and have not been associated with liver failure or other life-threatening conditions.

How Well It Works

COMT inhibitors are helpful to many people with Parkinson's disease. Treatment with tolcapone or entacapone can:1

  • Increase “on” time and decrease “off” time by 1 to 2 hours each per day.
  • Reduce motor fluctuations caused by the wearing-off effect of levodopa.
  • Improve motor function and the ability to do daily activities without increasing the dosage of levodopa in people taking levodopa who have not developed dose-related motor fluctuations. The levodopa dosage usually can be decreased without giving up any control over symptoms because the COMT inhibitor makes a larger portion of the levodopa dosage available to the brain.

A combination medicine (Stalevo) is available that combines entacapone, levodopa, and carbidopa. This may be more convenient for some people because they would need to take only one pill instead of two.2

Side Effects

Side effects of tolcapone and entacapone include:

  • Diarrhea (the most common side effect).
  • Bright yellow or orange urine.
  • Headache.
  • Abdominal pain.

By increasing the amount of levodopa that reaches the brain, a COMT inhibitor also may increase some of the side effects associated with levodopa use. The levodopa dosage usually can be decreased once the person begins taking a COMT inhibitor. If the dosage is not decreased, certain side effects may get worse, such as:

  • Jerky, involuntary movements (dyskinesias).
  • Low blood pressure when the person stands up (orthostatic hypotension).
  • Fainting.
  • Nausea.
  • Sleep disorders.
  • Loss of appetite.
  • Hallucinations (seeing or hearing things that aren't really there).

Several cases of fatal liver failure have been associated with tolcapone use. Liver monitoring every 2 weeks for the first year and every 2 months after the first year is required for anyone who takes tolcapone. Liver failure has not been associated with entacapone.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

Entacapone (Comtan) is a safe medicine; blood tests are not required for people using it.

Tolcapone (Tasmar) has been associated with several cases of fatal liver failure. Before beginning treatment with tolcapone, you must sign an informed consent form and agree to have your liver function monitored with regular (once every 2 weeks) blood tests during the first year of treatment. These measures are legally required by the U.S. Food and Drug Administration (FDA).

Complete the new medication information form (PDF)(What is a PDF document?) to help you understand this medication.



  1. Poewe W (2004). The role of COMT inhibition in the treatment of Parkinson's disease. Neurology, 62(1, Suppl 1): S31–S38.
  2. Stalevo for Parkinson's disease. (2004). Medical Letter on Drugs and Therapeutics, 46(1182): 39–40.

Last Updated: December 8, 2008

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