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COMT Inhibitors

What Are the Facts?

  • COMT inhibitors are only effective when used in combination with levodopa.
  • When a person takes levodopa, an enzyme in the body call catechol-O-methyl transerase (COMT) converts a portion of the levodopa into a form that is useless.
  • COMT inhibitors block the COMT enzyme from converting levodopa into a useless form, thus making more levodopa in the brain available and helping to reduce PD symptoms.
  • There are two COMT inhibitors on the market: Entacapone (Comtan®) and Tolcapone (Tasmar®).
  • Entacapone is prescribed with each dose of levodopa, whereas tolcapone is taken three times a day, no matter how many doses of levodopa are prescribed.
  • Due to earlier instances of liver function abnormalities during clinical trials of tolcapone, the FDA mandates that blood tests of liver function be conducted at the beginning of the treatment and, every 6 months after beginning treatment.
  • There is also a medication called Stalevo®, which is a combination of carbidopa, levodopa and entacapone. It is useful in people with advanced PD who experience motor fluctuations.
  • The U.S. Food and Drug Administration (FDA) is evaluating clinical trial data that may suggest that patients taking Stalevo for PD may be at an increased risk for developing prostate cancer. One trial showed higher incidence of prostate cancer, another apparently did not. More data from these trials is needed to reach a conclusion. FDA's review of Stalevo is ongoing and no new recommendations about the use of this drug have been made. For more information, read the FDA Safety Announcement (3/31/2010).
  • The U.S. Food and Drug Administration (FDA) is evaluating clinical trial data that may suggest that patients taking Stalevo for PD may be at an increased risk for cardiovascular events. The FDA has not concluded that Stalevo increases your risk of heart attack, strokes, or cardiovascular death. The Agency is still reviewing the available information about this safety concern. Do not stop taking your Stalevo or Comtan unless instructed to do so by your healthcare professional. Make sure your healthcare professional knows if you have a history of cardiovascular disease. For more information, read the FDA Safety Announcement (8/20/2010).

COMT inhibitors extend the benefit of levodopa by reducing “off” symptoms between doses. Without levodopa, COMT inhibitors have no effect on Parkinson’s symptoms.

What are the Side Effects?

  • May exaggerate some levodopa-related side effects especially dyskinesia.
  • Confusion
  • Hallucinations
  • Discoloration of urine (reddish brown or rust-colored)
  • Diarrhea

Caution: PD medications may have interactions with certain foods, other medications, vitamins, herbal supplements, over the counter cold pills and other remedies.  Anyone taking a PD medication should talk to their doctor and pharmacist about potential drug interactions.