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COMT Inhibitors

This class of PD medications includes entacapone (Comtan®) and tolcapone (Tasmar®). They have no direct effect on PD symptoms, but are used to prolong the effect of levodopaThe medication most commonly given to control the movement symptoms of Parkinson’s, usually with carbidopa. It is converted in the brain into dopamine. by blocking its metabolism. COMT (catechol-o-methyl transferase) An enzyme that inactivates levodopa in the body before it gets to the brain. COMT inhibitors block the work of the enzyme, so more levodopa is available to the brain. inhibitors are used primarily to help with “wearing off The time period when levodopa begins to lose its effect and symptoms start to become more noticeable.,” in which the effect of levodopa becomes short-lived. People taking Tasmar must have regular liver function blood tests. Entacapone is not only a COMT inhibitor, but is also a main ingredient in Stalevo, which is a combination of carbidopa A medication used together with levodopa to enhance its effects. When carbidopa is added to levodopa, the dose of levodopa you take can be smaller while still getting the same benefits, with fewer side effects., levodopa and entacopone.

What are the facts?

  • Only effective when used in combination with levodopa.
  • When taking levodopa, an enzyme in the body call catechol-O-methyl transerase (COMT) converts a portion of the levodopa into a form that is useless.
  • 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.
  • 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 six months after beginning treatment.

What are the side effects?

  • May exaggerate some levodopa-related side effects especially dyskinesiaAbnormal, involuntary body movements that can appear as jerking, fidgeting, twisting and turning movements; frequently caused by dopaminergic medications to treat Parkinson’s.
  • 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.

Medication Available Doses Initial Dosing Side Effects* Indications Interactions
Entacapone (Comtan®) 200 mg 200 mg with levodopa; max 8 per day Abdominal pain, back pain, constipation, nausea, diarrhea, blood in urine Secondary medication; delays wearing off by prolonging effectiveness of levodopa MAO inhibitors
Tolcapone (Tasmar®) 100 mg 200 mg 100 mg 3X/day Abdominal pain, back pain, constipation, nausea, diarrhea, blood in urine, liver failure Tertiary medication for motor fluctuations Changes in the ability to move, often related to medication timing; also called “on-off” fluctuations.; limited in use to those who have exhausted other treatment options MAO inhibitors  

*Please note that the side effects listed in the tables that accompany each class of medication are the most commonly experienced. Not all individuals will experience such side effects. For many people who do experience side effects, they can often be effectively limited or eliminated with careful adjustments to dosage or the timing of the individual doses.

Speak to the treating physician immediately if any side effects are experienced. For a complete description of each drug and its possible side effects, please request a “package insert” from your pharmacist for each drug used. It is recommended that all prescriptions be filled at the same pharmacy to avoid interactions between medications. Interactions can be dangerous and even life-threatening, so make sure the pharmacist knows of all medications and supplements being taken, including over-the-counter medications and supplements.

Page reviewed by Dr. Chauncey Spears, Movement Disorders Fellow at the University of Florida, a Parkinson’s Foundation Center of Excellence.

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