COMT Inhibitors

COMT Inhibitors

This class of PD medications has no direct effect on PD symptoms but is used to prolong the effect of levodopa by blocking its metabolism. COMT (catechol-o-methyl transferase) inhibitors are used primarily to help with “wearing off,” in which the effect of levodopa becomes short-lived.


Entacapone (Comtan®)

Available Doses: 200 mg
Typical Treatment Regimen: 4–8 times/day (with each levodopa dose)
Side Effects: Diarrhea, discolored urine, enhanced side effects of levodopa (especially dyskinesia and confusion)
Indications: Combination therapy with levodopa for motor fluctuations, not used without levodopa.

Tolcapone (Tasmar®)

Available Doses: 100 mg, 200 mg
Typical Treatment Regimen: 100 mg up to 3 times/day to maximum 200 mg three times/day
Side Effects: Diarrhea, discolored urine, enhanced side effects of levodopa (especially dyskinesia and confusion), risk of liver damage (needs regular blood tests for checking liver functions)
Indications: Combination therapy with levodopa for motor fluctuations, not used without levodopa. Should only be used after all PD medications have been tried and should be discontinued if no benefit in 3 weeks.

Due to 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

Carbidopa/levodopa/entacapone tablets (Stalevo)

This is a combination drug which includes entacapone and levodopa in one pill. It is more convenient compared with carbidopa/levodopa + entacapone taken separately.
Available Doses: 12.5/50/200 mg, 18.75/75/200 mg, 25/100/200 mg, 31.25/125/200 mg, 37.5/150/200 mg, 50/200/200 mg
Typical Treatment Regimen: 150-1600 mg of levodopa total daily dose, depending on daily need. Max 8 tab/day
Common Side Effects: Low blood pressure, nausea, confusion, dyskinesia, diarrhea and discolored urine
Indications for Usage: Replacement for carbidopa/ levodopa, for motor fluctuations (benefit of entacapone)

Opicapone (Ongentys®)

Available Doses: 25mg, 50mg capsules
Typical Treatment Regimen: 50mg by mouth once daily at bedtime
Side Effects: dyskinesia, constipation, low blood pressure/dizziness, weight loss
Indications: Combination therapy with levodopa for "off" time (not pharmacologically active by itself).

Common Side Effects of COMT Inhibitors

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

Quick Facts

  • Only effective when used in combination with levodopa
  • When taking levodopa, an enzyme in the body call catechol-O-methyl transferase (COMT) deactivates levodopa in the body before it is absorbed into the bloodstream; COMT inhibitors prevent this from happening


* 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.

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.


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