COMT Inhibitors

Key Facts

  • COMT inhibitors should not be used alone.
  • They are used to enhance and prolong the effects of levodopa.
  • COMT inhibitors can enhance side effects of levodopa especially dyskinesias.

Catechol-O-methyltransferase breaks down levodopa. COMT inhibitors extend the clinical benefit of levodopa, and without levodopa COMT-inhibitors have no effect in PD.  They typically do not require dose escalation and are thus simple to administer.

Presentation

 

Dosages in Milligrams

Typical Treatment Regimens

Indications for Usage

Entacapone

(Comtan®)

200

200 mg 4–8 times daily (with each levodopa dose)

Adjunct therapy for motor fluctuations

Tolcapone (Tasmar®)

100

100 mg up to 3 times daily

Adjunct therapy for motor fluctuations (second-line due to side effects)

Carbidopa/levodopa/entacapone

(Stalevo®)

 

12.5/50/200,

25/100/200,

37.5/150/200,

50/200/200

150–1000 mg of levodopa total daily dose, dosed 2–3 times/day (divided 3-4 times)

Replacement for carbidopa/levodopa, for motor fluctuations (benefit of entacapone)

 

Prescription Recommendations

Entacapone  

  • Prescribe entacapone 200 mg, with each dose of levodopa. Always give with sinemet doses
  • It may extend the life of sinemet but also increase the blood level of dopamine
  • Entacapone can turn the urine orange and this is a benign reaction and does not require treatment
  • Watch for dyskinesias as often dose of levodopa when given with entacapone needs to be reduced

Carbidopa/levodopa/entacapone

  • Prescribe entacapone and carbidopa/levodopa combination at a total daily dose of 150-1000 mg of levodopa, titrated to symptoms and side effects
  • Choose from 50, 100, 150 or 200 mg (the last number on the formulation is the amount of levodopa)
  • Always start small and work up slowly
  • Watch for dyskinesias as often dose of levodopa when given with entacapone needs to be reduced

Tolcapone

  • Prescribe Tolcapone 100 mg up to 3 tablets tid (requires periodic liver monitoring)–no matter how many doses of levodopa are prescribed
  • Watch for dyskinesias as often dose of levodopa when given with entacapone needs to be reduced
  • Must monitor liver function tests

Side Effects

  • Nausea and vomiting
  • Diarrhea
  • Discolored urine
  • Abdominal pain
  • Enhanced side effects of levodopa, especially dyskinesias
References: 

Ahlskog JE. Parkinson’s Disease Treatment Guide for Physicians. New York, NY: Oxford University Press; 2009.

Ahlskog JE. The Parkinson’s Disease Treatment Book: Partnering with Your Doctor to Get the Most from Your Medications. New York, NY: Oxford University Press; 2005.