COMT Inhibitor


COMT Inhibitor, Catechol O-methyltransferase Inhibitor, Entacapone, Comtan, Opicapone, Ongentys, Tolcapone, Tasmar, Stalevo

  • See Also
  • Indications
  1. Late-stage Parkinson's Disease to minimize "off" periods
  2. Extends Levodopa Half-Life to reduce off-time (not indicated as monotherapy)
  • Mechanism
  1. Catechol O-methyltransferase (COMT) catalyzes the transfer of a methyl group to the phenol group on Catecholamines
    1. Starts the intracellular metabolism of Catecholamines (Dopa, Dopamine, Epinephrine, Norepinephrine)
  2. COMT Inhibitors decrease the metabolism of Levodopa, increasing its Bioavailability and Half-Life
    1. Agents listed here (e.g. Entacapone, Tolcapone) are selective, reversible COMT Inhibitors
    2. COMT Inhibitors have no anti-Parkinsonism effect on their own (their only effect is when combined with Levodopa)
  • Precautions
  1. May need to reduce Levodopa dose after start of COMT Inhibitor
    1. Indicated if increased Dyskinesia, Nausea, Hallucinations
  2. Avoid Tolcapone due to hepatotoxicity
  3. Avoid stopping COMT Inhibitors abruptly
    1. Risk of Neuroleptic Malignant Syndrome
  • Dosing
  • Entacapone (Comtan)
  1. Peripherally acting with reduction of "off" time by 1 hour/day
  2. Entacapone (Comtan)
    1. Start 200 mg with each dose of Carbidopa/Levodopa
    2. Maximum: Up to 8 doses (1600 mg/day)
  3. Entacapone with Carbidopa/Levodopa (Stalevo)
    1. Patient takes Stalevo, just as they would take Carbidopa/Levodopa (Sinemet) alone
    2. Consider lowering the Carbidopa/Levodopa when adding Entacapone
    3. Maximum: 8 tabs/day (6 tabs if 200 mg/dose Entacapone)
  • Dosing
  • Opicapone (Ongentys)
  1. Peripherally acting with reduction of "off" time by 1 hour/day
  2. Start: 50 mg once nightly
  3. Decrease dose to 25 mg daily if moderate hepatic dysfunction
  • Dosing
  • Tolcapone (Tasmar)
  1. Listed for historical reasons
  2. Acts both peripherally and centrally
  3. AVOID due to rare lethal hepatotoxicity
    1. If used, obtain written consent and obtain Liver Function Tests every 2-4 weeks for 6 months
  4. Start: 100 mg orally three times daily
  5. May increase to 200 mg orally three times daily
  6. Maximum: 600 mg/day
  • Adverse Effects
  1. Safety: Class
    1. Pregnancy Category C
    2. Unknown Safety in Pregnancy
  2. Orthostatic Hypotension
  3. Dyskinesias associated with Carbidopa/Levodopa may worsen
  4. Urine Discoloration (dark orange-brown)
  5. Diarrhea (esp. Tolcapone)
  6. Hepatotoxicity (Tolcapone)
  • Drug Interactions
  1. Avoid with non-selective MAO Inhibitors
    1. Risk of Catecholamine toxicity
  2. Sedatives or CNS Depressants
    1. COMT Inhibitors may exaggerate CNS Depressant effects
  3. Caution with Catecholamines (risk of increased adrenergic effects)
    1. Isoproterenol
    2. Epinephrine
    3. Norepinephrine
    4. Dopamine
    5. Dobutamine
  • References
  1. (2021) Med Lett Drugs Ther 63(1618): 25-32
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 46-7
  3. Hamilton (2020) Tarascon Pocket Pharmacopoeia