II. Indications
- Late-stage Parkinson's Disease to minimize "off" periods
- Extends Levodopa Half-Life to reduce off-time (not indicated as monotherapy)
III. Mechanism
- Catechol O-methyltransferase (COMT) catalyzes the transfer of a methyl group to the phenol group on Catecholamines
- Starts the intracellular metabolism of Catecholamines (Dopa, Dopamine, Epinephrine, Norepinephrine)
- COMT Inhibitors decrease the metabolism of Levodopa, increasing its Bioavailability and Half-Life
- Agents listed here (e.g. Entacapone, Tolcapone) are selective, reversible COMT Inhibitors
- COMT Inhibitors have no anti-Parkinsonism effect on their own (their only effect is when combined with Levodopa)
IV. Precautions
- May need to reduce Levodopa dose after start of COMT Inhibitor
- Indicated if increased Dyskinesia, Nausea, Hallucinations
- Avoid Tolcapone due to hepatotoxicity
- Avoid stopping COMT Inhibitors abruptly
- Risk of Neuroleptic Malignant Syndrome
V. Dosing: Entacapone (Comtan)
- Peripherally acting with reduction of "off" time by 1 hour/day
- Entacapone (Comtan)
- Start 200 mg with each dose of Carbidopa/Levodopa
- Maximum: Up to 8 doses (1600 mg/day)
- Entacapone with Carbidopa/Levodopa (Stalevo)
- Patient takes Stalevo, just as they would take Carbidopa/Levodopa (Sinemet) alone
- Consider lowering the Carbidopa/Levodopa when adding Entacapone
- Maximum: 8 tabs/day (6 tabs if 200 mg/dose Entacapone)
VI. Dosing: Opicapone (Ongentys)
- Peripherally acting with reduction of "off" time by 1 hour/day
- Start: 50 mg once nightly
- Decrease dose to 25 mg daily if moderate hepatic dysfunction
VII. Dosing: Tolcapone (Tasmar)
- Listed for historical reasons
- Acts both peripherally and centrally
- AVOID due to rare lethal hepatotoxicity
- If used, obtain written consent and obtain Liver Function Tests every 2-4 weeks for 6 months
- Start: 100 mg orally three times daily
- May increase to 200 mg orally three times daily
- Maximum: 600 mg/day
VIII. Adverse Effects
- Safety: Class
- Pregnancy Category C
- Unknown Safety in Pregnancy
- Orthostatic Hypotension
- Dyskinesias associated with Carbidopa/Levodopa may worsen
- Urine Discoloration (dark orange-brown)
- Diarrhea (esp. Tolcapone)
- Hepatotoxicity (Tolcapone)
IX. Drug Interactions
- Avoid with non-selective MAO Inhibitors
- Risk of Catecholamine toxicity
-
Sedatives or CNS Depressants
- COMT Inhibitors may exaggerate CNS Depressant effects
- Caution with Catecholamines (risk of increased adrenergic effects)
X. Resources
- Entacapone (DailyMed)
- Opicapone (DailyMed)
- Tolcapone (DailyMed)
XI. References
- (2021) Med Lett Drugs Ther 63(1618): 25-32
- Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 46-7
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
Images: Related links to external sites (from Bing)
Related Studies
entacapone (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
ENTACAPONE 200 MG TABLET | Generic | $0.43 each |
ongentys (on 10/20/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
ONGENTYS 50 MG CAPSULE | $21.63 each |
Ontology: entacapone (C0165921)
Definition (NCI) | A nitrocatechol compound with anti-parkinsonian property. Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT), which catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure including dihydroxyphenylalanine (DOPA), catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. When administered in conjunction with dopaminergic agents such as L-DOPA, entacapone prevents the metabolism and inactivation of adjunct drugs, thereby increasing the bioavailability of these compounds by facilitating their passage across the blood-brain barrier. |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C071192 |
SnomedCT | 116116003, 387018000 |
English | 2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)propenamide, entacapone, (E)-2-cyano-3-(3,4-dihydroxy-5-nitro-phenyl)-N,N-diethyl-prop-2-enamide, entacapone (medication), ENTACAPONE, entacapone [Chemical/Ingredient], Entacapone, Entacapone (product), Entacapone (substance) |
Spanish | entacapona (producto), entacapona (sustancia), entacapona |
Ontology: tolcapone (C0246330)
Definition (NCI) | A benzophenone derivative and a catechol-O-methyltransferase (COMT) inhibitor. Tolcapone selectively and reversibly inhibits COMT, an enzyme that catalyzes the metabolism of biologically active catechols and their hydroxylated metabolites by transferring the methyl group of S-adenosyl-L-methionine to the phenolic group of catechol-containing substrates. When given in conjunction with a peripheral dopa decarboxylase inhibitor and levodopa, tolcapone may prevent the metabolism of levodopa to 3-methoxy-4-hydroxy- L-phenylalanine (3-OMD) in the brain and peripheral tissues leading to increased bioavailability and enhancement of delivery to the central nervous system (CNS) of levodopa. |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C066340 |
SnomedCT | 108464002, 386851002 |
English | 3,4-dihydroxy-5'-methyl-5-nitrobenzophenone, tolcapone, 3,4-dihydroxy-4'-methyl-5-nitrobenzophenone, Methanone,(3,4-dihydroxy-5-nitrophenyl)(4-methylphenyl)-, tolcapone (medication), tolcapone [Chemical/Ingredient], Tolcapone, Tolcapone (product), Tolcapone (substance), TOLCAPONE |
Spanish | tolcapona (producto), tolcapona (sustancia), tolcapona |
Ontology: Catechol-O-methyltransferase inhibitor (C0595267)
Definition (MSH) | Compounds and drugs that inhibit or block the activity of CATECHOL O-METHYLTRANSFERASE enzymes. Drugs in this class are used in management of central nervous system disorders such as PARKINSON DISEASE. |
Concepts | Pharmacologic Substance (T121) |
MSH | D065098 |
SnomedCT | 356845001, 372646000 |
English | Catech-O-methyltransferas inhb, Catechol-O-methyltransferase inhibitor, Catechol O Methyltransferase Inhibitors, Catechol O-Methyltransferase Inhibitors, O-Methyltransferase Inhibitors, Catechol, Catechol-O-methyltransferase inhibitor (product), Catechol-O-methyltransferase inhibitor (substance), Catechol O-methyltransferase (COMT) Inhibitors |
Spanish | inhibidor de catecol-O-metiltransferasa (sustancia), inhibidor de catecol-O-metiltransferasa, inhibidor de la catecol-O-metiltransferasa (producto), inhibidor de la catecol-O-metiltransferasa (sustancia), inhibidor de la catecol-O-metiltransferasa |
Ontology: Tasmar (C0595276)
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C066340 |
English | Tasmar, tolcapone (Tasmar), tasmar, Roche brand of tolcapone |
Ontology: Comtan (C0876730)
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C071192 |
English | Comtan, comtan, Novartis brand of entacapone |
Ontology: opicapone (C2933912)
Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
MSH | C549349 |
English | opicapone, 2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide |