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
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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 | |