COMT Inhibitor

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)
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)

May need to reduce Levodopa dose after start of COMT Inhibitor
1. Indicated if increased Dyskinesia, Nausea, Hallucinations
Avoid Tolcapone due to hepatotoxicity
Avoid stopping COMT Inhibitors abruptly
1. Risk of Neuroleptic Malignant Syndrome

Peripherally acting with reduction of "off" time by 1 hour/day
Entacapone (Comtan)
1. Start 200 mg with each dose of Carbidopa/Levodopa
2. Maximum: Up to 8 doses (1600 mg/day)
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)

Listed for historical reasons
Acts both peripherally and centrally
AVOID due to rare lethal hepatotoxicity
1. 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

Avoid with non-selective MAO Inhibitors
1. Risk of Catecholamine toxicity
Sedatives or CNS Depressants
1. COMT Inhibitors may exaggerate CNS Depressant effects
Caution with Catecholamines (risk of increased adrenergic effects)