Tolcapone

Tolcapone is a medication that acts as a catechol-O-methyltransferase (COMT) inhibitor used as an adjunct to levodopa therapy in Parkinson's disease to reduce motor fluctuations and extend the effect of levodopa. It crosses the blood-brain barrier, providing central and peripheral inhibition of COMT, in contrast to entacapone which acts peripherally only.

By inhibiting peripheral metabolism of levodopa to 3-O-methyldopa, tolcapone increases levodopa bioavailability in the brain and smooths fluctuations in motor function. Combined with carbidopa-levodopa, it can increase "on" time and reduce end-of-dose wearing-off.

Tolcapone is given orally in divided doses with carbidopa-levodopa. The total daily dose commonly ranges up to 600 mg, typically 100 mg three times daily or 200 mg three times daily depending on regimen. Dosing should be individualized.

Tolcapone carries a risk of serious hepatotoxicity and requires liver function monitoring before starting and regularly during treatment. It is generally considered after other options such as entacapone have been tried or when motor fluctuations persist. Discontinue if signs of liver injury occur (jaundice, elevated transaminases).

Common adverse effects include nausea, orthostatic hypotension, dyskinesias, confusion, and sleep disturbances. Caution with concomitant MAO inhibitors or other dopaminergic therapies; use in hepatic impairment is contraindicated.