Tolcapone is a potent, selective, reversible inhibitor of COMT. Coadministration of
tolcapone with
levodopa and a
decarboxylase inhibitor prolongs the elimination half-life of
levodopa and reduces the formation of 3-0-metildopa in a dose-dependent form. The improvement in the pharmacokinetics of
levodopa prolongs the motor effects of
levodopa. Clinical studies have shown that the concomitant administration of
levodopa and
tolcapone is effective on the management of the wearing-off phenomenon.
Tolcapone can significantly reduce the off time and increases the total on time while simultaneously reducing
levodopa dosage and frequency. Most adverse events are dopaminergic in nature and related to the increase in
levodopa bioavailability.
Dyskinesias may increase in frequency and severity in patients already having
dyskinesias and these may appear for the first time after adding
tolcapone in patients at risk. Diarrhoea is the main nondopaminergic adverse event leading to the stop of the
drug in less than 10% of cases. Taking into account that
tolcapone significantly enhance the action of
levodopa, it would be wise to reduce the total daily dose of
levodopa at the same time that
tolcapone is introduced. No tolerance effect was observed in 12-month studies.
Tolcapone can be used with standard or sustained release
levodopa, and, when appropriate, in conjunction with
dopamine agonists or
selegiline.