Tolcapone is indicated in combination with levodopa/benserazide or levodopa/carbidopa for use in patients with levodopa-responsive idiopathic Parkinson’s disease and motor fluctuations, who failed to respond to or are intolerant of other catechol-O-methyltransferase COMT inhibitors. Because of the risk of potentially fatal, acute liver injury, tolcapone should not be considered as a firstline adjunct therapy to levodopa/benserazide or levodopa/carbidopa.
Since tolcapone should be used only in combination with levodopa/benserazide and levodopa/carbidopa, the prescribing information for these levodopa preparations is also applicable to their concomitant use with tolcapone.
For this indication, competent medicine agencies globally authorize below treatments:
300 - 600 mg
From 100 To 200 mg 3 time(s) per day every day
The first dose of the day of tolcapone should be taken together the first dose of the day of a levodopa preparation, and the subsequent doses should be given approximately 6 and 12 hours later. Tolcapone may be taken with or without food.
The recommended dose of tolcapone is 100 mg three times daily, always as an adjunct to levodopa/benserazide or levodopa/carbidopa therapy. Only in exceptional circumstances, when the anticipated incremental clinical benefit justifies the increased risk of hepatic reactions, should the dose be increased to 200 mg three times daily. If substantial clinical benefits are not seen within 3 weeks of the initiation of the treatment (regardless of dose) tolcapone should be discontinued.
The maximum therapeutic dose of 200 mg three times daily should not be exceeded, as there is no evidence of additional efficacy at higher doses.
Liver function should be checked before starting treatment with tolcapone and then monitored every 2 weeks for the first year of therapy, every 4 weeks for the next 6 months and every 8 weeks thereafter. If the dose is increased to 200 mg tid, liver enzyme monitoring should take place before increasing the dose and then be reinitiated following the same sequence of frequencies as above.
Tolcapone treatment should also be discontinued if ALT (alanine amino transferase) and/or AST (aspartate amino transferase) exceed the upper limit of normal or symptoms or signs suggest the onset of hepatic failure.
As tolcapone decreases the breakdown of levodopa in the body, side effects due to increased levodopa concentrations may occur when beginning tolcapone treatment. In clinical trials, more than 70% of patients required a decrease in their daily levodopa dose if their daily dose of levodopa was >600 mg or if patients had moderate or severe dyskinesias before beginning treatment.
The average reduction in daily levodopa dose was about 30% in those patients requiring a levodopa dose reduction. When beginning tolcapone, all patients should be informed of the symptoms of excessive levodopa dose and what to do if it occurs.
The following suggestions are based on pharmacological considerations and have not been evaluated in clinical trials. Levodopa dose should not be decreased when tolcapone therapy is being discontinued due to side effects related to too much levodopa. However, when tolcapone therapy is being discontinued for reasons other than too much levodopa, levodopa dosemay have to be increased to levels equal to or greater than before initiation of tolcapone therapy, especially if the patient had large decreases in levodopa when starting tolcapone. In all cases, patients should be educated on the symptoms of levodopa under-dose and what to do if it occurs. Adjustments in levodopa are most likely to be required within 1-2 days of tolcapone discontinuation.
Tolcapone may be taken with or without food.