Tolcapone

Because of the risk of potentially fatal, acute fulminant liver failure, tolcapone should ordinarily be used in Parkinson's disease patients on levodopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to, or are not appropriate candidates for, other adjunctive therapies. Withdraw the patient if there is no substantial clinical benefit within 3 weeks of initiation; if a patient fails to show the expected incremental benefit on the 200 mg dose after a total of 3 weeks of treatment (regardless of dose), tolcapone should be discontinued. Do not initiate if the patient has clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values greater than the upper limit of normal. Patients who develop evidence of hepatocellular injury and are withdrawn for any reason may be at increased risk if the drug is reintroduced, and should not ordinarily be considered for retreatment. Treat patients with severe dyskinesia or dystonia with caution. Most patients in clinical trials required a decrease in their daily levodopa dose if that dose was >600 mg or if they had moderate or severe dyskinesias before starting; the average reduction was about 30% (greater than 70% of patients on levodopa doses above 600 mg daily required such a reduction). Withdrawal or abrupt dose reduction may lead to emergence of Parkinson's signs and symptoms or to hyperpyrexia and confusion, a syndrome resembling neuroleptic malignant syndrome — monitor closely and adjust other dopaminergic treatments as needed; tapering has not been systematically evaluated and, as COMT inhibition lasts on average only 5 to 6 hours, reducing dose frequency to twice or once daily may not in itself prevent withdrawal effects. Paediatric use: 'There is no identified potential use of tolcapone in pediatric patients' (§8.4). Source note: no UK SPC posology was available in the fetched bundle — this draft is from US labelling and must be verified against the UK SPC.