Safety and tolerability of adjunctive tolcapone treatment in patients with early Parkinson's disease

Objective: The safety and tolerability of adjunctive tolcapone initiated simultaneously with levodopa was evaluated with a focus on increases in liver transaminase and hepatotoxicity. Methods: 677 levodopa- naive patients with early stage Parkinson's disease ( PD) were randomised to receive placebo or tolcapone 100 mg three times daily, added to standard doses of levodopa plus carbidopa or benserazide. Results: Increases in liver transaminase above the upper limit of normal ( ULN) occurred in 69/ 342 ( 20.2%) and 92/ 335 ( 27.5%) patients in the placebo and tolcapone groups, respectively. Increases >= 3 times the ULN occurred in 4/ 342 ( 1.2%) and 6/ 335 ( 1.8%) patients receiving placebo and tolcapone, respectively ( p = 0.5). Liver transaminase values returned to normal in 65% of placebo and 80% of tolcapone treated patients. No instances of serious hepatotoxicity were seen. Diarrhoea was the most commonly reported AE - 36/ 342 ( 11.0%) placebo v 98/ 335 ( 29.0%) tolcapone - and caused discontinuation in 9.9% of tolcapone treated patients. Overall, study discontinuation due to adverse effects was 2.9% in the placebo group and 17.3% in the tolcapone group. Conclusions: Tolcapone seemed to be safe and was generally well tolerated as an adjunctive treatment in patients starting treatment with carbidopa/ levodopa for symptomatic PD. Mild increases in transaminase levels -, 3 times the ULN - occurred commonly in both placebo and tolcapone treated patients, whereas potentially serious increases of up to >= 3 times the ULN were infrequent.