RT Journal Article SR Electronic T1 Safety and tolerability of adjunctive tolcapone treatment in patients with early Parkinson’s disease JF Journal of Neurology, Neurosurgery & Psychiatry JO J Neurol Neurosurg Psychiatry FD BMJ Publishing Group Ltd SP 944 OP 948 DO 10.1136/jnnp.2006.097154 VO 78 IS 9 A1 A J Lees A1 V Ratziu A1 E Tolosa A1 W H Oertel YR 2007 UL http://jnnp.bmj.com/content/78/9/944.abstract AB 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-naïve 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.