Abstract

Purpose: The safety and tolerability of adjunctive tolcapone initiated simultaneously with levodopa was evaluated with a focus on liver transaminase elevations and hepatotoxicity.

Methods: 677 levodopa-naïve patients with early-stage Parkinson’s disease (PD) were randomized to receiveplacebo or tolcapone 100 mg three times daily, added to standard doses of levodopa plus carbidopa or benserazide.

Results: Liver transaminase elevations above the upper limit of normal (ULN) occurred in 20.2% and 27.5% of patients in the placebo and tolcapone groups, respectively. Elevations >=3 times the ULN occurred in 1.2% and 1.8% of placebo and tolcapone patients, respectively (p = 0.52). Liver transaminase values returned to the normal range in 65% of placebo- and 80% of tolcapone-treated patients. No instances of serious hepatotoxicity were observed. Diarrhea was the most frequently reported AE—11% (36/342) placebo vs. 29% (98/335) tolcapone—and caused discontinuation in 9.9% of tolcapone-treated patients. Overall, study discontinuation due to AEs was 2.9% in the placebo group and 17.3% in the tolcapone group.

Conclusions: Tolcapone appeared safe and was generally well tolerated as adjunctive therapy in patients initiating treatment with carbidopa/levodopa for symptomatic PD. Mild elevations in transaminase levels—<3 times the ULN—occurred commonly in both placebo- and tolcapone-treated patients, whereas potentially serious elevations to ≥3 times the ULN were infrequent.