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-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 > or = 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 > or = 3 times the ULN were infrequent.
Lees
A J
AJ
Reta Lila Weston Institute for Neurological Studies, University College London, 1 Wakefield St, London WC1N 1PJ, UK. alees@ion.ucl.ac.uk
Ratziu
V
V
Tolosa
E
E
Oertel
W H
WH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D001577:Benzophenones / Q000008:administration & dosage* / Q000009:adverse effects*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009596:Nitrophenols / Q000008:administration & dosage* / Q000009:adverse effects*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000201:enzymology; D000077867:Tolcapone
D000978:Antiparkinson Agents; D001577:Benzophenones; D009596:Nitrophenols; D007980:Levodopa; D000077867:Tolcapone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase