The tolerability and efficacy of entacapone over 3 years in patients with Parkinson's disease.
The long-term safety and efficacy of the catechol-O-methyltransferase (COMT) inhibitor entacapone was investigated in a 3-year open-label extension of the 6-month double-blind placebo-controlled Nordic (NOMECOMT) study. After a wash-out following this study, 132 patients with Parkinson's disease (PD) experiencing motor fluctuations treated with levodopa/dopa decarboxylase (DDC) inhibitor received additional therapy with entacapone 200 mg, administered with each dose of levodopa. The most common adverse events (AEs) were insomnia (30%), dizziness (20%), nausea (20%), aggravated parkinsonism (17%) and hallucinations (14%). Only 19 (14%) patients discontinued because of AEs. Most dopaminergic AEs occurred shortly after initiation of entacapone, and these could be managed by levodopa down-adjustment. The mean duration of benefit of a single dose of levodopa increased significantly from 2.1 to 2.8 h (P < 0.01) at 3 months and remained prolonged for the whole study. At the end of the study, the mean daily dose of levodopa was significantly decreased from baseline (from 737 to 696 mg; P < 0.05). The patients' global assessment indicated that 69% of patients improved when given entacapone and this proportion was maintained until the end of the study (64%). There was a significant worsening of disability upon withdrawal of entacapone. In conclusion, entacapone given in combination with levodopa, has a good long-term safety profile and a sustained beneficial effect in patients with PD with motor fluctuations.
Larsen
J P
JP
Department of Neurology, Rogaland Central Hospital, Stavanger, Norway. jpl@sir.no
Worm-Petersen
J
J
Sidén
A
A
Gordin
A
A
Reinikainen
K
K
Leinonen
M
M
D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002396:Catechols / Q000009:adverse effects* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004409:Dyskinesia, Drug-Induced / Q000453:epidemiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010300:Parkinson Disease / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D007980:Levodopa; C071192:entacapone