Twelve-month safety of entacapone in patients with Parkinson's disease

The safety of entacapone combined with levodopa and a dopadecarboxylase (DD C) inhibitor was tested in a 12-month double-blind study of 326 patients wi th idiopathic Parkinson's disease (PD). The study population represented 't ypical' PD outpatients, including patients with varying disease severity an d with various concomitant medications. Two-thirds of the patients were ran domized to receive 200 mg of entacapone with each of 2-10 daily levodopa do ses, and one-third to receive placebo, All entacapone patients were include d in the safety evaluation of adverse events (AEs), vital signs, EGG, and l aboratory parameters, Entacapone was well tolerated with a discontinuation rate due to AEs of 14% compared with 11% with placebo (NS), As expected, du e to dopaminergic enhancement, dyskinesia was more frequent as an AE with e ntacapone than with placebo. Dryness of mouth, urine discoloration and diar rhoea were more frequent nondopaminergic AEs with entacapone than with plac ebo. Entacapone had no adverse effects on hepatic enzyme activity, ECG or h aemodynamic parameters. and there was no evidence of any toxicity. As an in dication of levodopa enhancement with entacapone, patients taking 5-10 dose s of levodopa, most likely representing predominantly fluctuating patients, showed a significant decrease in their mean daily levodopa dose of 94 mg i n the entacapone group compared with a decrease of 39 mg in the placebo gro up (P < 0.01). The interval between the first two morning doses of levodopa increased by 17% with entacapone, whereas with placebo no extension was ob served (P < 0.05). Despite levodopa dose reduction, efficacy of entacapone was maintained. As further evidence of efficacy Parkinsonian symptoms marke dly worsened in all patients after withdrawal of entacapone. We conclude th at entacapone is safe in optimizing levodopa in long-term treatment of idio pathic Parkinson's disease, Monitoring of liver or other safety parameters during entacapone treatment is not required.