Catechol-O-methyltransferase inhibition with entacapone: Evidence from controlled clinical trials in Parkinson's disease

Adjunct therapy with the catechol-O-methyltransferase inhibitor entacapone is a first-line approach to treat wearing-off type motor fluctuations in levodopa-treated Parkinson's disease (PD) patients. Five randomized placebo-controlled trials including a total of >1000 patients have established its efficacy, showing increases in ON time between 0.7 and 1.6 h, with corresponding OFF-time reductions. These and other trials also found improvements in ON motor function and quality of life. Additional trials have tested the efficacy of adjunct entacapone in patients either without or with early and mild motor fluctuations and also found enhanced motor control and improved activities of daily living function and quality of life, whereas the STRIDE-PD trial failed to show efficacy of early entacapone use in delaying the onset of dyskinesias. Adjunct entacapone enhances dopaminergic activity and may increase levodopa-induced adverse events like dyskinesias, which can usually be controlled by modest levodopa dose reductions. There is no formal requirement to monitor liver function during entacapone treatment. Entacapone can be a rare cause of lymphocytic colitis with severe diarrhoea and need for treatment discontinuation. In 2003, a triple-combination pill of levodopa, carbidopa, and entacapone (LCE) was first introduced onto the market, and since then proprietary LCE (Stalevo^®) is indicated on the basis of those trials for patients with idiopathic PD to (i) substitute for immediate-release carbidopa/levodopa and entacapone previously administered as individual products or (ii) replace immediate-release carbidopa/levodopa therapy (without entacapone) when patients taking a total daily dose of levodopa of ≤600 mg and not experiencing dyskinesias experience signs and symptoms of end-of-dose wearing off.