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.