4.7 Review

Real-world considerations regarding the use of the combination of levodopa, carbidopa, and entacapone (Stalevo®) in Parkinson's disease

Journal

EUROPEAN JOURNAL OF NEUROLOGY
Volume 30, Issue -, Pages 15-20

Publisher

WILEY
DOI: 10.1111/ene.15992

Keywords

COMT inhibitors; dyskinesia; entacapone; levodopa; Parkinson's disease; wearing off

Ask authors/readers for more resources

The aim of long-term levodopa therapy is to prolong symptomatic efficacy without increasing peak plasma concentrations above the threshold for dyskinesias. Levodopa, carbidopa, and entacapone (LCE) is a combination medication that enhances levodopa delivery to the brain, leading to improved clinical efficacy. The safety and efficacy of LCE have been established through trials and experience.
An important aim in long-term levodopa therapy is to prolong the duration of symptomatic efficacy of each dose without increasing peak plasma concentrations above the threshold for the emergence of dyskinesias. One strategy is to enhance levodopa delivery to the brain by co-administering it with inhibitors of peripheral dopa-decarboxylase and catechol-O-methyltransferase (COMT). Levodopa, carbidopa and entacapone (LCE), available in a range of fixed-dose combinations as the branded formulation Stalevo (R) (Orion Pharma), has been developed to address this requirement and has been in general use for 20 years, having first been evaluated in randomized controlled trials. Experience with LCE has established that improved levodopa pharmacokinetics achieved with dual-enzyme inhibition are translated into improved clinical efficacy, including the possibility of reducing total levodopa dosage with no loss of therapeutic effect. The ease and tolerability of switching to LCE has been affirmed in the SIMCOM trial and by personal experience detailed in this review. Some 300,000 patient-years of safety data are available for LCE, including trial data for up to 5 years. Most adverse effects associated with LCE are attributable to the levodopa component rather than the enzyme inhibitors. The hepatotoxicity observed with the class comparator tolcapone has not been observed with entacapone, the COMT inhibitor in LCE, and there is no formal requirement to monitor liver function during LCE therapy. Other common side effects include diarrhoea, which is one of the more prominent non-dopaminergic adverse events, and urine discolouration, which is harmless but about which patients may require reassurance.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available