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opicapone ( ongentys °) and Parkinson’s disease with motor fluctuations A single daily dose, but more dyskinesia

 NOTHING NEW  In a comparative, double-blind, randomised trial in 600 patients suffering from Parkinson’s disease and affected by motor fluctuations, opicapone taken once daily has not been shown to be more effective in reducing the duration of “off” periods than entacapone taken with each dose of levodopa .The adverse effect profile of opicapone seems to be close to that of entacapone , but is less well known. Opicapone carries a greater risk of dyskin­ esia. In practice, opicapone does not represent a real advance.

The onset of motor fluctuations on levodopa should initially be managed by optimising dopamin­ ergic therapy, e.g. dividing the daily dose into several administrations, adjusting the timing of the doses, or even increasing the daily dose or resort- ing to an extended-release formulation. These measures are sometimes difficult to implement, particularly in patients with swallowing difficul- ties (1,2). In cases where these measures are insufficient, addition of entacapone is an option. By inhibiting peripheral catechol-O-methyltransferase (COMT), entacapone reduces the breakdown of levodopa , which leads to an increase in the quantity of levo- dopa available in the brain. Fixed-dose combinations of entacapone + levodopa + carbidopa reduce the number of tablets to be taken, but the ratio of levodopa to carbidopa doses is inadequate, expos- ing patients to an increased risk of dyskinesia and nausea ( b )(3-5). Tolcapone , another COMT inhibitor, carries a risk of liver damage, which is sometimes fatal, making its harm-benefit balance unfavourable. Liver dam- age has rarely been reported with entacapone (5). Opicapone (Ongentys°, Bial Portela) is a COMT inhibitor, like entacapone. It has been authorised in the European Union for use in patients with Parkin- son’s disease who are affected by motor fluctuations despite dopaminergic therapy (6). When a COMT inhibitor is considered in this situ­ ation, is addition of opicapone more effective in improving motor symptoms than addition of enta- capone taken separately with each dose of levo- dopa ? What are the adverse effects of opicapone , in particular on the liver? No more effective than entacapone on the duration of “off” periods. Clinical evaluation of opicapone in patients with Parkinson’s disease only includes one clinical trial that compared it to entacapone . What’s new?

ONGENTYS° - opicapone capsules • 50 mg of opicapone per capsule ■ antiparkinsonian drug; peripheral catechol-O- methyltransferase (COMT) inhibitor ■ Indication: in combination with dopaminergic therapy ( levodopa + peripheral dopa-decarboxylase inhibitor) in adult patients with Parkinson’s disease affected by end-of- dose motor fluctuations. [EU centralised procedure]

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Parkinson’s disease is a progressive central nervous system disorder. It manifests mainly through motor symptoms linked to progressive degeneration of the cerebral dopaminergic neurons: tremor at rest, slowness and poverty of movement, and rigidity (or stiffness) (1,2). In patients with Parkinson’s disease, treatment is aimed at relieving disease symptoms and maintain- ing satisfactory independence. Drugs are justified when the functional impairment constitutes a handicap. The first choice is then dopaminergic ther- apy that combines levodopa (a dopamine precursor) with a peripheral dopa-decarboxylase inhibitor ( car- bidopa or benserazide ) in order to reduce the gas- trointestinal and cardiovascular adverse effects of levodopa . All patients initially respond to dopami- nergic therapy. However, after 4 to 6 years of use, about 40% of patients treated with dopaminergic therapy experience motor fluctuations (end-of-dose akinesia, and “on-off” phenomena) or dyskinesia, often mid-dose.This proportion is around 90% after 9 years ( a )(1-4).

a- According to some reviewers of the draft text, the“on-off” phenomena aremore troublesome for patients thandyskin­ esia. b- In France, the immediate-release tablets containing levodopa + carbidopa have a dose ratioof 10:1. Infixed-dose combinations of levodopa + carbidopa + entacapone the dose ratio of levodopa to carbidopa is 4:1 (ref 10).

P rescrire I nternational S pecial E dition 2020 • P age 5

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