Levodopa

Detailed information

Comment on Fass environmental information

Levodopa has different classifications on fass.se. According to Lif (the trade association for the research-based pharmaceutical industry in Sweden) the various pharmaceutical companies compile environmental information for their active substances based on internal studies and published data. Based on data, which may thus differ between different pharmaceutical companies, the companies assess the environmental risk with guidance from “Environmental classification of pharmaceuticals at www.fass.se – Guidance for pharmaceutical companies 2012”. The Swedish Environmental Institute (IVL) reviews the assessment but does not have the task of coordinating/harmonizing environmental information from different pharmaceutical companies for the same active substance.

Fass environmental information Madopark

Fass environmental information for levodopa from Madopark (benserazide, levodopa) from Roche (downloaded 2023-02-06).

Hazard

Persistence: "Degradation. Biotic Degradation. Ready biodegradability:
72–73% after 28 days of incubation BOD/ThOD (OECD 301 F)
67–70% at the end of the 10-d window BOD/ThOD (OECD 301 F)
98% after 28 days of incubation DOC/TOC (OECD 301 F).
[...] Levodopa is readily biodegradable which justifies the phrase 'Levodopa is degraded in the environment.'"

Bioaccumulation: LogP : -2.39 EpiSuite experimental database match.

Acute toxicity: There are data for 3 trophic levels, most sensitive green alga ErC₅₀ 72 h (growth rate) = 3.2–5.6 mg/L (OECD 201).

Risk

PEC/PNEC is based on sales data in Sweden in year 2021. PEC/PNEC = 0.015 which gives the risk insignificant.

Fass environmental information Sinemet

Fass environmental information for levodopa from Sinemet (carbidopa, levodopa) from Organon Sweden (downloaded 2023-02-06). The environmental information for levodopa is produced by the company MSD for Sinemet, Sinemet Depot and Sinemet Depot Mite. These medicines from MSD are now withdrawn from use in Sweden.

Hazard

Persistence: Biotic degradation. Biodegradation: 72 %. Exposure time: 28 d. Readily biodegradable. Based on the data presented above, the phrase, “Levodopa is degraded in the environment” is chosen.

Bioaccumulation: Log K_ow = -2.39.

Acute toxicity: There are data for 2 trophic, lowest for crustacean (Daphnia Magna) "EC₅₀ 48 h (immobility)" = 16000 microg/L.

Risk

Risk of environmental impact cannot be excluded, since there is not sufficient ecotoxicity data available.

General information about assessment reports

Since 2006, an Environmental Risk Assessment (ERA) for the active pharmaceutical substance shall accompany an application for a marketing authorisation in EU for a medicinal product for human use. Parts of environmental data can be found in the public investigation report (PAR/EPAR for medicinal product through a centralized procedure). Since the benefit/risk assessment for human medicinal products at present does not include environmental effects, an update of the environmental risk assessment is not required for renewals of marketing authorizations. There is thus no requirement for companies to stay informed about the development of their substances from an environmental point of view and consequently to update the environmental risk assessment as new data are published.

Assessment report Levodopa/Carbidopa/Entacapone

Assessment report for levodopa from Levodopa/Carbidopa/Entacapone Orion, 18 August 2011
EMA/718241/2011.

"Based on the assumption that the product is intended to substitute for identical products on the market, the approval of the referred product should not result in an increase of the total quantity of the active ingredients released into the environment. Therefore, it should not result in any increase of the risk to the environment during storage, distribution, use and disposal."

Assessment report Inbrija

Assessment report for Inbrija (levodopa) 25 July 2019, EMA/CHMP/450567/2019.

"Levodopa is a natural substance, the use of which will not alter the concentration or distribution of the substance in the environment. Therefore levodopa is not expected to pose a risk for the environment."