Edoxaban
Summary
Persistence. Edoxaban is slowly degraded in the environment.
Bioaccumulation. Edoxaban has low potential for bioaccumulation.
Toxicity. Edoxaban has low chronic toxicity.
Risk. The use of edoxaban (risk from a European perspective for Lixiana (edoxaban), assaessment report from 2015) has been considered to result in insignificant environmental risk.
This summary information comes from Fass regarding bioaccumulation. The information on persistence comes from previous environmental information from Fass. The remaining information comes from the assaessment report for Lixiana.
Detailed information
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 are available in the public assessment report (PAR/EPAR for centrally approved medicines). Environmental considerations are not included in the benefit-risk assessment for human medicines. If new data emerge after approval that necessitate an update of the environmental risk assessment, a variation application (“type IB C.I.z variation”) must be submitted to the regulatory authority.
Assessment report
Assessment report for Lixiana (edoxaban) 23 April 2015, EMA/321083/2015.
Hazard
Persistence: DT50, water(20°C)= 1.1 d, DT50, sediment (20°C) = 59.1 d, DT50 sediment (12°C) = 126.1 d, DT50, whole system (20°C) = 6.1 d, % shifting to sediment = 60.7 (day 14) TP: D21-3231-0101 > 10%. Remarks: "P, significant shifting to the sediment, test on sediment organism is required."
Bioaccumulation: No data.
Chronic toxicity: There are data for 2 trophic levels, most sensitive fish (Pimephales promelas) NOEC 2.32 mg/L.
Risk
The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:
PEC = 0.3 microg/L
PNEC = Lowest NOEC, 2 320 microg/L/50 (Assessment Factor (AF) for 2 chronic studies) = 46.4 microg/L
PEC/PNEC = 0.00646 which gives the risk insignificant.
"In the context of the obligation of the MAH (Marketing Authorisation Holder ed. note) to take due account of technical and scientific progress, the CHMP recommends the following points to be addressed: (1) to provide an adsorption study for soils in accordance with OECD 106, (2) to submit a valid OECD 201 study for algae." No such information was found on EMA's website (2019-10-14). According to the Swedish Medical Products Agency, the company/MAH did not submit the requested studies and updated its nvironmental risk assessment (ERA) (2019-10-18).
Fass environmental information for Lixiana 2024-01-24
Fass environmental information for Lixiana (edoxaban) from Organon Sweden (downloaded 2024-01-24).
Hazard
Persistence: No data.
Bioaccumulation: Log Kow (Log Pow) = -1.455.
Chronic toxicity: No data.
Risk
Risk of environmental impact of edoxaban cannot be excluded, since no ecotoxicity data are available.
It is voluntary for manufacturers to provide information on the environmental impact on fass.se.
Fass miljöinformation for Lixiana 2019-10-19
Fass miljöinformation for Lixiana (edoxaban) from MSD (downloaded 2019-10-19) about persistence.
"Since half-life < 32 days for total system and >15% remaining as parent compound, the substance is slowly degraded in the environment."
Author: Health and Medical Care Administration, Region Stockholm