Rivaroxaban

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 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 for Xarelto

Assessment report for Xarelto (rivaroxaban) 22 September 2011, EMA/CHMP/301607/2011.

Hazard

Persistence: "DT_{50, whole system} = 51.9 d (worst case) % shifting to sediment = 35,4."

Bioaccumulation: "On the basis of the correct octanol/water partition coefficient of log P_OW = 1.5, no study on bioaccumulation in fish (OECD 305) is required according to the ERA guideline CHMP/SWP/4447/00 (June 2006), because the trigger value for this study of log P_OW = 3 is not reached."

Toxicity: There are data for 2 trophic levels, most sensitive fish (Danio rerio) NOEC 86 microg/L.

Risk

"In conclusion, all remaining issues have been addressed and the Applicant ́s responses were considered acceptable. As a result, the data allow to conclude that ribaroxaban does not have a potential risk to the environment."

Assessment report for Rivaroxaban Accord

Assessment report for Rivaroxaban Accord 17 September 2020, EMA/550657/2020.

"The applicant considered that the introduction of Rivaroxaban Accord manufactured by Accord Healthcare S.L.U. is unlikely to result in any significant increase in the combined sales volumes for all rivaroxaban containing products and the exposure of the environment to the active substance. Thus, the ERA is expected to be similar. However, from the data submitted and the trend for an overall increase in the sales of rivaroxaban containing products the CHMP recommended that the applicant should conduct an ERA in accordance with EMEA/CHMP/SWP/4447/00 corr.2."

Assessment report for Rivaroxaban Mylan

Assessment report for Rivaroxaban 16 September 2021, EMA/560715/2021.

"No Environmental Risk Assessment studies were submitted. This was justified by the applicant as the introduction of Rivaroxaban Mylan manufactured by Mylan Ireland Limited is considered unlikely to result in any significant increase in the combined sales volumes for all rivaroxaban containing products and the exposure of the environment to the active substance. Thus, the ERA is expected to be similar. However, from the data submitted and the trend for an overall increase in the sales of rivaroxaban containing products the CHMP recommended that the applicant should conduct an ERA in accordance with EMEA/CHMP/SWP/4447/00 corr.2."

Fass environmental information

Fass environmental information for Xarelto from Bayer (downloaded 2022-10-12).

Hazard

Persistence: Substance rivaroxaban was biodegradable. The phrase “rivaroxaban is slowly degraded in the environment” is thus chosen.

Bioaccumulation: Log K_ow = 1.5 (guideline not specified). Since log K_ow < 4, rivaroxaban has low potential for bioaccumulation.

Toxicity: There are data for 3 trophic levels, most sensitive fish (Pimephales promelas) NOEC 86 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2020. PEC/PNEC = 0.0038 which gives the risk insignificant.