Carfilzomib
Summary
Persistence. Carfilzomib is degraded in the environment. Two transformation products have been identified: metabolite K, which shows moderate persistence, and 2-morpholino-acetic acid, which is classified as very persistent but has low bioaccumulation potential (log Kow -0.955).
Bioaccumulation. Carfilzomib has high potential for bioaccumulation.
Toxicity. It cannot be excluded that carfilzomib is toxic, as data are lacking.
Risk. In connection with an extension of indication in the assessment report for Kyprolis (carfilzomib), an updated Environmental Risk Assessment (ERA) for carfilzomib has been submitted to EMA. The Phase I environmental analysis showed that the predicted environmental concentration in surface water (PECsurfacewater) from a European perspective was below the action limit of 0.01 µg/L, meaning that no additional studies are required. Based on the available data, carfilzomib should be used in accordance with the precautions stated in the Summary of Product Characteristics (SPC) to minimize any potential risks to the environment, as outlined in the Kyprolis assessment report. In the SPC for Kyprolis, under the section "Destruction": Unused medicines and waste should be disposed of in accordance with applicable regulations.
This summary information comes from assessment reports on Kyprolis. Environmental information is missing on fass.se for carfilzomib (2025-09-05).
Detailed information
Assessment report
There are three assessment reports containing environmental information on Kyprolis (carfilzomib). The most recent report is presented here and concerns an extension of indication, dated 12 November 2020, EMA/CHMP/593622/2020.
Hazard
Persistence: OECD 308.
Carfilzomib DT50 for the total system = 0.5 days.
Metabolite K DT50 for the total system = 16 days.
2-morpholino-acetic acid: The transformation product 2-morpholino-acetic acid is rapidly formed to an extent of 85%, but is slowly degraded (DT50 values of 237 and 303 days after normalization to 12 °C). It should be noted, however, that although 2-morpholinoacetic acid is classified as very persistent, it has a log Kow of -0.955.
Bioaccumulation: Log Pow carfilzomib at pH 7 = 4.6.
Toxicity: No data.
Risk
PECsurfacewater = 0.0049 µg/L.
Results from a phase I environmental study has been reported, resulting in a predicted environmental concentration in surface water (PECsurfacewater) below the action limit of 0.01 µg/L, indicating that no further studies are required. Regarding the PBT assessment, the log Kow value was 4.6, but additional testing (OECD308) demonstrated that carfilzomib is extensively degraded in aquatic systems. The transformation product 2-morpholino-acetic acid is rapidly formed (85 %) but slowly degraded (DT50 237–303 days at 12 °C). Despite being very persistent, its low log Kow (-0.955) indicates low bioaccumulation potential. No further B-assessment is needed, and the PBT evaluation can be concluded.
The summary in the Kyprolis assessment report states: Based on the available data, carfilzomib should be used in accordance with the precautions outlined in the Summary of Product Characteristics (SPC) to minimize any potential environmental risks.
In the SPC for Kyprolis, under the section "Destruction": Unused medicines and waste should be disposed of in accordance with applicable regulations.
Comment
Carfilzomib has only undergone a phase I study in accordance with regulatory requirements for environmental risk assessments (Guideline on the environmental risk assessment of medicinal products for human use, EMEA/CHMP/SWP/4447/00 Rev. 1- Corr.) A phase I study includes data on bioaccumulation and an estimation of the environmental concentration of carfilzomib (PECSurface water). If the specified threshold values are not exceeded, the company is not required to conduct a Phase II study, which includes data on toxicity, persistence, and risk assessment based on PEC/PNEC.
Author: Health and Medical Care Administration, Region Stockholm