Aprepitant

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.

The PEC (predicted environmental concentration) values used to calculate risk in the manufacturers' assessment reports are based on the estimated use of the medicinal product to which the assessment report relates, not all medicinal products containing the same active substance.

Assessment report

Assessment report for Emend (aprepitant), 22 October 2015, EMA/787667/2015.

Hazard

Persistens: "Aprepitant was not readily biodegraded and a DT₅₀ for the whole system in the OECD 308 study was not reproted due to steadily increase of test item in the sediment compartment. However, the DT₅₀ of the whole system was calculated to 388 and 1131 d (12°C). Thus, aprepitant is considered as very persistent even though evidence of some degradation was observed. There was significant shifting to the sediment compartment and a sediment risk assessment was conducted."

Bioackumulation: "Initially the log K_ow of 4.75 at pH 7 indicated potential for bioaccumulation, however based on the results of a bioconcentration study in fish where the BCFss was in the range of 39.2–47.9 it can be concluded that aprepitant has little potential to bioaccumulate."

Chronic toxicity: There are data for 3 trophic levels, most sensitive crustacean (Daphnia sp.) NOEC 18 microg/L.

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:

PEC_surfacewater = 0.82 microg/L.

PNEC = Lowest NOEC, 18 microg/L/10 (Assessment Factor (AF) for XX chronic studies) = 1.8 microg/L

PEC/PNEC = 0.456 which gives the risk low. "All PEC/PNEC quotients were below 1 (0.1 for micro-organisms) indicating that aprepitant, in the proposed use, does not pose a risk to the environment."

Fass environmental information

Fass environmental information for Emend from MSD (downloaded 2024-07-02).

Hazard

Persistence: "Biodegradation in sludge: Test results 50% degradation in 66 days based on CO evolution (not rapidly degradable) (OECD 314). Based on the data presented above, the phrase, “Aprepitant is potentially persistent” is chosen."

Bioaccumulation: "Steady state BCF (whole fish) 39.2–47.9. Since measured BCF range < 500, the substance has low potential for bioaccumulation."

Chronic toxicity: There are data for 3 trophic levels, most sensitive crustacean (Daphnia sp.) NOEC 18 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2022. PEC/PNEC = 0.0003 which gives the risk insignificant.