Everolimus

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.

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, as well as possibly other products from the same company, not all medicinal products containing the same active substance.

Assessment reports

There are several assessment reports available, including those related to the extended indication for Votubia (everolimus) and Afinitor (everolimus). Both are original products from Novartis but are approved for different indications. The most recent assessment report containing more comprehensive data is for Afinitor, dated 28 April 2016, EMA/390543/2016.

Hazard

Persistence: OECD 308: "DT_{50 whole system}: 2.5 resp. 5.1 d."

Bioaccumulation: Log K_ow = 4.0. Steady state BCF = 23 (plateau level at 10–14 days) (OECD 305).

Toxicity: There are data for 3 trophic levels, most sensitive crustacean (Daphnia magna) NOEC 0.014 microg/L.

Risk

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

PEC = 0.00017 microg/L.

PNEC = Lowest NOEC, 0.014 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 0.0014 microg/L

PEC/PNEC = 0.12 which gives the risk low.

Fass environmental information

Fass environmental information for Afinitor from Novartis (retrieved on 2025-06-30).

Hazard

Persistence: DT₅₀ in total system = 2.0–3.1 days (OECD 308).

Bioaccumulation: Log K_ow = 4.0. Steady state BCF = 23 (plateau level at 10–14 days) (OECD 305).

Toxicity: There are data for 3 trophic levels, most sensitive crustacean (Daphnia magna) NOEC 0.014 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2021. PEC/PNEC = 0.0935 which gives the risk insignificant.