Methotrexate

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 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 Jylamvo (metotrexat) 26 January 2017, EMA/78284/2017.

Persistence: "EPI* (EPA) – BIOWIN v4.10: Not readily biodegradable", i.e. P. EPI (Estimation Program Interface) BIOWIN is a computer program for QSAR calculations (Quantitative Structure Activity Relationship: quantitative mathematical connection between the chemical structure/physicochemical properties of the various substances and their biological and chemical activities). Conclusion P.

Bioaccumulation: BCF = 3.162 L/Kg wet-wt. Conclusion B (N).

Acute toxicity: There are EC₅₀ values ​​for algae and crustaceans, lowest for algae 10 mg/L.

"The Phase I PEC_surfacewater of Methotrexate was calculated according the EMA guideline formula. It exceeds the action limit of 0.01 μg/L (PEC=0.021 μg/L for a DOSEai of 4.29 mg/day). A standard Phase II fate and effects assessment was not performed by the applicant. [---] The Applicant did not carry out a Phase II environmental fate and chronic effect analysis based on relevant published scientific literature. This was justified by the applicant as the introduction of Jylamvo manufactured by Therakind Limited is considered unlikely to result in any significant increase in the combined sales volumes for all methotrexate containing products and the exposure of the environment to the active substance. Thus, the ERA is expected to be similar and not increased. [---] Methotrexate is a cytotoxic substance the applicant followed the request of the CHMP to include the following sentence into SmPC (point 6.6) and package leaflet (point 5): “Any unused product or waste should be disposed of in accordance with local requirements for cytotoxic products”."

Fass environmental information

Fass environmental information for Methotrexate Teva (downloaded 2023-10-04).

Hazard

Persistence: No data.

Bioaccumulation: Log P = - 1.85.

Toxicity: No data.

Risk

Risk of environmental impact cannot be excluded, since there is not sufficient ecotoxicity data available.

It is voluntary for manufacturers to provide information on the environmental impact.

Report from Goodpoint 2016

According to the report from Goodoint 2016, there is an exceptionally good margin between exposure based on Swedish conditions and known effect level.