Pemetrexed

Detailed information

Fass environmental information

Fass environmental information for Alimta (pemetrexed) from Eli Lilly Sweden AB (retrieved on 2026-03-18).

Excretion (metabolism)

"Pemetrexed is not metabolized to an appreciable extent, with 70% to 90% of the dose recovered unchanged within the first 24 hours following administration (Alimta Package Insert)."

Hazard

Persistence: Pemetrexed shows limited ready biodegradability with 20% mineralisation over 29 days, but is inherently biodegradable in activated sludge, where more than 90% disappears within one hour and none remains after 24 hours. In water–sediment systems, pemetrexed degraded rapidly with a half‑life of less than three days, and transformation products continued to degrade over the 100‑day study. Abiotic hydrolysis was low, with less than 10% degradation at pH 4, 7 and 9. Overall, pemetrexed is considered to be degradable in the environment.

Bioaccumulation: Log K_ow < 0.3 (OECD 117).

Toxicity: There are data for 3 trophic levels, most sensitive crustacean NOEC 1200 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2023.

PEC = 0.00065 microg/L.

PNEC = Lowest NOEC, 1200 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 120 microg/L.

PEC/PNEC = 0.00000538 which gives the risk insignificant.

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.

Scientific discussion Alimta 2006

Scientific discussion for Alimta 2006-02-09.

Hazard

Persistence: "Pemetrexed is highly biodegradable in sewage treatment sludge."

Bioaccumulation: "The K_ow of pemetrexed also indicates a low potential for bioaccumulation in aquatic organisms." No data are presented.

Toxicity: No data.

Risk

"Pemetrexed is highly biodegradable in sewage treatment sludge. Less than 1000 kg of the active ingredient in pemetrexed is expected to be used within a year in Europe, resulting in concentrations in the influent of sewage treatment facilities less than 0.03 µg/L. For these reasons, exposure to concentrations of pemetrexed in the environment would not pose an environmental concern."

Scientific discussion Alimta 2008

Scientific discussion for Alimta, London, 8 April 2008, EMEA/H/C/000564/II/0009.

"The MAH (Marketing Authorisation Holder) has also provided an environmental risk assessment (ERA) as part of the current application for the use of pemetrexed as first line treatment of non-small cell lung carcinoma. However, this ERA does not completely fulfil the Phase II requirements of the current Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use (CHMP/SWP/4447/00). As a consequence, the MAH has agreed to conduct the requested Phase II studies as a post-opinion commitment." No such data were found during a search of the EMA website (2026‑03‑18).

Assessment reports for generics

There are several assessment reports for generic products containing pemetrexed with similar information. Below is the most recent one: Pemetrexed Baxter, 13 October 2022, EMA/CHMP/251833/2022.

"No Environmental Risk Assessment studies were submitted. This was justified by the applicant as the introduction of Pemetrexed Baxter manufactured by Baxter Holding B.V. is considered unlikely to result in any significant increase in the combined sales volumes for all pemetrexed containing products and the exposure of the environment to the active substance. Thus, the ERA is expected to be similar."

Comment on generics

After the implementation of the latest European Medicines Agency (EMA) ERA guideline (1 September 2024), a generic company has the following options for Article 10 procedures under Directive 2001/83/EC:

i) to argue that a full ERA is not required because the pharmaceutical substance belongs to certain substance groups (e.g., so-called natural substances);

ii) to identify an official ERA from a previously accepted product and use it; or

iii) to develop its own ERA according to the latest EMA ERA guideline.

Arguments for not submitting an Environmental Risk Assessment (ERA) based on the claim that total environmental exposure has not increased (via total sales volumes) belong to the previous ERA guideline system (2006–2024) and are no longer applicable. Regarding option ii), it should be noted that if a reference ERA exists, the generic company must demonstrate that its conclusions remain technically relevant (since the latest ERA guideline introduced several new technical requirements absent in the previous ERA guideline) and in terms of exposure (showing that the estimated exposure used in the reference ERA remains reasonable). Regulatory authorities (national and EMA) recommend that generic companies attempt to obtain reference ERA documentation from other companies via a so-called Letter of Access (LoA). However, if this is not possible, it remains feasible to argue that the conclusions of an existing reference ERA are still relevant based on information gathered from public assessment reports (summarized descriptions of environmental risk assessments) and product information (to confirm that dosages, indications, etc., have not changed). It should be noted that in some cases, reference ERAs approved between 2006 and 2024 may need to be modified (e.g., with additional experimental studies). If no previous reference ERA can be identified or used, the generic company must commit to developing its own ERA.