Sitagliptin

Detailed information

Assessment report Januvia

Below are assessment reports for Januvia (sitagliptin).

Hazard

Persistence: "Sitagliptin is not readily biodegradable. The MAH (Marketing Authorisation Holder, ed. note.) submitted the results of a test on the aerobic and anaerobic transformation in aquatic sediment systems according to OECD 308. According to these results the submission of a sediment toxicity test deemed necessary. The MAH provided the results of a sediment toxicity test according OECD 218." (Assessment report 29 July 2009, EMEA/517697/2009.)

Bioaccumulation: Log K_ow = - 0,25 vid pH 7. "Citation, study report is missing." (Assessment report 02 June 2009 Doc. Ref: EMEA/363653/2009.)

Toxicity: There are data for 2 trophic levels, most sensitive fish (Pimephales promelas) NOEC 9.2 mg/L. "The MAH has committed to perform and submit the results of an algae growth inhibition test (OECD 201) by July 2009." (Assessment report 02 June 2009 Doc. Ref: EMEA/363653/2009.) "The MAH has submitted in July 2009 the requested new algal study pursuant to the latest OECD 201. The CHMP concluded that the test was valid and that the risk to the surface water of sitagliptin can be assumed to be negligible." (Assessment report september 2009, Doc. Ref: EMEA/777097/2009)

Risk

"The comparison of the predicted concentration in surface water with the predicted no effect concentration did not result in risk quotients above 1 (for algae, fish and water flea) or 0.1 (for micro-organisms)." (Assessment report 29 July 2009, EMEA/517697/2009.)

Assessment report Sitagliptin/Metformin hydrochloride Mylan

Assessment report about sitagliptin from Sitagliptin/Metformin hydrochloride Mylan, 16 December 2021, EMA/27581/2022.

"The environmental risk assessment including PEC_surfacewater calculation and information about log K_ow is submitted. The PEC values for both metformin hydrochloride and sitagliptin are above the action limit of 0.01 μg/L, therefore, Phase II studies are necessary. The PNEC_surfacewater for metformin has calculated by applying an assessment factor of 10 to the lowest NOEC from multiple chronic studies with algae, daphnids and fish. The PNEC_surfacewater for sitagliptin has calculated by applying an assessment factor of 10 to the lowest NOEC from a study with Pseudokirchneriella subcapitata (green algae). The PEC_surfacewater to PNEC_surfacewater ratio (risk quotient) for both metformin hydrochloride and sitagliptin is below 1, and it can be concluded that the active substances are unlikely to represented risk for aquatic environment. The log K_ow values for both metformin hydrochloride and sitagliptin are below the action limit 4.5, no further PBT (Persistence, Bioaccumulation, Toxicity) assessment is deemed necessary."

Generally about assessment reports for generics

A generic company can justify to the Swedish Medical Products Agency or the European Medicines Agency, why it has not submitted environmental risk assessment (ERA) studies for a medicinal product. The generic company may consider that the introduction of a generic will unlikely result in any significant increase in the combined sales volumes of all medicinal products with an active substance. The ERA is expected to be similar and not increased. This can be accepted by the authorities. However, in some cases the original medicinal product for an active substance can be withdrawn from the market and in that case, there is no public environmental information on the authority's website. The background to similar environmental risk can be questioned as the introduction of a generic, often with a much lower price, can change the market and the use can increase significantly, which could change the environmental risk.

Assessment reports for generics

Assessment reports about sitagliptin with similar information: Sitagliptin Accord, 24 February 2022, EMA/181231/2022, Sitagliptin/Metformin hydrochloride Accord 19 May 2022, EMA/568807/2022 and Sitagliptin SUN 14 October 2021, EMA/611380/2021. From the latter assessment report: "No Environmental Risk Assessment studies were submitted. This was justified by the applicant as the introduction of Sitagliptin SUN manufactured by Sun Pharmaceutical Industries Europe B.V. is considered unlikely to result in any significant increase in the combined sales volumes for all sitagliptin fumarate containing products and the exposure of the environment to the active substance. Thus, the ERA is expected to be similar."

Fass environmental information

Fass environmental information for Januvia from MSD (downloaded 2025-01-14).

Hazard

Persistence: "Sitagliptin is slightly degradable in biological systems, however does not meet the criteria for ready degradability. In addition, the half-life in the total system exceeded 120 days, therefore the phrase “Sitagliptin is potentially persistent in the environment” was thus chosen."

Bioaccumulation: Log K_ow = -0.03 at pH 7 (OECD 107).

Toxicity: There are data for 3 trophic levels, most sensitive algae (Pseudokirchneriella subcapitata) NOEC 2200 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2022. PEC/PNEC = 0.0013 which gives the risk insignificant.