Clopidogrel

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.

Assessment report for Pavix and Iscover

Assessment report for Plavix och Iscover, Sanofi-Aventis, 10 December 2020, EMA/CHMP/657331/2020.

Hazard

Persistence OECD 308: "Day 104: Water layer:parent compound: 0.0%. Transformation products: 14.8%. Sediment extract: parent compound: 0.0%. Transformation products: 47.9%."

Bioaccumulation: Log K_ow: 3.76±0.0013. OECD 305: "The evaluation of BCF expressed on a 5% lipid content basis is calculated to be 358 mg/L for the whole fish. The BCF values do not indicate any likelihood of significant bioconcentration of clopidogrel in the environment."

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish NOEC 310 microg/L.

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective and and from the premise that "this variation relates to an addition of a new therapeutic indication for clopidogrel to adult patients with high-risk transient ischemic attack or minor ischemic stroke."

PEC_surfacewater = 0.515 microg/L.

PNEC = Lowest NOEC, 310 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 31 microg/L

PEC/PNEC = 0.0166 which gives the risk insignificant.

Assessment report for Clopidogrel/Acetylsalicylic acid Mylan

Assessment report for Clopidogrel/Acetylsalicylic acid Mylan 14 November 2019, EMA/7091/2020.

"No Environmental Risk Assessment studies were submitted. The justification initially submitted by the Applicant for not providing new ERA studies was not considered adequate. In line with the Questions and answers on Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use (EMEA/CHMP/SWP/4447/00), the Applicant was requested during the procedure to justify the absence of a possible significant increase of environmental exposure to the drug substances, providing concrete relevant data such the consumed quantities of active substances in kg/year, and based on European disease prevalence data for the refinement of Fpen. Furthermore, the Applicant was requested to provide information on an experimentally derived n-octanol/water partition coefficient (log Kow) for acetylsalicylic acid and clopidogrel. The Applicant provided the requested revised justification which was considered acceptable by the CHMP. The introduction of Clopidogrel/Acetylsalicylic acid Mylan manufactured by Mylan S.A.S is considered unlikely to result in any significant increase in the combined sales volumes for all clopidogrel/acetylsalicylic acid containing products and the exposure of the environment to the active substance. Thus, the ERA is expected to be similar."

Assessment report for DuoCover

Below is information about clopidogrel from DuoCover's (clopidogrel, acetylsalicylic acid) assessment report 17 December 2009 Doc. Ref: EMA/CHMP/195986/2010, EMEA/H/C/001144.

"The submitted environmental risk assessment (ERA) includes a phase II tier A analysis. However, the ERA Phase II tier A analyses for clopidogrel have not been completed. The adsorption/desorption study (OECD106) submitted with the Applicant`s responses to the CHMP D120 LOQ (List of Questions) indicate that clopidogrel is not expected to pose a risk to the terrestrial compartment. The aerobic transformation study in aquatic sediment system (OECD308), also submitted with the Applicant`s responses to the CHMP D120 LOQ, indicates the need to perform a sediment organism toxicity test. The applicant commits to submit an updated ERA that includes the ongoing and agreed studies, namely: the log Kow determination and if required a bioconcentration test (OECD 305), the repetition of the activated sludge respiration inhibition test (OECD 209) and the consequent revision of the PEC/PNEC ratio, and the sediment organism toxicity test. The commitment includes identifying the metabolite (transformation product > 10% as well as in water as in sediment, detected in chromatography region 4) as requested in OECD guideline 308. This was acceptable to CHMP." Ingen ytterligare information har återfunnits på EMAs webbplats.

Fass environmental information

Fass environmental information for Plavix (clopidogrel) from Sanofi AB (downloaded 2022-04-26).

Hazard

Persistence OECD 308: "DT50_{total system} = 7.5 (sediment 1) - 13.5 (sediment 2) days; DT50_water = 7.2 (sediment 1) - 8.1 (sediment 2) days."

Bioaccumulation: Log P_ow = 3.76 at pH 7.

Chronic toxicity: There is NOEC for 3 trophic levels, lowest NOEC for fish (Pimephales promelas) 310 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2019. PEC/PNEC = 0.014 which gives the risk insignificant.