Ticagrelor

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 Brilique from 2017

Assessment report for Brilique (ticagrelor) 26 March 2017, EMA/274695/2017.

"The revised ERA was not submitted with the current application. The MAH justified that since the dose, indication and patient population for this extension application have not changed, no increase in the predicted environmental exposure concentration is foreseen and ticagrelor is not expected to pose a risk to the environment. Accordingly, based on EMA CHMP guideline documents (Guideline on the environmental risk assessment of medicinal products for human use [EMEA/CHMP/SWP/4447/00 corr 2]; and Questions and answers on 'Guideline on the environmental risk assessment of medicinal products for human use [CHMP/SWP/44609/2010]), a revision of the ERA for ticagrelor was not required."

Assessment report for Brilique from 2015

Assessment report for Brilique (ticagrelor) 17 December 2015, EMA/CHMP/18297/2016.

Hazard

Persistence: "DegT50: DT_{50, water} = 4.7/6.2 d, DT_{50, sediment} = 49/66 d, DT_{50, system} = 23/42 d. Conclusion: DT₅₀ values corrected to 12°C. Conclusion: not P.
OECD 308: DT_{50, water} = 2.2/2.9 d, DT_{50, sediment} = 23/31 d, DT_{50, whole system} = 11/20 d. shifting to sediment > 10%. DT₅₀values at 20°C; Significant shifting to sediment observed." According to expert ticagrlor is not persistent (Researcher at the Department of Environmental Science and Analytical Chemistry (ACES), Stockholm University 2019-10-21).

Bioaccumulation: log D_ow > 4.0, BCF < 6.4 L/kg. Conclusion: not B.

Toxicity: There are data for 3 trophic levels, most sensitive crustacean (Daphnia sp.) NOEC 530 microg/L.

Risk

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

PEC_surfacewater, default Fpen = 0.9 microg/L.

PNEC = Lowest NOEC, 530 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 53 microg/L

PEC/PNEC = 0.017 which gives the risk insignificant.

Fass environmental information

Environmental information is missing on fass.se for ticagrelor (2022-04-26). It is voluntary for manufacturers to provide information on environmental impact on fass.se. Below is Fass environmental information for Brilique from AstraZeneca (downloaded 2019-10-21).

Hazard

Persistence: "Overall, evidence from the OECD 308 study suggests that ticagrelor will not be persistent in the aquatic environment. [---] Therefore, the phrase “Ticagrelor is degraded in the environment” has been assigned." For details see Fass.

Bioaccumulation: BCF = 6.36.

Chronic toxicity: There are data for 3 trophic levels, most sensitive crustacean (Daphnia magna) NOEC 530 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2017. PEC/PNEC = 0.0025 which gives the risk insignificant.