Irbesartan

Detailed information

Fass environmental information

Fass environmental information for Approvel (irbesartan) from Sanofi AB (downloaded 2020-11-04).

Hazard

Persistence: "As DT50_{total system} < 32 days with still more than 15% of the parent compounds remaining at the end of the study, the correct phrase is: “Irbesartan is slowly degraded in the environment”."

Bioaccumulation: Log K_ow = 1.13 at pH 7 (OECD 107).

Chronic toxicityt: There is NOEC for 3 trophic levels, lowest NOEC for fish (Pimephales promelas) ("NOEC 28 days (growth)") 7 040 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2016. PEC/PNEC = 0.000387 which gives the risk insignificant, i.e. consideration has not been given to measured levels in the environment.

EMA's scientific discussion

Scientific discussion for different medicinal products with irbesartan with the same conclusion for example Approvel "EPAR - Scientific Dissussion" published 16/10/2004.

Hazard

Persistence: No data.

Bioaccumulation: No data.

Toxicity: No data.

Risk

"The risk of an environmental impact from the use of irbesartan is of no concern."

Since 2006, an Environmental Risk Assessment (ERA) for the active pharmaceutical substances 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.

Report Goodpoint 2019

Comparative assessment of environmental risk when using angiotensin II antagonists candesartan, losartan, valsartan, irbesartan, eprosartan and telmisartan from a Swedish perspective (Report Goodpoint 2019).

Angiotensin receptor blockers are relatively stable and can reach the aquatic environment at concentrations higher than that of many other pharmaceuticals. They are all fat-soluble, suggesting high potential for bioconcentration in biota, which has been documented for irbesartan, since telmisartan does not bioconcentrate in proportion to its very high fat solubility. Bioconcentration data for the other substances are missing. The target is preserved in fish but not invertebrates and algae. However, growth studies (28–32 days) of fish for four of the substances (candesartan, losartan, valsartan, irbesartan) show low toxicity, but mechanism-based efficacy data are completely lacking for all.

Based on the information, none of the angiotensin receptor blockers can be attributed to "high" environmental risk, at the same time irbesartan stands out as a substance with higher risk than the others, based on available data. Sales of irbesartan are low in relation to candesartan and losartan. In 2018, over 18 times more losartan than irbesartan was prescribed and just over 18 times more candesartan than irbesartan in Sweden (in DDD count, excluding combination preparation). Therefore, if irbesartan was substituted for losartan or candesartan, the levels of losartan or candesartan in the environment would probably only increase by about 6% on average and therefore increase the environmental risk for these marginally, but it would eliminate the environmental risk with irbesartan. However, it should be mentioned that the environmental risk is unclear for all substances studied.

Based on concentrations of irbesartan over CEC (critical environmental concentration) in Swedish surface water, as well as bioconcentration in wild fish and a relatively high persistence in wastewater treatment plants and the environment, there is a risk picture that should be further investigated. The reasons for the replacement of irbesartan are moderate at present, and the situation is difficult to assess. An exchange of irbesartan with either losartan or candesartan may be justified, primarily based on the fact that the environmental exposure to losartan or candesartan would increase only marginally.

Region Stockholm – pharmaceuticals with risk for negative environmental impact

Irbesartan is included in Region Stockholm's list of pharmaceuticals with risk for negative environmental impact according to the environmental program 2017–2021. Irbesartan has been detected in treated wastewater and surface water in Region Stockholm in 2018.

Suggestions on how to reduce the emissions of irbesartan

Concrete proposals on how to work to reduce emissions of environmentally harmful pharmaceuticals on the list have been developed in close cooperation with the Stockholm Drug and Therapeutics Committee's expert groups. The action proposals were developed from an environmental perspective. The patient's best always goes first and several pharmaceuticals on the list are also included in the Wise list. (The Wise list is the drug formulary of essential medicines for common diseases in Region Stockholm from the Drug and Therapeutics Committee.) However, for such pharmaceuticals, there may be measures that could reduce the environmental impact.