Candesartan

Detailed information

Fass environmental information

Fass environmental information for Candesartan Krka from Krka (downloaded 2021-06-11).

Hazard

Persistence according to OECD 308: 0.1 mg/L in overlying water with high organic matter sediment Note 3 (= results are expressed as nominal concentrations) T = 222 d.

0.1 mg/L in overlying water with low organic matter T = 97 d.

There was no significant degradation of candesartan under the test conditions. Degradation half lives for the total system could not be calculated. In Fass: Candesartan is potentially persistent. The database, Pharmaceuticals and Environment, reference group believes that based on these results, a drug substance is persistent and not potentially persistent, hence the information that candesartan is persistent in the initial summary information.

Bioaccumulation according to OECD 107: Log D = 2.11 @ pH 5, 20 degrees C, Log D = - 0.68 @ pH 7, 20 degrees C. "Since Log P < 4 the phrase ‘Candesartan has low potential for bioaccumulation’ is assigned."

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish (Pimephales promelas) NOEC 1000 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2016. PEC/PNEC = 0.00145 which gives the risk insignificant.

Report Goodpoint 2019 from a Swedish perspective

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

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.