Hazard 4 P 3 B 0 T 1 Risk See below
The T-value in the score for hazard refers to chronic toxicity. Underlying data for P, B and T are from Fass. For the risk, see report Goodpoint 2019.
Several assessment reports for different medicinal products have been found on the EMA's website, however, without available data for the environmental risk assessment, for example, an ssessment report for telmisartan from Twynsta (telmisartan, amlodipin) 22 July 2010, EMA/576613/2010.
"The applicant provided a revised environmental risk assessment for the active ingredients telmisartan and amlodipine. Some minor corrective changes in the Phase II assessment of telmisartan were included. The changes made for telmisartan have no influence on the overall conclusion of the risk assessment of telmisartan. [...] The applicant provided a revised environmental risk assessment for the active ingredients telmisartan and amlodipine. However, a study on sediment dwelling organisms is missing and is requested as a Follow Up Measure." No such information has been found on EMA's website.
Fass environmental information for Micardis (telmisartan) from Boehringer Ingelheim (downloaded 2019-11-27).
Persistence: "Telmisartan was not readily biodegradable (FDA, TAD 3.11, GLP). Further, in an OECD Guideline 308 simulation study, Telmisartan was considered persistent. Based on these combined data, Telmisartan is considered “potentially persistent”." Se Fass för detaljer.
Bioaccumulation: "BCF of 5 in fish was derived in an OECD 305."
Chronic toxicity: There are data for 3 trophic levels, most sensitive algae (Desmodesmus subspicatus) NOEC 490 microg/L.
PEC/PNEC is based on sales data in Sweden in year 2016. PEC/PNEC = 0.00027 which gives the risk insignificant.
Telmisartan has been detected in treated wastewater and in surface water in Region Stockholm during 2018.
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.
Author: Health and Medical Care Administration, Region Stockholm