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Irbesartan

Antihypertensive Agents
CATEGORIES

Antihypertensive Agents, Angiotensin II Type 1 Receptor Blockers, Angiotensin Receptor Antagonists


ALIASES

Aprovel, CoAprovel, Ifirmacombi, Ifirmasta, Irbesartan Accord, Irbesartan Actavis, Irbesartan Aurobindo, Irbesartan Bluefish, Irbesartan Jubilant, Irbesartan Mylan, Irbesartan Ranbaxy, Irbesartan STADA, Irbesartan Sandoz, Irbesartan Teva, Irbesartan/Hydrochlorothiazide STADA, Irbesartan/Hydrochlorothiazide Sandoz, Irbesartan/Hydrochlorothiazide Teva, Irbesartan/Hydroklortiazid Actavis, Karvea, Karvezide


SUBSTANCES

irbesartan, irbesartan hydrochloride (anhydrous), irbesartan hydrochloride sesquihydrate


ENVIRONMENTAL CONCERN: HIGH
Irbesartan is an angiotensin receptor blocker (ARB) used mainly for the treatment of hypertension. It competes with angiotensin II for binding at the AT1 receptor subtype. Unlike ACE inhibitors, ARBs do not have the adverse effect of dry cough. The use of ARBs is pending revision due to findings from several clinical trials suggesting that this class of drugs may be associated with a small increased risk of cancer.

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HIGH
The T-value in the score for hazard refers to chronic toxicity. Underlying data for P and T are from Fass.se, see below. Data for B is from the report Relative assessment of environmental risk when using angiotensin II antagonists irbesartan and losartan (Goodpoint 2018), see below.

Measured concentrations of irbesartan in surface water are estimated to accumulate in fish at therapeutic concentrations. However, measured concentrations found in single fish have been lower. Mechanism-based data is missing.

Irbesartan is included in the Stockholm County Council's table 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 Stockholm County in the last five years (2012-2016).

Below is Hazard and Risk from Fass environmental information for Approvel (irbesartan) (downloaded 2018-07-09)


Hazard
Persistence: "As DT50total 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 Kow = 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.

Suggestions on how to reduce the release 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 advice. 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. However, for such pharmaceuticals, there may be measures that could reduce the environmental impact.

Concrete proposal for irbesartan
• Irbesartan is not recommended in the Wise List.
• Alternatives such as angiotensin receptor blockers may be candesartan (recommended in the Wise List but insufficient data make it impossible to determine whether it is beneficial from an environmental perspective) or losartan (recommended in the Wise List).
• Candesartan and losartan starter packages are available within the reimbursement system.

Relative assessment of environmental risk when using angiotensin II antagonists irbesartan and losartan in Sweden (Report Goodpoint 2018)
Measurements of irbesartan in incoming and outgoing wastewater in three wastewater treatment plants in Stockholm since 2012 in SLL's internal measurement series, show levels of up to 373 ng/L and, in principle, irbesartan is not reduced in the wastewater treatment plants. Irbesartan is also not microbially readily degradable in laboratory studies.

According to Fass (Aprovel, Sanofi), irbesartan has a log P of 1.13 but Drugbank reports significantly higher predicted log P between 4.5 and 5.56. The fact that irbesartan is found in wild Swedish fish speaks strongly against a log P of 1.13. 

Losartan, recommended in the Wise List, is better from an environmental point of view than irbesartan.

REFERENCES

  1. Goodpoint. Prioritering av läkemedel med miljörisk inom SLL. Stockholm: Goodpoint; 2016. Rapport LS 2016–0634.
  2. IVL Swedish Environmental Research Institute Ltd. Fick J, Lindberg RH, Kaj L, Brorström-Lundén E. Results from the Swedish National Screening Programme 2010. Subreport 3. Pharmaceuticals.
  3. IVL Swedish Environmental Research Institute Ltd Fick J, Lindberg RH, Fång J, Magnér J, Kaj L, Brorström-Lundén E. Screening 2014. Analysis of pharmaceuticals and hormones in samples from WWTPs and receiving waters. Rapport C 135.
  4. Fick J, Lindberg RH, Tysklind M, Larsson DG. Predicted critical environmental concentrations for 500 pharmaceuticals. Regul Toxicol Pharmacol. 2010;58:516-23.
  5. SLL. Sammanställning av läkemedelsprovtagningar - Bearbetning av regional försäljningsstatistik av läkemedel samt datamaterial från Stockholms läns landstings mätprogram för läkemedelssubstanser i vattenmiljö, 2012–2016.
  6. Fass.se för vårdpersonal
  7. Stockholms läns landsting. Förteckning över miljöbelastande läkemedel med åtgärdsförslag framtagen inom ramen för SLL:s miljöprogram 2017–2021.
  8. Goodpoint. Relativ bedömning av miljörisk vid användning av angiotensin II-antagonisterna irbesartan och losartan. Stockholm: Goodpoint; 2018.