Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Levonorgestrel

Hazard 9 P 3 B 3 T 3 Risk See below

Information

Levonorgestrel has a log P 3.8, i.e. below 4 which is the limit for a substance to be considered to have low potential for bioaccumulation. However, the substance binds to Sex Hormone Binding Globulin (SHBG), and binding to SHBG is supposed of contributing to the exceptionally high bioconcentration ability (and thus potency) observed in fish.

Estimated levels in Swedish surface water may be sufficient to interfere with reproduction in fish. Fish exposed to purified effluent accumulates levonorgestrel to concentrations exceeding the serum concentrations achieved in women using birth control pills.

Levonorgestrel is included in the Stockholm County Council's table of pharmaceuticals with risk for negative environmental impact according to the environmental program 2017–2021 based on lowest effect concentration, LOEC = 0.8 ng/L, and concentrations found in the environment.

Levonorgestrel is recommended in The Wise list.

Environmental classification of pharmaceuticals is taken into consideration, sometimes with other environmental aspects, when selecting pharmaceuticals for the Wise list. When comparable pharmaceuticals are equivalent to medical effects, safety and pharmaceutical efficacy, environmental impact and price are considered.

In comparison between levonorgestrel, norethisterone and medroxyprogesterone, medroxyprogesterone is preferred from an environmental point of view.

When using combination preparations with gestagen and estrogen, the estrogen component must also be considered. In particular, levonogestrel stands out as a drug with increased environmental risk. Environmental risk assessment is therefore relevant for both the gestagen and the estrogenic component.

In total, levonorgestrel + ethinylestradiol and etonogestrel + ethinylestradiol are considered to be the highest environmental risk, drospirenone + ethinylestradiol lower risk (based on gestagen component) and nomegestrol and estradiol lowest risk (based primarily on the gestagen component but also the estrogen component).

Suggestions on how to reduce the release of levonorgestrel

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 levonorgestrel

  • Levonorgestrel is recommended in The Wise list.
  • Individual adjustment of contraception is important to optimize treatment and avoid side effects.
  • When using oral combined hormonal contraceptives, the amount of levonorgestrel administered per day is multiply higher than the dose given by the long-acting levonorgestrel-releasing hormone spirals. Jaydess, Mirena and Kyleena (recommended in the Wise list) can therefore be an alternative to combined contraceptives from an environmental point of view. The long-acting Nexplanon p-implant with etonogestrel is another option (recommended in the Wise list).
  • Ensure that you, in your own business, discard any leftover pharmaceuticals and use the hormone spirals and p-implants correctly, http://www.janusinfo.se/Rutiner/Hantering-av-lakemedel/ 
  • Inform the patient about the importance of discarding the leftover pharmaceutical correctly. Order the folder for patients "Protect the Environment – Throw in the Right Way".

The risk classification high, according to Fass.se, is based on total sold amount (kg) of the substance in Sweden during the year 2013 and the toxicity of the substance.

References

  1. Goodpoint. Prioritering av läkemedel med miljörisk inom SLL. Stockholm: Goodpoint; 2016. Rapport LS 2016–0634.
  2. Zeilinger J, Steger-Hartmann T, Maser E, Goller S, Vonk R, Länge R. Effects of synthetic gestagens on fish reproduction. Environ Toxicol Chem. 2009;28:2663-70.
  3. Fick J, Lindberg RH, Parkkonen J, Arvidsson B, Tysklind M, Larsson DG. Therapeutic levels of levonorgestrel detected in blood plasma of fish: results from screening rainbow trout exposed to treated sewage effluents. Environ Sci Technol. 2010;44:2661-6.
  4. Miguel-Queralt S, Hammond GL. Sex hormone-binding globulin in fish gills is a portal for sex steroids breached by xenobiotics. Endocrinology. 2008;149:4269-75.
  5. Friel PN, Hinchcliffe C, Wright JV. Hormone replacement with estradiol: conventional oral doses result in excessive exposure to estrone. Altern Med Rev. 2005;10:36-41.
  6. Fick J, Lindberg RH, Tysklind M, Larsson DG. Predicted critical environmental concentrations for 500 pharmaceuticals. Regul Toxicol Pharmacol. 2010;58:516-23.
  7. Fent K. Progestins as endocrine disrupters in aquatic ecosystems: Concentrations, effects and risk assessment. Environ Int. 2015;84:115-30.
  8. Runnalls TJ, Beresford N, Kugathas S, Margiotta-Casaluci L, Scholze M, Scott AP et al. From single chemicals to mixtures--reproductive effects of levonorgestrel and ethinylestradiol on the fathead minnow. Aquat Toxicol. 2015;169:152-67.
  9. Stockholms läns landsting. Förteckning över miljöbelastande läkemedel med åtgärdsförslag framtagen inom ramen för SLL:s miljöprogram 2017–2021.
  10. Fass.se för vårdpersonal
  11. Stockholms läns landsting. Kloka listan (Wise list).
  12. Stockholm County Council. The Wise List 2015.

Author: Health and Medical Care Administration, Region Stockholm