Levonorgestrel

Detailed information

Fass environmental information

Fass environmental information for Jaydess (levonorgestrel) from Bayer (downloaded 2020-11-05).

Hazard

Persistence: OECD 308: "Levonorgestrel was incubated in glass vessels containing sediment and overlaying water over 100 days. [...] The degradation rate was 6–7% at the end of the incubation period. The DT₅₀ (disappearance half-life from the water phase) for parent compound in water was estimated with 2.5 and 3.2 days for the fine and coarse sediment, respectively. The overall disappearance half-life from the system exceeded the threshold of 120 days described in the FASS guidance. Therefore, levonorgestrel can be classified as being 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 levonorgestrel is persistent in the initial summary information.

Bioaccumulation: "Log P_OW 3.55 (Shake flask method, FDA TAD 3.02). [...] According to the BCF of 119 to 250, levonorgestrel has low potential for bioaccumulation."

Toxicity: There are data for 3 trophic levels, most sensitive fish fathead minnow Pimephales promelas) NOEC 21 days (fish reproduction test; fecundity, sexual reversal) = 0.0001 microg/L (EC10) (OECD 229).

Risk

PEC/PNEC is based on sales data in Sweden in year 2019. PEC/PNEC = 141 which gives the risk high.

Report Goodpoint 2016

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 Region Stockholm'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.

Report on progestogens from Goodpoint

Levonorgestrel has a BCF value that is below the limit value for a substance to be considered to have a high potential to bioaccumulate. However, the substance binds to SHBG, and binding to SHBG is supposed of contributing to the exceptionally high bioconcentration ability (and thus potency) observed in fish.

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).

The method, tablets versus long-acting reversible contraception (LARC), is also important, see below under "Concrete proposal for levonorgestrel".

The Wise list

Levonorgestrel is recommended 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.

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.

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