This summary information on persistence, biockumulation and toxicity comes from Fass UCB Nordic. The risk comes from the Goodpoint report.
Persistence. Levetiracetam is potentially persistent.
Bioaccumulation. Levetiracetam has low potential for bioaccumulation.
Toxicity. Levetiracetam has moderate acute toxicity.
Risk. No obvious environmental risk from a Swedish perspective.
Levetiracetam has different classifications on fass.se. According to Lif (the trade association for the research-based pharmaceutical industry in Sweden) the various pharmaceutical companies compile environmental information for their active substances based on internal studies and published data. Based on data, which may thus differ between different pharmaceutical companies, the companies assess the environmental risk with guidance from “Environmental classification of pharmaceuticals at www.fass.se – Guidance for pharmaceutical companies 2012”. The Swedish Environmental Institute (IVL) reviews the assessment but does not have the task of coordinating/harmonizing environmental information from different pharmaceutical companies for the same active substance.
Persistence: "Ready degradability: Results show not more than 4 % degradation in 28 days. (Protocol: OECD 301) (Ref II and III) Levetiracetam does not pass the criteria for ready biodegradability and since there is no information available on grade of mineralisation the phrase: ”Levetiracetam is potentially persistent” should be used."
Bioaccumulation: Log Pow = -0.64 at pH 7,4 (method unknown).
Acute toxicity: There is data for 1 trophic level, Crustacean (Daphnia magna) EC50 48 h (immobilization): >100 000 microg/L (Protocol: OECD 202). Comment: Values reported as greater than are not according to the guidelines. The actual value may be lower.
"Environmental risk classification (PEC/PNEC ratio). The PEC/PNEC ratio could not be determined because there are not sufficient ecotoxicological test results, hence justifies for the environmental risk standard phrase ”Risk of environmental impact of levetiracetam cannot be excluded, since there is not sufficient ecotoxicity data available”."
Persistence: Levetiracetam is potentially persistent.
Bioaccumulation: Levetiracetam has low potential for bioaccumulation.
Toxicity: No data.
Risk of environmental impact of levetiracetam cannot be excluded, since there is not sufficient ecotoxicity data available.
Persistence: It cannot be excluded that levetiracetam is persistent, due to the lack of data.
Bioaccumulation: It cannot be excluded that levetiracetam bioaccumulates, due to the lack of data.
Toxicity: No data.
Risk of environmental impact of levetiracetam cannot be excluded, due to the lack of environmental toxicity data.
Since 2006, an Environmental Risk Assessment (ERA) for the active pharmaceutical substance shall accompany an application for a marketing authorisation in EU for a medicinal product for human use. Parts of environmental data can be found in the public investigation report (PAR/EPAR for medicinal product through a centralized procedure). Since the benefit/risk assessment for human medicinal products at present does not include environmental effects, an update of the environmental risk assessment is not required for renewals of marketing authorizations. There is thus no requirement for companies to stay informed about the development of their substances from an environmental point of view and consequently to update the environmental risk assessment as new data are published.
"The predicted environmental concentrations are 0.3 µg/l in surface water, 1 ng/kg in soil and insignificant in the air."
There are several assessment reports for generics with more or less the same information. Information from one of the recent assessment reports is presented below.
"No environmental risk assessment was submitted. This was justified by the applicant as the introduction of Levetiracetam Hospira is considered unlikely to result in any significant increase in the combined sales volumes for all levetiracetam containing products and the exposure of the environment to the active substance. Thus, the environmental risk was expected to remain unchanged and not to increase."
Comparative assessment of environmental risk when using antiepileptics: lamotrigine, levetiracetam, oxcarbazepine, topiramate and zonisamide from a Swedish perspective.
Although lamotrigine is linked to a slightly higher risk than other substances (based on higher fat solubility), there is no obvious environmental risk for any of the substances. Therefore, no exchanges from an environmental risk point of view are recommended. Measurements of lamotrigine in Swedish wastewater/biota are recommended.
Author: Health and Medical Care Administration, Region Stockholm