Zonisamide

Detailed information

General information about assessment reports

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.

Assessment report for Zonegran (zonisamide), Eisai GmbH, scientific discussion 2008-01-29

"The ERA of zonisamide was performed based on the most recent draft CPMP Note for Guidance (24 July 2003). The Phase I assessment indicated that a Phase II assessment is needed. Phase II A studies to determine the PNEC (predicted no effect concentration) value and fate studies have been performed, although not to the OECD standard. However, the justification for these studies was considered to be acceptable. Based on the default Fpen value (1%) the PEC/PNEC is lower than 1 (ratio=0.2). It is therefore concluded that the use of zonisamide does not pose a risk to the environment."

Assessment report for Zonegran (zonisamide), Eisai GmbH, EMA/CHMP/345694/2012

"The CHMP however did not agree that the elimination/removal in wastewater treatment plants and other aqueous environmental compartments was plausible due to the observed photodegradation. In wastewater treatment plants water is not clear and therefore there is insufficient sunlight. From toxicity tests in clear water zonisamide was hardly degraded after 2–3 days. [...] The MAH concludes that no environmental risk is presented by zonisamide from the use of Zonegran Hard Capsules (25 mg, 50 mg, 100 mg) and Zonegran Orodispersible Tablets (25 mg, 50 mg, 100 mg, 300 mg), taking into account the indication as adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation, in adults and the extension of the indication to include adjunctive use in paediatric patients (aged 6 years and above) and monotherapy in newly diagnosed adult patients. The conclusion of the completed Phase II environmental risk assessments for zonisamide was supported by CHMP."

Assessment report for Zonegran (zonisamide), Eisai GmbH, 25 July 2013, EMA/470045/2013

"However, a final conclusion on the environmental risk cannot be drawn due to the absence of a valid algae growth inhibition test and a sediment organism toxicity test. The MAH was requested to provide a valid algae growth inhibition test and a study on sediment dwelling organisms. Further justification by the MAH as to why the provided algae growth inhibition test and sediment organism toxicity test can be considered valid was not accepted by the CHMP. The alga test previously submitted for procedure EMEA/H/C/0577/II/59 is not valid due to irregular testing within the first 24 hours. Within this time there was no illumination resulting in a missing exponential growth. This is a formal aspect of the OECD 201 guideline which cannot be waived by the argumentation of the applicant. [...] A final conclusion on the environmental risk posed by Zonisamide cannot be drawn due to missing information on the potential effects on sediment dwelling organisms and algae growth. The Applicant is recommended to submit a valid algae growth inhibition test and a sediment organism toxicity test." No such requested data has been found on the EMA website (2021-04-14).

Report Goodpoint 2020

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.