Riluzole

Detailed information

Fass environmental information

Fass environmental information for Rilutek (riluzol) from Sanofi AB (retrieved on 2026-04-20).

Excretion (metabolism)

"Less than 1% of riluzole is excreted unchanged. The metabolites (more than 85% are glucurono-conjugated derivatives) are mainly eliminated in urine (90% of the dose). 20 metabolites are identified (in urine). 5-hydroxy-riluzole and hydroxylamine compounds are active but the maximum concentrations of the metabolites are considered too low to be of importance. The pharmacological activity of the other metabolites is not known and has not been investigated."

The environmental information highlights riluzole.

Hazard

Persistence: Biotic degradation was assessed in an inherent biodegradability test, which showed 0 percent degradation after 14 days according to ISO 9408:1991. Since riluzole does not meet the criteria for inherent biodegradability, the use of the phrase that the substance is potentially persistent is justified.

Bioaccumulation: Log K_ow = 3.0.

Acute toxicity: There are data for 3 trophic levels, most sensitive fish LC₅₀ 96 h (lethality): 3 780 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2024.

PEC = 0.00377 microg/L.

PNEC = Lowest LC₅₀, 3 780 microg/L/1000 (Assessment Factor (AF) for 3 acute studies) = 3.78 microg/L.

PEC/PNEC = 9.97*10^-4 which gives the risk insignificant.

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 are available in the public assessment report (PAR/EPAR for centrally approved medicines). Environmental considerations are not included in the benefit-risk assessment for human medicines. If new data emerge after approval that necessitate an update of the environmental risk assessment, a variation application (“type IB C.I.z variation”) must be submitted to the regulatory authority.

The PEC (predicted environmental concentration) values used to calculate risk in the manufacturers' assessment reports are based on the estimated use of the medicinal product to which the assessment report relates, as well as possibly other products from the same company, not all medicinal products containing the same active substance.

EMA’s scientific discussion on Rilutek

EMA’s scientific discussion on Rilutek, 21 October 2005.

"Exposure of the environment to Rilutek was not considered to be a concern as judged from the risk assessment supplied." No data are presented.

Assessment report Riluzole Zentiva

Assessment report for Riluzole Zentiva, Aventis Pharma S.A., 15 March 2012, EMA/241210/2012.

"The ERA provided for this application consists of an adequate justification for the absence of specific study data. The medicinal product subject to this application is intended to be administered in the indication and with posology already approved in the European Community for Rilutek. Based on the assumption that the product is intended to substitute for an identical product on the market, the approval of Riluzole Zentiva should not result in an increase of the total quantity of the active ingredients released in to the environment. Therefore, the CHMP was of the view that it should not result in an increase of risk to the environment during storage, distribution, use and disposal."

Comment on generics

After the implementation of the latest European Medicines Agency (EMA) ERA guideline (1 September 2024), a generic company has the following options for Article 10 procedures under Directive 2001/83/EC:

i) to argue that a full ERA is not required because the pharmaceutical substance belongs to certain substance groups (e.g., so-called natural substances);

ii) to identify an official ERA from a previously accepted product and use it; or

iii) to develop its own ERA according to the latest EMA ERA guideline.

Arguments for not submitting an Environmental Risk Assessment (ERA) based on the claim that total environmental exposure has not increased (via total sales volumes) belong to the previous ERA guideline system (2006–2024) and are no longer applicable. Regarding option ii), it should be noted that if a reference ERA exists, the generic company must demonstrate that its conclusions remain technically relevant (since the latest ERA guideline introduced several new technical requirements absent in the previous ERA guideline) and in terms of exposure (showing that the estimated exposure used in the reference ERA remains reasonable). Regulatory authorities (national and EMA) recommend that generic companies attempt to obtain reference ERA documentation from other companies via a so-called Letter of Access (LoA). However, if this is not possible, it remains feasible to argue that the conclusions of an existing reference ERA are still relevant based on information gathered from public assessment reports (summarized descriptions of environmental risk assessments) and product information (to confirm that dosages, indications, etc., have not changed). It should be noted that in some cases, reference ERAs approved between 2006 and 2024 may need to be modified (e.g., with additional experimental studies). If no previous reference ERA can be identified or used, the generic company must commit to developing its own ERA.