Fenofibrate

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 Pravafenix (fenofibrate, pravastatin), Laboratoires SMB S.A., EMA/333119/2011

"The environmental risk assessment (ERA) is based on data from bibliographic references on fenofibrate and pravastatin. The CHMP raised several concerns regarding the submitted data and considered the ERA as not yet acceptable. Determination of the partition coefficient octanol/water for any of the active substances, the Predicted No Effect Concentration (PNEC) calculation and lower values of assessment factors should be re-assessed. The results from the additional studies were not considered required by the Committee before the adoption of the positive CHMP opinion and it is confirmed that these applications comply with Article 6 of Regulation 726/2004 having regard to the requirements of Article 8(3) (ca) of Directive 2001/83. Therefore, a specific post-authorisation follow up measure has been agreed to perform an environmental risk assessment fully in accordance with the Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use (EMEA/CHMP/SWP/4447/00). The regards amongst others determination of the adsorption/desorption behaviour of the substances, determination of bioaccumulation, determination of the ready biodegradability, determination of the long-term fish toxicity, and other tests. [...] The submitted environmental risk assessment is not fully acceptable and a new ERA programme will be conducted as agreed in form of a specific follow up measure. " No such requested data has been found on the EMA website (2021-04-15).

Assessment report for Cholib (fenofibrate, simvastatin) 27 June 2013, EMA/CHMP/308856/2013

"Since Cholib is intended for a substitution of two already approved products, this will not lead to an increased exposure to the environment. The justification of the lack of ERA is thus acceptable to the CHMP. Fenofibrate and simvastatin are already used in existing marketed products and no significant increase in environmental exposure is anticipated. Therefore the fixed dose combination of fenofibrate and simvastatin is not expected to pose any additional risk to the environment. [...] Repeat dose toxicity studies were recently conducted with fenofibric acid in dogs and rats and these provide updated information on its toxicological profile, which is adequately reflected in the SmPC of Cholib. Furthermore, as concluded by the CHMP, the fixed dose combination of fenofibrate and simvastatin is not expected to pose any additional risk to the environment."

Fass environmental information

Fass environmental information for Lipanthyl (fenofibrat) from Abbott (downloaded 2013-06-25).

Hazard

Persistence: "Ready degradability (OECD 301B; Schaefer & Matthews, 2009) 31% degradation in 28 days Aerobic transformation (OECD 308; Takes & Boelhouwers, 2011) DT50 in two sediment types: 176 or 81 days."Fenofibrate is slowly degraded in the environment.

Bioaccumulation: "Adsorption coefficient (OECD 121; Egdom, 2011) log K_oc 2.65 ± 0.28 at pH 3 Partitioning coefficient (OECD 117; Egdom, 2011) log K_ow 2.91 ± 0.29 at pH 3 Since the retention behavior of fenofibric acid decreases at higher pH resulting in a lower K_ow and K_oc, it can be concluded that the phrase “Fenofibrate (in the form of fenofibric acid) has low potential for bioaccumulation.” is justified."

Chronic toxicity: There are data for 3 trophic levels, most sensitive crustacean (Daphnia magna) EC₅₀ (21 d) for number of living young per brood = 1900 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2011. PEC/PNEC = 0.03 which gives the risk insignificant.

Report Goodpoint 2020

Comparative assessment of environmental risk when using the fibrates bezafibrate, fenofibrate and gemfibrozil from a Swedish perspective.

The three fibrates and the active metabolite fenofibratic acid are likely to occur in concentrations of single ng/L in Swedish aquatic environments exposed to treated municipal wastewater. A comparative assessment of the risk of receptor influence via the fish plasma model shows a very low risk for all substances studied. Ecotoxicological studies are extensive for gemfibrozil and scarce for other fibrates. However, many studies are considered to be of low quality and reliability. Available and reliable efficacy data indicate a very low risk for all investigated fibrates.

Recommendation

The use of bezafibrate, fenofibrate and gemfibrozil is not considered to pose an environmental risk. Therefore, no exchanges from an environmental risk point of view are recommended.