Fluticasone propionate

Detailed information

Comment on Fass environmental information

Fluticasone propionate 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.

Fass environmental information for Flutide Diskus (fluticasone propionate) (downloaded 2022-01-17)

Hazard

Persistence: "Ready degradability: < 1.50% degradation in 28 days (TAD 3.11). Soil Metabolism: 9–50% degradation in 64 days (OECD 307). The phrase "fluticasone propionate is potentially persistent" is thus chosen."

Bioaccumulation: Log K_ow = 2.80 at pH 7 (TAD 3.02).

Toxicity: There are data for 2 trophic levels, most sensitive fish (Pimephales promelas) NOEC 0.58 microg/L.

Risk

PPEC/PNEC is based on sales data in Sweden in year 2015. "PNEC (μg/L) = lowest NOEC/10, where 10 is the assessment factor applied for one long-term NOECs but where there is a high degree of confidence that the dataset includes the most sensitive species (fish) and addresses the specific mode of action (endocrine disruption). On this basis the NOEC for fish has been used in the calculation." PEC/PNEC = 0.0289 which gives the risk insignificant.

According to ECHA's guidelines for long-term data for one trophic level, AF is 100. This gives PEC/PNEC = 1.68 x 10^-3/0.0058 = 0.290 which gives the risk low.

Fass environmental information for Dymista (azelastine,fluticasone propionate) (downloaded 2022-01-17)

Hazard

Persistence: No data.

Bioaccumulation: An experimentally derived Log P of 3.5 (OECD 117).

Toxicity: No data.

Risk

Risk of environmental impact of fluticasone propionate cannot be excluded, due to the lack of environmental toxicity data.

Manufacturer has on fass.se stated that data about the environmental impact is missing for the substance so that the environmental risk cannot be calculated. It is voluntary for manufacturers to provide information on the environmental impact on fass.se.

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 reports

Assessment report for Seffalair Spiromax (salmeterol/fluticasone propionate), Teva, 28 January 2021, EMA/99377/2021. Assessment report for BroPair Spiromax (salmeterol/fluticasone propionate), Teva, 28 January 2021, EMA/CHMP/21349/2021.

"No Environmental Risk Assessment (ERA) was submitted. This was justified by the applicant as the introduction of FS Spiromax containing fluticasone propionate and salmeterol xinafoate is considered unlikely to result in any significant increase in the exposure of the environment to the active substance. Moreover, taking into account that the predicted environmental concentration in surface water (PECsw) for FS PMDI was lower than the PECsw of approved fluticasone/salmeterol products, no additional Phase 1 and 2 data were deemed necessary to provide as part of this application. Thus, the ERA is expected not to be increased and therefore salmeterol xinafoate/fluticasone propionate is considered unlikely to present a risk to the environment by the applicant."