Salmeterol

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 Seffalair Spiromax and BroPair Spiromax, respectively

Assessment report for Seffalair Spiromax (salmeterol, flutikasonpropionat) from Teva 28 January 2021, EMA/99377/2021.

Assessment report for BroPair Spiromax (salmeterol, flutikasonpropionat) from 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."

Assessment report för Labazenit 

Assessment report for Labazenit (budesonide, salmeterol) 27 June 2013, EMA/465765/2013.

Hazard

Persistence: "The compound undergoes degradation in the environment and has no potential to accumulate in aquatic organisms (FASS.se-salmeterol)."

Bioaccumulation: "The Octanol/Water partition coefficient (Log K_ow) measured at 3 different pH conditions and 3 concentrations of the substance was found to be between 1.32 and 2.20 (Environmental Assessment, Serevent, NDA 20-692, Attachment 4). The value provided by the originator of salmeterol is Log K_ow = 2.2 at pH 7 (MSDS-2, Serevent Diskus). Also according to the ERA of salmeterol (Serevent) available on the website of the Swedish Medicine Agency (MPA) there is no significant bioaccumulation potential for salmeterol as its Octanol/Water partition coefficient was found to be 1.71 at pH 7, 2.06 at pH 5, 1.71 at pH 7, and 1.32 at pH 9."

Toxicity: No data.

Risk

"PEC_surfacewater is 0.0005 μg/L. PEC_surfacewater is below 0.01 μg/L, and thus a phase II assessment is not necessary. [---] As the PEC < 0.01 μg/l and the log K_ow <4.5, it can be assumed according to EMA guideline on the ERA of medicinal products for human use (CPMP/SWP/4447/00).that the medicinal product is unlikely to represent a risk for the environment following its prescribed usage in patients."

Fass environmental information

Fass environmental information for Seretide Diskus (fluticasone propionate, salmeterol) from GlaxoSmithKline (downloaded 2022-03-21).

Hazard

Persistence: "Biotic degradation, Ready degradability: No data. Inherent degradability: 50% degradation in 12.80 days (TAD 3.11). Soil metabolism: 29.9 to 49.9% degradation in 64 days (OECD 304). Abiotic degradation, Hydrolysis: 50% degradation > 1 year (TAD 3.09). Photolysis: No data. Salmeterol is not readily degradable but it is inherently primarily degradable in that removal of the parent API in the Sewage Treatment Plant is expected to a significant extent. The phrase “Salmeterol is potentially persistent” is thus chosen."

Bioaccumulation: Log D_ow at pH 5 = 2.06, Log D_ow at pH 7 = 1.71, Log D_ow at pH 9 = 1.32.

Chronic toxicity: There are data for 3 trophic levels, most sensitive crustacean (Ceriodaphnia dubia) NOEC 8 days (reproduction) = 1 100 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2019. PEC/PNEC = 0.0000122 which gives the risk insignificant.

Report Pharmaceutial residues in the Stockholm aquatic environment

Salmeterol has been detected in waste water treatment plants in both incoming and outgoing water.