Oseltamivir

Scientific discussion

Scientific discussion Tamiflu (oseltamivir) 2005.

"In a carbon dioxide evolution test for determination of biodegradability, Ro 64-0796/002 was not readily biodegradable. In an acute toxicity study in Daphnia magna, Ro 64-0796/002 was classified as harmful according to the EU Directive 67/548/EEC as amended. Exposure estimations according to the worst case scenario for the environment has been carried out. According to the draft regulations a quotient of PEC and PNEC Predicted No-Effect Concentration equal or less than one is taken as indicative of environmental compatibility for a given active substance. (PECwater [Europe] /PNECwater = µg/l 33 ng/l 173 ˜0.005). As the PEC/PNEC ratio is significantly smaller than 1, no long-term negative effect on the aquatic environment is to be expected. Even using the lowest NOEC (NOEbC algae, 10 mg/l) for extrapolating the PNEC, the PEC/PNEC ratio is still below 0.02. Considering ecotoxicological properties,use pattern, dosage and maximal estimated amounts of oseltamivir to be placed on the market, no exposure levels of concern to the environment are to be expected."

Assessment report

Assessment report for Tamiflu 26 March 2015 EMA/CHMP/186699/2015.

"The estimated theoretical increase of oseltamivir usage followed by the addition of the new indication for Tamiflu in children <1 year of age with the dosing regimen 3 mg/kg twice daily (BID) for 5 days would be <0.5% of the population of Europe. The environmental risk arising from widespread Tamiflu administration during an influenza pandemic in Europe have been previously assessed and resulted in no significant environmental risk. The addition of a new indication for Tamiflu as treatment of influenza in infants below 1 year of age is not expected to lead to a significant increase in environmental exposure even following widespread use of oseltamivir in the newly indicated population."

Fass environmental information

Fass environmental information for Tamiflu from Roche (downloaded 2020-04-07).

Hazard

Persistence: "Ready biodegradability: 3% after 28 days of incubation CO2/ThCO2 (OECD 301 B) OEP not readily biodegradable. [...] Not biodegradable (OECD 308) OE+OA 1:4. Oseltamivir ethylester phosphate (OEP) is not readily degradable. This justifies the phrase 'Oseltamivir ethylester phosphate (OEP) is potentially persistent.'"

Bioaccumulation: "Log K_OW = 0.36 (pH 7.4, 25 °C) OEP. Log K_OW = 0.95. Oseltamivir ethylester phosphate (OEP) has low potential for bioaccumulation (log K_OW <4)."

Toxicity: There are data for 3 trophic levels, most sensitive crustacean and fish NOEC 1000 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2017. PEC/PNEC = 0.000013 which gives the risk insignificant.