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Dabigatran etexilate

Hazard 1 P 0 B 0 T 1 Risk Insignificant

Information

The T-value in the score for hazard refers to chronic toxicity. Underlying data for P, B, T and risk are from Fass.

Assessment report

Assessment report for Pradaxa (dabigatran etexilate) EMEA/174363/2008 from 2008.

Hazard

Persistence: "It was expected that DAB (dabigatran, ed. note) will disappear rapidly from aerobic aquatic systems mainly via binding to sediment and formation of several minor metabolites (OECD 308). The level of 14C-DAB in the sediment reached a plateau between days 3 and 14 with a maximal detected value of 5.7%. However, due to the structural resemblance to not ready biodegradable substances, a tier B study on transformation in aquatic sediment systems was performed (OECD 308)." See below under Risk.

Bioaccumulation: "Log Kow for DAB was below 4.5 thus a screening for persistence, bioaccumulation and toxicity was not needed."

Toxicity: No data.

Risk

"The calculated PEC/PNEC ratios were all below 1. In summary, due to the low risk further testing in for effects on the aquatic environment, microorganisms and the terrestrial compartment were not required. In addition, due to the low Kow a bioaccumulation study was not needed. PECsediment values were obtained for EU (0.453 μg/kg) and the “worst-case scenario” France (0.718 μg/kg). Since the PEC/PNEC ratio for the sediment was clearly below 1, it was concluded that with the present use pattern, DAB constitutes an insignificant risk for the sediment compartment. In conclusion, it is unlikely that DAB use will result in an environmental risk."

Fass environmental information

Fass environmental information for Pradaxa from Bayer (downloaded 2019-10-14).

Hazard

Persistence: "OECD Guideline 308 study showed, in accordance with FASS criteria (IV), 50% dissipation times (DT50) of ≤ 32days, where Dabigatran rapidly and strongly binds to sediment. Extraction with acetonitrile/water did not significantly affect the amount of extractable substance, though extraction with acetonitrile/HCL under reflux conditions did increase the amount of extractable substance, however this is not considered environmentally relevant. Based on these data Dabigatran etexilate is considered “degraded in the environment”."

Bioaccumulation: "Log Kow of < -2.2 at pH 7 was determined for Dabigatran in an OECD 107 study with no pH dependency between pH 5 to 9."

Chronic toxicity: There are data for 3 trophic levels, most sensitive crustacean (Daphnia magna, 21 days, mortality) NOEC 1.0 mg/L.

Risk

PEC/PNEC uis based on sales data in Sweden in year 2016. PEC/PNEC = 0.0013, which gives the risk insignificant.

Author: The Pharmaceutical unit of Region Stockholm