Bupivacaine
Summary
Persistence. It cannot be excluded that bupivacaine is persistent, due to the lack of data.
Bioaccumulation. Bupivacaine has low potential for bioaccumulation.
Toxicity. Bupivacaine har high acute toxicity. There is only data for one trophic level and the data has been recalculated by the factor of 5, see further under Classification.
Risk. Risk of environmental impact of bupivacaine cannot be excluded, since there is not sufficient ecotoxicity data available.
This summary information comes from Fass.se. Data on persistence is also supported by assessment report.
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.
The PEC (predicted environmental concentration) values used to calculate risk in the manufacturers' assessment reports are based on the estimated use of the medicinal product to which the assessment report relates, not all medicinal products containing the same active substance.
Bupivacaine has only undergone a phase I study according to regulatory requirements for environmental risk assessments (European Medicines Agency, EMA: Committee for Medicinal Products for Human Use (CHMP). Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use. 1 June 2006.) A phase I study includes data on bioaccumulation and calculates the concentration of bupivacaine in the environment (PECSurface water). If specified limit values are not exceeded, the company does not need to conduct a phase II study that includes data on toxicity and persistence and calculation of risk based on PEC/PNEC.
Assessment report Exparel liposomal 2020
Assessment report for Exparel liposomal (bupivacaine), 17 September 2020, EMA/CHMP/528272/2020.
Hazard
Persistence: No data.
Bioaccumulation: OECD107. 2.2 at pH7.
Toxicity: No data.
Risk
"Two calculations of the Phase I PECSURFACEWATER of bupivacaine (0.0036 and 0.0027 μg/L) did not exceed the action limit of 0.01 μg/L. Based on pre-clinical data of toxicity in developmental and reproductive toxicity studies in mammalian species, bupivacaine is not expected to affect the reproduction of vertebrate or lower animals at concentrations lower than the action limit of 0.01 μg/L. Therefore, a further Phase II environmental fate and effects assessment is not required."
Assessment report Exparel liposomal 2022
Assessment report for Exparel liposomal "extension of indication", 15 September 2022, EMA/CHMP/794139/2022.
Hazard
Persistence: No data.
Bioaccumulation: 0.5 at pH 5, 2.2 at pH 7 and 3.1 at pH 9.
Toxicity: No data.
Risk
"The Phase I PECSURFACEWATER of bupivacaine was 0.0036 μg/L and does not exceed the action limit of 0.01μg/L. Bupivacaine is also not expected to affect the reproduction of vertebrate or lower animals at concentrations lower than the action limit of 0.01 μg/L. Therefore, it can be concluded 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 Marcain (bupivacaine) from Aspen Nordic (downloaded 2024-09-11).
Hazard
Persistence: No data.
Bioaccumulation: Log D = 2.54 at pH 7.4.
Acute toxicity: There are data for 1 trophic levels, crustacean EC50 39 mg/L.
Risk
Risk of environmental impact of bupivacaine cannot be excluded, since there is not sufficient ecotoxicity data available.
References
- European Medicines Agency. European public assessment report (EPAR) for Exparel liposomal (bupivacaine), 17 September 2020, EMA/CHMP/528272/2020.
- European Medicines Agency. European public assessment report (EPAR) for Exparel liposomal "extension of indication", 15 September 2022, EMA/CHMP/794139/2022.
- Fass för vårdpersonal.
Author: Health and Medical Care Administration, Region Stockholm