Aripiprazole

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 Abilify Maintena

Assessment report for Abilify Maintena (aripiprazole), Otsuka Pharmaceutical Europe Ltd, 19 September 2013, EMA/737723/2013.

Hazard

Persistence: OECD 308: DT₅₀, whole system = 177 and 30.9 days % shifting to sediment = 68.7 and 37.7 % at day 14.

Bioaccumulation: log K_ow pH 5 = 2.70, log K_ow pH 7 = 2.95, log K_ow pH 9 = 2.86.

Toxicity: There are data for 3 trophic levels, most sensitive crustaceans (Daphnia sp.) NOEC 2.61 microg/L.

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:

PEC = No data.

PNEC = Lowest NOEC, XX microg/L/X (Assessment Factor (AF) for XX chronic studies) = microg/L

PEC/PNEC = No value because data is missing on PEC.

Assessment report Abilify type II variation

Assessment report for Abilify (aripiprazole), Otsuka Pharmaceutical Europe Ltd, 15 September 2016, EMA/702260/2016.

"During the procedure, the applicant was requested to discuss the possible significant environmental exposure conditioned by the increase of the therapeutic use (adolescents in the 13–15 age range). The applicant updated the ERA and PEC/PNEC ratios were recalculated taking into account the addition of both PECs_{surface water}: paediatric population and adult / adolescent population. Having reviewed the data, the CHMP concluded that no significant increase of environmental exposure to this medicinal product was to be expected."

Fass environmental information

Fass environmental information for Abilify from Otsuka Pharmaceutical Europe Ltd (downloaded 2024-04-12).

Hazard

Persistence: DT₅₀ values for aripiprazole (total system) were 30.9 and 177 days for the two sediments (higher vs. lower organic carbon content). ... Based on the two DT₅₀ values, aripiprazole is considered to be slowly degraded in the environment.

Bioaccumulation: The Log K_ow (< 3) indicates little potential for bioconcentration in aquatic species. Therefore, based on the low Log Kow value, a bioconcentration study was not considered to be required. The estimated BCF is 53.9 –85.7. ... Since estimated BCF < 500 and log D_ow < 4 at pH 7, aripiprazole is considered to have “low potential for bioaccumulation”.

Toxicity: There are data for 3 trophic levels, most sensitive crustaceans (Daphnia magna) NOEC 2.61 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2022. PEC/PNEC = 0.03926 which gives the risk insignificant.

Report from Goodpoint about comparison with flupentixol, haloperidol and risperidone

Both haloperiodol and risperidone have been reported in wild Swedish fish at levels above therapeutic concentrations in humans, which is also reasonable based on their high fat solubility and measured concentrations in Swedish wastewater. There is also a risk that flupentixol may accumulate in fish close to therapeutic concentration. Flupentixol, haloperidol and risperidone are all included in the Region Stockholm's table of pharmaceuticals with risk for negative environmental impact according to the environmental program 2017–2021. The risk of aripripazole accumulating in fish at potent levels is estimated to be lower.