Brimonidine

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.

Assessment report for Mirvaso

Assessment report for Mirvaso (brimonidine), 19 December 2013, EMA/CHMP/115246/2014.

Hazard

Persistence: OECD 308. Water phase: DT₅₀ = 1.1 and 1.7 day. Remarks. Low degradation in sediment, 50% of applied radioactivity in the sediment after 97 day.

Bioaccumulation: OECD 107.
log P_ow ≤ -1.0 at pH 4
log P_ow = -0.2 at pH 7
log P_ow = 0.6 at pH 9

Toxicity: There are data for 3 trophic levels, most sensitive fish (Danio rerio) 32 day-EC₁₀ 19 microg/L.

Risk

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

PEC_surfacewater = 0.025 microg/L.

PNEC = Lowest 32 day-EC₁₀, 19 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 1.9 microg/L

PEC/PNEC = 0.013 which gives the risk insignificant. "The current estimate of PEC/PNEC ratio (0.025/1.9 = 0.013) is below the threshold but CHMP does not know the response in the full range due to the extrapolation and therefore cannot endorse the comment of the Applicant stating that “is unlikely that a refined NOEC value as low as 0.25 μg/L (76 times lower than the current EC₁₀) will be obtained with the new run of experiment”. The CHMP recommends therefore the Applicant to repeat the Early Life Stage (ELS) Toxicity test with Danio rerio, and to provide the Agency with the test results in the context of a recommendation." No such information has been found on the EMA website (2024-08-09).

Assessment report for Simbrinza

Assessment report for Simbrinza (brimonidine, brinzolamide) about brimonidine, 22 May 2014, EMA/366328/2014.

Hazard

Persistence: No data.

Bioaccumulation: OECD 107. 0.42 (pH 9).

Toxicity: No data.

Risk

PEC_surfacewater = 0.0014 microg/L. "Conclusion: > 0.01 threshold - No."

"In addition, based on the lower than 4.5 log K_ow value obtained (0.42) and the PEC_{surfacewater value} (1.4 x 10^-3) which is lower than action limit (0.01 μg/L), brimonidine 2 mg/mL in the combination product Simbrinza is considered unlikely to represent a risk for the environment following its prescribed use. These results indicate that further environmental studies are not required."

Comment. Brimonidine (Simbrinza) 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 brimonidine in the environment (PEC_surfacewater). 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.

Fass environmental information

Fass environmental information for Simbrinza (brimonidine, brinzolamide) about brimonidin from Novartis (downloaded 2024-08-09).

Hazard

Persistence: No data.

Bioaccumulation: No data.

Toxicity: No data.

Risk

Risk of environmental impact of brimonidine cannot be excluded, due to the lack of environmental toxicity data.