Detaljerad miljöinformation

Environmental Risk Classification

Predicted Environmental Concentration (PEC)

PEC is calculated according to the following formula:

PEC (μg/L) = (A*10⁹*(100-R))/(365*P*V*D*100) = 1.37*10^-6 * A * (100 - R) = 1.37*10^-6 * 2.46 kg * 100 = 0.000337 μg/L = 0.337 ng/L

Where:

A = 2.4595 kg (total sold amount API in Sweden year 2022, data from IQVIA).

R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation) = 0, if no data is available.

P = number of inhabitants in Sweden = 10 * 10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (ECHA 2008)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (ECHA 2008).

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae: no data available

Crustacean (Daphnia magna): no data available

Fish: no data available

Other ecotoxicity data: No data available

PNEC derivation:

No PNEC can be calculated since there is no environmental toxicity data available.

Environmental risk classification (PEC/PNEC ratio)

Calculation of a risk ratio is not possible, due to the lack of environmental toxicity data. Therefore, the following phrase is used: "Risk of environmental impact of brimonidin cannot be excluded, since no ecotoxicity data are available." According to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00), use of brimonidin is unlikely to represent a risk for the environment, because the predicted environmental concentration (PEC) at the time of registration is below the action limit 0.01 μg/L.

Degradation

Biotic degradation

Ready degradability: no data available

Justification of chosen degradation phrase:

As no data on biological degradation is available, the following phrase is used: The potential for persistence of brimonidin cannot be excluded, due to lack of data.

Bioaccumulation

Partitioning coefficient:

No data available

Justification of chosen bioaccumulation phrase:

As no information on the octanol-water partition coefficient is available, the following statement is used for fluorescein: The potential for bioaccumulation of brimonidin cannot be excluded, due to lack of data.

Excretion (metabolism)

Following administration of brimonidine tartrate gel (1 g of gel containing 5 mg of brimonidine tartrate applied to the entire face) once daily for 29 days in patients with erythema associated with rosacea, peak plasma concentration and area under the concentration-time curve (AUC) were 40 and 20%, respectively, those observed following administration of brimonidine tartrate 0.2% ophthalmic solution (1 drop in each eye every 8 hours for 24 hours). Mean peak plasma concentration and AUC were highest on day 15 in patients receiving brimonidine gel. Systemic exposure was slightly lower on day 29, indicating no further drug accumulation with brimonidine gel application.

Brimonidine is extensively metabolized by the liver.1 Urinary excretion is the major route of elimination of brimonidine and its metabolites (Medicines Complete 2017).

References

• ECHA 2008, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment. http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm

• MedicinesComplete © 2017 Royal Pharmaceutical Society. AHFS Drug Information. https://www.medicinescomplete.com/mc/ahfs/current/a315044.htm?q=brimonidine&t=search&ss=text&tot=2&p=1#_hit