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Evoltra

Sanofi AB

Koncentrat till infusionsvätska, lösning 1 mg/ml
(klar, nästan färglös, med ett pH på 4,5 till 7,5 och en osmolaritet på 270 till 310 mOsm/l)

Cytostatikum

Aktiv substans:
ATC-kod: L01BB06
Läkemedel från Sanofi AB omfattas av Läkemedelsförsäkringen.
  • Vad är miljöinformation?

Miljöinformation

Miljöpåverkan

Klofarabin

Miljörisk: Risk för miljöpåverkan av klofarabin kan inte uteslutas då ekotoxikologiska data saknas.
Nedbrytning: Det kan inte uteslutas att klofarabin är persistent, då data saknas.
Bioackumulering: Klofarabin har låg potential att bioackumuleras.


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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) = 1.5*10-6*A*(100-R)


PEC = 2.84 *10-7 µg/l


Where:
A = 0.00189 kg (total sold amount API in Sweden year 2018, 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 = 9*106
V (l/day) = volume of wastewater per capita and day = 200 (ECHA default) (Ref I)
D = factor of dilution of waste water by surface water flow = 10 (ECHA default) (Ref I)


According to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00), use of clofarabine is unlikely to represent a risk for the environment, because the predicted environmental concentration (PEC) is below the action limit 0.01 µg/L.


Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

No ecotoxicity data are available.


Environmental Risk Classification (PEC/PNEC ratio)

The PEC/PNEC ratio could not be calculated since there is no ecotoxicity data available, hence justifying the phrase: "Risk of environmental impact of clofarabine cannot be excluded, since no ecotoxicity data are available."


Degradation

No data are available, therefore the degradation phrase should be: "The potential for persistence of clofarabine cannot be excluded, due to lack of data."


Bioaccumulation

Partitioning coefficient:

Log Pow = -0.29 at neutral pH (predicted by ChemAxon, method used see Ref II ) (Ref III)


Justification of chosen bioaccumulation phrase: Since log Pow < 4 at pH 7, clofarabine has low potential for bioaccumulation.


Metabolism and excretion

Clofarabine is sequentially metabolized intracellularly to the 5’-monophosphate metabolite by deoxycytidine kinase and mono- and di-phosphokinases to the active 5’-triphosphate metabolite. Clofarabine has high affinity for the activating phosphorylating enzyme, deoxycytidine kinase, equal to or greater than that of the natural substrate, deoxycytidine. (Ref III).

The pharmacological activity of the metabolites is not known.


References

  1. ECHA, European Chemicals Agency, 2008 Guidance on information requirements and chemical safety assessment. Available at https://echa.europa.eu/guidance-documents/guidance-on-information-requirements-and-chemical-safety-assessment

  2. Vellarkad N et al. Atomic physicochemical parameters for three dimensional structure directed quantitative structure-activity relationships. 4. Additional parameters for hydrophobic and dispersive interactions and their application for an automated superposition of certain naturally occurring nucleoside antibiotics. J. Chem. Inf. Comput. Sci., 1989, 29 (3), pp 163–172.

  3. Law V et al. DrugBank 4.0: shedding new light on drug metabolism. Nucleic Acids Res. 2014 Jan 1;42(1):D1091-7. Available at https://www.drugbank.ca/drugs/DB00631