Nilotinib

Assessment report

Assessment report för Tasigna (nilotinib) från 20 December 2010 EMA/CHMP/678167/2010 och 21 April 2017 EMA/313746/2017.

Fara

Persistens: "Nilotinib showed a half-life of 179-213 days for the total water-sediment systems (normalized to 12°C) and a half-life of 369 days for soils (normalized to 12°C). Consequently the criteria for a very persistent (vP) substance of 180 days in water-sediment systems and soils defined in the REACH guidance on PBT assessment is exceeded for both compartments."

Bioackumulation: "Bioconcentration factor of 127. This assessment revealed that nilotinib cannot be considered as a PBT substance based on its low bioconcentration potential in fish."

Toxicitet: Finns data för 3 trofinivåer, för kräftdjur Daphnia magna NOEC-21 dagar = 12,7 mikrog/L. "However algae toxicity and fish chronic toxicity need to be further characterised." Inga sådana data finns i dagsläget enligt kontakt med Läkemedelsverket 2018-09-04.

"The active ingredient is not considered as PBT substance. However, the active ingredient and its transformation products are very persistent in soil and sediment."

Risk

Risken, PEC/PNEC, uträknad från data i assessment report från ett europeiskt perspektiv:

PEC = 4 mikrog/L (worst case, finns också 0,036 och 0,009 "[prevalence and proposal for market data, used in Phase II]") (EMA/313746/2017).

PNEC = NOEC 12,7 mikrog/L/100 (bedömningsfaktorn (AF) för 1 kronisk studie) = 0,127 mikrog/L.

PEC/PNEC = 31,496 vilket ger risken hög.

Enligt EMA/CHMP/678167/2010: "Based on data on Daphnia magna, effects on microorganism, sub-chronic effects on fish early life stage, at the predicted environmental concentration (PEC) and calculation of PEC/PNEC ratios, it can be concluded that nilotinib HCl would not represent a relevant risk to surface water and groundwater microorganisms (sewage treatment plant)."

Fass miljöinformation

Fass miljöinformation för Tasigna (hämtad 2018-09-05).

Fara

Persistens: "DT50 (total system) = 84.0–100.0 days. Based on the DT50 for the total system, the phrase 'Nilotinb is slowly degraded in the environment' is chosen.""

Bioackumulation: BCFss = 65–75.

Toxicitet: Finns data för 3 trofinivåer, lägst för fisk (zebrafisk) NOEC 7 dagar = 2,6 mikrog/L.

Risk

PEC/PNEC utgår från försäljningsdata i Sverige under år 2016. PEC = 0,0069 mikrog/L. PNEC = 0,26 mikrog/L. PEC/PNEC = 0,027 vilket ger risken försumbar.