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Jakavi

Novartis

Tablett 5 mg
(Runda, konvexa, vita till nästan vita tabletter, cirka 7,5 mm i diameter, präglade med ”NVR” på ena sidan och ”L5” på den andra sidan.)

Antineoplastiska medel, proteinkinashämmare

Aktiv substans:
ATC-kod: L01EJ01
Läkemedel från Novartis omfattas av Läkemedelsförsäkringen.
Läkemedlet distribueras också av företag som inte omfattas av Läkemedelsförsäkringen, se Förpackningar.
  • Vad är miljöinformation?

Miljöinformation

Miljöpåverkan

Ruxolitinib

Miljörisk: Användning av ruxolitinib har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning: Ruxolitinib är potentiellt persistent.
Bioackumulering: Ruxolitinib 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)= 0.00053 μg/L

PEC = 0.00053 μg/L

Where:

A = 3.53301 kg Ruxolitinib phosphate (total amount of API sold in Sweden in 2019, data from IQVIA).

R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis, or biodegradation)

P = number of inhabitants in Sweden = 9 ×106 

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

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


Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Pseudokirchneriella subcapitata) (OECD 201) (NOTOX Project 495601):

ErC50 72 h (growth rate) = 15,000 μg/L

NOEC = 1,000 μg/L


Crustacean (Daphnia magna):

Acute toxicity

EC50 48 h (immobilization) = 13,000 μg/L (OECD 202) (NOTOX Project 495598)


Fish (Cyprinus carpio):

Acute toxicity

LC50 96 h (lethality) = 15,000 μg/L (OECD 203) (NOTOX Project 495598)

PNEC = 13.0 μg/L

The PNEC (μg/L) is based on the lowest EC50/1000, where 1000 is the assessment factor used if acute data for 3 trophic levels is available. EC50 for Daphnia magna has been used for this calculation since it is the most sensitive of the three tested species.


Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.00053 μg/L / 13.0 μg/L = 0.000041, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase "Use of Ruxolitinib has been considered to result in insignificant environmental risk."


Degradation 

Biotic degradation

Ready degradability:

4-22 % degradation in 28 days (OECD 301B). (NOTOX Project 495602)

Justification of chosen degradation phrase:

Ruxolitinib is not readily biodegradable. The phrase “Ruxolitinib is potentially persistent” is thus chosen.


Bioaccumulation

Partitioning coefficient:

Log Dow = 2.3-2.4 at pH 7 (EC440/2008 A.8; OECD 107). (NOTOX Project 495597)

Justification of chosen bioaccumulation phrase:

Since log Dow < 4 at pH 7, ruxolitinib has a low potential for bioaccumulation.


Excretion (metabolism)

Following a single oral dose of [14C]-labeled ruxolitinib in healthy adult subjects, elimination was predominately through metabolism with 74% of the radioactivity excreted in urine and 22% excretion via feces. The unchanged drug accounted for less than 1% of the excreted total radioactivity. (Novartis Core Data Sheet, 2017).

PBT/vPvB assessment

According to the established EU criteria, ruxolitinib cannot be regarded as a PBT/vPvB substance, as it has a low potential for bioaccumulation and it is relatively non toxic.

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

  • NOTOX Project 495601. Freshwater algal growth inhibition test with INC424-AZA. Final report: 17 June 2011.

  • NOTOX Project 495598. Acute toxicity study in Daphnia magna with INC424- AZA (static). Final report: 17 June 2011.

  • NOTOX Project 495598. 96-hour acute toxicity study in carp with INC424-AZA (static). Final report: 17 June 2011.

  • NOTOX Project 495602. Determination of ‘ready’ biodegradability: carbon dioxide (CO2) evolution test (Modified Sturm Test) of INC424-AZA. Final report: 17 June 2011.

  • NOTOX Project 495597. Determination of physic-chemical properties of INC424-AZA. Final report: 19 April 2011.

Novartis Core Data Sheet, JAKAVI® (ruxolitinib), Version 2.3, 12 May 2017.