Jakafi® (ruxolitinib) Dosing Guide for Myelofibrosis

Indications and UsageJakafi is indicated for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF in adults.

Important safety considerations Treatment with Jakafi can cause thrombocytopenia, anemia and neutropenia, which are each dose-related effects. Perform a pre-treatment complete blood count (CBC) and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated

Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting Jakafi until active serious infections have resolved. Observe patients receiving Jakafi for signs and symptoms of infection and manage promptly. Use active surveillance and prophylactic antibiotics according to clinical guidelines

Please see Important Safety Information on the last page for related and other risk information. Please click here for Full Prescribing Information for complete dosing recommendations.

Individualized dosing for Jakafi

HCP.Jakafi.com/MF-Dosing

For patients with intermediate or high-risk myelofibrosis

MFJakatrG ruxolitinib (tablets)

0

•

•

https://www.jakafi.com/pdf/prescribing-information.pdf

https://hcp.jakafi.com/myelofibrosis/dosing

Important Safety InformationTreatment with Jakafi® (ruxolitinib) can cause thrombocytopenia, anemia and neutropenia, which are each dose-relatedeffects. Perform a pre-treatment complete blood count (CBC) and monitor CBCs every 2 to 4 weeks until doses arestabilized, and then as clinically indicated

Manage thrombocytopenia by reducing the dose or temporarily interrupting Jakafi. Platelet transfusions may be necessary

Patients developing anemia may require blood transfusions and/or dose modifications of Jakafi

Severe neutropenia (ANC <0.5 × 109/L) was generally reversible by withholding Jakafi until recovery

Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting Jakafi until active seriousinfections have resolved. Observe patients receiving Jakafi for signs and symptoms of infection and manage promptly.Use active surveillance and prophylactic antibiotics according to clinical guidelines

Tuberculosis (TB) infection has been reported. Observe patients taking Jakafi for signs and symptoms of active TB andmanage promptly. Prior to initiating Jakafi, evaluate patients for TB risk factors and test those at higher risk for latentinfection. Consult a physician with expertise in the treatment of TB before starting Jakafi in patients with evidence of activeor latent TB. Continuation of Jakafi during treatment of active TB should be based on the overall risk-benefit determination

Progressive multifocal leukoencephalopathy (PML) has occurred with Jakafi treatment. If PML is suspected, stop Jakafiand evaluate

Advise patients about early signs and symptoms of herpes zoster and to seek early treatment

Increases in hepatitis B viral load with or without associated elevations in alanine aminotransferase and aspartateaminotransferase have been reported in patients with chronic hepatitis B virus (HBV) infections. Monitor and treatpatients with chronic HBV infection according to clinical guidelines

When discontinuing Jakafi, myeloproliferative neoplasm-related symptoms may return within one week. Afterdiscontinuation, some patients with myelofibrosis have experienced fever, respiratory distress, hypotension, DIC, ormulti-organ failure. If any of these occur after discontinuation or while tapering Jakafi, evaluate and treat any intercurrentillness and consider restarting or increasing the dose of Jakafi. Instruct patients not to interrupt or discontinue Jakafiwithout consulting their physician. When discontinuing or interrupting Jakafi for reasons other than thrombocytopenia orneutropenia, consider gradual tapering rather than abrupt discontinuation

Non-melanoma skin cancers including basal cell, squamous cell, and Merkel cell carcinoma have occurred. Performperiodic skin examinations

Treatment with Jakafi has been associated with increases in total cholesterol, low-density lipoprotein cholesterol, andtriglycerides. Assess lipid parameters 8-12 weeks after initiating Jakafi. Monitor and treat according to clinical guidelinesfor the management of hyperlipidemia

In myelofibrosis and polycythemia vera, the most common nonhematologic adverse reactions (incidence ≥15%) werebruising, dizziness, headache, and diarrhea. In acute graft-versus-host disease, the most common nonhematologicadverse reactions (incidence >50%) were infections and edema

Dose modifications may be required when administering Jakafi with strong CYP3A4 inhibitors or fluconazole or in patientswith renal or hepatic impairment. Patients should be closely monitored and the dose titrated based on safety and efficacy

Use of Jakafi during pregnancy is not recommended and should only be used if the potential benefit justifies the potentialrisk to the fetus. Women taking Jakafi should not breastfeed during treatment and for 2 weeks after the final dose

Please see accompanying Full Prescribing Information for Jakafi.References:1.Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation. 2. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind,placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799-807. 3. Verstovsek S, Mesa RA, Gotlib J, et al.Efficacy, safety and survival with ruxolitinib in patients with myelofibrosis: results of a median 2-year follow-up of COMFORT-I. Haematologica. 2013;98(12):1865-1871.4. Harrison C, Kiladjian J-J, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis.N Engl J Med. 2012;366(9):787-798. 5. Data on file. Incyte Corporation. Wilmington, DE.

XX% Total Recycled Fiber

Jakafi and the Jakafi logo are registered trademarks of Incyte. © 2020, Incyte Corporation. MAT-JAK-01832 02/20

XXXXXXX

MONITOR frequently Monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated

PLT Count(× 109/L)

RecommendedStarting Dose

50 to <1005 mg twice daily

100 to 20015 mg twice daily

>20020 mg twice daily

In intermediate or high-risk myelofibrosis

Individualized dose adjustments for optimized efficacy and safety1

A CBC and platelet (PLT) count must be performed before initiating therapy, every 2 to 4 weeks until doses are stabilized and then as clinically indicated.The recommended starting dose of Jakafi for MF is based on PLT count.

CBC, complete blood count. Tablets shown are not actual size.

See STARTING PLT COUNT 50 TO <100 × 109/L tab for recommended dose modifications in patients with a starting platelet count of 50 to <100 × 109/L. See SPECIAL POPULATIONS tab for dosing information in patients with renal or hepatic impairment and for information on drug interactions.

Jakafi is also available in 10 mg and 25 mg tablets

INCREASE DOSE

DECREASE DOSE

In the case of an insufficient response, consider an increase in the dose if patient meets all these criteria:

Insufficient spleen reduction†

PLT count >125 × 109/L at 4 weeks and never <100 × 109/L

Absolute neutrophil count (ANC) >0.75 × 109/L

Increase dose by 5-mg twice-daily increments to a maximum of 25 mg twice daily

Doses should not be increased during the first 4 weeks of therapy and not more frequently than every 2 weeks.

Discontinue Jakafi if there is no spleen size reduction or symptom improvement after 6 months of therapy.

Thrombocytopenia

Anemia

In the case of a Hematologic Toxicity including:

Discontinuation can be avoided by reducing the dose or temporarily withholding Jakafi

Dose modifications of Jakafi and/or blood transfusions may be required for patients developing anemia

CBC, complete blood count; SEM, standard error of the mean.

Adapted with permission from Haematologica.

† Failure to achieve a reduction from pre-treatment baseline in either palpable spleen length of 50% or spleen volume of 35% as measured by CT or MRI.

Interrupt Jakafi treatment for: Bleeding requiring intervention, regardless of current platelet count,

Thrombocytopenia (PLT <50 × 109/L), or

Neutropenia (ANC <0.5 × 109/L)

See RESTARTING tab for dose modifications.

Risk for thrombocytopenia, anemia, and neutropenia

Treatment with Jakafi can cause thrombocytopenia, anemia and neutropenia, which are each dose-related effects. Perform a pre-treatment complete blood count (CBC) and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated




Please see Important Safety Information on the back cover for related and other risk information. Please click here for Full Prescribing Information for complete dosing recommendations.

* COMFORT-I (COntrolled MyeloFibrosis study with ORal JAK inhibitorTreatment-I) was a randomized, double-blind, placebo-controlled phase 3study with 309 patients with intermediate-2–risk or high-risk myelofibrosis.The primary endpoint was the proportion of subjects achieving a ≥35%reduction in spleen volume from baseline to week 24 as measured by CT or MRI. A secondary endpoint was the proportion of subjects with a ≥50% reduction in Total Symptom Score from baseline to week 24 as measured by the daily patient diary, the modified Myelofibrosis Symptom Assessment Form.1,2

‡ COMFORT-II (COntrolled MyeloFibrosis study with ORal JAK inhibitorTreatment-II) was a randomized, open-label phase 3 study with 219 patients with intermediate-2–risk or high-risk myelofibrosis. The primary endpointwas the proportion of patients achieving a ≥35% reduction in spleen volume from baseline at week 48 as measured by CT or MRI. Best available therapyin COMFORT-II included hydroxyurea (46.6%) and glucocorticoids (16.4%), as well as no medication, anagrelide, epoetin alfa, thalidomide, lenalidomide,mercaptopurine, thioguanine, danazol, peginterferon alfa-2a, interferon-α, melphalan, acetylsalicylic acid, cytarabine, and colchicine.1,4,5

OPTIMIZE to balance safety and efficacySTART here

✔

✔

✔

In patients receiving Jakafi in the COMFORT studies, PLT counts and hemoglobin levels generally stabilized after 8 to 12 weeks1-4*‡

Jaka�

Placebo

Mea

n He

mog

lobi

n ±

SEM

(g/L

)

110

100

90

120

0 2 4 6 8 12 16 20 24 30 36Study Week

Conduct CBC between weeks 2 and 4

COMFORT-I: Mean Hemoglobin Levels Over Time2

Mea

n Ch

ange

(%)

(n = 106)8.1

−16.7 −28.1 −33.4 −36.3 −39.5

(n = 19) (n = 35) (n = 22) (n = 41) (n = 22)

Placebo <10 mg twice daily

10 mg twice daily

15 mg twice daily

20 mg twice daily

>20 mg twice daily

2010

0−10−20−30−40−50

Titrated Dose

COMFORT-Ia: Mean Change in Spleen Volume by Dose at Week 243

PLT, platelet.

Twice-Daily Dose at Time of PLT Decline 25 mg 20 mg 15 mg 10 mg 5 mg

PLT Count(× 109/L)

New recommended twice daily dose

100 to <125 20 mg 15 mg No change

75 to <100 10 mg No change

50 to <75 5 mg No change

<50 Hold

Star

ting

PLT

Coun

t ≥10

0 ×

109 /L

Early dose adjustments as needed help to optimize efficacy and safety In the phase 3 COMFORT-I trial of patients with intermediate-2–risk or high-risk MF, the primary endpoint was the proportion of patients achieving a ≥35% reduction in spleen volume from baseline to week 24.1,2*

42% of patients receiving Jakafi achieved a ≥35%reduction in spleen volume at week 24 vs 0.7% of patients receiving placebo (P < 0.0001)2

Based on limited clinical data, long-term maintenance at 5-mg twice-daily dosing has not shown responses. Continued use at this dose should be limited to patients in whom the benefits outweigh the potential risks

of patients receiving Jakafi in COMFORT-I required a dose adjustment in the first 12 weeks of therapy3

70%

INTERRUPT DOSE

Jakafi Mean Spleen Volume Reduction (-31.6%)

In COMFORT-I, 60% of patients treated with Jakafi and 38% of patients receiving placebo received red blood cell transfusions during randomized treatment1

In patients receiving Jakafi in the COMFORT studies, mean decreases in hemoglobin reached a nadir of approximately 1.5 to 2.0 g/dL below baseline after 8 to 12 weeks of therapy and then gradually recovered to a new steady state that was approximately 1.0 g/dL below baseline1

In COMFORT-I, grade 3 and 4 thrombocytopenia or anemia occurred in 13% and 45% of patients receiving Jakafi, respectively2

<1% of patients receiving Jakafi in the COMFORT studies discontinued due to anemia or thrombocytopenia1-4

COMFORT-I: Mean Change in Spleen Volume by Dose at Week 243

MF

CBC, complete blood count; SEM,standard error of the mean.

Restarting

INTERRUPT FOR:Bleeding requiring intervention regardless of current platelet count,PLT counts <25 × 10

9/L, orAN

C <0.5 × 109/L

RESTARTAfter recovery of PLT counts to >35 × 10

9/L and ANC >0.75 × 10

9/L at the higher of:5 m

g once daily or5 m

g twice daily below

the largest dose in the week prior to the decrease in PLT

count below 25 × 10

9/L or ANC below

0.5 × 109/L that led to dose interruption

Please see Important Safety Inform

ation on the back cover for related and other risk information.

Refer to the accompanying Full Prescribing Inform

ation for complete dosing recom

mendations.

Only after the first 4 weeks of therapy and not m

ore frequently than every 2 weeks if

patient meets all these criteria:

Insufficient spleen reduction*

PLT count has remained ≥40 × 10

9/L and has not decreased by >20% in the prior 4 w

eeks

AN

C >1.0 × 109/L

No dose reduction or interruption for an adverse event or hem

atological toxicityin the prior 4 w

eeks

Increase dose by increments of 5 m

g daily to a maxim

um of 10 m

g twice daily

Continuation of treatment for m

ore than 6 months should be lim

ited to patientsin w

hom the benefits outw

eigh the risks.Discontinue Jakafi

® (ruxolitinib) if there is no spleen size reduction or symptom

improvem

ent after 6 months of therapy.

Reduce the dose of Jakafi in patients with platelet counts <35 × 10

9/L

PLT, platelet.

Starting PLT C

ount 50 to <100 × 109/L

INC

RE

AS

E D

OS

E

DEC

RE

AS

E D

OS

E

* Failure to achieve a reduction from pre-treatm

ent baseline in either palpable spleen length of 50% or spleen volum

e of 35%as m

easured by CT or MRI.

Starting PLT Count 50 to <100 × 109/L

✔✔✔✔

PLT CountD

osing Recomm

endations

<25 × 109/L

• Interrupt dosing

25 to <35 × 109/L and the

platelet count decline is <20%during the prior 4 w

eeks

• Decrease dose by 5 mg once daily

• For patients on 5 mg once daily, m

aintain dose at 5 mg once daily

25 to <35 × 109/L and the

platelet count decline is ≥20%during the prior 4 w

eeks

• Decrease dose by 5 mg tw

ice daily

• For patients on 5 mg tw

ice daily, decrease the dose to 5 mg

once daily

• For patients on 5 mg once daily, m

aintain dose at 5 mg once daily

The recomm

ended starting dose in MF for patients w

ith a starting PLT count of50 to <100 × 10

9/L is 5 mg tw

ice daily

See SPEC

IAL P

OPU

LAT

ION

S tab for dosing inform

ation in patients with renal or hepatic

impairm

ent and for information on drug interactions.





mendations.

Restarting dose in case of bleedingOnce the bleeding event has resolved, consider resum

ing treatment at the prior

dose if the underlying cause of bleeding has been controlled. If the bleeding eventhas resolved but the underlying cause persists, consider resum

ing treatment w

ithJakafiat a low

er dose

Restarting dose in case of hem

atologic toxicity inpatients w

ith starting PLT count ≥100 × 109/L

Treatment interrup

tion and restarting dosingAfter recovery of PLT counts >50 × 10

9/L and ANC >0.75 × 10

9/L, dosing m

ay be restarted

The maxim

um allow

able dose that may be used in restarting Jakafi

® (ruxolitinib)after a previous interruption is as show

n below

Maxim

um restarting doses for Jakafi after

safety interruption for throm

bocytopenia

Following treatm

ent interruption for ANC <0.5 × 10

9/L, after ANC recovers

to ≥0.75 × 109/L, restart dosing at the higher of 5 m

g once daily or 5 mg tw

icedaily below

the largest dose in the week prior to the treatm

ent interruption

Current PLT Count (× 10

9/L) M

aximum

Dose W

hen Restarting Treatm

ent With Jakafi

a

≥12520 m

g twice daily

100 to <12515 m

g twice daily

75 to <10010 m

g twice daily for at least 2 w

eeks; if stable,m

ay increase to 15 mg tw

ice daily

50 to <755 m

g twice daily for at least 2 w

eeks; if stable,m

ay increase to 10 mg tw

ice daily

<50Continue hold

a Maxim

um doses are displayed. W

hen restarting, begin with a dose at least 5 m

g twice daily below

the dose at interruption.

PLT, platelet.

Restarting A

fter Safety Interrup

tion

Drug

interactions

Modify the dose of Jakafi

® (ruxolitinib) when coadm

inistered with strong

CYP3A4 inhibitors and fluconazole doses of ≤200 m

g

Avoid the use of fluconazole doses of >200 mg daily w

ith Jakafi

Additional dose modifications should be m

ade with careful m

onitoring of safetyand efficacy





mendations.

Renal or hepatic im

pairment

Additional dose modifications should be m

ade with frequent m

onitoring ofsafety and efficacy

Impairm

ent StatusPLT Count (× 10

9/L)Recom

mended

Starting Dose

Renal impairm

ent: Moderate

(CrCl 30-59 mL/m

in)or severe (CrCl 15-29 m

L/min)

OR

Hepatic im

pairment: M

ild, moderate, or

severe (Child-Pugh class A, B, C)

>150N

o modification needed

100 to 15010 m

g twice daily

50 to <1005 m

g daily

<50Avoid use

End-stage renal disease on dialysis100 to 200

15 mg once daily after

dialysis session

>20020 m

g once daily afterdialysis session

End-stage renal disease(CrCl <15 m

L/min) not requiring dialysis

Avoid use

CrCl, creatinine clearance; PLT, platelet.

Special Populations

Special Populations

For Patients Coadministered Strong

CYP3A4 Inhibitors or

Fluconazole Doses of ≤200 m

gRecom

mended D

ose Modification

Starting dose for patients with M

F w

ith a PLT count:

≥100 × 109/L

10 mg tw

ice daily

50 to <100 × 109/L

5 mg once daily

If on stable dose for patients with M

F:

≥10 mg tw

ice dailyDecrease dose by 50%

(round up to the closest available tablet strength)

5 mg tw

ice daily5 m

g once daily

5 mg once daily

Avoid strong CYP3A4 inhibitor or fluconazoletreatm

ent, or interrupt treatment w

ith Jakafifor the duration of strong CYP3A4 inhibitor orfluconazole use

MF, m

yelofibrosis;PLT, platelet.


Special PopulationsRestarting

Jakaff Q ruxolitinib (tablets)

□

□ •

•

•

l I -------------------------------•---------·t::== +-- --I-

• • •

0

•

•

•

•


Important S

afety Information

Treatment w

ith Jakafi® (ruxolitinib) can cause throm

bocytopenia, anemia and neutropenia, w

hich are each dose-relatedeffects. Perform

a pre-treatment com

plete blood count (CBC) and monitor CBCs every 2 to 4 w

eeks until doses arestabilized, and then as clinically indicated

Manage throm

bocytopenia by reducing the dose or temporarily interrupting Jakafi. Platelet transfusions m

ay be necessary

Patients developing anemia m

ay require blood transfusions and/or dose modifications of Jakafi

Severe neutropenia (ANC <0.5 × 10

9/L) was generally reversible by w

ithholding Jakafi until recovery

Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting Jakafi until active serious

infections have resolved. Observe patients receiving Jakafi for signs and symptom

s of infection and manage prom

ptly.Use active surveillance and prophylactic antibiotics according to clinical guidelines

Tuberculosis (TB) infection has been reported. Observe patients taking Jakafi for signs and symptom

s of active TB andm

anage promptly. Prior to initiating Jakafi, evaluate patients for TB risk factors and test those at higher risk for latent

infection. Consult a physician with expertise in the treatm

ent of TB before starting Jakafi in patients with evidence of active

or latent TB. Continuation of Jakafi during treatment of active TB should be based on the overall risk-benefit determ

ination

Progressive multifocal leukoencephalopathy (PM

L) has occurred with Jakafi treatm

ent. If PML is suspected, stop Jakafi

and evaluate

Advise patients about early signs and symptom

s of herpes zoster and to seek early treatment

Increases in hepatitis B viral load with or w

ithout associated elevations in alanine aminotransferase and aspartate

aminotransferase have been reported in patients w

ith chronic hepatitis B virus (HBV) infections. Monitor and treat

patients with chronic HBV infection according to clinical guidelines

When discontinuing Jakafi, m

yeloproliferative neoplasm-related sym

ptoms m

ay return within one w

eek. Afterdiscontinuation, som

e patients with m

yelofibrosis have experienced fever, respiratory distress, hypotension, DIC, orm

ulti-organ failure. If any of these occur after discontinuation or while tapering Jakafi, evaluate and treat any intercurrent

illness and consider restarting or increasing the dose of Jakafi. Instruct patients not to interrupt or discontinue Jakafiw

ithout consulting their physician. When discontinuing or interrupting Jakafi for reasons other than throm

bocytopenia orneutropenia, consider gradual tapering rather than abrupt discontinuation

Non-m

elanoma skin cancers including basal cell, squam

ous cell, and Merkel cell carcinom

a have occurred. Performperiodic skin exam

inations

Treatment w

ith Jakafi has been associated with increases in total cholesterol, low

-density lipoprotein cholesterol, andtriglycerides. Assess lipid param

eters 8-12 weeks after initiating Jakafi. M

onitor and treat according to clinical guidelinesfor the m

anagement of hyperlipidem

ia

In myelofibrosis and polycythem

ia vera, the most com

mon nonhem

atologic adverse reactions (incidence ≥15%) w

erebruising, dizziness, headache, and diarrhea. In acute graft-versus-host disease, the m

ost comm

on nonhematologic

adverse reactions (incidence >50%) w

ere infections and edema

Dose modifications m

ay be required when adm

inistering Jakafi with strong CYP3A4 inhibitors or fluconazole or in patients

with renal or hepatic im

pairment. Patients should be closely m

onitored and the dose titrated based on safety and efficacy

Use of Jakafi during pregnancy is not recomm

ended and should only be used if the potential benefit justifies the potentialrisk to the fetus. W

omen taking Jakafi should not breastfeed during treatm

ent and for 2 weeks after the final dose

Please see accompanying Full Prescribing Inform

ation for Jakafi.R

eferences:1.Jakafi P

rescribin

g Inform

ation

. Wilm

ing

ton

, DE: In

cyte Corp

oration

. 2. Verstovsek S

, Mesa R

A, G

otlib J, et al. A

do

uble-b

lind

,p

lacebo

-con

trolled trial o

f ruxo

litinib for m

yelofib

rosis. N

Engl J Med. 2012;366(9):799-807. 3. V

erstovsek S, M

esa RA

, Go

tlib J, et al.E

fficacy, safety and survival w

ith ruxo

litinib in p

atients w

ith myelo

fibro

sis: results of a m

edian 2-year fo

llow

-up of C

OM

FOR

T-I. Haem

atologica. 2013;98(12):1865-1871.4. H

arrison C

, Kilad

jian J-J, Al-A

li HK

, et al. JAK

inhib

ition w

ith ruxo

litinib versu

s best availab

le therap

y for myelo

fibro

sis.N

Engl J Med. 2012;366(9):787-798. 5. D

ata on file. In

cyte Corp

oration

. Wilm

ing

ton

, DE

.

XX

% Total R

ecycled Fiber

Jakafi and the Jakafi logo are registered trademarks of Incyte.

© 2020, Incyte C

orporation. MA

T-JAK

-01832 02

/20

XXXXXXX

MO

NIT

OR

freq

uent

lyM

onito

r CBC

s ev

ery

2 to

4 w

eeks

unt

il do

ses

are

stab

ilize

d,an

d th

en a

s cl

inic

ally

indi

cate

d

PLT

Coun

t(×

109 /L

)Re

com

men

ded

Star

ting

Dos

e

5

0 to

<10

05

mg

twic

e da

ily

10

0 to

200

15 m

g tw

ice

daily

>2

0020

mg

twic

e da

ily

In in

term

edia

te o

r hig

h-ris

k m

yelo

fibro

sis

Indi

vidu

aliz

ed d

ose

adju

stm

ents

for o

ptim

ized

effi

cacy

and

saf

ety1

A CB

C an

d pl

atel

et (P

LT) c

ount

mus

tbe

per

form

ed b

efor

e in

itiat

ing

ther

apy,

ever

y 2 to

4 w

eeks

unt

il dos

es a

rest

abiliz

ed a

nd th

en a

s clin

ical

ly in

dica

ted.

The

reco

mm

ende

d st

artin

g do

seof

Jak

afi fo

r MF i

s bas

ed o

n PL

T co

unt.

CBC,

com

plet

e bl

ood

coun

t.Ta

blet

s sho

wn

are

not a

ctua

l size

.

See

STA

RT

ING

PLT

CO

UN

T 5

0 T

O<1

00×

109 /

L ta

b fo

r rec

omm

ende

d do

sem

odifi

catio

ns in

pat

ient

s with

a s

tart

ing

plat

elet

cou

nt o

f 50 t

o <1

00 ×

109 /L

.

See

SPE

CIA

L P

OPU

LAT

ION

S ta

b fo

rdo

sing

info

rmat

ion

in p

atie

nts w

ith re

nal

or h

epat

ic im

pairm

ent a

nd fo

r inf

orm

atio

non

dru

g in

tera

ctio

ns.

Jaka

fi is

als

o av

aila

ble

in10

mg

and

25 m

g ta

blet

s

INC

RE

AS

E D

OS

E

DEC

RE

AS

E D

OS

E

In th

e ca

se o

f an

insu

ffici

ent r

espo

nse,

con

side

r an

incr

ease

in th

e do

seif

patie

nt m

eets

all t

hese

crit

eria

:

Insu

ffici

ent s

plee

n re

duct

ion†

PLT

coun

t >12

5 ×

109 /L

at 4

wee

ks a

nd n

ever

<10

0 ×

109 /L

Abs

olut

e ne

utro

phil

coun

t (A

NC)

>0.

75 ×

109 /L

Incr

ease

dos

e by

5-m

g tw

ice-

daily

incr

emen

ts to

a m

axim

um o

f 25

mg

twic

e da

ily

Dose

s sho

uld

not b

e in

crea

sed

durin

g th

e fir

st 4

wee

ks o

f the

rapy

and

not

mor

e fre

quen

tly th

an e

very

2 w

eeks

.

Disc

ontin

ue J

akafi

if th

ere

is n

o sp

leen

size

redu

ctio

n or

sym

ptom

impr

ovem

ent a

fter 6

mon

ths o

f the

rapy

.

Thro

mbo

cyto

peni

a

Ane

mia

In th

e ca

se o

f a H

emat

olog

ic T

oxic

ity in

clud

ing:

Disc

ontin

uatio

n ca

n be

avo

ided

by

redu

cing

the

dose

or

tem

pora

rily

with

hold

ing

Jaka

fi

Dos

e m

odifi

catio

ns o

f Jak

afi a

nd/o

r blo

od tr

ansf

usio

ns m

ay b

e re

quir

ed fo

r pat

ient

s de

velo

ping

ane

mia

CBC,

com

plet

e bl

ood

coun

t; SE

M, s

tand

ard

erro

r of t

he m

ean.

Adap

ted

with

per

mis

sion

from

Haematologica.

† Fai

lure

to a

chie

ve a

redu

ctio

n fro

m p

re-tr

eatm

ent b

asel

ine

in e

ither

pal

pabl

e sp

leen

leng

th o

f 50%

or s

plee

n v

olum

e of

35%

as m

easu

red

by C

T or

MRI

.

Inte

rrup

t Jak

afi tr

eatm

ent f

or:

Blee

ding

requ

iring

inte

rven

tion,

rega

rdle

ss o

f cur

rent

pla

tele

t cou

nt,

Thro

mbo

cyto

peni

a (P

LT <

50 ×

109 /L

), or

Neu

trope

nia

(AN

C <0

.5 ×

109 /L

)

See

RE

STA

RT

ING

tab

for d

ose

mod

ifica

tions

.

Ris

k fo

r thr

ombo

cyto

peni

a,an

emia

, and

neu

trop

enia

Trea

tmen

t with

Jak

afi c

an c

ause

thro

mbo

cyto

peni

a, a

nem

ia a

nd n

eutro

peni

a,w

hich

are

eac

h do

se-r

elat

ed e

ffect

s.Pe

rfor

m a

pre

-trea

tmen

t com

plet

e bl

ood

coun

t (CB

C) a

nd m

onito

r CBC

s eve

ry 2

to 4

wee

ks u

ntil d

oses

are

sta

biliz

ed, a

nd th

en a

scl

inic

ally

indi

cate

dM

anag

e th

rom

bocy

tope

nia

by re

duci

ngth

e do

se o

r tem

pora

rily i

nter

rupt

ing

Jaka

fi.Pl

atel

et tr

ansf

usio

ns m

ay b

e ne

cess

ary

Patie

nts d

evel

opin

g an

emia

may

requ

irebl

ood

trans

fusi

ons a

nd/o

r dos

em

odifi

catio

ns o

f Jak

afiSe

vere

neu

trope

nia

(AN

C <0

.5 ×

109 /L

) w

as g

ener

ally

reve

rsib

le b

y with

hold

ing

Jaka

fi un

til re

cove

ry

Plea

se s

ee Im

port

ant S

afet

y In

form

atio

n on

the

back

cov

er fo

r rel

ated

and

oth

er ri

sk

info

rmat

ion.

Ref

er to

the

acco

mpa

nyin

g

Full

Pres

crib

ing

Info

rmat

ion

for c

ompl

ete

dosi

ng re

com

men

datio

ns.

* COM

FORT

-I (C

Ontro

lled

Mye

loFib

rosis

st

udy

with

OR

al JA

K in

hibi

tor

Trea

tmen

t-I)

was

a r

ando

mize

d, d

oubl

e-bl

ind,

pla

cebo

-con

trolle

d ph

ase

3st

udy

with

309

pat

ient

s w

ith in

term

edia

te-2

–risk

or h

igh-

risk

mye

lofib

rosis

.Th

e pr

imar

y en

dpoi

nt w

as t

he p

ropo

rtion

of

subj

ects

ach

ievin

g a

≥35%

redu

ctio

n in s

plee

n vol

ume f

rom

base

line t

o wee

k 24 a

s mea

sure

d by C

T or M

RI.

A se

cond

ary e

ndpo

int w

as th

e pr

opor

tion

of s

ubje

cts w

ith a

≥50

% re

duct

ion

in To

tal S

ympt

om S

core

from

bas

eline

to w

eek

24 a

s m

easu

red

by th

e da

ilypa

tient

diar

y, th

e mod

ified

Mye

lofib

rosis

Sym

ptom

Ass

essm

ent F

orm

.1,2

‡CO

MFO

RT-II

(C

Ontro

lled

Mye

loFib

rosis

st

udy

with

OR

al JA

K in

hibi

tor

Trea

tmen

t-II)

was

a ra

ndom

ized,

ope

n-la

bel p

hase

3 s

tudy

with

219

pat

ient

sw

ith i

nter

med

iate

-2–r

isk o

r hi

gh-ri

sk m

yelo

fibro

sis.

The

prim

ary

endp

oint

was

the

prop

ortio

n of

pat

ient

s ac

hiev

ing

a ≥3

5% re

duct

ion

in sp

leen

vol

ume

from

bas

eline

at w

eek

48 a

s m

easu

red

by C

T or

MRI

. Bes

t ava

ilabl

e th

erap

yin

COM

FORT

-II in

clude

d hy

drox

yure

a (4

6.6%

) and

glu

coco

rtico

ids

(16.4

%),

asw

ell a

s no

med

icatio

n, an

agre

lide,

epoe

tin a

lfa, t

halid

omid

e, le

nalid

omid

e,m

erca

ptop

urin

e, th

iogu

anin

e, da

nazo

l, pe

gint

erfe

ron

alfa

-2a,

inte

rfero

n-α

, m

elph

alan

, ace

tylsa

licyli

c acid

, cyt

arab

ine,

and c

olch

icine

.1,4,5

OP

TIM

IZE

to b

alan

ce s

afet

y an

d ef

ficac

yS

TAR

T h

ere

✔ ✔ ✔

In p

atie

nts

rece

ivin

g Ja

kafi

in th

e CO

MFO

RT s

tudi

es,

PLT

coun

ts a

nd h

emog

lobi

n le

vels

gen

eral

ly s

tabi

lized

afte

r8

to 1

2 w

eeks

1-4*

‡

Jaka

�

Pla

cebo

MeanHemoglobin±SEM(g/L)

110

100

90120

02

46

812

1620

2430

36S

tudy

Wee

k

Con

duct

CB

C b

etw

een

wee

ks 2

and

4

CO

MFO

RT-

I: M

ean

Hem

og

lob

in L

evel

s O

ver

Tim

e2

Mean Change (%)

(n =

106)

8.1

−16.

7−2

8.1

−33.

4−3

6.3

−39.

5

(n =

19)

(n =

35)

(n =

22)

(n =

41)

(n =

22)

Plac

ebo

<10

mg

twice

dai

ly10

mg

twice

dai

ly15

mg

twice

dai

ly20

mg

twice

dai

ly>2

0 m

g tw

ice d

aily

20 10 0−1

0−2

0−3

0−4

0−5

0

Titra

ted

Dose

CO

MFO

RT-

Ia : Mea

n C

han

ge in

Sp

leen

Vo

lum

e by

Do

se a

t Wee

k 24

3

PLT,

pla

tele

t.

Twic

e-D

aily

Dos

e at

Tim

e of

PLT

Dec

line

25 m

g20

mg

15 m

g10

mg

5 m

g

PLT

Coun

t(×

109 /L

)N

ew re

com

men

ded

twic

e da

ily d

ose

100

to <

125

20 m

g15

mg

No

chan

ge

75 to

<10

010

mg

No

chan

ge

50 to

<75

5 m

gN

o ch

ange

<50

Ho

ld

Starting PLT Count ≥100 × 109/L

Ear

ly d

ose

ad

just

men

tsas

nee

ded

hel

p t

o o

pti

miz

eef

fica

cy a

nd

saf

ety

In th

e ph

ase

3 COM

FORT

-I tri

al o

f pat

ient

s with

inte

rmed

iate

-2–r

isk o

r hig

h-ris

k MF,

the

prim

ary

endp

oint

was

the

prop

ortio

n of

pat

ient

s ach

ievi

nga

≥35%

redu

ctio

n in

spl

een

volu

me

from

bas

elin

e to

wee

k 24.

1,2 *

42%

of p

atie

nts r

ecei

ving

Jak

afi a

chie

ved

a ≥3

5%re

duct

ion

in s

plee

n vo

lum

e at

wee

k 24 v

s 0.7

% o

fpa

tient

s rec

eivi

ng p

lace

bo (P

< 0

.000

1)2

Base

d on

limite

d cl

inic

al d

ata,

long

-term

mai

nten

ance

at 5

-mg

twic

e-da

ilydo

sing

has

not

sho

wn

resp

onse

s. C

ontin

ued

use

at th

is d

ose

shou

ld b

elim

ited

to p

atie

nts i

n w

hom

the

bene

fits o

utw

eigh

the

pote

ntia

l ris

ks

of p

atie

nts

rece

ivin

g Ja

kafi

in C

OM

FOR

T-I r

equ

ired

ad

ose

ad

just

men

t in

th

efi

rst

12 w

eeks

of t

her

apy

3

70%

INT

ER

RU

PT D

OS

E

Jaka

fi Mea

n Sp

leen

Vol

ume

Redu

ctio

n (-3

1.6%

)

In C

OM

FORT

-I, 6

0% o

f pat

ient

s tr

eate

d w

ith J

akafi

and

38%

of

patie

nts

rece

ivin

g pl

aceb

o re

ceiv

ed re

d bl

ood

cell

tran

sfus

ions

du

ring

rand

omiz

ed tr

eatm

ent1

In p

atie

nts

rece

ivin

g Ja

kafi

in th

e CO

MFO

RT s

tudi

es, m

ean

decr

ease

s in

hem

oglo

bin

reac

hed

a na

dir o

f app

roxi

mat

ely

1.5

to 2

.0 g

/dL

belo

w

base

line

afte

r 8 to

12

wee

ks o

f the

rapy

and

then

gra

dual

ly re

cove

red

to a

new

ste

ady

stat

e th

at w

as a

ppro

xim

atel

y 1.

0 g/

dL b

elow

bas

elin

e1

In C

OMFO

RT-I,

gra

de 3

and

4 th

rom

bocy

tope

nia

or a

nem

ia o

ccur

red

in 1

3% a

nd 4

5% o

f pat

ient

s re

ceiv

ing

Jaka

fi, re

spec

tivel

y2

<1%

of p

atie

nts r

ecei

ving

Jak

afi in

the

COM

FORT

stu

dies

dis

cont

inue

ddu

e to

ane

mia

or t

hrom

bocy

tope

nia1-

4

CO

MFO

RT-

I: M

ean

Ch

ang

e in

Sp

leen

Vo

lum

e b

y D

ose

at

Wee

k 24

3

MF

CBC,

com

plet

e bl

ood

coun

t; SE

M,s

tand

ard

erro

r of t

he m

ean.

Restarting

INTERRUPT FOR: Bleeding requiring intervention regardless of current platelet count, PLT counts <25 × 109/L, or ANC <0.5 × 109/L

RESTARTAfter recovery of PLT counts to >35 × 109/L and ANC >0.75 × 109/L at the higher of:

5 mg once daily or 5 mg twice daily below the largest dose in the week prior to the decrease in PLT count below 25 × 109/L or ANC below 0.5 × 109/L that led to dose interruption

Only after the first 4 weeks of therapy and not more frequently than every 2 weeks if patient meets all these criteria:


PLT count has remained ≥40 × 109/L and has not decreased by >20% in the prior 4 weeks

ANC >1.0 × 109/L

No dose reduction or interruption for an adverse event or hematological toxicity in the prior 4 weeks

Increase dose by increments of 5 mg daily to a maximum of 10 mg twice daily

Continuation of treatment for more than 6 months should be limited to patients in whom the benefits outweigh the risks. Discontinue Jakafi® (ruxolitinib) if there is no spleen size reduction or symptom improvement after 6 months of therapy.

Reduce the dose of Jakafi in patients with platelet counts <35 × 109/L

PLT, platelet.


INCREASE DOSE

DECREASE DOSE

* Failure to achieve a reduction from pre-treatment baseline in either palpable spleen length of 50% or spleen volume of 35% as measured by CT or MRI.


✔

✔

✔

✔

PLT Count Dosing Recommendations

<25 × 109/L • Interrupt dosing

25 to <35 × 109/L and the platelet count decline is <20% during the prior 4 weeks


• For patients on 5 mg once daily, maintain dose at 5 mg once daily

25 to <35 × 109/L and the platelet count decline is ≥20% during the prior 4 weeks

• Decrease dose by 5 mg twice daily

• For patients on 5 mg twice daily, decrease the dose to 5 mgonce daily


The recommended starting dose in MF for patients with a starting PLT count of 50 to <100 × 109/L is 5 mg twice daily

See SPECIAL POPULATIONS tab for dosing information in patients with renal or hepatic impairment and for information on drug interactions.

Please see Important Safety Information on the back cover for related and other risk information.Refer to the accompanying Full Prescribing Information for complete dosing recommendations.

Restarting dose in case of bleedingOnce the bleeding event has resolved, consider resuming treatment at the priordose if the underlying cause of bleeding has been controlled. If the bleeding eventhas resolved but the underlying cause persists, consider resuming treatment withJakafiat a lower dose

Restarting dose in case of hematologic toxicity inpatients with starting PLT count ≥100 × 109/L

Treatment interruption and restarting dosingAfter recovery of PLT counts >50 × 109/L and ANC >0.75 × 109/L, dosing may be restarted

The maximum allowable dose that may be used in restarting Jakafi® (ruxolitinib)after a previous interruption is as shown below

Maximum restarting doses for Jakafi aftersafety interruption for thrombocytopenia

Following treatment interruption for ANC <0.5 × 109/L, after ANC recoversto ≥0.75 × 109/L, restart dosing at the higher of 5 mg once daily or 5 mg twicedaily below the largest dose in the week prior to the treatment interruption

Current PLT Count (× 109/L)

Maximum Dose When Restarting Treatment With Jakafia

≥125 20 mg twice daily

100 to <125 15 mg twice daily

75 to <100 10 mg twice daily for at least 2 weeks; if stable,may increase to 15 mg twice daily


<50 Continue hold

a Maximum doses are displayed. When restarting, begin with a dose at least 5 mg twice daily below the dose at interruption.

PLT, platelet.

Restarting After Safety Interruption

Drug interactions

Modify the dose of Jakafi® (ruxolitinib) when coadministered with strongCYP3A4 inhibitors and fluconazole doses of ≤200 mg

Avoid the use of fluconazole doses of >200 mg daily with Jakafi

Additional dose modifications should be made with careful monitoring of safetyand efficacy


Renal or hepatic impairment

Additional dose modifications should be made with frequent monitoring ofsafety and efficacy

Impairment StatusPLT Count (× 109/L)


Renal impairment: Moderate (CrCl 30-59 mL/min)

or severe (CrCl 15-29 mL/min)OR

Hepatic impairment: Mild, moderate, or severe (Child-Pugh class A, B, C)

>150 No modification needed

100 to 150 10 mg twice daily

50 to <100 5 mg daily

<50 Avoid use

End-stage renal disease on dialysis100 to 200 15 mg once daily after

dialysis session

>200 20 mg once daily afterdialysis session

End-stage renal disease(CrCl <15 mL/min) not requiring dialysis Avoid use


Special Populations

Special Populations

For Patients Coadministered Strong CYP3A4 Inhibitors or Fluconazole Doses of ≤200 mg

Recommended Dose Modification

Starting dose for patients with MF with a PLT count:

≥100 × 109/L 10 mg twice daily

50 to <100 × 109/L 5 mg once daily

If on stable dose for patients with MF:

≥10 mg twice daily Decrease dose by 50% (round up to the closest available tablet strength)

5 mg twice daily 5 mg once daily

5 mg once daily

Avoid strong CYP3A4 inhibitor or fluconazoletreatment, or interrupt treatment with Jakafifor the duration of strong CYP3A4 inhibitor orfluconazole use

MF, myelofibrosis; PLT, platelet.

Important S

afety Information

Treatment w




a pre-treatment com



Manage throm


ay be necessary











s of active TB andm





ination




and evaluate










ptoms m



e patients with m






Non-m




inations

Treatment w






ia



mon nonhem



ost comm

on nonhematologic














ation for Jakafi.R


rescribin

g Inform

ation

. Wilm

ing

ton

, DE: In

cyte Corp

oration

. 2. Verstovsek S

, Mesa R

A, G

otlib J, et al. A

do

uble-b

lind

,p

lacebo

-con

trolled trial o

f ruxo

litinib for m

yelofib

rosis. N

Engl J Med. 2012;366(9):799-807. 3. V

erstovsek S, M

esa RA

, Go

tlib J, et al.E


ith ruxo

litinib in p

atients w

ith myelo

fibro

sis: results of a m

edian 2-year fo

llow

-up of C

OM

FOR

T-I. Haem

atologica. 2013;98(12):1865-1871.4. H

arrison C

, Kilad

jian J-J, Al-A

li HK

, et al. JAK

inhib

ition w

ith ruxo

litinib versu

s best availab

le therap

y for myelo

fibro

sis.N

Engl J Med. 2012;366(9):787-798. 5. D

ata on file. In

cyte Corp

oration

. Wilm

ing

ton

, DE

.

XX

% Total R

ecycled Fiber


© 2020, Incyte C

orporation. MA

T-JAK

-01832 02

/20

XXXXXXX

MO

NIT

OR

freq

uent

lyM

onito

r CBC

s ev

ery

2 to

4 w

eeks

unt

il do

ses

are

stab

ilize

d,an

d th

en a

s cl

inic

ally

indi

cate

d

PLT

Coun

t(×

109 /L

)Re

com

men

ded

Star

ting

Dos

e

5

0 to

<10

05

mg

twic

e da

ily

10

0 to

200

15 m

g tw

ice

daily

>2

0020

mg

twic

e da

ily

In in

term

edia

te o

r hig

h-ris

k m

yelo

fibro

sis

Indi

vidu

aliz

ed d

ose

adju

stm

ents

for o

ptim

ized

effi

cacy

and

saf

ety1

A CB

C an

d pl

atel

et (P

LT) c

ount

mus

tbe

per

form

ed b

efor

e in

itiat

ing

ther

apy,

ever

y 2 to

4 w

eeks

unt

il dos

es a

rest

abiliz

ed a

nd th

en a

s clin

ical

ly in

dica

ted.

The

reco

mm

ende

d st

artin

g do

seof

Jak

afi fo

r MF i

s bas

ed o

n PL

T co

unt.

CBC,

com

plet

e bl

ood

coun

t.Ta

blet

s sho

wn

are

not a

ctua

l size

.

See

STA

RT

ING

PLT

CO

UN

T 5

0 T

O<1

00×

109 /

L ta

b fo

r rec

omm

ende

d do

sem

odifi

catio

ns in

pat

ient

s with

a s

tart

ing

plat

elet

cou

nt o

f 50 t

o <1

00 ×

109 /L

.

See

SPE

CIA

L P

OPU

LAT

ION

S ta

b fo

rdo

sing

info

rmat

ion

in p

atie

nts w

ith re

nal

or h

epat

ic im

pairm

ent a

nd fo

r inf

orm

atio

non

dru

g in

tera

ctio

ns.

Jaka

fi is

als

o av

aila

ble

in10

mg

and

25 m

g ta

blet

s

INC

RE

AS

E D

OS

E

DEC

RE

AS

E D

OS

E

In th

e ca

se o

f an

insu

ffici

ent r

espo

nse,

con

side

r an

incr

ease

in th

e do

seif

patie

nt m

eets

all t

hese

crit

eria

:

Insu

ffici

ent s

plee

n re

duct

ion†

PLT

coun

t >12

5 ×

109 /L

at 4

wee

ks a

nd n

ever

<10

0 ×

109 /L

Abs

olut

e ne

utro

phil

coun

t (A

NC)

>0.

75 ×

109 /L

Incr

ease

dos

e by

5-m

g tw

ice-

daily

incr

emen

ts to

a m

axim

um o

f 25

mg

twic

e da

ily

Dose

s sho

uld

not b

e in

crea

sed

durin

g th

e fir

st 4

wee

ks o

f the

rapy

and

not

mor

e fre

quen

tly th

an e

very

2 w

eeks

.

Disc

ontin

ue J

akafi

if th

ere

is n

o sp

leen

size

redu

ctio

n or

sym

ptom

impr

ovem

ent a

fter 6

mon

ths o

f the

rapy

.

Thro

mbo

cyto

peni

a

Ane

mia

In th

e ca

se o

f a H

emat

olog

ic T

oxic

ity in

clud

ing:

Disc

ontin

uatio

n ca

n be

avo

ided

by

redu

cing

the

dose

or

tem

pora

rily

with

hold

ing

Jaka

fi

Dos

e m

odifi

catio

ns o

f Jak

afi a

nd/o

r blo

od tr

ansf

usio

ns m

ay b

e re

quir

ed fo

r pat

ient

s de

velo

ping

ane

mia

CBC,

com

plet

e bl

ood

coun

t; SE

M, s

tand

ard

erro

r of t

he m

ean.

Adap

ted

with

per

mis

sion

from

Haematologica.

† Fai

lure

to a

chie

ve a

redu

ctio

n fro

m p

re-tr

eatm

ent b

asel

ine

in e

ither

pal

pabl

e sp

leen

leng

th o

f 50%

or s

plee

n v

olum

e of

35%

as m

easu

red

by C

T or

MRI

.

Inte

rrup

t Jak

afi tr

eatm

ent f

or:

Blee

ding

requ

iring

inte

rven

tion,

rega

rdle

ss o

f cur

rent

pla

tele

t cou

nt,

Thro

mbo

cyto

peni

a (P

LT <

50 ×

109 /L

), or

Neu

trope

nia

(AN

C <0

.5 ×

109 /L

)

See

RE

STA

RT

ING

tab

for d

ose

mod

ifica

tions

.

Ris

k fo

r thr

ombo

cyto

peni

a,an

emia

, and

neu

trop

enia

Trea

tmen

t with

Jak

afi c

an c

ause

thro

mbo

cyto

peni

a, a

nem

ia a

nd n

eutro

peni

a,w

hich

are

eac

h do

se-r

elat

ed e

ffect

s.Pe

rfor

m a

pre

-trea

tmen

t com

plet

e bl

ood

coun

t (CB

C) a

nd m

onito

r CBC

s eve

ry 2

to 4

wee

ks u

ntil d

oses

are

sta

biliz

ed, a

nd th

en a

scl

inic

ally

indi

cate

dM

anag

e th

rom

bocy

tope

nia

by re

duci

ngth

e do

se o

r tem

pora

rily i

nter

rupt

ing

Jaka

fi.Pl

atel

et tr

ansf

usio

ns m

ay b

e ne

cess

ary

Patie

nts d

evel

opin

g an

emia

may

requ

irebl

ood

trans

fusi

ons a

nd/o

r dos

em

odifi

catio

ns o

f Jak

afiSe

vere

neu

trope

nia

(AN

C <0

.5 ×

109 /L

) w

as g

ener

ally

reve

rsib

le b

y with

hold

ing

Jaka

fi un

til re

cove

ry

Plea

se s

ee Im

port

ant S

afet

y In

form

atio

n on

the

back

cov

er fo

r rel

ated

and

oth

er ri

sk

info

rmat

ion.

Ref

er to

the

acco

mpa

nyin

g

Full

Pres

crib

ing

Info

rmat

ion

for c

ompl

ete

dosi

ng re

com

men

datio

ns.

* COM

FORT

-I (C

Ontro

lled

Mye

loFib

rosis

st

udy

with

OR

al JA

K in

hibi

tor

Trea

tmen

t-I)

was

a r

ando

mize

d, d

oubl

e-bl

ind,

pla

cebo

-con

trolle

d ph

ase

3st

udy

with

309

pat

ient

s w

ith in

term

edia

te-2

–risk

or h

igh-

risk

mye

lofib

rosis

.Th

e pr

imar

y en

dpoi

nt w

as t

he p

ropo

rtion

of

subj

ects

ach

ievin

g a

≥35%

redu

ctio

n in s

plee

n vol

ume f

rom

base

line t

o wee

k 24 a

s mea

sure

d by C

T or M

RI.

A se

cond

ary e

ndpo

int w

as th

e pr

opor

tion

of s

ubje

cts w

ith a

≥50

% re

duct

ion

in To

tal S

ympt

om S

core

from

bas

eline

to w

eek

24 a

s m

easu

red

by th

e da

ilypa

tient

diar

y, th

e mod

ified

Mye

lofib

rosis

Sym

ptom

Ass

essm

ent F

orm

.1,2

‡CO

MFO

RT-II

(C

Ontro

lled

Mye

loFib

rosis

st

udy

with

OR

al JA

K in

hibi

tor

Trea

tmen

t-II)

was

a ra

ndom

ized,

ope

n-la

bel p

hase

3 s

tudy

with

219

pat

ient

sw

ith i

nter

med

iate

-2–r

isk o

r hi

gh-ri

sk m

yelo

fibro

sis.

The

prim

ary

endp

oint

was

the

prop

ortio

n of

pat

ient

s ac

hiev

ing

a ≥3

5% re

duct

ion

in sp

leen

vol

ume

from

bas

eline

at w

eek

48 a

s m

easu

red

by C

T or

MRI

. Bes

t ava

ilabl

e th

erap

yin

COM

FORT

-II in

clude

d hy

drox

yure

a (4

6.6%

) and

glu

coco

rtico

ids

(16.4

%),

asw

ell a

s no

med

icatio

n, an

agre

lide,

epoe

tin a

lfa, t

halid

omid

e, le

nalid

omid

e,m

erca

ptop

urin

e, th

iogu

anin

e, da

nazo

l, pe

gint

erfe

ron

alfa

-2a,

inte

rfero

n-α

, m

elph

alan

, ace

tylsa

licyli

c acid

, cyt

arab

ine,

and c

olch

icine

.1,4,5

OP

TIM

IZE

to b

alan

ce s

afet

y an

d ef

ficac

yS

TAR

T h

ere

✔ ✔ ✔

In p

atie

nts

rece

ivin

g Ja

kafi

in th

e CO

MFO

RT s

tudi

es,

PLT

coun

ts a

nd h

emog

lobi

n le

vels

gen

eral

ly s

tabi

lized

afte

r8

to 1

2 w

eeks

1-4*

‡

Jaka

�

Pla

cebo


110

100

90120

02

46

812

1620

2430

36S

tudy

Wee

k

Con

duct

CB

C b

etw

een

wee

ks 2

and

4

CO

MFO

RT-

I: M

ean

Hem

og

lob

in L

evel

s O

ver

Tim

e2

Mean Change (%)

(n =

106)

8.1

−16.

7−2

8.1

−33.

4−3

6.3

−39.

5

(n =

19)

(n =

35)

(n =

22)

(n =

41)

(n =

22)

Plac

ebo

<10

mg

twice

dai

ly10

mg

twice

dai

ly15

mg

twice

dai

ly20

mg

twice

dai

ly>2

0 m

g tw

ice d

aily

20 10 0−1

0−2

0−3

0−4

0−5

0

Titra

ted

Dose

CO

MFO

RT-

Ia : Mea

n C

han

ge in

Sp

leen

Vo

lum

e by

Do

se a

t Wee

k 24

3

PLT,

pla

tele

t.

Twic

e-D

aily

Dos

e at

Tim

e of

PLT

Dec

line

25 m

g20

mg

15 m

g10

mg

5 m

g

PLT

Coun

t(×

109 /L

)N

ew re

com

men

ded

twic

e da

ily d

ose

100

to <

125

20 m

g15

mg

No

chan

ge

75 to

<10

010

mg

No

chan

ge

50 to

<75

5 m

gN

o ch

ange

<50

Ho

ld


Ear

ly d

ose

ad

just

men

tsas

nee

ded

hel

p t

o o

pti

miz

eef

fica

cy a

nd

saf

ety

In th

e ph

ase

3 COM

FORT

-I tri

al o

f pat

ient

s with

inte

rmed

iate

-2–r

isk o

r hig

h-ris

k MF,

the

prim

ary

endp

oint

was

the

prop

ortio

n of

pat

ient

s ach

ievi

nga

≥35%

redu

ctio

n in

spl

een

volu

me

from

bas

elin

e to

wee

k 24.

1,2 *

42%

of p

atie

nts r

ecei

ving

Jak

afi a

chie

ved

a ≥3

5%re

duct

ion

in s

plee

n vo

lum

e at

wee

k 24 v

s 0.7

% o

fpa

tient

s rec

eivi

ng p

lace

bo (P

< 0

.000

1)2

Base

d on

limite

d cl

inic

al d

ata,

long

-term

mai

nten

ance

at 5

-mg

twic

e-da

ilydo

sing

has

not

sho

wn

resp

onse

s. C

ontin

ued

use

at th

is d

ose

shou

ld b

elim

ited

to p

atie

nts i

n w

hom

the

bene

fits o

utw

eigh

the

pote

ntia

l ris

ks

of p

atie

nts

rece

ivin

g Ja

kafi

in C

OM

FOR

T-I r

equ

ired

ad

ose

ad

just

men

t in

th

efi

rst

12 w

eeks

of t

her

apy

3

70%

INT

ER

RU

PT D

OS

E

Jaka

fi Mea

n Sp

leen

Vol

ume

Redu

ctio

n (-3

1.6%

)

In C

OM

FORT

-I, 6

0% o

f pat

ient

s tr

eate

d w

ith J

akafi

and

38%

of

patie

nts

rece

ivin

g pl

aceb

o re

ceiv

ed re

d bl

ood

cell

tran

sfus

ions

du

ring

rand

omiz

ed tr

eatm

ent1

In p

atie

nts

rece

ivin

g Ja

kafi

in th

e CO

MFO

RT s

tudi

es, m

ean

decr

ease

s in

hem

oglo

bin

reac

hed

a na

dir o

f app

roxi

mat

ely

1.5

to 2

.0 g

/dL

belo

w

base

line

afte

r 8 to

12

wee

ks o

f the

rapy

and

then

gra

dual

ly re

cove

red

to a

new

ste

ady

stat

e th

at w

as a

ppro

xim

atel

y 1.

0 g/

dL b

elow

bas

elin

e1

In C

OMFO

RT-I,

gra

de 3

and

4 th

rom

bocy

tope

nia

or a

nem

ia o

ccur

red

in 1

3% a

nd 4

5% o

f pat

ient

s re

ceiv

ing

Jaka

fi, re

spec

tivel

y2

<1%

of p

atie

nts r

ecei

ving

Jak

afi in

the

COM

FORT

stu

dies

dis

cont

inue

ddu

e to

ane

mia

or t

hrom

bocy

tope

nia1-

4

CO

MFO

RT-

I: M

ean

Ch

ang

e in

Sp

leen

Vo

lum

e b

y D

ose

at

Wee

k 24

3

MF

CBC,

com

plet

e bl

ood

coun

t; SE

M,s

tand

ard

erro

r of t

he m

ean.

Restarting

INTERRUPT FOR:Bleeding requiring intervention regardless of current platelet count,PLT counts <25 × 109/L, or

ANC <0.5 × 109/LRESTARTAfter recovery of PLT counts to >35 × 109/L and ANC >0.75 × 109/L at the higher of:

5 mg once daily or

5 mg twice daily below the largest dose in the week prior to the decrease in PLTcount below 25 × 109/L or ANC below 0.5 × 109/L that led to dose interruption


Only after the first 4 weeks of therapy and not more frequently than every 2 weeks ifpatient meets all these criteria:



ANC >1.0 × 109/L

No dose reduction or interruption for an adverse event or hematological toxicityin the prior 4 weeks


Continuation of treatment for more than 6 months should be limited to patientsin whom the benefits outweigh the risks.Discontinue Jakafi® (ruxolitinib) if there is no spleen size reduction or symptomimprovement after 6 months of therapy.


PLT, platelet.


INCREASE DOSE

DECREASE DOSE

* Failure to achieve a reduction from pre-treatment baseline in either palpable spleen length of 50% or spleen volume of 35%as measured by CT or MRI.


✔

✔

✔

✔



25 to <35 × 109/L and theplatelet count decline is <20%during the prior 4 weeks



25 to <35 × 109/L and theplatelet count decline is ≥20%during the prior 4 weeks




The recommended starting dose in MF for patients with a starting PLT count of50 to <100 × 109/L is 5 mg twice daily

See SPECIAL POPULATIONS tab for dosing information in patients with renal or hepaticimpairment and for information on drug interactions.

Restarting dose in case of bleeding Once the bleeding event has resolved, consider resuming treatment at the prior dose if the underlying cause of bleeding has been controlled. If the bleeding event has resolved but the underlying cause persists, consider resuming treatment with Jakafi at a lower dose

Restarting dose in case of hematologic toxicity in patients with starting PLT count ≥100 × 109/L

Treatment interruption and restarting dosing After recovery of PLT counts >50 × 109/L and ANC >0.75 × 109/L, dosing may be restarted

The maximum allowable dose that may be used in restarting Jakafi® (ruxolitinib) after a previous interruption is as shown below

Maximum restarting doses for Jakafi after safety interruption for thrombocytopenia

Following treatment interruption for ANC <0.5 × 109/L, after ANC recovers to ≥0.75 × 109/L, restart dosing at the higher of 5 mg once daily or 5 mg twice daily below the largest dose in the week prior to the treatment interruption





75 to <100 10 mg twice daily for at least 2 weeks; if stable, may increase to 15 mg twice daily

50 to <75 5 mg twice daily for at least 2 weeks; if stable, may increase to 10 mg twice daily

<50 Continue hold


PLT, platelet.


Drug interactions

Modify the dose of Jakafi® (ruxolitinib) when coadministered with strongCYP3A4 inhibitors and fluconazole doses of ≤200 mg


Additional dose modifications should be made with careful monitoring of safetyand efficacy



Additional dose modifications should be made with frequent monitoring ofsafety and efficacy









<50 Avoid use


dialysis session

>200 20 mg once daily afterdialysis session

End-stage renal disease(CrCl <15 mL/min) not requiring dialysis Avoid use


Special Populations

Special Populations









5 mg once daily

Avoid strong CYP3A4 inhibitor or fluconazoletreatment, or interrupt treatment with Jakafifor the duration of strong CYP3A4 inhibitor orfluconazole use


Important S

afety Information

Treatment w




a pre-treatment com



Manage throm


ay be necessary











s of active TB andm





ination




and evaluate










ptoms m



e patients with m






Non-m




inations

Treatment w






ia



mon nonhem



ost comm

on nonhematologic














ation for Jakafi.R


rescribin

g Inform

ation

. Wilm

ing

ton

, DE: In

cyte Corp

oration

. 2. Verstovsek S

, Mesa R

A, G

otlib J, et al. A

do

uble-b

lind

,p

lacebo

-con

trolled trial o

f ruxo

litinib for m

yelofib

rosis. N

Engl J Med. 2012;366(9):799-807. 3. V

erstovsek S, M

esa RA

, Go

tlib J, et al.E


ith ruxo

litinib in p

atients w

ith myelo

fibro

sis: results of a m

edian 2-year fo

llow

-up of C

OM

FOR

T-I. Haem

atologica. 2013;98(12):1865-1871.4. H

arrison C

, Kilad

jian J-J, Al-A

li HK

, et al. JAK

inhib

ition w

ith ruxo

litinib versu

s best availab

le therap

y for myelo

fibro

sis.N

Engl J Med. 2012;366(9):787-798. 5. D

ata on file. In

cyte Corp

oration

. Wilm

ing

ton

, DE

.

XX

% Total R

ecycled Fiber


© 2020, Incyte C

orporation. MA

T-JAK

-01832 02

/20

XXXXXXX

MO

NIT

OR

freq

uent

lyM

onito

r CBC

s ev

ery

2 to

4 w

eeks

unt

il do

ses

are

stab

ilize

d,an

d th

en a

s cl

inic

ally

indi

cate

d

PLT

Coun

t(×

109 /L

)Re

com

men

ded

Star

ting

Dos

e

5

0 to

<10

05

mg

twic

e da

ily

10

0 to

200

15 m

g tw

ice

daily

>2

0020

mg

twic

e da

ily

In in

term

edia

te o

r hig

h-ris

k m

yelo

fibro

sis

Indi

vidu

aliz

ed d

ose

adju

stm

ents

for o

ptim

ized

effi

cacy

and

saf

ety1

A CB

C an

d pl

atel

et (P

LT) c

ount

mus

tbe

per

form

ed b

efor

e in

itiat

ing

ther

apy,

ever

y 2 to

4 w

eeks

unt

il dos

es a

rest

abiliz

ed a

nd th

en a

s clin

ical

ly in

dica

ted.

The

reco

mm

ende

d st

artin

g do

seof

Jak

afi fo

r MF i

s bas

ed o

n PL

T co

unt.

CBC,

com

plet

e bl

ood

coun

t.Ta

blet

s sho

wn

are

not a

ctua

l size

.

See

STA

RT

ING

PLT

CO

UN

T 5

0 T

O<1

00×

109 /

L ta

b fo

r rec

omm

ende

d do

sem

odifi

catio

ns in

pat

ient

s with

a s

tart

ing

plat

elet

cou

nt o

f 50 t

o <1

00 ×

109 /L

.

See

SPE

CIA

L P

OPU

LAT

ION

S ta

b fo

rdo

sing

info

rmat

ion

in p

atie

nts w

ith re

nal

or h

epat

ic im

pairm

ent a

nd fo

r inf

orm

atio

non

dru

g in

tera

ctio

ns.

Jaka

fi is

als

o av

aila

ble

in10

mg

and

25 m

g ta

blet

s

INC

RE

AS

E D

OS

E

DEC

RE

AS

E D

OS

E

In th

e ca

se o

f an

insu

ffici

ent r

espo

nse,

con

side

r an

incr

ease

in th

e do

seif

patie

nt m

eets

all t

hese

crit

eria

:

Insu

ffici

ent s

plee

n re

duct

ion†

PLT

coun

t >12

5 ×

109 /L

at 4

wee

ks a

nd n

ever

<10

0 ×

109 /L

Abs

olut

e ne

utro

phil

coun

t (A

NC)

>0.

75 ×

109 /L

Incr

ease

dos

e by

5-m

g tw

ice-

daily

incr

emen

ts to

a m

axim

um o

f 25

mg

twic

e da

ily

Dose

s sho

uld

not b

e in

crea

sed

durin

g th

e fir

st 4

wee

ks o

f the

rapy

and

not

mor

e fre

quen

tly th

an e

very

2 w

eeks

.

Disc

ontin

ue J

akafi

if th

ere

is n

o sp

leen

size

redu

ctio

n or

sym

ptom

impr

ovem

ent a

fter 6

mon

ths o

f the

rapy

.

Thro

mbo

cyto

peni

a

Ane

mia

In th

e ca

se o

f a H

emat

olog

ic T

oxic

ity in

clud

ing:

Disc

ontin

uatio

n ca

n be

avo

ided

by

redu

cing

the

dose

or

tem

pora

rily

with

hold

ing

Jaka

fi

Dos

e m

odifi

catio

ns o

f Jak

afi a

nd/o

r blo

od tr

ansf

usio

ns m

ay b

e re

quir

ed fo

r pat

ient

s de

velo

ping

ane

mia

CBC,

com

plet

e bl

ood

coun

t; SE

M, s

tand

ard

erro

r of t

he m

ean.

Adap

ted

with

per

mis

sion

from

Haematologica.

† Fai

lure

to a

chie

ve a

redu

ctio

n fro

m p

re-tr

eatm

ent b

asel

ine

in e

ither

pal

pabl

e sp

leen

leng

th o

f 50%

or s

plee

n v

olum

e of

35%

as m

easu

red

by C

T or

MRI

.

Inte

rrup

t Jak

afi tr

eatm

ent f

or:

Blee

ding

requ

iring

inte

rven

tion,

rega

rdle

ss o

f cur

rent

pla

tele

t cou

nt,

Thro

mbo

cyto

peni

a (P

LT <

50 ×

109 /L

), or

Neu

trope

nia

(AN

C <0

.5 ×

109 /L

)

See

RE

STA

RT

ING

tab

for d

ose

mod

ifica

tions

.

Ris

k fo

r thr

ombo

cyto

peni

a,an

emia

, and

neu

trop

enia

Trea

tmen

t with

Jak

afi c

an c

ause

thro

mbo

cyto

peni

a, a

nem

ia a

nd n

eutro

peni

a,w

hich

are

eac

h do

se-r

elat

ed e

ffect

s.Pe

rfor

m a

pre

-trea

tmen

t com

plet

e bl

ood

coun

t (CB

C) a

nd m

onito

r CBC

s eve

ry 2

to 4

wee

ks u

ntil d

oses

are

sta

biliz

ed, a

nd th

en a

scl

inic

ally

indi

cate

dM

anag

e th

rom

bocy

tope

nia

by re

duci

ngth

e do

se o

r tem

pora

rily i

nter

rupt

ing

Jaka

fi.Pl

atel

et tr

ansf

usio

ns m

ay b

e ne

cess

ary

Patie

nts d

evel

opin

g an

emia

may

requ

irebl

ood

trans

fusi

ons a

nd/o

r dos

em

odifi

catio

ns o

f Jak

afiSe

vere

neu

trope

nia

(AN

C <0

.5 ×

109 /L

) w

as g

ener

ally

reve

rsib

le b

y with

hold

ing

Jaka

fi un

til re

cove

ry

Plea

se s

ee Im

port

ant S

afet

y In

form

atio

n on

the

back

cov

er fo

r rel

ated

and

oth

er ri

sk

info

rmat

ion.

Ref

er to

the

acco

mpa

nyin

g

Full

Pres

crib

ing

Info

rmat

ion

for c

ompl

ete

dosi

ng re

com

men

datio

ns.

* COM

FORT

-I (C

Ontro

lled

Mye

loFib

rosis

st

udy

with

OR

al JA

K in

hibi

tor

Trea

tmen

t-I)

was

a r

ando

mize

d, d

oubl

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ind,

pla

cebo

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d ph

ase

3st

udy

with

309

pat

ient

s w

ith in

term

edia

te-2

–risk

or h

igh-

risk

mye

lofib

rosis

.Th

e pr

imar

y en

dpoi

nt w

as t

he p

ropo

rtion

of

subj

ects

ach

ievin

g a

≥35%

redu

ctio

n in s

plee

n vol

ume f

rom

base

line t

o wee

k 24 a

s mea

sure

d by C

T or M

RI.

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cond

ary e

ndpo

int w

as th

e pr

opor

tion

of s

ubje

cts w

ith a

≥50

% re

duct

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in To

tal S

ympt

om S

core

from

bas

eline

to w

eek

24 a

s m

easu

red

by th

e da

ilypa

tient

diar

y, th

e mod

ified

Mye

lofib

rosis

Sym

ptom

Ass

essm

ent F

orm

.1,2

‡CO

MFO

RT-II

(C

Ontro

lled

Mye

loFib

rosis

st

udy

with

OR

al JA

K in

hibi

tor

Trea

tmen

t-II)

was

a ra

ndom

ized,

ope

n-la

bel p

hase

3 s

tudy

with

219

pat

ient

sw

ith i

nter

med

iate

-2–r

isk o

r hi

gh-ri

sk m

yelo

fibro

sis.

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prim

ary

endp

oint

was

the

prop

ortio

n of

pat

ient

s ac

hiev

ing

a ≥3

5% re

duct

ion

in sp

leen

vol

ume

from

bas

eline

at w

eek

48 a

s m

easu

red

by C

T or

MRI

. Bes

t ava

ilabl

e th

erap

yin

COM

FORT

-II in

clude

d hy

drox

yure

a (4

6.6%

) and

glu

coco

rtico

ids

(16.4

%),

asw

ell a

s no

med

icatio

n, an

agre

lide,

epoe

tin a

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halid

omid

e, le

nalid

omid

e,m

erca

ptop

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e, th

iogu

anin

e, da

nazo

l, pe

gint

erfe

ron

alfa

-2a,

inte

rfero

n-α

, m

elph

alan

, ace

tylsa

licyli

c acid

, cyt

arab

ine,

and c

olch

icine

.1,4,5

OP

TIM

IZE

to b

alan

ce s

afet

y an

d ef

ficac

yS

TAR

T h

ere

✔ ✔ ✔

In p

atie

nts

rece

ivin

g Ja

kafi

in th

e CO

MFO

RT s

tudi

es,

PLT

coun

ts a

nd h

emog

lobi

n le

vels

gen

eral

ly s

tabi

lized

afte

r8

to 1

2 w

eeks

1-4*

‡

Jaka

�

Pla

cebo


110

100

90120

02

46

812

1620

2430

36S

tudy

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k

Con

duct

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C b

etw

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wee

ks 2

and

4

CO

MFO

RT-

I: M

ean

Hem

og

lob

in L

evel

s O

ver

Tim

e2

Mean Change (%)

(n =

106)

8.1

−16.

7−2

8.1

−33.

4−3

6.3

−39.

5

(n =

19)

(n =

35)

(n =

22)

(n =

41)

(n =

22)

Plac

ebo

<10

mg

twice

dai

ly10

mg

twice

dai

ly15

mg

twice

dai

ly20

mg

twice

dai

ly>2

0 m

g tw

ice d

aily

20 10 0−1

0−2

0−3

0−4

0−5

0

Titra

ted

Dose

CO

MFO

RT-

Ia : Mea

n C

han

ge in

Sp

leen

Vo

lum

e by

Do

se a

t Wee

k 24

3

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pla

tele

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aily

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e at

Tim

e of

PLT

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line

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g20

mg

15 m

g10

mg

5 m

g

PLT

Coun

t(×

109 /L

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ew re

com

men

ded

twic

e da

ily d

ose

100

to <

125

20 m

g15

mg

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chan

ge

75 to

<10

010

mg

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chan

ge

50 to

<75

5 m

gN

o ch

ange

<50

Ho

ld


Ear

ly d

ose

ad

just

men

tsas

nee

ded

hel

p t

o o

pti

miz

eef

fica

cy a

nd

saf

ety

In th

e ph

ase

3 COM

FORT

-I tri

al o

f pat

ient

s with

inte

rmed

iate

-2–r

isk o

r hig

h-ris

k MF,

the

prim

ary

endp

oint

was

the

prop

ortio

n of

pat

ient

s ach

ievi

nga

≥35%

redu

ctio

n in

spl

een

volu

me

from

bas

elin

e to

wee

k 24.

1,2 *

42%

of p

atie

nts r

ecei

ving

Jak

afi a

chie

ved

a ≥3

5%re

duct

ion

in s

plee

n vo

lum

e at

wee

k 24 v

s 0.7

% o

fpa

tient

s rec

eivi

ng p

lace

bo (P

< 0

.000

1)2

Base

d on

limite

d cl

inic

al d

ata,

long

-term

mai

nten

ance

at 5

-mg

twic

e-da

ilydo

sing

has

not

sho

wn

resp

onse

s. C

ontin

ued

use

at th

is d

ose

shou

ld b

elim

ited

to p

atie

nts i

n w

hom

the

bene

fits o

utw

eigh

the

pote

ntia

l ris

ks

of p

atie

nts

rece

ivin

g Ja

kafi

in C

OM

FOR

T-I r

equ

ired

ad

ose

ad

just

men

t in

th

efi

rst

12 w

eeks

of t

her

apy

3

70%

INT

ER

RU

PT D

OS

E

Jaka

fi Mea

n Sp

leen

Vol

ume

Redu

ctio

n (-3

1.6%

)

In C

OM

FORT

-I, 6

0% o

f pat

ient

s tr

eate

d w

ith J

akafi

and

38%

of

patie

nts

rece

ivin

g pl

aceb

o re

ceiv

ed re

d bl

ood

cell

tran

sfus

ions

du

ring

rand

omiz

ed tr

eatm

ent1

In p

atie

nts

rece

ivin

g Ja

kafi

in th

e CO

MFO

RT s

tudi

es, m

ean

decr

ease

s in

hem

oglo

bin

reac

hed

a na

dir o

f app

roxi

mat

ely

1.5

to 2

.0 g

/dL

belo

w

base

line

afte

r 8 to

12

wee

ks o

f the

rapy

and

then

gra

dual

ly re

cove

red

to a

new

ste

ady

stat

e th

at w

as a

ppro

xim

atel

y 1.

0 g/

dL b

elow

bas

elin

e1

In C

OMFO

RT-I,

gra

de 3

and

4 th

rom

bocy

tope

nia

or a

nem

ia o

ccur

red

in 1

3% a

nd 4

5% o

f pat

ient

s re

ceiv

ing

Jaka

fi, re

spec

tivel

y2

<1%

of p

atie

nts r

ecei

ving

Jak

afi in

the

COM

FORT

stu

dies

dis

cont

inue

ddu

e to

ane

mia

or t

hrom

bocy

tope

nia1-

4

CO

MFO

RT-

I: M

ean

Ch

ang

e in

Sp

leen

Vo

lum

e b

y D

ose

at

Wee

k 24

3

MF

CBC,

com

plet

e bl

ood

coun

t; SE

M,s

tand

ard

erro

r of t

he m

ean.

Restarting

INTERRUPT FOR:Bleeding requiring intervention regardless of current platelet count,PLT counts <25 × 109/L, or

ANC <0.5 × 109/LRESTARTAfter recovery of PLT counts to >35 × 109/L and ANC >0.75 × 109/L at the higher of:

5 mg once daily or

5 mg twice daily below the largest dose in the week prior to the decrease in PLTcount below 25 × 109/L or ANC below 0.5 × 109/L that led to dose interruption


Only after the first 4 weeks of therapy and not more frequently than every 2 weeks ifpatient meets all these criteria:



ANC >1.0 × 109/L

No dose reduction or interruption for an adverse event or hematological toxicityin the prior 4 weeks


Continuation of treatment for more than 6 months should be limited to patientsin whom the benefits outweigh the risks.Discontinue Jakafi® (ruxolitinib) if there is no spleen size reduction or symptomimprovement after 6 months of therapy.


PLT, platelet.


INCREASE DOSE

DECREASE DOSE

* Failure to achieve a reduction from pre-treatment baseline in either palpable spleen length of 50% or spleen volume of 35%as measured by CT or MRI.


✔

✔

✔

✔



25 to <35 × 109/L and theplatelet count decline is <20%during the prior 4 weeks



25 to <35 × 109/L and theplatelet count decline is ≥20%during the prior 4 weeks




The recommended starting dose in MF for patients with a starting PLT count of50 to <100 × 109/L is 5 mg twice daily

See SPECIAL POPULATIONS tab for dosing information in patients with renal or hepaticimpairment and for information on drug interactions.


Restarting dose in case of bleedingOnce the bleeding event has resolved, consider resuming treatment at the priordose if the underlying cause of bleeding has been controlled. If the bleeding eventhas resolved but the underlying cause persists, consider resuming treatment withJakafiat a lower dose

Restarting dose in case of hematologic toxicity inpatients with starting PLT count ≥100 × 109/L

Treatment interruption and restarting dosingAfter recovery of PLT counts >50 × 109/L and ANC >0.75 × 109/L, dosing may be restarted

The maximum allowable dose that may be used in restarting Jakafi® (ruxolitinib)after a previous interruption is as shown below

Maximum restarting doses for Jakafi aftersafety interruption for thrombocytopenia

Following treatment interruption for ANC <0.5 × 109/L, after ANC recoversto ≥0.75 × 109/L, restart dosing at the higher of 5 mg once daily or 5 mg twicedaily below the largest dose in the week prior to the treatment interruption







<50 Continue hold


PLT, platelet.


Drug interactions

Modify the dose of Jakafi® (ruxolitinib) when coadministered with strong CYP3A4 inhibitors and fluconazole doses of ≤200 mg


Additional dose modifications should be made with careful monitoring of safety and efficacy

Please see Important Safety Information on the last page for related and other risk information.Please click here for Full Prescribing Information for complete dosing recommendations.


Additional dose modifications should be made with frequent monitoring of safety and efficacy


Recommended Starting Dose







<50 Avoid use


dialysis session

>200 20 mg once daily after dialysis session

End-stage renal disease (CrCl <15 mL/min) not requiring dialysis Avoid use


Special PopulationsSpecial Populations









5 mg once daily

Avoid strong CYP3A4 inhibitor or fluconazole treatment, or interrupt treatment with Jakafi for the duration of strong CYP3A4 inhibitor or fluconazole use


l _____ J □ □ □ □

e . • •

• •

• •

•

•

_~ _ ___J_ __ _J

• • •






Important Safety Information Treatment with Jakafi® (ruxolitinib) can cause thrombocytopenia, anemia and neutropenia, which are each dose-related effects. Perform a pre-treatment complete blood count (CBC) and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated




Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting Jakafi until active serious infections have resolved. Observe patients receiving Jakafi for signs and symptoms of infection and manage promptly. Use active surveillance and prophylactic antibiotics according to clinical guidelines

Tuberculosis (TB) infection has been reported. Observe patients taking Jakafi for signs and symptoms of active TB and manage promptly. Prior to initiating Jakafi, evaluate patients for TB risk factors and test those at higher risk for latent infection. Consult a physician with expertise in the treatment of TB before starting Jakafi in patients with evidence of active or latent TB. Continuation of Jakafi during treatment of active TB should be based on the overall risk-benefit determination

Progressive multifocal leukoencephalopathy (PML) has occurred with Jakafi treatment. If PML is suspected, stop Jakafi and evaluate

Advise patients about early signs and symptoms of herpes zoster and to seek early treatment

Increases in hepatitis B viral load with or without associated elevations in alanine aminotransferase and aspartate aminotransferase have been reported in patients with chronic hepatitis B virus (HBV) infections. Monitor and treat patients with chronic HBV infection according to clinical guidelines

When discontinuing Jakafi, myeloproliferative neoplasm-related symptoms may return within one week. After discontinuation, some patients with myelofibrosis have experienced fever, respiratory distress, hypotension, DIC, or multi-organ failure. If any of these occur after discontinuation or while tapering Jakafi, evaluate and treat any intercurrent illness and consider restarting or increasing the dose of Jakafi. Instruct patients not to interrupt or discontinue Jakafi without consulting their physician. When discontinuing or interrupting Jakafi for reasons other than thrombocytopenia or neutropenia, consider gradual tapering rather than abrupt discontinuation

Non-melanoma skin cancers including basal cell, squamous cell, and Merkel cell carcinoma have occurred. Perform periodic skin examinations

Treatment with Jakafi has been associated with increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Assess lipid parameters 8-12 weeks after initiating Jakafi. Monitor and treat according to clinical guidelines for the management of hyperlipidemia

In myelofibrosis and polycythemia vera, the most common nonhematologic adverse reactions (incidence ≥15%) were bruising, dizziness, headache, and diarrhea. In acute graft-versus-host disease, the most common nonhematologic adverse reactions (incidence >50%) were infections and edema

Dose modifications may be required when administering Jakafi with strong CYP3A4 inhibitors or fluconazole or in patients with renal or hepatic impairment. Patients should be closely monitored and the dose titrated based on safety and efficacy

Use of Jakafi during pregnancy is not recommended and should only be used if the potential benefit justifies the potential risk to the fetus. Women taking Jakafi should not breastfeed during treatment and for 2 weeks after the final dose

Please click here for Full Prescribing Information for Jakafi.References: 1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation. 2. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799-807. 3. Verstovsek S, Mesa RA, Gotlib J, et al. Efficacy, safety and survival with ruxolitinib in patients with myelofibrosis: results of a median 2-year follow-up of COMFORT-I. Haematologica. 2013;98(12):1865-1871. 4. Harrison C, Kiladjian J-J, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787-798. 5. Data on file. Incyte Corporation. Wilmington, DE.

Jakafi and the Jakafi logo are registered trademarks of Incyte. © 2020, Incyte Corporation. MAT-JAK-02128 03/20

MONITOR frequentlyMonitor CBCs every 2 to 4 weeks until doses are stabilized,and then as clinically indicated

PLT Count(× 109/L)


50 to <1005 mg twice daily

100 to 20015 mg twice daily

>20020 mg twice daily

In intermediate or high-risk myelofibrosis

Individualized dose adjustments for optimized efficacy and safety1

A CBC and platelet (PLT) count mustbe performed before initiating therapy,every 2 to 4 weeks until doses arestabilized and then as clinically indicated.The recommended starting doseof Jakafi for MF is based on PLT count.

CBC, complete blood count.Tablets shown are not actual size.

See STARTING PLT COUNT 50 TO<100× 109/L tab for recommended dosemodifications in patients with a startingplatelet count of 50 to <100 × 109/L.

See SPECIAL POPULATIONS tab fordosing information in patients with renalor hepatic impairment and for informationon drug interactions.

Jakafi is also available in10 mg and 25 mg tablets

INCREASE DOSE

DECREASE DOSE

In the case of an insufficient response, consider an increase in the doseif patient meets all these criteria:

Insufficient spleen reduction†

PLT count >125 × 109/L at 4 weeks and never <100 × 109/L

Absolute neutrophil count (ANC) >0.75 × 109/L

Increase dose by 5-mg twice-daily increments to a maximum of 25 mgtwice daily

Doses should not be increased during the first 4 weeks of therapy and notmore frequently than every 2 weeks.

Discontinue Jakafi if there is no spleen size reduction or symptomimprovement after 6 months of therapy.

Thrombocytopenia

Anemia

In the case of a Hematologic Toxicity including:

Discontinuation can be avoided by reducing the dose or temporarily withholding Jakafi

Dose modifications of Jakafi and/or blood transfusions may be required for patients developing anemia

CBC, complete blood count; SEM, standard error of the mean.

Adapted with permission from Haematologica.

† Failure to achieve a reduction from pre-treatment baseline in either palpable spleen length of 50% or spleen volume of 35% as measured by CT or MRI.

Interrupt Jakafi treatment for:Bleeding requiring intervention,regardless of current platelet count,

Thrombocytopenia (PLT <50 × 109/L), or

Neutropenia (ANC <0.5 × 109/L)

See RESTARTING tab for dose modifications.

Risk for thrombocytopenia,anemia, and neutropenia

Treatment with Jakafi can causethrombocytopenia, anemia and neutropenia,which are each dose-related effects.Perform a pre-treatment complete bloodcount (CBC) and monitor CBCs every 2 to 4weeks until doses are stabilized, and then asclinically indicatedManage thrombocytopenia by reducingthe dose or temporarily interrupting Jakafi.Platelet transfusions may be necessaryPatients developing anemia may requireblood transfusions and/or dosemodifications of JakafiSevere neutropenia (ANC <0.5 × 109/L) was generally reversible by withholdingJakafi until recovery

Please see Important Safety Information on the back cover for related and other risk information. Refer to the accompanying Full Prescribing Information for complete dosing recommendations.

* COMFORT-I (COntrolled MyeloFibrosis study with ORal JAK inhibitorTreatment-I) was a randomized, double-blind, placebo-controlled phase 3study with 309 patients with intermediate-2–risk or high-risk myelofibrosis.The primary endpoint was the proportion of subjects achieving a ≥35%reduction in spleen volume from baseline to week 24 as measured by CT or MRI.A secondary endpoint was the proportion of subjects with a ≥50% reductionin Total Symptom Score from baseline to week 24 as measured by the dailypatient diary, the modified Myelofibrosis Symptom Assessment Form.1,2

‡COMFORT-II (COntrolled MyeloFibrosis study with ORal JAK inhibitorTreatment-II) was a randomized, open-label phase 3 study with 219 patientswith intermediate-2–risk or high-risk myelofibrosis. The primary endpointwas the proportion of patients achieving a ≥35% reduction in spleen volumefrom baseline at week 48 as measured by CT or MRI. Best available therapyin COMFORT-II included hydroxyurea (46.6%) and glucocorticoids (16.4%), aswell as no medication, anagrelide, epoetin alfa, thalidomide, lenalidomide,mercaptopurine, thioguanine, danazol, peginterferon alfa-2a, interferon-α, melphalan, acetylsalicylic acid, cytarabine, and colchicine.1,4,5

OPTIMIZE to balance safety and efficacy START here

✔

✔

✔

In patients receiving Jakafi in the COMFORT studies,PLT counts and hemoglobin levels generally stabilized after8 to 12 weeks1-4*‡

Jaka�

Placebo

MeanHem

oglobin ± SEM(g/L)

110

100

90

120

02468121620243036StudyWeek

Conduct CBC between weeks 2 and 4

COMFORT-I: Mean Hemoglobin Levels Over Time2

Mean Change (%

)

(n = 106)8.1

−16.7−28.1−33.4−36.3−39.5

(n = 19)(n = 35)(n = 22)(n = 41)(n = 22)

Placebo<10 mg twice daily

10 mg twice daily

15 mg twice daily

20 mg twice daily

>20 mg twice daily

2010

0−10−20−30−40−50

Titrated Dose

COMFORT-Ia: Mean Change in Spleen Volume by Dose at Week 24

3

PLT, platelet.

Twice-Daily Dose atTime of PLT Decline25 mg20 mg15 mg10 mg5 mg

PLT Count(× 109/L)

New recommended twice daily dose

100 to <12520 mg15 mgNo change

75 to <10010 mgNo change

50 to <755 mgNo change

<50 Hold


Early dose adjustmentsas needed help to optimizeefficacy and safetyIn the phase 3 COMFORT-I trial of patients withintermediate-2–risk or high-risk MF, the primaryendpoint was the proportion of patients achievinga ≥35% reduction in spleen volume from baseline toweek 24.1,2*

42% of patients receiving Jakafi achieved a ≥35%reduction in spleen volume at week 24 vs 0.7% ofpatients receiving placebo (P < 0.0001)2

Based on limited clinical data, long-term maintenance at 5-mg twice-dailydosing has not shown responses. Continued use at this dose should belimited to patients in whom the benefits outweigh the potential risks

of patients receiving Jakafiin COMFORT-I required adose adjustment in thefirst 12 weeks of therapy3 70

%

INTERRUPT DOSE

Jakafi Mean Spleen Volume Reduction (-31.6%)

In COMFORT-I, 60% of patients treated with Jakafi and 38% of patients receiving placebo received red blood cell transfusions during randomized treatment1

In patients receiving Jakafi in the COMFORT studies, mean decreases in hemoglobin reached a nadir of approximately 1.5 to 2.0 g/dL below baseline after 8 to 12 weeks of therapy and then gradually recovered to a new steady state that was approximately 1.0 g/dL below baseline1

In COMFORT-I, grade 3 and 4 thrombocytopenia or anemia occurredin 13% and 45% of patients receiving Jakafi, respectively2

<1% of patients receiving Jakafi in the COMFORT studies discontinueddue to anemia or thrombocytopenia1-4

COMFORT-I: Mean Change in Spleen Volume by Dose at Week 243

MF

CBC, complete blood count; SEM,standard error of the mean.

Restarting

INTE

RRUP

T FO

R:Bl

eedi

ng re

quiri

ng in

terv

entio

n re

gard

less

of c

urre

nt p

late

let c

ount

,PL

T co

unts

<25

× 10

9 /L, o

r

ANC

<0.5

× 10

9 /LRE

STAR

TAf

ter r

ecov

ery o

f PLT

cou

nts t

o >3

5 × 10

9 /L a

nd A

NC

>0.7

5 × 10

9 /L a

t the

hig

her o

f:5 m

g on

ce d

aily

or

5 mg

twic

e da

ily b

elow

the

larg

est d

ose

in th

e w

eek p

rior t

o th

e de

crea

se in

PLT

coun

t bel

ow 2

5 × 10

9 /L o

r AN

C be

low

0.5

× 10

9 /L th

at le

d to

dos

e in

terr

uptio

n

Plea

se se

e Im

porta

nt S

afet

y Inf

orm

atio

n on

the

back

cov

er fo

r rel

ated

and

oth

er ri

sk in

form

atio

n.Re

fer t

o th

e ac

com

pany

ing

Full

Pres

crib

ing

Info

rmat

ion

for c

ompl

ete

dosi

ng re

com

men

datio

ns.

Only

afte

r the

firs

t 4 w

eeks

of t

hera

py a

nd n

ot m

ore

frequ

ently

than

eve

ry 2

wee

ks if

patie

nt m

eets

all t

hese

crit

eria

:

Insu

ffici

ent s

plee

n re

duct

ion*

PLT c

ount

has r

emai

ned ≥

40 ×

109 /L

and h

as no

t dec

reas

ed by

>20%

in th

e prio

r 4 w

eeks

ANC

>1.0

× 10

9 /L

No

dose

redu

ctio

n or

inte

rrup

tion

for a

n ad

vers

e ev

ent o

r hem

atol

ogic

al to

xici

tyin

the

prio

r 4 w

eeks

Incr

ease

dos

e by

incr

emen

ts o

f 5 m

g da

ily to

a m

axim

um o

f 10 m

g tw

ice

daily

Cont

inua

tion

of tr

eatm

ent f

or m

ore

than

6 m

onth

s sho

uld

be lim

ited

to p

atie

nts

in w

hom

the

bene

fits o

utw

eigh

the

risks

.Di

scon

tinue

Jak

afi®

(rux

oliti

nib)

if th

ere

is no

sple

en si

ze re

duct

ion

or s

ympt

omim

prov

emen

t afte

r 6 m

onth

s of t

hera

py.

Redu

ce th

e do

se o

f Jak

afi in

pat

ient

s w

ith p

late

let c

ount

s <3

5 ×

109 /L

PLT,

plat

elet

.

Sta

rtin

g PL

T C

ount

50

to <

100

× 10

9 /L

INC

RE

AS

E D

OS

E

DEC

RE

AS

E D

OS

E

* Fa

ilure

to a

chie

ve a

redu

ctio

n fro

m p

re-tr

eatm

ent b

asel

ine

in e

ither

pal

pabl

e sp

leen

leng

th o

f 50%

or s

plee

n vo

lum

e of

35%

as m

easu

red

by C

T or

MRI

.


✔ ✔ ✔ ✔

PLT

Coun

tDo

sing

Rec

omm

enda

tions

<25 ×

109 /L

• Int

erru

pt d

osin

g

25 to

<35

× 10

9 /L a

nd th

epl

atel

et c

ount

dec

line

is <

20%

durin

g th

e pr

ior 4

wee

ks

• Dec

reas

e do

se b

y 5 m

g on

ce d

aily

• For

pat

ient

s on

5 mg

once

dai

ly, m

aint

ain

dose

at 5

mg

once

dai

ly

25 to

<35

× 10

9 /L a

nd th

epl

atel

et c

ount

dec

line

is ≥

20%

durin

g th

e pr

ior 4

wee

ks

• Dec

reas

e do

se b

y 5 m

g tw

ice

daily

• For

pat

ient

s on

5 mg

twic

e da

ily, d

ecre

ase

the

dose

to 5

mg

once

dai

ly

• For

pat

ient

s on

5 mg

once

dai

ly, m

aint

ain

dose

at 5

mg

once

dai

ly

The

reco

mm

ende

d st

artin

g do

se in

MF f

or p

atie

nts w

ith a

sta

rtin

g PL

T co

unt o

f50

to <

100 ×

109 /L

is 5

mg

twic

e da

ily

See

SPE

CIA

L PO

PULA

TIO

NS

tab

for d

osin

g in

form

atio

n in

pat

ient

s with

rena

l or h

epat

icim

pairm

ent a

nd fo

r inf

orm

atio

n on

dru

g in

tera

ctio

ns.

Plea

se se

e Im

porta

nt S

afet

y Inf

orm

atio

n on

the

back

cov

er fo

r rel

ated

and

oth

er ri

sk in

form

atio

n.Re

fer t

o th

e ac

com

pany

ing

Full

Pres

crib

ing

Info

rmat

ion

for c

ompl

ete

dosi

ng re

com

men

datio

ns.

Res

tart

ing

dose

in c

ase

of b

leed

ing

Once

the

blee

ding

eve

nt h

as re

solv

ed, c

onsid

er re

sum

ing

treat

men

t at t

he p

rior

dose

if th

e un

derly

ing

caus

e of

ble

edin

g ha

s bee

n co

ntro

lled.

If th

e bl

eedi

ng e

vent

has r

esol

ved

but t

he u

nder

lyin

g ca

use

pers

ists

, con

sider

resu

min

g tre

atm

ent w

ithJa

kafia

t a lo

wer

dos

e

Res

tart

ing

dose

in c

ase

of h

emat

olog

ic t

oxic

ity

inpa

tien

ts w

ith

star

ting

PLT

cou

nt ≥

100

× 10

9 /L

Trea

tmen

t in

terr

upti

on a

nd r

esta

rtin

g do

sing

Afte

r rec

over

y of P

LT c

ount

s >50

× 10

9 /L a

nd A

NC

>0.7

5 × 10

9 /L,

dosin

g m

ay b

e re

star

ted

The

max

imum

allo

wab

le d

ose

that

may

be

used

in re

star

ting

Jaka

fi® (r

uxol

itini

b)af

ter a

pre

viou

s int

erru

ptio

n is

as sh

own

belo

w

Max

imum

res

tart

ing

dose

s fo

r Ja

kafi

afte

rsa

fety

inte

rrup

tion

for

thro

mbo

cyto

peni

a

Follo

win

g tre

atm

ent i

nter

rupt

ion

for A

NC

<0.5

× 10

9 /L, a

fter A

NC

reco

vers

to ≥

0.75

× 10

9 /L, r

esta

rt do

sing

at th

e hi

gher

of 5

mg

once

dai

ly o

r 5 m

g tw

ice

daily

bel

ow th

e la

rges

t dos

e in

the

wee

k prio

r to

the

treat

men

t int

erru

ptio

n

Curr

ent P

LT C

ount

(×

109 /L

) M

axim

um D

ose

Whe

n Re

star

ting

Tr

eatm

ent W

ith J

akafi

a

≥125

20 m

g tw

ice

daily

100

to <

125

15 m

g tw

ice

daily

75 to

<10

010

mg

twic

e da

ily fo

r at l

east

2 w

eeks

; if s

tabl

e,m

ay in

crea

se to

15 m

g tw

ice

daily

50 to

<75

5 m

g tw

ice

daily

for a

t lea

st 2

wee

ks; i

f sta

ble,

may

incr

ease

to 1

0 m

g tw

ice

daily

<50

Cont

inue

hol

d

a Max

imum

dos

es a

re d

ispl

ayed

. Whe

n re

star

ting,

beg

in w

ith a

dos

e at

leas

t 5 m

g tw

ice

daily

bel

ow th

e do

se a

t int

erru

ptio

n.

PLT,

plat

elet

.

Res

tart

ing

Aft

er S

afet

y In

terr

upti

on

Dru

gin

tera

ctio

ns

Mod

ify th

e do

se o

f Jak

afi®

(rux

oliti

nib)

whe

n co

adm

inis

tere

d w

ith s

trong

CYP3

A4 in

hibi

tors

and

fluc

onaz

ole

dose

s of ≤

200 m

g

Avoi

d th

e us

e of

fluc

onaz

ole

dose

s of >

200 m

g da

ily w

ith J

akafi

Addi

tiona

l dos

e m

odifi

catio

ns sh

ould

be

mad

e w

ith c

aref

ul m

onito

ring

of sa

fety

and

effic

acy

Plea

se se

e Im

porta

nt S

afet

y Inf

orm

atio

n on

the

back

cov

er fo

r rel

ated

and

oth

er ri

sk in

form

atio

n.Re

fer t

o th

e ac

com

pany

ing

Full

Pres

crib

ing

Info

rmat

ion

for c

ompl

ete

dosi

ng re

com

men

datio

ns.

Ren

al o

r he

pati

c im

pair

men

t

Addi

tiona

l dos

e m

odifi

catio

ns s

houl

d be

mad

e w

ith fr

eque

nt m

onito

ring

ofsa

fety

and

effi

cacy

Impa

irm

ent S

tatu

sPL

T Co

unt

(× 1

09 /L)

Reco

mm

ende

dSt

artin

g Do

se

Rena

l im

pairm

ent:

Mod

erat

e (C

rCl 3

0-59

mL/

min

)or

sev

ere

(CrC

l 15-

29 m

L/m

in)

ORHe

patic

impa

irmen

t: M

ild, m

oder

ate,

or

seve

re (C

hild

-Pug

h cl

ass

A, B

, C)

>150

No

mod

ifica

tion

need

ed

100

to 1

5010

mg

twic

e da

ily

50 to

<10

05

mg

daily

<50

Avoi

d us

e

End-

stag

e re

nal d

isea

se o

n di

alys

is10

0 to

200

15 m

g on

ce d

aily

afte

rdi

alys

is s

essi

on

>200

20 m

g on

ce d

aily

afte

rdi

alys

is s

essi

on

End-

stag

e re

nal d

iseas

e(C

rCl <

15 m

L/m

in) n

ot re

quiri

ng d

ialy

sisAv

oid

use

CrCl

, cre

atin

ine

clea

ranc

e; P

LT, p

late

let.

Spe

cial

Pop

ulat

ions

Special Populations

For P

atie

nts

Coad

min

iste

red

Stro

ng

CYP3

A4 In

hibi

tors

or

Fluc

onaz

ole

Dose

s of

≤20

0 m

gRe

com

men

ded

Dose

Mod

ifica

tion

Star

ting

dose

for p

atie

nts

with

MF

with

a P

LT c

ount

:

≥100

× 1

09 /L10

mg

twic

e da

ily

50 to

<10

0 ×

109 /L

5 m

g on

ce d

aily

If on

sta

ble

dose

for p

atie

nts

with

MF:

≥10

mg

twic

e da

ilyDe

crea

se d

ose

by 5

0% (r

ound

up

to th

e

clos

est a

vaila

ble

tabl

et s

treng

th)

5 m

g tw

ice

daily

5 m

g on

ce d

aily

5 m

g on

ce d

aily

Avoi

d st

rong

CYP

3A4 i

nhib

itor o

r fluc

onaz

ole

treat

men

t, or

inte

rrupt

trea

tmen

t with

Jak

afifo

r the

dur

atio

n of

stro

ng C

YP3A

4 inh

ibito

r or

fluco

nazo

le u

se

MF,

mye

lofib

rosis

;PLT

, pla

tele

t.

•

• • • •

•

• • •

•

• •

•

• •

MIX fJ, Paper from FSC reaponslble sources

www . ....., FSC-JakatrO

ruxolitinib (tablets)


Jakafi® (ruxolitinib) Dosing Guide for Myelofibrosis

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Transcript of Jakafi® (ruxolitinib) Dosing Guide for Myelofibrosis