For adults with intermediate- or high-risk MF1

Once-daily dosing with JAKAFI XRTM (ruxolitinib)1

Dose optimization is key to maintaining the balance between safety and efficacy1

1
START

For adults with intermediate- or high-risk MF, the recommended starting doses of JAKAFI XR are based on platelet counts1

A CBC, including platelet count, must be performed before initiating JAKAFI XR

  • Platelet count of 50 to <100 × 10⁹/L: 11 mg once daily
  • Platelet count of 100 to 200 × 10⁹/L: 33 mg once daily
  • Platelet count >200 × 10⁹/L: 44 mg once daily

Before initiating JAKAFI XR, inquire about past infections, including tuberculosis, herpes simplex, herpes zoster, and hepatitis B.

JAKAFI® (ruxolitinib) dosages

  • 5 mg twice daily 

    Jakafi tablet with 5 imprint

  • 10 mg twice daily 

    Jakafi tablet with 10 imprint

  • 15 mg twice daily 

    Jakafi tablet with 15 imprint

  • 20 mg twice daily 

    Jakafi tablet with 20 imprint

  • 25 mg twice daily 

    Jakafi tablet with 25 imprint

JAKAFI XR dosages

  • 11 mg once daily 

    Jakafi XR tablet with 11 imprint

  • 22 mg once daily 

    Jakafi XR tablet with 22 imprint

  • 33 mg once daily 

    Jakafi XR tablet with 33 imprint

  • 44 mg once daily 

    Jakafi XR tablet with 44 imprint

  • 55 mg once daily 

    Jakafi XR tablet with 55 imprint
  • Jakafi XR 11 mg tablet
  • Jakafi XR 33 mg tablet
  • Jakafi XR 44 mg tablet

Tablet images shown are for demonstration purposes only and do not represent actual medications.

Dose modifications should be considered based on monitoring complete blood count (CBC), including platelet counts, absolute neutrophil count (ANC), and hemoglobin; treatment interruption and restarting dosing; or other adverse reactions, as described in the Full Prescribing Information for JAKAFI and JAKAFI XR.

JAKAFI XR is also available in 22-mg and 55-mg tablets.

Taking JAKAFI XR

  • JAKAFI XR is dosed orally and can be administered with or without food
  • Patients must swallow JAKAFI XR tablets whole. Do not split, chew, or crush tablets

Special populations: Please refer to the Full Prescribing Information for starting dose and other dose modifications, and for when to avoid treatment in patients with renal or hepatic impairment and in those receiving concomitant strong CYP3A4 inhibitors or fluconazole.

 
2
MONITOR

Monitoring patients after initiation of JAKAFI XR is essential, especially during the first 12 weeks of therapy1

  • A CBC must be performed every 2 to 4 weeks until doses are stabilized, and then as clinically indicated. Doses may be titrated based on safety and efficacy
  • Assess lipid parameters approximately 8 to 12 weeks following initiation of JAKAFI XR

Missed dose

  • If a dose is missed, patients should not take an additional dose but should take the next usual prescribed dose
 
3
OPTIMIZE

Individualize dosing of JAKAFI XR to optimize the balance between safety and efficacy1

Managing anemia, thrombocytopenia, neutropenia, and bleeding

  • Dose modifications, temporarily withholding JAKAFI XR, and/or transfusions may be required for patients developing anemia or thrombocytopenia
  • Interrupt treatment for bleeding, neutropenia (ANC <0.5 × 109/L), or thrombocytopenia (based on starting platelet count)

MF=myelofibrosis.

The effectiveness and safety of JAKAFI XR have been established based on adequate and well-controlled studies of JAKAFI

JAKAFI XR received approval based on comprehensive data demonstrating bioequivalence to JAKAFI1

There are no contraindications for use of JAKAFI XR, including in patients with anemia1

In COMFORT-I, 46% of patients receiving JAKAFI had anemia at baseline; among these patients, mean Hb was 9.2 g/dL (range, 6.6 g/dL to 13.7 g/dL)2

Adverse events with JAKAFI XR are expected to be similar to JAKAFI.1

Dose may be increased in the case of an insufficient response1

Efficacy based on titrated dose

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

Results were assessed with JAKAFI, not JAKAFI XR. Please see the Full Prescribing Information for JAKAFI XR dosing information.

COMFORT‑I bar chart showing mean spleen volume change at Week 24 by dose

All patients in the clinical trials received JAKAFI twice daily.1

This material is under a CC BY-NC License and is the property of the Ferrata Storti Foundation. © 2026 Ferrata Storti Foundation. All rights reserved.

  • Doses may be increased if the response is insufficient and platelet and neutrophil counts are adequate and treatment has not been reduced or interrupted in the prior 4 weeks1
  • Doses should not be increased during the first 4 weeks of therapy and not more frequently than every 2 weeks1
  • Discontinue JAKAFI XR if there is no spleen size reduction or symptom improvement after 6 months of therapy1
  • Continuation of treatment for more than 6 months should be limited to patients in whom the benefits outweigh the potential risks1

BID=twice daily; COMFORT=COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment.

Dosing in COMFORT-I1

  • Treatment with JAKAFI XR can cause thrombocytopenia, anemia, and neutropenia, which are each dose-related effects. Perform a pretreatment CBC and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated
    • Manage thrombocytopenia by reducing the dose or temporarily interrupting JAKAFI XR. Platelet transfusions may be necessary
    • Patients developing anemia may require blood transfusions and/or dose modifications of JAKAFI XR
    • Severe neutropenia (ANC <0.5 × 109/L) was generally reversible by withholding JAKAFI XR until recovery

Anemia clinical trial data

Dose modifications of JAKAFI XR and/or blood transfusions may be required for patients developing anemia1

  • In patients receiving JAKAFI in the COMFORT studies, mean decreases in Hb levels reached a nadir of approximately 1.5 g/dL 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, 60% of patients treated with JAKAFI and 38% of patients receiving placebo had RBC transfusions during randomized treatment1

COMFORT-I: Mean Hb Levels Over Time4

Results were assessed with JAKAFI, not JAKAFI XR. Please see the Full Prescribing Information for JAKAFI XR dosing information.

COMFORT‑I line graph comparing mean hemoglobin levels over time for Jakafi and placebo

From The New England Journal of Medicine, Verstovsek S, Mesa RA, Gotlib J, et al, A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis, 366(9):799-807. Supplementary appendix available at: doi:10.1056/NEJMoa1110557. © 2012 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

  • In COMFORT-I, grade 3 or 4 anemia occurred in 45% of patients receiving JAKAFI1
  • <1% of patients receiving JAKAFI in the COMFORT studies discontinued due to anemia or thrombocytopenia4

COMFORT-I: Patients Requiring RBC Transfusions3

Results were assessed with JAKAFI, not JAKAFI XR. Please see the Full Prescribing Information for JAKAFI XR dosing information.

COMFORT‑I line graph comparing RBC transfusion rates for Jakafi and placebo

This material is under a CC BY-NC License and is the property of the Ferrata Storti Foundation. © 2026 Ferrata Storti Foundation. All rights reserved.

All patients in the clinical trials received JAKAFI twice daily. Adverse events with JAKAFI XR once daily are expected to be similar to JAKAFI twice daily.1

ANC=absolute neutrophil count; CBC=complete blood count; COMFORT=COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment; Hb=hemoglobin; RBC=red blood cell; SEM=standard error of the mean.

Thrombocytopenia clinical trial data

In patients with cytopenias, consider dose reductions, temporarily withholding JAKAFI XR, or transfusions as clinically indicated.1

Monitor CBCs during treatment, beginning as early as weeks 2 to 4.1

COMFORT-I: Mean Platelet Counts Over Time2

Results were assessed with JAKAFI, not JAKAFI XR. Please see the Full Prescribing Information for JAKAFI XR dosing information.

COMFORT‑I line graph comparing mean platelet counts over time for Jakafi and placebo

aProtocol-mandated dose modifications occurred based on platelet count.

  • In COMFORT-I, grade 3 or 4 thrombocytopenia occurred in 13% of patients receiving JAKAFI1
  • Initial reductions in Hb and platelets can occur in as early as 2 to 4 weeks2,4
  • Dosing may need to be modified to avoid dose interruption, with the goal of achieving clinical benefit1

All patients in the clinical trials received JAKAFI twice daily. Adverse events with JAKAFI XR once daily are expected to be similar to JAKAFI twice daily.1

CBC=complete blood count; COMFORT=COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment; Hb=hemoglobin; LLN=lower limit of normal.

Appropriate dose management

Dose modifications for patients with starting platelet count ≥100 × 109/L1

In the case of a hematologic toxicity, including:

Thrombocytopenia

Discontinuations can be avoided by reducing the dose or temporarily withholding JAKAFI XR.

Table showing recommended Jakafi XR dose adjustments based on platelet count at the time of platelet decline

In patients receiving JAKAFI in the COMFORT studies, platelet counts and Hb levels generally stabilized after 8 to 12 weeks2,4

All patients in the clinical trials received JAKAFI twice daily. Adverse events with JAKAFI XR once daily are expected to be similar to JAKAFI twice daily.1

Anemia
Dose modifications of JAKAFI XR and/or blood transfusions may be required for patients developing anemia.1

COMFORT=COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment; Hb=hemoglobin.

Interrupt JAKAFI XR treatment for:

  • Bleeding requiring intervention, regardless of current platelet count,
  • Thrombocytopenia (platelet count <50 × 109/L), or
  • Neutropenia (ANC <0.5 × 109/L)

Restarting after treatment interruption

  • After recovery of platelet counts >50 × 109/L and ANC >0.75 × 109/L, dosing may be restarted
  • Begin with a dose of JAKAFI XR that is at least 11 mg once daily below the dose at interruption
  • The maximum allowable dose that may be used in restarting JAKAFI XR after a previous interruption is shown below

Maximum restarting doses for JAKAFI XR after safety interruption for thrombocytopenia

Table showing the maximum doses when restarting treatment with Jakafi XR based on current platelet count
  • Following treatment interruption for ANC <0.5 × 109/L, after ANC recovers to >0.75 × 109/L:
    • For patients on 11 mg once daily prior to the first interruption, restart at 11 mg once daily. Discontinue for a second interruption
    • For patients with a JAKAFI XR dose greater than 11 mg once daily prior to interruption, restart at 11 mg once daily below the largest dose in the week prior to interruption

ANC=absolute neutrophil count.

Increasing dose for insufficient response

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

  • Insufficient spleen reduction*
  • Platelet count >125 × 109/L at 4 weeks and never <100 × 109/L
  • ANC >0.75 × 109/L

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

Increase dose by increments of 11 mg once daily to a maximum of 55 mg once daily

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

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

ANC=absolute neutrophil count; CT=computed tomography; MRI=magnetic resonance imaging.

Appropriate dose management

Dose modifications for patients with starting platelet count ≥100 × 109/L1

In the case of a hematologic toxicity, including:

Thrombocytopenia

Discontinuations can be avoided by reducing the dose or temporarily withholding JAKAFI XR.

Table showing recommended Jakafi XR dose adjustments based on platelet count at the time of platelet decline

In patients receiving JAKAFI in the COMFORT studies, platelet counts and Hb levels generally stabilized after 8 to 12 weeks2,4

All patients in the clinical trials received JAKAFI twice daily. Adverse events with JAKAFI XR once daily are expected to be similar to JAKAFI twice daily.1

Anemia
Dose modifications of JAKAFI XR and/or blood transfusions may be required for patients developing anemia.1

COMFORT=COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment; Hb=hemoglobin.

Interrupt JAKAFI XR treatment for:

  • Bleeding requiring intervention, regardless of current platelet count,
  • Thrombocytopenia (platelet count <50 × 109/L), or
  • Neutropenia (ANC <0.5 × 109/L)

Restarting after treatment interruption

  • After recovery of platelet counts >50 × 109/L and ANC >0.75 × 109/L, dosing may be restarted
  • Begin with a dose of JAKAFI XR that is at least 11 mg once daily below the dose at interruption
  • The maximum allowable dose that may be used in restarting JAKAFI XR after a previous interruption is shown below

Maximum restarting doses for JAKAFI XR after safety interruption for thrombocytopenia

Table showing the maximum doses when restarting treatment with Jakafi XR based on current platelet count
  • Following treatment interruption for ANC <0.5 × 109/L, after ANC recovers to >0.75 × 109/L:
    • For patients on 11 mg once daily prior to the first interruption, restart at 11 mg once daily. Discontinue for a second interruption
    • For patients with a JAKAFI XR dose greater than 11 mg once daily prior to interruption, restart at 11 mg once daily below the largest dose in the week prior to interruption

ANC=absolute neutrophil count.

Increasing dose for insufficient response

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

  • Insufficient spleen reduction*
  • Platelet count >125 × 109/L at 4 weeks and never <100 × 109/L
  • ANC >0.75 × 109/L

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

Increase dose by increments of 11 mg once daily to a maximum of 55 mg once daily

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

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

ANC=absolute neutrophil count; CT=computed tomography; MRI=magnetic resonance imaging.

Dose modifications for patients with starting platelet count of 50 to <100 × 109/L1

Decreasing dose for hematologic toxicity

Reduce the dose of JAKAFI XR in patients with platelet counts <35 × 109/L.

Table showing Jakafi XR dosing recommendations based on platelet count

Interrupt JAKAFI XR treatment for:

  • Bleeding requiring intervention, regardless of current platelet count,
  • Thrombocytopenia (platelet count <25 × 109/L), or
  • Neutropenia (ANC <0.5 × 109/L)

Restarting after treatment interruption

After treatment interruption, restart dosing after recovery of platelet counts to >35 × 109/L and ANC <0.75 × 109/L:

  • Begin with a dose of JAKAFI XR that is at least 11 mg once daily below the largest dose in the week prior to the treatment interruption
  • For patients on JAKAFI XR 11 mg once daily prior to the first interruption, continue JAKAFI XR 11 mg once daily
  • Discontinue JAKAFI XR for a second interruption

ANC=absolute neutrophil count.

The recommended starting dose of JAKAFI XR in MF for patients with a starting platelet count of 50 to <100 x 109/L is 11 mg once daily

Increasing dose for insufficient response

In the case of an insufficient response, consider an increase in the dose only after the first 4 weeks of therapy and not more frequently than every 2 weeks if patients meet all of these criteria:

  • Insufficient spleen reduction*
  • Platelet count has remained ≥40 × 109/L at 4 weeks and has not decreased by >20% in the prior 4 weeks
  • ANC >1.0 × 109/L
  • No dose reduction or interruption for an AE or hematological toxicity in the prior 4 weeks

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

Increase dose by increments of 11 mg once daily to a maximum of 22 mg once daily

Continuation of treatment for more than 6 months should be limited to patients in whom the benefits outweigh the risks.

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

AE=adverse event; ANC=absolute neutrophil count; CT=computed tomography; MF=myelofibrosis; MRI=magnetic resonance imaging.

Dose modifications for patients with starting platelet count of 50 to <100 × 109/L1

Decreasing dose for hematologic toxicity

Reduce the dose of JAKAFI XR in patients with platelet counts <35 × 109/L.

Table showing Jakafi XR dosing recommendations based on platelet count

Interrupt JAKAFI XR treatment for:

  • Bleeding requiring intervention, regardless of current platelet count,
  • Thrombocytopenia (platelet count <25 × 109/L), or
  • Neutropenia (ANC <0.5 × 109/L)

Restarting after treatment interruption

After treatment interruption, restart dosing after recovery of platelet counts to >35 × 109/L and ANC <0.75 × 109/L:

  • Begin with a dose of JAKAFI XR that is at least 11 mg once daily below the largest dose in the week prior to the treatment interruption
  • For patients on JAKAFI XR 11 mg once daily prior to the first interruption, continue JAKAFI XR 11 mg once daily
  • Discontinue JAKAFI XR for a second interruption

ANC=absolute neutrophil count.

The recommended starting dose of JAKAFI XR in MF for patients with a starting platelet count of 50 to <100 x 109/L is 11 mg once daily

Increasing dose for insufficient response

In the case of an insufficient response, consider an increase in the dose only after the first 4 weeks of therapy and not more frequently than every 2 weeks if patients meet all of these criteria:

  • Insufficient spleen reduction*
  • Platelet count has remained ≥40 × 109/L at 4 weeks and has not decreased by >20% in the prior 4 weeks
  • ANC >1.0 × 109/L
  • No dose reduction or interruption for an AE or hematological toxicity in the prior 4 weeks

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

Increase dose by increments of 11 mg once daily to a maximum of 22 mg once daily

Continuation of treatment for more than 6 months should be limited to patients in whom the benefits outweigh the risks.

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

AE=adverse event; ANC=absolute neutrophil count; CT=computed tomography; MF=myelofibrosis; MRI=magnetic resonance imaging.

Dose modification for bleeding1

Interrupt treatment for bleeding requiring intervention regardless of current platelet count. 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 XR at a lower dose.

Dose modifications for special populations1

Dose modifications in patients with renal or hepatic impairment, or when coadministered with strong CYP3A4 inhibitors or fluconazole

Table showing recommended Jakafi XR starting doses based on renal or hepatic impairment status and platelet count

Patients with ESRD on dialysis

  • Do not use JAKAFI XR for patients with MF who have ESRD (CLcr <15 mL/min) and are on dialysis with a platelet count between 100 × 109/L and 200 × 109/L or >200 × 109/L
  • Avoid use of JAKAFI XR in patients with ESRD (CLcr <15 mL/min) not requiring dialysis

Concomitant use with strong CYP3A4 inhibitors or fluconazole

  • Modify the dose of JAKAFI XR when coadministered with strong CYP3A4 inhibitors and fluconazole doses of ≤200 mg for MF
  • Avoid the use of fluconazole doses >200 mg daily with JAKAFI XR
  • Additional dose modifications should be made with frequent monitoring of safety and efficacy
Table showing recommended Jakafi XR dose modifications for patients with myelofibrosis receiving strong CYP3A4 inhibitors or fluconazole (≤200 mg), based on platelet count and stable dosing status

CLcr=creatinine clearance; ESRD=end-stage renal disease; MF=myelofibrosis.

EXPLORE SVR AND
5-YEAR OS DATA HEAR FROM MPN EXPERTS

COMFORT=COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment; Hb=hemoglobin; MF=myelofibrosis; MPN=myeloproliferative neoplasm; OS=overall survival; SVR=spleen volume reduction.

References: 1. JAKAFI/JAKAFI XR Prescribing Information. Wilmington, DE: Incyte Corporation. 2. Data on file. Incyte Corporation. Wilmington, DE. 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. Supplementary appendix available at: https://haematologica.org/article/view/6861. 4. 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. Supplementary appendix available at: https://www.nejm.org/doi/full/10.1056/nejmoa1110557.

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INDICATIONS AND USAGE

JAKAFI®/JAKAFI XR™ (ruxolitinib) is for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF in adults.

JAKAFI/JAKAFI XR is for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.

JAKAFI/JAKAFI XR is for treatment of steroid-refractory acute graft-versus-host disease (aGVHD) in adult and pediatric patients 12 years and older.

JAKAFI/JAKAFI XR is for treatment of chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia, Anemia and Neutropenia

  • JAKAFI/JAKAFI XR can cause dose-related effects of thrombocytopenia, anemia and neutropenia. 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.
  • Manage thrombocytopenia by reducing the dose or temporarily interrupting JAKAFI/JAKAFI XR. Platelet transfusions may be necessary.
  • Patients developing anemia may require blood transfusions and/or dose modifications of JAKAFI/JAKAFI XR.
  • Severe neutropenia (ANC <0.5 × 109/L) was generally reversible by withholding JAKAFI/JAKAFI XR until recovery.

Risk of Infection

Tuberculosis

  • Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting JAKAFI/JAKAFI XR until active serious infections have resolved. Observe patients receiving JAKAFI/JAKAFI XR for signs and symptoms of infection and manage promptly.
  • Tuberculosis (TB) infection with JAKAFI/JAKAFI XR has been reported. Observe patients taking JAKAFI/JAKAFI XR for signs and symptoms of active TB and manage promptly. Prior to initiating, 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 in patients with evidence of active or latent TB. Continuation during treatment of active TB should be based on the overall risk-benefit determination.

Progressive Multifocal Leukoencephalopathy

  • Progressive multifocal leukoencephalopathy (PML) has occurred with JAKAFI/JAKAFI XR treatment. If PML is suspected, stop JAKAFI/JAKAFI XR and evaluate.

Herpes Zoster and Herpes Simplex

  • Herpes zoster infection, reactivation and/or dissemination has been reported in patients receiving JAKAFI/JAKAFI XR. Advise patients about early signs and symptoms of herpes zoster and seek treatment. Monitor patients for the development of herpes simplex infections. If a patient develops evidence of dissemination of herpes simplex, consider interrupting treatment.

Hepatitis B

  • 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.

Symptom Exacerbation Following Interruption or Discontinuation of Treatment

  • When discontinuing JAK-Inhibitors, including JAKAFI/JAKAFI XR, myeloproliferative neoplasm-related signs and symptoms may flare. After discontinuation, some patients with myelofibrosis have experienced fever, respiratory distress, hypotension, disseminated intravascular coagulation (DIC), or multi-organ failure. If any of these occur after discontinuation or while tapering JAKAFI/JAKAFI XR, evaluate and treat any intercurrent illness and consider restarting or increasing the dose. Instruct patients not to interrupt or discontinue JAKAFI/JAKAFI XR without consulting their physician. When discontinuing or interrupting JAKAFI/JAKAFI XR for reasons other than life-threatening toxicities, consider gradual tapering rather than abrupt discontinuation.

Non-Melanoma Skin Cancer (NMSC)

  • NMSC including basal cell, squamous cell, and Merkel cell carcinoma have occurred. Perform periodic skin examinations.

Lipid Elevations

  • Treatment with JAKAFI/JAKAFI XR has been associated with increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Assess lipid parameters 8-12 weeks after initiation.

Major Adverse Cardiovascular Events (MACE)

  • Another JAK-inhibitor has increased the risk of major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and stroke (compared to those treated with TNF blockers), in patients with rheumatoid arthritis, a condition for which JAKAFI/JAKAFI XR is not indicated. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur.

Thrombosis

  • Another JAK-inhibitor has increased the risk of thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis (compared to those treated with TNF blockers), in patients with rheumatoid arthritis, a condition for which JAKAFI/JAKAFI XR is not indicated. In patients with myelofibrosis (MF) and polycythemia vera (PV), the rates of thromboembolic events were similar in JAKAFI/JAKAFI XR and control treated patients. Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately.

Secondary Malignancies

  • Another JAK-inhibitor has increased the risk of lymphoma and other malignancies, excluding NMSC (compared to those treated with TNF blockers), in patients with rheumatoid arthritis, a condition for which JAKAFI/JAKAFI XR is not indicated. Patients who are current or past smokers are at additional increased risk.

Adverse Reactions

  • In myelofibrosis, the most common hematologic adverse reactions (incidence >20%) were thrombocytopenia and anemia. The most common nonhematologic adverse reactions (incidence ≥15%) were bruising, dizziness, headache and diarrhea.
  • In polycythemia vera, the most common hematologic adverse reactions (incidence >20%) were thrombocytopenia and anemia. The most common nonhematologic adverse reactions (incidence ≥15%) were bruising, dizziness, headache and diarrhea.
  • In acute graft-versus-host disease, the most common hematologic adverse reactions (incidence >50%) were anemia, thrombocytopenia and neutropenia. The most common nonhematologic adverse reactions (incidence >50%) were infections (pathogen not specified) and edema.
  • In chronic graft-versus-host disease, the most common hematologic adverse reactions (incidence >35%) were anemia and thrombocytopenia. The most common nonhematologic adverse reactions (incidence ≥20%) were infections (pathogen not specified) and viral infections.

Drug Interactions

  • Avoid concomitant use with fluconazole doses greater than 200 mg. Dose modifications may be required when administering fluconazole doses of 200 mg or less, or with strong CYP3A4 inhibitors, or in patients with renal or hepatic impairment. Patients should be closely monitored and the dose titrated based on safety and efficacy.

Pregnancy

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

Please see Full Prescribing Information for JAKAFI and JAKAFI XR.

INDICATIONS AND USAGE

JAKAFI®/JAKAFI XR™ (ruxolitinib) is for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF in adults.

JAKAFI/JAKAFI XR is for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.

JAKAFI/JAKAFI XR is for treatment of steroid-refractory acute graft-versus-host disease (aGVHD) in adult and pediatric patients 12 years and older.

JAKAFI/JAKAFI XR is for treatment of chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia, Anemia and Neutropenia

  • JAKAFI/JAKAFI XR can cause dose-related effects of thrombocytopenia, anemia and neutropenia. 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.
  • Manage thrombocytopenia by reducing the dose or temporarily interrupting JAKAFI/JAKAFI XR. Platelet transfusions may be necessary.
  • Patients developing anemia may require blood transfusions and/or dose modifications of JAKAFI/JAKAFI XR.
  • Severe neutropenia (ANC <0.5 × 109/L) was generally reversible by withholding JAKAFI/JAKAFI XR until recovery.

Risk of Infection

Tuberculosis

  • Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting JAKAFI/JAKAFI XR until active serious infections have resolved. Observe patients receiving JAKAFI/JAKAFI XR for signs and symptoms of infection and manage promptly.
  • Tuberculosis (TB) infection with JAKAFI/JAKAFI XR has been reported. Observe patients taking JAKAFI/JAKAFI XR for signs and symptoms of active TB and manage promptly. Prior to initiating, 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 in patients with evidence of active or latent TB. Continuation during treatment of active TB should be based on the overall risk-benefit determination.

Progressive Multifocal Leukoencephalopathy

  • Progressive multifocal leukoencephalopathy (PML) has occurred with JAKAFI/JAKAFI XR treatment. If PML is suspected, stop JAKAFI/JAKAFI XR and evaluate.

Herpes Zoster and Herpes Simplex

  • Herpes zoster infection, reactivation and/or dissemination has been reported in patients receiving JAKAFI/JAKAFI XR. Advise patients about early signs and symptoms of herpes zoster and seek treatment. Monitor patients for the development of herpes simplex infections. If a patient develops evidence of dissemination of herpes simplex, consider interrupting treatment.

Hepatitis B

  • 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.

Symptom Exacerbation Following Interruption or Discontinuation of Treatment

  • When discontinuing JAK-Inhibitors, including JAKAFI/JAKAFI XR, myeloproliferative neoplasm-related signs and symptoms may flare. After discontinuation, some patients with myelofibrosis have experienced fever, respiratory distress, hypotension, disseminated intravascular coagulation (DIC), or multi-organ failure. If any of these occur after discontinuation or while tapering JAKAFI/JAKAFI XR, evaluate and treat any intercurrent illness and consider restarting or increasing the dose. Instruct patients not to interrupt or discontinue JAKAFI/JAKAFI XR without consulting their physician. When discontinuing or interrupting JAKAFI/JAKAFI XR for reasons other than life-threatening toxicities, consider gradual tapering rather than abrupt discontinuation.

Non-Melanoma Skin Cancer (NMSC)

  • NMSC including basal cell, squamous cell, and Merkel cell carcinoma have occurred. Perform periodic skin examinations.

Lipid Elevations

  • Treatment with JAKAFI/JAKAFI XR has been associated with increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Assess lipid parameters 8-12 weeks after initiation.

Major Adverse Cardiovascular Events (MACE)

  • Another JAK-inhibitor has increased the risk of major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and stroke (compared to those treated with TNF blockers), in patients with rheumatoid arthritis, a condition for which JAKAFI/JAKAFI XR is not indicated. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur.

Thrombosis

  • Another JAK-inhibitor has increased the risk of thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis (compared to those treated with TNF blockers), in patients with rheumatoid arthritis, a condition for which JAKAFI/JAKAFI XR is not indicated. In patients with myelofibrosis (MF) and polycythemia vera (PV), the rates of thromboembolic events were similar in JAKAFI/JAKAFI XR and control treated patients. Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately.

Secondary Malignancies

  • Another JAK-inhibitor has increased the risk of lymphoma and other malignancies, excluding NMSC (compared to those treated with TNF blockers), in patients with rheumatoid arthritis, a condition for which JAKAFI/JAKAFI XR is not indicated. Patients who are current or past smokers are at additional increased risk.

Adverse Reactions

  • In myelofibrosis, the most common hematologic adverse reactions (incidence >20%) were thrombocytopenia and anemia. The most common nonhematologic adverse reactions (incidence ≥15%) were bruising, dizziness, headache and diarrhea.
  • In polycythemia vera, the most common hematologic adverse reactions (incidence >20%) were thrombocytopenia and anemia. The most common nonhematologic adverse reactions (incidence ≥15%) were bruising, dizziness, headache and diarrhea.
  • In acute graft-versus-host disease, the most common hematologic adverse reactions (incidence >50%) were anemia, thrombocytopenia and neutropenia. The most common nonhematologic adverse reactions (incidence >50%) were infections (pathogen not specified) and edema.
  • In chronic graft-versus-host disease, the most common hematologic adverse reactions (incidence >35%) were anemia and thrombocytopenia. The most common nonhematologic adverse reactions (incidence ≥20%) were infections (pathogen not specified) and viral infections.

Drug Interactions

  • Avoid concomitant use with fluconazole doses greater than 200 mg. Dose modifications may be required when administering fluconazole doses of 200 mg or less, or with strong CYP3A4 inhibitors, or in patients with renal or hepatic impairment. Patients should be closely monitored and the dose titrated based on safety and efficacy.

Pregnancy

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

Please see Full Prescribing Information for JAKAFI and JAKAFI XR.