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The dose of Jakafi should be individualized in order to optimize the balance between safety and efficacy

A complete blood count (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.1 (See Getting started with Jakafi below.)

Consider a dose increase for insufficient response. (See Dose modification based on insufficient response below.)

Consider a dose reduction for thrombocytopenia. (See Dose reductions for avoiding treatment interruptions below.)

Interrupt dose for bleeding requiring intervention (regardless of current PLT count), thrombocytopenia (PLT <50 × 109/L), or neutropenia (absolute neutrophil count [ANC] <0.5 × 109/L), but consider restarting after recovery of PLT counts and ANC. (See Dose modification for hematologic toxicity and Dose modification for bleeding below.)

For dose modifications for Special Populations, see Special Populations below.

For clinical trial experience with blood counts, see Cytopenias: Trial Data below.

The dose of Jakafi should be individualized in order to optimize the balance between safety and efficacy

A complete blood count (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.1 (See Getting started with Jakafi below.)

Consider a dose increase for insufficient response. (See Dose modification based on insufficient response below.)

Consider a dose reduction for thrombocytopenia. (See Dose reductions for avoiding treatment interruptions below.)

Interrupt dose for bleeding requiring intervention (regardless of current PLT count), thrombocytopenia (PLT <50 × 109/L), or neutropenia (absolute neutrophil count [ANC] <0.5 × 109/L), but consider restarting after recovery of PLT counts and ANC. (See Dose modification for hematologic toxicity and Dose modification for bleeding below.)

For dose modifications for Special Populations, see Special Populations below.

For clinical trial experience with blood counts, see Cytopenias: Trial Data below.

Getting started with Jakafi

Start, monitor, and optimize

In 3 steps you can start, monitor, and optimize Jakafi dosing for your patients1:

Image of Jakafi bottle and steps to start dosing – 1=Start, 2=Monitor, 3=Optimize
1 START
1 START

For intermediate or high-risk myelofibrosis (MF) in adults, starting doses are based on PLT counts.1 A CBC must be performed before initiating Jakafi.

2 MONITOR
  • A CBC and PLT count must be performed before initiating Jakafi, every 2 to 4 weeks until doses are stabilized and then as clinically indicated.1 Doses may be titrated based on safety and efficacy
  • For dosing information in patients with renal or hepatic impairment or information on drug interactions, see information about Special Populations
3 OPTIMIZE

Individualize dosing of Jakafi to optimize balance between safety and efficacy.1

Dose modification based on insufficient response

Starting PLT count ≥100 × 109/L1

  • If the response is insufficient and PLT and neutrophil counts are adequate, doses may be increased in 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
  • Consider dose increases in patients who meet all of the following conditions:
    • Failure to achieve a reduction from pre-treatment baseline in either palpable spleen length of 50% or spleen volume of 35% as measured by computed tomography or magnetic resonance imaging, and
    • PLT count >125 × 109/L at 4 weeks and PLT count never <100 × 109/L, and
    • ANC levels >0.75 × 109/L
  • Based on limited clinical data, long-term maintenance at a 5 mg twice daily dose has not shown responses, and continued use at this dose should be limited to patients in whom the benefits outweigh the potential risks. Discontinue Jakafi if there is no spleen size reduction or symptom improvement after 6 months of therapy

Starting PLT count 50 to <100 × 109/L1

  • Do not increase doses during the first 4 weeks of therapy, and do not increase the dose more frequently than every 2 weeks
  • Consider dose increases in patients who meet the following condition:
    • Failure to achieve a reduction from pre-treatment baseline in either palpable spleen length of 50% or spleen volume of 35% as measured by computed tomography or magnetic resonance imaging
  • If the response is insufficient, doses may be increased by increments of 5 mg daily to a maximum of 10 mg twice daily if:
    • The PLT count has remained ≥40 × 109/L, and
    • The PLT count has not decreased by >20% in the prior 4 weeks, and
    • The ANC is >1 × 109/L, and
    • The dose has not been reduced or interrupted for an adverse event or hematologic toxicity in the prior 4 weeks
  • Continuation of treatment for more than 6 months should be limited to patients in whom the benefits outweigh the potential risks. Discontinue Jakafi if there is no spleen size reduction or symptom improvement after 6 months of therapy

Dose reductions for avoiding treatment interruptions

Dose reductions as set forth in the table below: Starting PLT count ≥100 × 109/L

Dose reductions should be considered if the PLT counts decrease, with the goal of avoiding dose interruptions for thrombocytopenia.1

Dosing recommendations for thrombocytopenia in patients starting treatment with a PLT count of ≥100 × 109/L1:

Image of Jakafi Dose at Time of Platelet Decline

Dose reductions:

Reduce the dose of ruxolitinib for PLT counts <35 × 109/L as shown in this table:

MF: Dosing modifications for thrombocytopenia in patients with starting PLT count of 50 to <100 × 109/L1

Image of Platelet Count –Jakafi Dosing Recommendations Image of Platelet Count –Jakafi Dosing Recommendations

Treatment interruption and restarting dosing

Starting PLT count ≥100 × 109/L1

  • Interrupt treatment for PLT counts <50 × 109/L or ANC <0.5 × 109/L
  • After recovery of PLT counts >50 × 109/L and ANC >0.75 × 109/L, dosing may be restarted

Maximum restarting doses for Jakafi after safety interruption for thrombocytopenia in patients starting treatment with a PLT count of ≥100 × 109/L:

Image of Current Platelet Count – Maximum Dose When Restarting Treatment with Jakafi Image of Current Platelet Count – Maximum Dose When Restarting Treatment with Jakafi

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.1

Starting PLT count 50 to <100 × 109/L1

  • Interrupt treatment for PLT counts <25 × 109/L or ANC <0.5 × 109/L
  • Dosing may be restarted after recovery of PLT counts >35 × 109/L and ANC >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 decrease in PLT count <25 × 109/L or ANC <0.5 × 109/L that led to dose interruption

Dose modification for bleeding

Interrupt treatment for bleeding requiring intervention regardless of current PLT 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 at a lower dose.1

Special populations

Special populations: Concomitant use with strong CYP3A4 inhibitors or fluconazole

Modify the dose of Jakafi when coadministered with strong CYP3A4 inhibitors and fluconazole doses of ≤200 mg as shown in this table:

Image of chart that says Patients on Concomitant Strong CYP3A4 Inhibitors or Fluconazole Doses of ≤200 mg –Jakafi Recommended Dose Modification Image of chart that says Patients on Concomitant Strong CYP3A4 Inhibitors or Fluconazole Doses of ≤200 mg –Jakafi Recommended Dose Modification

  • Avoid the use of fluconazole doses of >200 mg daily with Jakafi
  • Additional dose modifications should be made with frequent monitoring of safety and efficacy

Special populations: Dose modifications in patients with renal or hepatic impairment

Dosing for renal and hepatic impairment:

Image of table that says – Renal Impairment Status/Hepatic Impairment Status – Platelet Count Recommended Starting Dosage Image of table that says – Renal Impairment Status/Hepatic Impairment Status – Platelet Count Recommended Starting Dosage

Special populations: Patients on dialysis

  • The recommended starting dose in patients with MF who have end-stage renal disease and are on dialysis is:
    • 15 mg once after a dialysis session in those with a PLT count between 100 × 109/L and 200 × 109/L or
    • 20 mg once after a dialysis session for patients with a PLT count of >200 × 109/L
  • Additional dose modifications should be made with frequent monitoring of safety and efficacy
  • Avoid use of Jakafi in patients with end-stage renal disease (creatinine clearance <15 mL/min) not requiring dialysis

Cytopenias: Trial data

Treatment with Jakafi can cause thrombocytopenia, anemia and neutropenia, which are each dose-related effects. Perform a pre‐treatment CBC and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated.1

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.


Thrombocytopenia and anemia: What to expect with Jakafi—data from clinical trials in MF

Cytopenias are expected dose-related effects due to JAK2 inhibition.2,3

  • Anemia and thrombocytopenia may occur with JAK2 inhibition because erythropoietin and thrombopoietin signal through JAK21,3
  • Cytopenias may not be signs of worsening disease

Thrombocytopenia and anemia were the most common adverse reactions in COMFORT-I.*

  • During the first 24 weeks, incidence of grade 3 and 4 anemia and thrombocytopenia was 45% and 13%, respectively; discontinuations for these events occurred in <1% of patients1
    • Overall discontinuation rate for adverse events, regardless of causality, was 11% for Jakafi vs 11% for placebo1,4
    • CBC values, including PLT counts, were closely monitored as part of the trial, and dose modifications were made as necessary based on platelet counts2,4
  • Thrombocytopenia was usually managed by reducing the dose or temporarily withholding Jakafi. PLT transfusions may be necessary1

In patients with cytopenias, consider dose reductions, temporarily withholding Jakafi, or transfusions as clinically indicated1

Monitor CBCs during treatment, beginning as early as weeks 2 to 41

Image of chart – COMFORT-I: Mean Platelet Levels Over Time Image of chart – COMFORT-I: Mean Platelet Levels Over Time

  • Initial reductions in hemoglobin and platelets can occur in as early as 2 to 4 weeks2
  • Dosing may need to be modified to avoid dose interruption, with the goal of achieving clinical benefit2

COMFORT-I: Hemoglobin levels and red blood cell transfusion throughout study—data in patients with MF

Image of chart – COMFORT-I: Mean Hemoglobin Levels Over Time Image of chart – COMFORT-I: Mean Hemoglobin Levels Over Time

  • Mean decreases in hemoglobin levels reached a nadir of approximately 1.5 g/dL to 2 g/dL below baseline after 8 to 12 weeks of therapy and then gradually recovered to a new steady state that was approximately 1 g/dL below baseline1
  • Dose modifications of Jakafi and/or blood transfusions for patients developing anemia may be required1

Image of chart – COMFORT-I: Patients Requiring Red Blood Cell Transfusions Image of chart – COMFORT-I: Patients Requiring Red Blood Cell Transfusions

  • In this randomized, placebo-controlled study, 60% of patients treated with Jakafi and 38% of patients receiving placebo required red blood cell transfusions during randomized treatment1

References

  1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
  2. Data on file. Incyte Corporation. Wilmington, DE.
  3. Vainchenker W, Dusa A, Constantinescu SN. JAKs in pathology: role of Janus kinases in hematopoietic malignancies and immunodeficiencies. Semin Cell Dev Biol. 2008;19(4):385-393.
  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.
  5. 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)(suppl):1-38.

Indications and Usage

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

Jakafi 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.

Jakafi is indicated for treatment of steroid‐refractory acute graft‐versus‐host disease (GVHD) in adult and pediatric patients 12 years and older.

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
  • 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 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 three most common nonhematologic adverse reactions (incidence >10%) were bruising, dizziness and headache. 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 two weeks after the final dose

Please see Full Prescribing Information for Jakafi.