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Starting a Patient on Jakafi

Dose optimization is key to maintaining the balance between safety and efficacy.

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START: The recommended starting dose of Jakafi for myelofibrosis (MF) is based on platelet count1

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START: The recommended starting dose of Jakafi for myelofibrosis (MF) is based on platelet count1

A complete blood count (CBC) and platelet (PLT) count must be performed before initiating Jakafi.

Image of 5 mg bottle of Jakafi Image of 5 mg bottle of Jakafi
Image of 15 mg bottle of Jakafi Image of 15 mg bottle of Jakafi
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Jakafi is also available in 10 mg and 25 mg tablets.

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MONITOR: Monitoring patients after initiation of Jakafi is essential, especially during the first 12 weeks of therapy

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MONITOR: Monitoring patients after initiation of Jakafi is essential, especially during the first 12 weeks of therapy

A CBC and PLT count 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.1

Image that shows a circle with 70% and says - …of patients receiving Jakafi in COMFORT-I required a dose adjustment in the first 12 weeks of therapy

...of patients receiving Jakafi in COMFORT-I* required a dose adjustment in the first 12 weeks of therapy2

Monitoring blood counts and using appropriate dose management are essential to achieve desired efficacy and manage cytopenias1

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OPTIMIZE: Individualize dosing of Jakafi to optimize the balance between safety and efficacy1

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OPTIMIZE: Individualize dosing of Jakafi to optimize the balance between safety and efficacy1

Managing anemia and thrombocytopenia

  • Dose modifications, temporarily withholding Jakafi, and/or transfusions may be required for patients developing anemia or thrombocytopenia1
  • Interrupt treatment for bleeding, neutropenia (absolute neutrophil count [ANC] <0.5 × 109/L), or thrombocytopenia (based on starting platelet count)1
  • In COMFORT-I, grades 3 and 4 thrombocytopenia or anemia occurred in 13% and 45% of patients receiving Jakafi, respectively. All grades of thrombocytopenia or anemia occurred in 70% and 96% of patients receiving Jakafi, respectively1,3

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

Dosing in COMFORT-I

  • 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
    • 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 (absolute neutrophil count [ANC] <0.5 × 109/L) was generally reversible by withholding Jakafi until recovery

Dose may be increased in the case of an insufficient response1

Efficacy based on titrated dose

Image of chart showing COMFORT-I: Mean Change in Spleen Volume by Dose at Week 24 Image of chart showing COMFORT-I: Mean Change in Spleen Volume by Dose at Week 24

Graphic adapted with permission from Haematologica.

  • Doses may be increased if the response is insufficient and platelet, hemoglobin, and neutrophil counts are adequate, and treatment has not been reduced or interrupted in the prior 4 weeks.1 (See next section, Appropriate Dose Management, for criteria for increasing dose)
  • Doses should not be increased during the first 4 weeks of therapy and not more frequently than every 2 weeks1
  • Discontinue Jakafi if there is no spleen size reduction or symptom improvement after 6 months of therapy1
  • In patients with starting platelet counts ≥100 × 109/L, based on limited clinical data, long-term maintenance at a 5 mg twice daily dose has not shown responses. Continued use at this dose should be limited to patients in whom the benefits outweigh the potential risks1

Appropriate dose management

Dose Modifications for Patients With Starting PLT Count ≥100 × 109/L

Dose Modifications for Patients With Starting PLT Count 50 to <100 × 109/L

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.

Special populations

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

For further information and to download the Jakafi dosing guide, click here.

*COMFORT-I (COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment-I) was a randomized, double-blind, placebo-controlled phase 3 study with 309 patients with intermediate-2–risk or high-risk myelofibrosis. The primary endpoint was the proportion of patients achieving a ≥35% reduction in spleen volume from baseline to week 24 as measured by computed tomography (CT) or magnetic resonance imaging (MRI). A secondary endpoint was the proportion of patients 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. 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).1,3

COMFORT-II (COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment-II) was a randomized, open-label phase 3 study with 219 patients with intermediate-2–risk or high-risk myelofibrosis. The primary endpoint was the proportion of patients achieving a ≥35% reduction in spleen volume from baseline at week 48 as measured by CT or MRI.1,4

References

  1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
  2. 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.
  3. 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.
  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.

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 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 see Full Prescribing Information for Jakafi.