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Getting Started With Jakafi

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

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START: The recommended starting doses are based on platelet counts1

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START: The recommended starting doses are based on platelet counts1

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

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Jakafi is also available in 10 mg and 25 mg tablets.

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

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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

  • 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
  • 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

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

Dosing in clinical trials

Dose may be increased in the case of an insufficient response1

Efficacy based on tritrated 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 weeks1
  • 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 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

Starting PLT Count ≥100 × 109/L

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.

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

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

CrCl, creatinine clearance.

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 platelet 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

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

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 subjects 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 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. 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. Best available therapy in 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

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.
  5. Data on file. Incyte Corporation. Wilmington, DE.

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.