Safety Profile for Jakafi
in Acute Graft-Versus-Host Disease

Safety Profile for Jakafi
in Acute Graft-Versus-Host Disease

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

REACH1 Safety Results

Patients in REACH1 received steroids with or without other immunosuppressive medications, in addition to Jakafi.1,2

Infections were the most common nonhematologic adverse reactions occurring in 15% or more of patients in REACH1.1*

Image that shows a list of adverse reactions Image that shows a list of adverse reactions

REACH, Ruxolitinib in PatiEnts with RefrACtory Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation.

aNational Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.
bThe Infections category included any MedDRA terms that were site- or organ-specific (eg, urinary tract, lung).
cThese categories included any infections that were attributed to a particular organism, regardless of site of infection (eg, Clostridium difficile, CMV, BK virus).

*As of the 3-month data cutoff.

There were no fatal adverse reactions to Jakafi in the REACH1 study.1

Adverse reactions resulting in treatment discontinuation occurred in 31% of patients, and the most common adverse reaction leading to treatment discontinuation was infection (10%).1

Infections (Treatment-emergent Adverse Events in ≥5% Patients)3†

Image that shows a list of Infections Image that shows a list of Infections

CMV, cytomegalovirus.

As of the 6-month data cutoff.

Selected Laboratory Abnormalities Worsening From Baseline

Discontinuations due to treatment-emergent cytopenia were seen in 3% of patients (2/71).2

Image that shows selected laboratory abnormalities worsening from baseline Image that shows selected laboratory abnormalities worsening from baseline

ALT, alanine aminotransferase; AST, aspartate aminotransferase.

aAs of the 3-month data cutoff.
bNational Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.

Cytopenias Are a Known, Dose-Related Effect of Jakafi1,4

Treatment-emergent cytopenias were managed in some REACH1 patients using dose reduction and interruption.2

Image that shows graph of mean (SE) of hemoglobin over time (safety evaluable patients) Image that shows graph of mean (SE) of hemoglobin over time (safety evaluable patients)

SE, standard error.

aTransfusion support was permitted.2

Image that shows graph of mean (SE) of platelets over time (safety evaluable patients) Image that shows graph of mean (SE) of platelets over time (safety evaluable patients)

SE, standard error.

aTransfusion support was permitted, and dose reductions/interruptions were required for platelet counts <10 × 109/L or <50% of baseline.2

Image that shows graph of mean (SE) of neutrophils over time (safety evaluable patients) Image that shows graph of mean (SE) of neutrophils over time (safety evaluable patients)

ANC, absolute neutrophil count; SE, standard error.

aGrowth factor supplementation was permitted, and dose reductions/interruptions were required for ANCs <1.0 × 109/L.2

Get dosing information.

References

  1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
  2. Data on file. Incyte Corporation. Wilmington, DE.
  3. Jagasia M, Zeiser R, Arbushites M, et al. Ruxolitinib for the treatment of patients with steroid-refractory GVHD: an introduction to the REACH trials. Presented at: 60th American Society of Hematology (ASH) Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 601.
  4. Arana Yi C, Tam CS, Verstovsek S. Efficacy and safety of ruxolitinib in the treatment of patients with myelofibrosis. Future Oncol. 2015:11(5):719-733.

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.