Dosing

Dosing for patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea

Start–Standard starting dose in PV: 10 mg twice daily1

Monitor

A CBC and platelet count must be performed before initiating Jakafi, every 2 to 4 weeks until doses are stabilized, and then as clinically indicated.1

Optimize

Doses may be titrated based on safety and efficacy1

  • Most dose adjustments occurred within the first 8 weeks of treatment
    • 37% of patients increased from the starting dose in the first 8 weeks
    • 9% of patients decreased from the starting dose in the first 8 weeks

Dose reductions

Dose reductions should be considered for hemoglobin and platelet count decreases as shown in the following table with the goal of avoiding dose interruptions1

Treatment interruption and restarting dosing

Interrupt treatment for:

  • Hemoglobin <8 g/dL or
  • Platelet counts <50 x 109/L or
  • Absolute neutrophil count (ANC) <1.0 x 109/L

After recovery of the hematologic parameters(s) to acceptable levels, dosing may be restarted.

  • Use the most severe category of a patient’s hemoglobin, platelet count, or ANC abnormality to determine the corresponding maximum restarting dose
  • Patients who had required dose interruption while receiving a dose of 5 mg twice daily, may restart at a dose of 5 mg twice daily or 5 mg once daily, but not higher, once hemoglobin is greater than or equal to 10 g/dL, platelet count is greater than or equal to 75 X 109/L, and ANC is greater than or equal to 1.5 X 109/L
  • After restarting Jakafi following treatment interruption, doses may be titrated, but the maximum total daily dose should not exceed 5 mg less than the dose that resulted in the dose interruption. An exception to this is dose interruption following phlebotomy-associated anemia, in which case the maximal total daily dose allowed after restarting Jakafi would not be limited

Dose modification based on insufficient response

If the response is insufficient and platelet, hemoglobin, 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 two weeks.

Consider dose increases in patients who meet all of the following conditions:

  1. Inadequate efficacy as demonstrated by one or more of the following:
    1. Continued need for phlebotomy
    2. WBC greater than the upper limit of normal range
    3. Platelet count greater than the upper limit of normal range
    4. Palpable spleen that is reduced by less than 25% from baseline
  2. Platelet count greater than or equal to 140 X 109/L
  3. Hemoglobin greater than or equal to 12 g/dL
  4. ANC greater than or equal to 1.5 X 109/L

Learn more about dose modifications for drug interactions or organ impairment.

Individualized dosing for patients with intermediate to high-risk myelofibrosis

Start–Starting doses are based on platelet counts1

Monitor

A CBC and platelet count must be performed before initiating Jakafi, every 2 to 4 weeks until doses are stabilized, and then as clinically indicated.1

Optimize

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

  • Approximately 70% of patients in COMFORT-I required a dose adjustment in the first 12 weeks of therapy2
  • In COMFORT-I, titrating doses to 10 mg twice daily or higher provided similar efficacy3,4

Dose reductions

Dose reductions should be considered for platelet count decreases as shown in the following table with the goal of avoiding dose interruptions.1

Treatment interruption and restarting dosing

Interrupt treatment for:

  • Platelet counts <50 x 109/L or
  • Absolute neutrophil count (ANC) <0.5 x 109/L

After recovery of the hematologic parameters(s) to acceptable levels (platelet counts >50 x 109/L, ANC >0.75 x 109/L), dosing may be restarted

Chart shows efficacy by titrated dose for spleen volume vs total symptom score – Jakafi.com/hcp.
  • Following treatment interruption for ANC below 0.5 X 109/L, after ANC recovers to 0.75 X 109/L or greater, 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.

Dose modification for hematologic toxicity for patients with myelofibrosis starting treatment with platelet counts of 50 X 109/L to less than 100 X 109/L1

Interrupt treatment for:

  • Platelet counts <25 x 109/L, OR
  • ANC <0.5 x 109/L

After recovery of platelet counts above 35 X 109/L and ANC above 0.75 X 109/L, dosing may be restarted. 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 platelet count below 25 x 109/L or ANC below 0.5 X 109/L that led to dose interruption.

Reduce the dose of Jakafi for platelet counts less than 35 X 109/L as shown in the table.

Dose modification based on insufficient response1

If the response is insufficient and platelet and neutrophil counts are adequate, the Jakafi dose may be increased. An insufficient response is defined as failure to achieve a reduction from pretreatment baseline in either palpable spleen length of 50% or a 35% reduction in spleen volume as measured by computed tomography (CT) or magnetic resonance imaging (MRI).

Consider dose increases in patients who meet all the conditions listed in the table.

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

Dose modification for bleeding

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 at a lower dose.

See Full Prescribing Information for dosing instructions for patients with myelofibrosis starting treatment with platelet counts of 50 X 109/L to less than 100 X 109/L.

Learn more about dose modifications for drug interactions or organ impairment.

Efficacy by titrated dose

Chart shows efficacy by titrated dose for spleen volume vs total symptom score – Jakafi.com/hcp.

Dose modifications for drug interactions

Concomitant use with strong CYP3A4 inhibitors or fluconazole1

Modify the dose of Jakafi when given concomitantly with strong CYP3A4 inhibitors, such as, but not limited to:1

  • Boceprevir
  • Clarithromycin
  • Conivaptan
  • grapefruit juice
  • Indinavir
  • Itraconazole
  • Ketoconazole
  • Lopinavir/ritonavir
  • Mibefradil
  • Nefazodone
  • Nelfinavir
  • Posaconazole
  • Ritonavir
  • Saquinavir
  • Telaprevir
  • Telithromycin
  • Voriconazole

Modify the dose of Jakafi when given concomitantly with fluconazole doses of less than or equal to 200 mg. Avoid the use of fluconazole doses of greater than 200 mg daily concomitantly with Jakafi.1

Chart shows efficacy by titrated dose for spleen volume vs total symptom score – Jakafi.com/hcp.

Additional dose modifications should be made with careful monitoring of safety and efficacy.

Dose modifications for organ impairment

Renal impairment1

Modify the dose of Jakafi in patients with moderate or severe renal impairment as shown in the following table.1

Chart shows efficacy by titrated dose for spleen volume vs total symptom score – Jakafi.com/hcp.

Additional dose modifications should be made with careful monitoring of safety and efficacy.

Patients on dialysis1

The recommended starting dose for myelofibrosis patients with end stage renal disease on dialysis is 15 mg once after a dialysis session for patients with a platelet count between 100 X 109/L and 200 X 109/L or 20 mg for patients with a platelet count of greater than 200 X 109/L. The recommended starting dose for polycythemia vera patients with end stage renal disease on dialysis is 10 mg. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Avoid use of Jakafi in patients with end stage renal disease (CrCl less than 15 mL/min) not requiring dialysis.

Hepatic impairment1

The dose of Jakafi should be reduced in patients with hepatic impairment.1

Expand References +
  • Jakafi Prescribing Information. Incyte Corporation.
  • Verstovsek S, Gotlib J, Gupta V, et al. Management of cytopenias in patients with myelofibrosis treated with ruxolitinib and effect of dose modifications on efficacy outcomes. Onco Targets Ther. 2014;7:13-21.
  • Data on file. Incyte Corporation.
  • Verstovsek S, Mesa RA, Gotlib J, et al. N Engl J Med. 2012;366:799-807. [also supplementary appendix: http://www.nejm.org/action/showSupplements?doi=10.1056%2FNEJMoa1110557&viewType=Popup&viewClass=Suppl]
  • Verstovsek S, Mesa RA, Gotlib J, et al. Haematologica. 2013;98:1865-1871.

INDICATIONS AND USAGE

Jakafi is indicated for treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.

Jakafi is indicated for treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF.

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 x 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
  • 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 ruxolitinib treatment for myelofibrosis. 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
  • The three most frequent non‐hematologic adverse reactions (incidence >10%) were bruising, dizziness and headache
  • A dose modification is recommended 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 breast‐feed

Please see Full Prescribing Information for Jakafi.

 
IMPORTANT SAFETY INFORMATION
 
INDICATIONS AND USAGE
Jakafi is indicated for treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.

Jakafi is indicated for treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF.
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 x 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
  • 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 ruxolitinib treatment for myelofibrosis. 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
  • The three most frequent non‐hematologic adverse reactions (incidence >10%) were bruising, dizziness and headache
  • A dose modification is recommended 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 breast‐feed

Please see Full Prescribing Information for Jakafi.