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Jakafi

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Jakafi

INDICATIONS

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

DOSAGE AND ADMINISTRATION

Recommended Starting Dose

The recommended starting dose of Jakafi is based on platelet count (Table 1). A complete blood count (CBC) and platelet count must be performed before initiating therapy, every 2 to 4 weeks until doses are stabilized, and then as clinically indicated [see WARNINGS AND PRECAUTIONS]. Doses may be titrated based on safety and efficacy.

Table 1: Proposed Jakafi Starting Doses

Platelet Count Starting Dose
Greater than 200 X 109/L 20 mg orally twice daily
100 X 109/L to 200 X 109/L 15 mg orally twice daily
50 X 109/L to less than 100 X 109/L 5 mg orally twice daily

Dose Modification Guidelines For Hematologic Toxicity For Patients Starting Treatment With A Platelet Count Of 100 X 109/L Or Greater

Treatment Interruption and Restarting Dosing

Interrupt treatment for platelet counts less than 50 X 109/L or absolute neutrophil count (ANC) less than 0.5 X 109/L.

After recovery of platelet counts above 50 X 109/L and ANC above 0.75 X 109/L, dosing may be restarted. Table 2 illustrates the maximum allowable dose that may be used in restarting Jakafi after a previous interruption.

Table 2: Maximum Restarting Doses for Jakafi after Safety Interruption for Thrombocytopenia for Patients Starting Treatment with a Platelet Count of 100 X 109/L or Greater

Current Platelet Count Maximum Dose When Restarting Jakafi Treatment*
Greater than or equal to 125 X 109/L 20 mg twice daily
100 to less than 125 X 109/L 15 mg twice daily
75 to less than 100 X 109/L 10 mg twice daily for at least 2 weeks; if stable, may increase to 15 mg twice daily
50 to less than 75 X 109/L 5 mg twice daily for at least 2 weeks; if stable, may increase to 10 mg twice daily
Less than 50 X 109/L Continue hold
*Maximum doses are displayed. When restarting, begin with a dose at least 5 mg twice daily below the dose at interruption.

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 Reductions

Dose reductions should be considered if the platelet counts decrease as outlined in Table 3 with the goal of avoiding dose interruptions for thrombocytopenia.

Table 3: Dosing Recommendations for Thrombocytopenia for Patients Starting Treatment with a Platelet Count of 100 X 109/L or Greater

Platelet Count Dose at Time of Platelet Decline
25 mg twice daily 20 mg twice daily 15 mg twice daily 10 mg twice daily 5 mg twice daily
New Dose New Dose New Dose New Dose New Dose
100 to less than 125 X 109/L 20 mg twice daily 15 mg twice daily No Change No Change No Change
75 to less than 100 X 109/L 10 mg twice daily 10 mg twice daily 10 mg twice daily No Change No Change
50 to less than 75 X 109/L 5 mg twice daily 5 mg twice daily 5 mg twice daily 5 mg twice daily No Change
Less than 50 X 109/L Hold Hold Hold Hold Hold

Dose Modification Based On Insufficient Response For Patients Starting Treatment With A Platelet Count Of 100 X 109/L Or Greater

If the response is insufficient and platelet 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 pretreatment baseline in either palpable spleen length of 50% or a 35% reduction in spleen volume as measured by CT or MRI; Platelet count greater than 125 X 109/L at 4 weeks and platelet count never below 100 X 109/L; ANC Levels greater than 0.75 X 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.

Dose Modifications For Hematologic Toxicity For Patients Starting Treatment With Platelet Counts Of 50 X 109/L To Less Than 100 X 109/L

This section applies only to patients with platelet counts of 50 X 109/L to less than 100 X 109/L prior to any treatment with ruxolitinib. See Section on Dose Modification Guidelines for dose modifications for hematological toxicity in patients whose platelet counts were 100 X 109/L or more prior to starting treatment with ruxolitinib.

Treatment Interruption and Restarting Dosing

Interrupt treatment for platelet counts less than 25 X 109/L or ANC less than 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.

Dose Reductions

Reduce the dose of ruxolitinib for platelet counts less than 35 X 109/L as described in Table 4.

Table 4: Dosing Modifications for Thrombocytopenia for Patients with Starting Platelet Count of 50 X 109/L to Less Than 100 X 109/L

Platelet Count Dosing Recommendations
Less than 25 X 109/L
  • Interrupt dosing.
25 X 109/L to less than 35 X 109/L AND the platelet count decline is less than 20% during the prior four weeks
  • Decrease dose by 5 mg once daily.
  • For patients on 5 mg once daily, maintain dose at 5 mg once daily.
25 X 109/L to less than 35 X 109/L AND the platelet count decline is 20% or greater during the prior four weeks
  • Decrease dose by 5 mg twice daily.
  • For patients on 5 mg twice daily, decrease the dose to 5 mg once daily.
  • For patients on 5 mg once daily, maintain dose at 5 mg once daily.

Dose Modifications Based On Insufficient Response For Patients With Starting Platelet Count Of 50 X 109/L To Less Than 100 X 109/L

Do not increase doses during the first 4 weeks of therapy, and do not increase the dose more frequently than every 2 weeks.

If the response is insufficient as defined in Section 2.3, doses may be increased by increments of 5 mg daily to a maximum of 10 mg twice daily if:

  1. the platelet count has remained at least 40 X 109/L, and
  2. the platelet count has not fallen by more than 20% in the prior 4 weeks, and
  3. the ANC is more than 1 X 109/L, and
  4. the dose has not been reduced or interrupted for an adverse event or hematological 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 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.

Dose Modification For Drug Interactions

Concomitant Use With Strong CYP3A4 Inhibitors Or Fluconazole

Modify the dose of Jakafi when given concomitantly with strong CYP3A4 inhibitors (such as but not limited to boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) and fluconazole doses less than or equal to 200 mg as follows [see DRUG INTERACTIONS]:

  • Starting dose, platelet count greater than or equal to 100 X 109/L: 10 mg twice daily
  • Starting dose, platelet counts 50 to less than 100 X 109/L: 5 mg once daily
  • Patients on stable Jakafi dose of greater than or equal to 10 mg twice daily: Reduce dose by 50% (rounded up to the closest available tablet strength).
  • Patients on stable Jakafi dose of 5 mg twice daily: Reduce dose to 5 mg once daily.
  • Patients on stable Jakafi dose of 5 mg once daily: Avoid strong CYP3A4 inhibitor or fluconazole treatment or interrupt Jakafi treatment for the duration of strong CYP3A4 inhibitor or fluconazole use.

Avoid the use of fluconazole doses of greater than 200 mg daily concomitantly with Jakafi.

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

Organ Impairment

Renal Impairment

On the basis of pharmacokinetic studies in volunteers with renal impairment, the recommended starting dose is 10 mg twice daily for patients with a platelet count between 100 X 109/L and 150 X 109/L and moderate (CrCl 30-59 mL/min) or severe renal impairment (CrCl 15-29 mL/min). Additional dose modifications should be made with careful monitoring of safety and efficacy.

The recommended starting dose for 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. Subsequent doses should be administered on dialysis days following each dialysis session. 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 and in patients with moderate or severe renal impairment with platelet counts less than 100 X 109/L [see Use In Specific Populations].

Hepatic Impairment

On the basis of pharmacokinetic studies in volunteers with hepatic impairment, the recommended starting dose is 10 mg twice daily for patients with a platelet count between 100 X 109/L and 150 X 109/L. Additional dose modifications should be made with careful monitoring of safety and efficacy.

Avoid use of Jakafi in patients with hepatic impairment with platelet counts less than 100 X 109/L [see Use in Specific Populations].

Method Of Administration

Jakafi is dosed orally and can be administered with or without food.

If a dose is missed, the patient should not take an additional dose, but should take the next usual prescribed dose.

When discontinuing Jakafi therapy for reasons other than thrombocytopenia, gradual tapering of the dose of Jakafi may be considered, for example by 5 mg twice daily each week.

For patients unable to ingest tablets, Jakafi can be administered through a nasogastric tube (8 French or greater) as follows:

  • Suspend one tablet in approximately 40 mL of water with stirring for approximately 10 minutes.
  • Within 6 hours after the tablet has dispersed, the suspension can be administered through a nasogastric tube using an appropriate syringe.

The tube should be rinsed with approximately 75 mL of water. The effect of tube feeding preparations on Jakafi exposure during administration through a nasogastric tube has not been evaluated.

HOW SUPPLIED

Dosage Forms And Strengths

5 mg tablets - round and white with “INCY” on one side and “5” on the other.

10 mg tablets - round and white with “INCY” on one side and “10” on the other.

15 mg tablets - oval and white with “INCY” on one side and “15” on the other.

20 mg tablets -capsule-shaped and white with “INCY” on one side and “20” on the other.

25 mg tablets - oval and white with “INCY” on one side and “25” on the other.

Storage And Handling

Jakafi (ruxolitinib) Tablets are available as follows:

Jakafi Trade Presentations

NDC Number Strength Description Tablets per Bottle
50881-005-60 5 mg Round tablet with “INCY” on one side and “5” on the other 60
50881-010-60 10 mg Round tablet with “INCY” on one side and “10” on the other 60
50881-015-60 15 mg Oval tablet with “INCY” on one side and “15” on the other 60
50881-020-60 20 mg Capsule shaped tablet with “INCY” on one side and “20” on the other 60
50881-025-60 25 mg Oval tablet with “INCY” on one side and “25” on the other 60

Store at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

Manufactured by: DSM Pharmaceuticals, Inc. Greenville, NC 27834. Manufactured for: Incyte Corporation Wilmington, DE 19880.Issued: July 2014

Last reviewed on RxList: 1/10/2014
This monograph has been modified to include the generic and brand name in many instances.

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