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.

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

Dose Modification Guidelines for Thrombocytopenia

Treatment Interruption

Interrupt treatment for platelet counts less than 50 X 10⁹/L. After recovery of platelet counts above this level, dosing may be restarted or increased following recovery of platelet counts to acceptable levels. 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*

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

Dose Modification Based on Response

If efficacy is considered 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. Discontinue treatment after 6 months if there is no spleen size reduction or symptom improvement since initiation of therapy with Jakafi.

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.

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

1. 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;
2. Platelet count greater than 125 X 10⁹/L at 4 weeks and platelet count never below 100 X 10⁹/L;
3. ANC levels greater than 0.75 X 10⁹/L.

Dose Adjustment with Concomitant Strong CYP3A4 Inhibitors

On the basis of pharmacokinetic studies in healthy volunteers, when administering Jakafi 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), the recommended starting dose is 10 mg twice daily for patients with a platelet count greater than or equal to 100 X 10⁹/L. Additional dose modifications should be made with careful monitoring of safety and efficacy.

Concurrent administration of Jakafi with strong CYP3A4 inhibitors should be avoided in patients with platelet counts less than 100 X 10⁹/L [see DRUG INTERACTIONS].

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 1529 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 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 careful monitoring of safety and efficacy.

Jakafi should be avoided 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.

Jakafi should be avoided 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.

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

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. Revised: 12/2011

Last reviewed on RxList: 6/29/2012
This monograph has been modified to include the generic and brand name in many instances.