Jakafi

Ruxolitinib comes as a tablet to take by mouth. It is usually taken with or without food two times a day. Take ruxolitinib at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take ruxolitinib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Your doctor may start you on a low dose of ruxolitinib for the first four weeks of treatment, and gradually increase your dose after that time, not more than once every 2 weeks.

If you are unable to swallow, your doctor may tell you to take ruxolitinib through a nasogastric (NG) tube. If so, your doctor or pharmacist will explain how to prepare ruxolitinib to give through an NG tube.

Your doctor will order blood tests before and during your treatment to see how you are affected by this medication. Your doctor may increase or decrease your dose of ruxolitinib during your treatment, or may tell you to stop taking ruxolitinib for awhile. This depends on how well the medication works for you and if you experience side effects. Talk to your doctor about how you are feeling during your treatment. Continue to take ruxolitinib even if you feel well. Do not stop taking ruxolitinib without talking to your doctor. If your treatment with ruxolitinib is stopped, your doctor may decrease your dose gradually.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Oral Administration

May administer with or without food

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

When discontinuing for reasons other than thrombocytopenia, consider gradual tapering the dose (eg, by 5 mg q12hr per week)

NG tube administration

• If unable to ingest tablets, can be administered through a nasogastric tube (8 French or greater) as follows
  • Suspend 1 tablet in approximately 40 mL of water with stirring for approximately 10 minutes
  • Administer suspension within 6 hr after the tablet has dispersed through NG using an appropriate syringe
  • Rinse NG tube with ~75 mL of water
  • Effect of tube feeding preparations on ruxolitinib exposure during administration through NG has not been evaluated

Myelofibrosis

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.

Polycythemia Vera

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

Jakafi is a prescription medicine used to treat people with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis.

Jakafi is also used to treat patients with polycythemia vera, a chronic type of bone marrow disease.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Before taking Jakafi, tell your healthcare provider if you:

• have an infection.
• have or have had liver or kidney problems.
• are on dialysis. Jakafi should be taken after your dialysis.
• have any other medical conditions.
• are pregnant, or plan to become pregnant.
• are breast-feeding or plan to breast-feed. 

Tell your healthcare provider about all the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements. Taking Jakafi with certain other medicines may affect how Jakafi works.

Your pharmacist can provide more information about ruxolitinib.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 1.01. Revision date: 2/15/2012.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take ruxolitinib with or without food.

The ruxolitinib tablet can also be given through a nasogastric (NG) feeding tube as follows:

• Place the tablet into 40 milliliters of water, stirring occasionally for 10 minutes.

• When the tablet is completely dispersed, place the mixture into a syringe attached to the NG tube.

• Push the plunger down to empty the syringe into the tube. Then flush the tube with 75 milliliters of water to wash the contents down.

• You must give the mixture within 6 hours after placing the tablet into the water.

To be sure this medication is helping your condition and not causing harmful effects, your blood will need to be tested often. This will help your doctor determine the best dose for you to use. When you first start taking ruxolitinib, your blood will need to be tested every 2 to 4 weeks. Do not miss any follow-up visits to your doctor.

You should not stop using ruxolitinib suddenly. Follow your doctor's instructions about tapering your dose.

Store at room temperature away from moisture and heat.

Storage

Oral

20–25°C (may be exposed to 15–30°C).1

• Importance of informing patients that ruxolitinib is associated with thrombocytopenia, anemia, and neutropenia, and to have CBCs monitored before and during treatment.1 12 Advise patients to contact their clinicians if unusual bleeding, bruising, fatigue, shortness of breath, or fever occurs.1

• Advise patients to notify clinician immediately if signs and/or symptoms of infection (e.g., chills, aches, fever, nausea, vomiting, weakness ) occur.1

• Importance of informing patients about early signs and symptoms of herpes zoster (e.g., painful skin rash or blisters) and advising patients to seek treatment as soon as possible.1

• Importance of informing patients with ESRD receiving dialysis to take their dose of ruxolitinib following completion of the dialysis session only on days when hemodialysis is scheduled.1

• Inform patients of importance of adherence to dosing schedule; advise patients not to change dosage or discontinue drug without consulting their clinicians.1 Inform patients that myelofibrosis signs and symptoms are expected to return after treatment discontinuance.1

• Importance of not drinking grapefruit juice while receiving ruxolitinib therapy.1

• Importance of not doubling the next dose if a dose is missed; take next dose at the regularly scheduled time.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Importance of advising women not to breast-feed during therapy with the drug.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., fungal, bacterial, or HIV infection).

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Distribution is restricted. (See Restricted Distribution under Dosage and Administration.)

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Black, tarry stools
• bladder pain
• bleeding gums
• blood in the urine or stools
• bruising
• chills
• cloudy urine
• collection of blood under the skin
• cough
• deep, dark purple bruise
• difficult, burning, or painful urination
• fever
• frequent urge to urinate
• itching, pain, redness, or swelling
• large, flat, blue or purplish patches in the skin
• lower back or side pain
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• pus in the urine
• shortness of breath
• small, red or purple spots on the skin
• sore throat
• troubled breathing with exertion
• ulcers, sores, or white spots in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness

• Painful blisters on the trunk of the body

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bloated or full feeling
• dizziness or lightheadedness
• excess air or gas in the stomach or intestines
• feeling of constant movement of self or surroundings
• headache
• passing gas
• sensation of spinning
• weight gain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Myelofibrosis

Two randomized Phase 3 studies (Studies 1 and 2) were conducted in patients with myelofibrosis (either primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia-myelofibrosis). In both studies, patients had palpable splenomegaly at least 5 cm below the costal margin and risk category of intermediate 2 (2 prognostic factors) or high risk (3 or more prognostic factors) based on the International Working Group Consensus Criteria (IWG).

The starting dose of Jakafi was based on platelet count. Patients with a platelet count between 100 and 200 X 109/L were started on Jakafi 15 mg twice daily and patients with a platelet count greater than 200 X 109/L were started on Jakafi 20 mg twice daily. Doses were then individualized based upon tolerability and efficacy with maximum doses of 20 mg twice daily for patients with platelet counts between 100 to less than or equal to 125 X 109/L, of 10 mg twice daily for patients with platelet counts between 75 to less than or equal to 100 X 109/L, and of 5 mg twice daily for patients with platelet counts between 50 to less than or equal to 75 X 109/L.

Study 1

Study 1 was a double-blind, randomized, placebo-controlled study in 309 patients who were refractory to or were not candidates for available therapy. The median age was 68 years (range 40 to 91 years) with 61% of patients older than 65 years and 54% were male. Fifty percent (50%) of patients had primary myelofibrosis, 31% had post-polycythemia vera myelofibrosis and 18% had post-essential thrombocythemia myelofibrosis. Twenty-one percent (21%) of patients had red blood cell transfusions within 8 weeks of enrollment in the study. The median hemoglobin count was 10.5 g/dL and the median platelet count was 251 X 109/L. Patients had a median palpable spleen length of 16 cm below the costal margin, with 81% having a spleen length 10 cm or greater below the costal margin. Patients had a median spleen volume as measured by magnetic resonance imaging (MRI) or computed tomography (CT) of 2595 cm3 (range 478 cm3 to 8881 cm3). (The upper limit of normal is approximately 300 cm3).

Patients were dosed with Jakafi or matching placebo. The primary efficacy endpoint was the proportion of patients achieving greater than or equal to a 35% reduction from baseline in spleen volume at Week 24 as measured by MRI or CT.

Secondary endpoints included duration of a 35% or greater reduction in spleen volume and proportion of patients with a 50% or greater reduction in Total Symptom Score from baseline to Week 24 as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 diary.

Study 2

Study 2 was an open-label, randomized study in 219 patients. Patients were randomized 2:1 to Jakafi versus best available therapy. Best available therapy was selected by the investigator on a patient-by-patient basis. In the best available therapy arm, the medications received by more than 10% of patients were hydroxyurea (47%) and glucocorticoids (16%). The median age was 66 years (range 35 to 85 years) with 52% of patients older than 65 years and 57% were male. Fifty-three percent (53%) of patients had primary myelofibrosis, 31% had post-polycythemia vera myelofibrosis and 16% had post-essential thrombocythemia myelofibrosis. Twenty-one percent (21%) of patients had red blood cell transfusions within 8 weeks of enrollment in the study. The median hemoglobin count was 10.4 g/dL and the median platelet count was 236 X 109/L. Patients had a median palpable spleen length of 15 cm below the costal margin, with 70% having a spleen length 10 cm or greater below the costal margin. Patients had a median spleen volume as measured by MRI or CT of 2381 cm3 (range 451 cm3 to 7765 cm3).

The primary efficacy endpoint was the proportion of patients achieving 35% or greater reduction from baseline in spleen volume at Week 48 as measured by MRI or CT.

A secondary endpoint in Study 2 was the proportion of patients achieving a 35% or greater reduction of spleen volume as measured by MRI or CT from baseline to Week 24.

Study 1 and 2 Efficacy Results

Efficacy analyses of the primary endpoint in Studies 1 and 2 are presented in Table 14 below. A significantly larger proportion of patients in the Jakafi group achieved a 35% or greater reduction in spleen volume from baseline in both studies compared to placebo in Study 1 and best available therapy in Study 2. A similar proportion of patients in the Jakafi group achieved a 50% or greater reduction in palpable spleen length.

Figure 1 shows the percent change from baseline in spleen volume for each patient at Week 24 (Jakafi N=139, placebo N=106) or the last evaluation prior to Week 24 for patients who did not complete 24 weeks of randomized treatment (Jakafi N=16, placebo N=47). One (1) patient (placebo) with a missing baseline spleen volume is not included.

In Study 1, myelofibrosis symptoms were a secondary endpoint and were measured using the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 diary. The modified MFSAF is a daily diary capturing the core symptoms of myelofibrosis (abdominal discomfort, pain under left ribs, night sweats, itching, bone/muscle pain and early satiety). Symptom scores ranged from 0 to 10 with 0 representing symptoms "absent" and 10 representing "worst imaginable" symptoms. These scores were added to create the daily total score, which has a maximum of 60.

Table 15 presents assessments of Total Symptom Score from baseline to Week 24 in Study 1 including the proportion of patients with at least a 50% reduction (ie, improvement in symptoms). At baseline, the mean Total Symptom Score was 18.0 in the Jakafi group and 16.5 in the placebo group. A higher proportion of patients in the Jakafi group had a 50% or greater reduction in Total Symptom Score than in the placebo group, with a median time to response of less than 4 weeks.

Figure 2 shows the percent change from baseline in Total Symptom Score for each patient at Week 24 (Jakafi N=129, placebo N=103) or the last evaluation on randomized therapy prior to Week 24 for patients who did not complete 24 weeks of randomized treatment (Jakafi N=16, placebo N=42). Results are excluded for 5 patients with a baseline Total Symptom Score of zero, 8 patients with missing baseline and 6 patients with insufficient post-baseline data.

Figure 3 displays the proportion of patients with at least a 50% improvement in each of the individual symptoms that comprise the Total Symptom Score indicating that all 6 of the symptoms contributed to the higher Total Symptom Score response rate in the group treated with Jakafi.

Overall survival was a secondary endpoint in both Study 1 and Study 2. Patients in the control groups were eligible for crossover in both studies, and the median times to crossover were 9 months in Study 1 and 17 months in Study 2.

Figure 4 and Figure 5 show Kaplan-Meier curves of overall survival at prospectively planned analyses after all patients remaining on study had completed 144 weeks on study.

Polycythemia Vera

Study 3 was a randomized, open-label, active-controlled Phase 3 study conducted in 222 patients with polycythemia vera. Patients had been diagnosed with polycythemia vera for at least 24 weeks, had an inadequate response to or were intolerant of hydroxyurea, required phlebotomy and exhibited splenomegaly. All patients were required to demonstrate hematocrit control between 40-45% prior to randomization. The age ranged from 33 to 90 years with 30% of patients over 65 years of age and 66% were male. Patients had a median spleen volume as measured by MRI or CT of 1272 cm3 (range 254 cm3 to 5147 cm3) and median palpable spleen length below the costal margin was 7 cm.

Patients were randomized to Jakafi or best available therapy. The starting dose of Jakafi was 10 mg twice daily. Doses were then individualized based upon tolerability and efficacy with a maximum dose of 25 mg twice daily. At Week 32, 98 patients were still on Jakafi with 8% receiving greater than 20 mg twice daily, 15% receiving 20 mg twice daily, 33% receiving 15 mg twice daily, 34% receiving 10 mg twice daily, and 10% receiving less than 10 mg twice daily. Best available therapy (BAT) was selected by the investigator on a patient-by-patient basis and included hydroxyurea (60%), interferon/pegylated interferon (12%), anagrelide (7%), pipobroman (2%), lenalidomide/thalidomide (5%), and observation (15%).

The primary endpoint was the proportion of subjects achieving a response at Week 32, with response defined as having achieved both hematocrit control (the absence of phlebotomy eligibility beginning at the Week 8 visit and continuing through Week 32) and spleen volume reduction (a greater than or equal to 35% reduction from baseline in spleen volume at Week 32). Phlebotomy eligibility was defined as a confirmed hematocrit greater than 45% that is at least 3 percentage points higher than the hematocrit obtained at baseline or a confirmed hematocrit greater than 48%, whichever was lower. Secondary endpoints included the proportion of all randomized subjects who achieved the primary endpoint and who maintained their response 48 weeks after randomization, and the proportion of subjects achieving complete hematological remission at Week 32 with complete hematological remission defined as achieving hematocrit control, platelet count less than or equal to 400 X 109/L, and white blood cell count less than or equal to 10 X 109/L.

Results of the primary and secondary endpoints are presented in Table 16. A significantly larger proportion of patients on the Jakafi arm achieved a response for the primary endpoint compared to best available therapy at Week 32 and maintained their response 48 weeks after randomization.  A significantly larger proportion of patients on the Jakafi arm compared to best available therapy also achieved complete hematological remission at Week 32.

Additional analyses for Study 3 to assess durability of response were conducted at Week 80 only in the Jakafi arm. On this arm, 91 (83%) patients were still on treatment at the time of the Week 80 data cut-off. Of the 25 patients who achieved a primary response at Week 32, 19 (76% of the responders) maintained their response through Week 80, and of the 26 patients who achieved complete hematological remission at Week 32, 15 (58% of the responders) maintained their response through Week 80. 

In an assessment of the individual components that make up the primary endpoint, there were 66 (60%) patients with hematocrit control on the Jakafi arm vs. 21 (19%) patients on best available therapy at Week 32; 51 (77% of hematocrit responders) patients on the Jakafi arm maintained hematocrit control through Week 80. There were 44 (40%) patients with spleen volume reduction from baseline greater than or equal to 35% on the Jakafi arm vs. 1 (<1%) patient on best available therapy at Week 32; 43 (98% of spleen volume reduction responders) patients on the Jakafi arm maintained spleen volume reduction through Week 80.

See FDA-approved patient labeling (Patient Information).

Discuss the following with patients prior to and during treatment with Jakafi:

Thrombocytopenia, Anemia and Neutropenia

Inform patients that Jakafi is associated with thrombocytopenia, anemia and neutropenia, and of the need to monitor complete blood counts before and during treatment. Advise patients to observe for and report bleeding.

Infections

Inform patients of the signs and symptoms of infection and to report any such signs and symptoms promptly.

Inform patients regarding the early signs and symptoms of herpes zoster and of progressive multifocal leukoencephalopathy, and advise patients to seek advice of a clinician if such symptoms are observed.

Symptom Exacerbation Following Interruption or Discontinuation of Treatment with Jakafi

Inform patients that after discontinuation of treatment, signs and symptoms from myeloproliferative neoplasms are expected to return. Instruct patients not to interrupt or discontinue Jakafi therapy without consulting their physician.

Non-Melanoma Skin Cancer

Inform patients that Jakafi may increase their risk of certain non-melanoma skin cancers. Advise patients to inform their healthcare provider if they have ever had any type of skin cancer or if they observe any new or changing skin lesions.

Lipid Elevations

Inform patients that Jakafi may increase blood cholesterol, and of the need to monitor blood cholesterol levels.

Drug-drug Interactions

Advise patients to inform their healthcare providers of all medications they are taking, including over-the-counter medications, herbal products and dietary supplements.

Dialysis

Inform patients on dialysis that their dose should not be taken before dialysis but only following dialysis.

Compliance

Advise patients to continue taking Jakafi every day for as long as their physician tells them and that this is a long-term treatment. Patients should not change dose or stop taking Jakafi without first consulting their physician. Patients should be aware that after discontinuation of treatment, signs and symptoms from myeloproliferative neoplasms are expected to return.

Manufactured for:
Incyte Corporation
Wilmington, DE 19803

Jakafi is a registered trademark of Incyte. All rights reserved.
U.S. Patent Nos. 7598257; 8415362; 8722693; 8822481; 8829013; 9079912
© 2011-2016 Incyte Corporation. All rights reserved.

This Patient Information has been approved by the U.S. Food and Drug Administration.         Revised: March 2016

You should not use Jakafi if you are allergic to it.

Tell your doctor if you have ever had tuberculosis, if anyone in your household has tuberculosis, or if you have recently traveled to an area where tuberculosis is common.

To make sure Jakafi is safe for you, tell your doctor if you have:

• any type of active infection;

• kidney disease (or if you are on dialysis);

• liver disease (especially hepatitis B);

• a history of skin cancer; or

• high cholesterol or triglycerides (a type of fat in the blood).

Using Jakafi may increase your risk of developing skin cancer. Talk to your doctor about this risk and what skin symptoms to watch for.

It is not known whether Jakafi will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medcine.

It is not known whether ruxolitinib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using ruxolitinib.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.