Jakafi (Ruxolitinib)

How Does Jakafi Work?

Jakafi (ruxolitinib) is a protein kinase inhibitor that inhibits certain enzymes called Janus kinases (JAK), which are involved in blood cell production and immune signaling. In myelofibrosis (bone marrow cancer) or polycythemia vera (a rare blood disorder), the Janus kinases are overactive, which leads to uncontrolled production of blood cells that can accumulate in other organs, such as the spleen, causing enlargement. Ruxolitinib inhibits specific signaling pathways and thus stops this overproduction of blood cells.

Janus kinases are part of a signaling pathway known as the JAK-STAT pathway, which helps regulate blood cell production, inflammation, and immune function. When this pathway becomes overactive, it can cause excessive blood cell production and inflammation, contributing to disease symptoms.

By inhibiting JAK1 and JAK2 enzymes, Jakafi helps reduce abnormal signaling, which can lead to improvements in symptoms such as spleen enlargement, fatigue, night sweats, and itching. Since JAK signaling also plays a role in immune function, treatment may affect blood counts and increase infection risk, which is why regular monitoring is required.

Benefits of Treatment

Jakafi may provide several benefits for patients with myelofibrosis, polycythemia vera, or graft-versus-host disease, including:

• Reduction in spleen size
• Improvement in disease-related symptoms such as fatigue, night sweats, bone pain, and itching
• Better disease control when other treatments are not effective or tolerated
• A steroid-sparing treatment option for graft-versus-host disease in some patients

Individual results may vary, and it may take several weeks or months to experience full benefits.

What Is Jakafi Used For?

• Myelofibrosis: Jakafi is indicated for the treatment of intermediate or high-risk myelofibrosis (MF). This includes primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults. 
• Polycythemia vera: Jakafi is indicated for the treatment of polycythemia vera (PV) for adults who have experienced an inadequate response to or intolerance of hydroxyurea.
• Acute graft-versus-host disease: Jakafi is indicated for the treatment of steroid-refractory acute graft-versus-host disease (aGVHD) in adults and pediatric patients who are over 12 years of age. 
• Chronic graft-versus-host disease: Jakafi is indicated for the treatment of chronic graft-versus-host disease (cGVHD) in adults and pediatric patients (over 12) after failure of one or two lines of systemic therapy.

How To Take Jakafi

Jakafi is taken by mouth, usually twice daily, as prescribed by your doctor.

• Jakafi can be taken with or without food
  
• Take doses at the same time each day
  
• Swallow tablets whole unless your doctor tells you otherwise
  
• If you miss a dose, skip it and take your next dose at the scheduled time
  
• Do not take two doses at the same time to make up for a missed dose
  

Always follow your doctor’s instructions when taking Jakafi.

Dosage

Myelofibrosis

The recommended starting dose is based on platelet count:  

• For platelets between 50,000/mm³ and 100,000/mm³ : 5 mg twice daily
• For platelets between 100,000/mm³ and 200,000/mm³ : 15 mg twice daily
• For platelets > 200,000/mm³ : 20 mg twice daily

Blood work is done before initiating therapy, every 2 to 4 weeks until doses are stabilized, and then as clinically indicated. 

Doses will be titrated and adjusted by your doctor based on safety, efficacy, and ongoing platelet count.

Polycythemia Vera

For polycythemia vera, the recommended dose is 10 mg twice daily.

Blood work is monitored regularly as clinically indicated.

Doses will be titrated and adjusted by your doctor based on safety, efficacy, and ongoing hemoglobin and platelet count.

Acute Graft-Versus-Host Disease

For acute graft-versus-host disease, the recommended dose is 5 mg given orally twice daily.

Blood work is monitored regularly as clinically indicated.

Doses will be titrated and adjusted by your doctor based on safety, efficacy, and ongoing absolute neutrophil count (ANC) and bilirubin level.

Chronic Graft-Versus-Host Disease

For chronic graft-versus-host disease, the recommended dose is 10 mg given orally twice daily.

Blood work is monitored regularly as clinically indicated.

Doses will be titrated and adjusted by your physician based on safety, efficacy, and ongoing ANC and bilirubin level.

Jakafi Dose Modifications

Concomitant Use With Strong CYP3A4 Inhibitors

Certain medications that are CYP3A4 inhibitors, such as fluconazole, increase the amount of Jakafi in the blood. This can therefore increase the risk of adverse reactions. Let your doctor know about all medications you are taking before starting Jakafi as a dose reduction may be required if taken with any CYP3A4 inhibitors. 

Concomitant Use With Strong CYP3A4 Inducers

Certain medications that are CYP3A4 inducers decrease the amount of Jakafi in the blood. This can therefore decrease efficacy.  Let your doctor know about all medications you are taking before starting Jakafi as a dose adjustment may be required if taken with any CYP3A4 inducers. 

Kidney Dysfunction

If you have kidney impairment, your dose will need to be adjusted. If you have end-stage renal disease (ESRD) not requiring dialysis, Jakafi should be avoided. Let your doctor know if you have any type of kidney impairment. 

Liver Dysfunction

If you have liver impairment, your dose will need to be adjusted. Let your doctor know if you have any type of liver impairment. 

Duration of Therapy

Your doctor may allow up to 6 months to see if Jakafi works for you. If there is no improvement after 6 months of treatment, your doctor may have you stop taking the medication.  

It is important you take Jakafi exactly as prescribed. Do not stop taking it without speaking to your doctor first. The only exception is if you experience significant bleeding. If this happens, stop taking Jakafi and call your doctor immediately.

Drug Interactions

Jakafi can interact with other medications and supplements.

• Strong CYP3A4 inhibitors or inducers may affect Jakafi levels
• Other immunosuppressive medications may increase infection risk
• Live vaccines should generally be avoided during treatment
• Herbal supplements, such as St. John’s wort, may interfere with treatment

Always tell your healthcare provider about all medications, supplements, and vaccines before starting Jakafi.

Monitoring and Follow-Up

Regular monitoring is an important part of Jakafi treatment.

• Blood counts are checked to monitor red blood cells, white blood cells, and platelets
• Liver and kidney function may be monitored
• Dose adjustments are common and based on lab results and side effects

Monitoring schedules may change over time depending on how you respond to treatment.

Side Effects

The most common side effects are: 

• Thrombocytopenia (low platelets)
• Anemia (low red blood cell counts) 
• Neutropenia (low white blood cell counts)
• Risk of infection (i.e., tuberculosis, progressive multifocal leukoencephalopathy, herpes zoster, and hepatitis B) 
• Bruising
• Dizziness
• Headache
• Diarrhea

Jakafi for Specific Populations

Pregnant Women

Jakafi should not be used during pregnancy or when planning to become pregnant. It is not known if Jakafi will harm an unborn baby.

Breastfeeding Women

Do not breastfeed during treatment or for 2 weeks after the final dose. It is not known if Jakafi passes into breast milk.