"The U.S. Food and Drug Administration today approved Imbruvica (ibrutinib) to treat patients with mantle cell lymphoma (MCL), a rare and aggressive type of blood cancer.
MCL is a rare form of non-Hodgkin lymphoma and represents about 6 "...
Jakafi Side Effects Center
Medical Editor: Charles Patrick Davis, MD, PhD
Jakafi (ruxolitinib) is a kinase inhibitor used in the treatment of intermediate or high-risk types of myelofibrosis, a potentially life-threatening blood cancer. There is no generic equivalent available for Jakafi. Common side effects include bruising, dizziness, headache and urinary tract infections.
The starting dose of Jakafi is 20 mg given orally twice daily for patients with a platelet count greater than 200 X 109/L, and 15 mg twice daily for patients with a platelet count between 100 X 109/L and 200 X 109/L. Jakafi is available in the following forms and strengths: 5, 10, 15, 20, and 25 mg tablets. The most serious side effects seen in patients treated with Jakafi include low blood platelet levels (thrombocytopenia), anemia, fatigue, diarrhea, shortness of breath (dyspnea), headache, dizziness, and nausea. There are no adequate and well-controlled studies of Jakafi in pregnant women. In embryofetal toxicity studies, treatment with ruxolitinib resulted in reduced fetal weights at maternally toxic doses. Jakafi should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether ruxolitinib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Jakafi, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. The safety and effectiveness of Jakafi in the pediatric population has not been established.
Our Jakafi Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Jakafi FDA Prescribing Information: Side Effects
The following serious adverse reactions are discussed in greater detail in other sections of the labeling:
- Myelosuppression [see WARNINGS AND PRECAUTIONS]
- Risk of Infection [see WARNINGS AND PRECAUTIONS]
- Myelofibrosis Symptom Exacerbation Following Interruption or Discontinuation of Treatment with Jakafi [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of Jakafi was assessed in 617 patients in six clinical studies with a median duration of follow-up of 10.9 months, including 301 patients with myelofibrosis in two Phase 3 studies.
In these two Phase 3 studies, patients had a median duration of exposure to Jakafi of 9.5 months (range 0.5 to 17 months), with 88.7% of patients treated for more than 6 months and 24.6% treated for more than 12 months. One hundred and eleven (111) patients started treatment at 15 mg twice daily and 190 patients started at 20 mg twice daily. In patients starting treatment with 15 mg twice daily (pretreatment platelet counts of 100 to 200 X 109/L) and 20 mg twice daily (pretreatment platelet counts greater than 200 X 109/L), 65% and 25% of patients, respectively, required a dose reduction below the starting dose within the first 8 weeks of therapy.
In a double-blind, randomized, placebo-controlled study of Jakafi, among the 155 patients treated with Jakafi, the most frequent adverse drug reactions were thrombocytopenia and anemia [see Table 6]. Thrombocytopenia, anemia and neutropenia are dose related effects. The three most frequent non-hematologic adverse reactions were bruising, dizziness and headache [see Table 5].
Discontinuation for adverse events, regardless of causality, was observed in 11% of patients treated with Jakafi and 10.6% of patients treated with placebo.
Table 5 presents the most common adverse reactions occurring in patients who received Jakafi in the double-blind, placebo-controlled study during randomized treatment.
Table 5: Adverse Reactions Occurring in Patients on
Jakafi in the Double-blind, Placebo-controlled Study During Randomized
|All Gradesa (%)||Grade 3 (%)||Grade 4 (%)||All Grades (%)||Grade 3 (%)||Grade 4 (%)|
|Urinary Tract Infectionsd||9.0||0||0||5.3||0.7||0.7|
|aNational Cancer Institute Common Terminology
Criteria for Adverse Events (CTCAE), version 3.0
bincludes contusion, ecchymosis, hematoma, injection site hematoma, periorbital hematoma, vessel puncture site hematoma, increased tendency to bruise, petechiae, purpura
cincludes dizziness, postural dizziness, vertigo, balance disorder, Meniere's Disease, labyrinthitis
dincludes urinary tract infection, cystitis, urosepsis, urinary tract infection bacterial, kidney infection, pyuria, bacteria urine, bacteria urine identified, nitrite urine present
eincludes weight increased, abnormal weight gain
fincludes herpes zoster and post-herpetic neuralgia
Description of Selected Adverse Drug Reactions
In the two Phase 3 clinical studies, median time to onset of first CTCAE Grade 2 or higher anemia was approximately 6 weeks. One patient (0.3%) discontinued treatment because of anemia. In patients receiving Jakafi, mean decreases in hemoglobin reached a nadir of approximately 1.5 to 2.0 g/dL below baseline after 8 to 12 weeks of therapy and then gradually recovered to reach a new steady state that was approximately 1.0 g/dL below baseline. This pattern was observed in patients regardless of whether they had received transfusions during therapy.
In the randomized, placebo-controlled study, 60% of patients treated with Jakafi and 38% of patients receiving placebo received red blood cell transfusions during randomized treatment. Among transfused patients, the median number of units transfused per month was 1.2 in patients treated with Jakafi and 1.7 in placebo treated patients.
In the two Phase 3 clinical studies, in patients who developed Grade 3 or 4 thrombocytopenia, the median time to onset was approximately 8 weeks. Thrombocytopenia was generally reversible with dose reduction or dose interruption. The median time to recovery of platelet counts above 50 X 109/L was 14 days. Platelet transfusions were administered to 4.7% of patients receiving Jakafi and to 4.0% of patients receiving control regimens. Discontinuation of treatment because of thrombocytopenia occurred in 0.7% of patients receiving Jakafi and 0.9% of patients receiving control regimens. Patients with a platelet count of 100 X 109/L to 200 X 109/L before starting Jakafi had a higher frequency of Grade 3 or 4 thrombocytopenia compared to patients with a platelet count greater than 200 X 109/L (16.5% versus 7.2%).
In the two Phase 3 clinical studies, 1.0% of patients reduced or stopped Jakafi because of neutropenia.
Table 6 provides the frequency and severity of clinical hematology abnormalities reported for patients receiving treatment with Jakafi or placebo in the placebo-controlled study.
Table 6: Worst Hematology Laboratory Abnormalities in
the Placebo-Controlled Studya
|All Gradesb (%)||Grade 3 (%)||Grade 4 (%)||All Grades (%)||Grade 3 (%)||Grade 4 (%)|
|a Presented values are worst Grade values regardless of
b National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0
Additional Data from the Placebo-controlled Study
25.2% of patients treated with Jakafi and 7.3% of patients treated with placebo developed newly occurring or worsening Grade 1 abnormalities in alanine transaminase (ALT). The incidence of greater than or equal to Grade 2 elevations was 1.9% for Jakafi with 1.3% Grade 3 and no Grade 4 ALT elevations.
17.4% of patients treated with Jakafi and 6.0% of patients treated with placebo developed newly occurring or worsening Grade 1 abnormalities in aspartate transaminase (AST). The incidence of Grade 2 AST elevations was 0.6% for Jakafi with no Grade 3 or 4 AST elevations.
16.8% of patients treated with Jakafi and 0.7% of patients treated with placebo developed newly occurring or worsening Grade 1 elevations in cholesterol. The incidence of Grade 2 cholesterol elevations was 0.6% for Jakafi with no Grade 3 or 4 cholesterol elevations.
Read the entire FDA prescribing information for Jakafi (Ruxolitinib) »
Additional Jakafi Information
- Jakafi Drug Interactions Center: ruxolitinib oral
- Jakafi Side Effects Center
- Jakafi FDA Approved Prescribing Information including Dosage
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