Fedratinib

Fedratinib is an oral kinase inhibitor with activity against wild type and mutationally activated Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). Fedratinib is a JAK2-selective inhibitor with higher inhibitory activity for JAK2 over family members JAK1, JAK3 and TYK2.

• INREBIC ® is indicated for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF). INREBIC is a kinase inhibitor indicated for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF) ( 1 ).

• None Nonecontraindicated

• Recommended Dosage: 400 mg orally once daily with or without food for patients with a baseline platelet count of greater than or equal to 50 × 10 9 /L ( 2.2 ). • For patients who have difficulty swallowing capsules whole or those with a nasogastric tube, the content of the capsule(s) may be dispersed in Ensure ® Plus ( 2.2 ). • Reduce dose for patients taking strong CYP3A inhibitors or with severe renal impairment ( 2.3 , 2.4 , 7.1 , 8.6 ). 2.1 Required Concomitant Medications During treatment with INREBIC, all patients should receive prophylaxis with thiamine 100 mg orally daily [see Dosage and Administration (2.7) and Warnings and Precautions (5.1) ]. 2.2 Recommended Dosage Conduct baseline testing of thiamine (Vitamin B1) levels prior to initiation of INREBIC [see Dosage and Administration (2.7) , Warnings and Precautions (5.1) ] . The recommended dosage of INREBIC is 400 mg taken orally once daily for patients with a baseline platelet count of greater than or equal to 50 × 10 9 /L. Modify the dose for patients using concomitant strong CYP3A4 inhibitors, and in patients with severe renal impairment (creatinine clearance (CL cr ) 15 mL/min to 29 mL/min) [see Dosage and Administration (2.4 , 2.5) ] . Patients that are on treatment with ruxolitinib before the initiation of INREBIC must taper and discontinue according to the ruxolitinib prescribing information. Administration Information: • INREBIC may be taken with or without food. Administration with a high fat meal may reduce the incidence of nausea and vomiting.

• Anemia and Thrombocytopenia: Manage by dose reduction, interruption, or transfusion ( 5.2 ). • Gastrointestinal Toxicity: Manage by dose reduction or interruption if patient develops severe diarrhea, nausea, or vomiting. Prophylaxis with antiemetics and treatment with antidiarrhea medications are recommended ( 5.3 ). • Hepatic Toxicity: Manage by dose reduction or interruption ( 5.4 ). • Amylase and Lipase Elevation: Manage by dose reduction or interruption ( 5.5 ). • Uveitis: Monitor for symptoms and refer for ophthalmological evaluation ( 5.6 ). • Major Adverse Cardiac Events (MACE): Monitor for development of MACE ( 5.7 ). • Thrombosis: Evaluate and treat symptoms of thrombosis promptly ( 5.8 ). • Secondary Malignancies: Monitor for development of secondary malignancies, particularly in patients who are current or past smokers ( 5.9 ). • Symptom Exacerbation Following Interruption or Discontinuation of Treatment: Manage with supportive care and consider resuming treatment with INREBIC ( 5.10 ). 5.1 Encephalopathy, Including Wernicke's Serious and fatal encephalopathy, including Wernicke's encephalopathy, has occurred in INREBIC-treated patients. Serious cases were reported in 1.3% (8/608) of patients treated with INREBIC in clinical trials and 0.16% (1/608) of cases were fatal. Wernicke's encephalopathy is a neurologic emergency resulting from thiamine (Vitamin B1) deficiency. Signs and symptoms of Wernicke's encephalopathy may include ataxia, mental status changes, and ophthalmoplegia (e.g., nystagmus, diplopia).

The following clinically significant adverse reactions are described elsewhere in the labeling: • Encephalopathy, including Wernicke's [see Warnings and Precautions (5.1) ] • Anemia and Thrombocytopenia [see Warnings and Precautions (5.2) ] • Gastrointestinal Toxicity [see Warnings and Precautions (5.3) ] • Hepatic Toxicity [see Warnings and Precautions (5.4) ] • Amylase and Lipase Elevation [see Warnings and Precautions (5.5) ] • Uveitis [see Warnings and Precautions (5.6) ] • Major Adverse Cardiac Events [see Warnings and Precautions (5.7) ] • Thrombosis [see Warnings and Precautions (5.8) ] • Secondary Malignancies [see Warnings and Precautions (5.9) ] • Symptom Exacerbation Following Interruption or Discontinuation of Treatment [see Warnings and Precautions (5.10) ] The most common adverse reactions (≥20%) are diarrhea, nausea, anemia, and vomiting ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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.

• Lactation: Advise not to breastfeed ( 8.2 ). 8.1 Pregnancy Risk Summary There are no available data on INREBIC use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of fedratinib to pregnant rats during organogenesis at doses considerably lower than the recommended human daily dose of 400 mg/day resulted in adverse developmental outcomes (see Data ) . Consider the benefits and risks of INREBIC for the mother and possible risks to the fetus when prescribing INREBIC to a pregnant woman. The background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study in pregnant rats, fedratinib administration at a dose of 30 mg/kg/day during organogenesis (gestation days 6 to 17) was associated with adverse developmental outcomes including skeletal variations (such as additional ossification center of neuronal arches).

Metabolism

INREBIC at 300 mg to 500 mg once daily (0.75 to 1.25 times the recommended dose) results in a dose proportional increase in geometric mean fedratinib peak concentrations (C max ) and the area under the plasma concentration time curve over the dosing interval (AUC tau ). The mean steady state levels are achieved within 15 days of daily dosing.

Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

• Aug 16, 2019NDANDA212327Bristol-myers

1. 1Diarrhoea13911%
2. 2Death13711%
3. 3Nausea1168.9%
4. 4Fatigue1098.4%
5. 5Vomiting715.5%
6. 6Constipation594.5%
7. 7Haemoglobin Decreased534.1%
8. 8Off Label Use534.1%
9. 9Asthenia493.8%
10. 10Platelet Count Decreased493.8%
11. 11Full Blood Count Decreased453.5%
12. 12Pruritus413.2%
13. 13Drug Ineffective403.1%
14. 14Anaemia382.9%
15. 15Dizziness362.8%

The 10 most recently updated of 33 ClinicalTrials.gov registrations naming Fedratinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Fedratinib in Myelodysplastic /Myeloproliferative Neoplasms (MDS/MPNs) and Chronic Neutrophilic Leukemia (CNL)
  Completed · Phase 2 · Interventional · 25 enrolled · H. Lee Moffitt Cancer Center and Research Institute
  NCT05177211updated 2026-06-09
• A Study to Assess the Safety and Tolerability of BMS-986158 Alone and in Combination With Either Ruxolitinib or Fedratinib in Participants With Blood Cancer (Myelofibrosis)
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 216 enrolled · Bristol-Myers Squibb
  NCT04817007updated 2026-05-08
• Fedratinib in Combination With Nivolumab
  Completed · Phase 2 · Interventional · 30 enrolled · Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
  NCT05393674updated 2026-04-08
• Decitabine With Ruxolitinib, Fedratinib or Pacritinib for the Treatment of Accelerated/Blast Phase Myeloproliferative Neoplasms
  Recruiting · Phase 2 · Interventional · 25 enrolled · University of Washington
  NCT04282187updated 2026-03-16
• Reduced Intensity Haploidentical Transplantation for the Treatment of Primary or Secondary Myelofibrosis
  Recruiting · Phase 2 · Interventional · 20 enrolled · Fred Hutchinson Cancer Center
  NCT04370301updated 2026-01-12
• Maintenance Fedratinib to Prevent Post-Transplant Relapse in Myeloproliferative Neoplasms
  Terminated · Phase 1 · Interventional · 12 enrolled · H. Lee Moffitt Cancer Center and Research Institute
  NCT05127174updated 2025-12-04
• A Study of Fedratinib in Japanese Subjects With DIPSS (Dynamic International Prognostic Scoring System)- Intermediate or High-risk Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (Post-PV MF), or Post-essential Thrombocythemia Myelofibrosis (Post-ET MF)
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 31 enrolled · Bristol-Myers Squibb
  NCT04446650updated 2025-10-21
• A Study to Evaluate Single Agent Selinexor Versus Physician's Choice in Participants With Previously Treated Myelofibrosis
  Active not recruiting · Phase 2 · Interventional · 112 enrolled · Karyopharm Therapeutics Inc
  NCT04562870updated 2025-10-03
• To Assess the Safety, Tolerability and Efficacy of Itacitinib Immediate Release Tablets in Participants With Primary or Secondary Myelofibrosis Who Have Received Prior Ruxolitinib and/or Fedratinib Monotherapy (LIMBER-213)
  Completed · Phase 2 · Interventional · 4 enrolled · Incyte Corporation
  NCT04629508updated 2025-09-02
• An Efficacy and Safety Study of Fedratinib Compared to Best Available Therapy in Subjects With DIPSS-intermediate or High-risk Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib
  Completed · Phase 3 · Interventional · 202 enrolled · Celgene
  NCT03952039updated 2025-08-28

Frequently asked questions

How does Fedratinib work?

Fedratinib is an oral kinase inhibitor with activity against wild type and mutationally activated Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). Fedratinib is a JAK2-selective inhibitor with higher inhibitory activity for JAK2 over family members JAK1, JAK3 and TYK2.

What is Fedratinib used for?

According to FDA labeling, Fedratinib carries indications including: INREBIC ® is indicated for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF). INREBIC is a kinase inhibitor indicated for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF) ( 1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Fedratinib?

Fedratinib is classified as Janus-associated kinase (JAK) inhibitors, Janus Kinase Inhibitors, Tyrosine Kinase Inhibitors, Cellular Proliferation Alteration, Increased Cellular Death.

What are the brand names for Fedratinib?

Fedratinib is marketed under brand names including Inrebic.

What are the contraindications for Fedratinib?

Fedratinib labeling lists contraindications including: None None. Always consult the full prescribing information and a clinician.