Fedratinib Hydrochloride (1 brand name, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- INREBIC
Boxed Warning
Serious and fatal encephalopathy, including Wernicke’s, has occurred in patients treated with INREBIC. Wernicke’s encephalopathy is a neurologic emergency. Assess thiamine levels in all patients prior to starting INREBIC. Do not start INREBIC in patients with thiamine deficiency; replete thiamine prior to treatment initiation. While on treatment all patients should receive prophylaxis with daily oral thiamine and should have thiamine levels assessed as clinically indicated. If encephalopathy is suspected, immediately discontinue INREBIC and initiate parenteral thiamine. Monitor until symptoms resolve or improve and thiamine levels normalize [see Dosage and Administration (2.6), Warnings and Precautions (5.1) and Adverse Reactions (6.1)].
Indications and Usage
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).
Contraindications
None
Adverse Reactions
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)]
Mechanism of Action
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. Abnormal activation of JAK2 is associated with myeloproliferative neoplasms (MPNs), including myelofibrosis and polycythemia vera. In cell models expressing mutationally active JAK2V617F or FLT3ITD, fedratinib reduced phosphorylation of signal transducer and activator of transcription (STAT3/5) proteins, inhibited cell proliferation, and induced apoptotic cell death. In mouse models of JAK2V617F-driven myeloproliferative disease, fedratinib blocked phosphorylation of STAT3/5, and improved survival, white blood cell counts, hematocrit, splenomegaly, and fibrosis.
Overdosage
Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.