Fedratinib Hydrochloride

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). 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 ).

6 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) ] The most common adverse reactions (≥20%) are diarrhea, nausea, anemia, and vomiting ( 6.1 ).

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.

WARNING: ENCEPHALOPATHY INCLUDING WERNICKE'S 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. 5 WARNINGS AND PRECAUTIONS • 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 ). 4 CONTRAINDICATIONS None. None.