Fedratinib Hydrochloride
Generic Name: fedratinib hydrochloride
Brand Names:
Inrebic
11 DESCRIPTION INREBIC (fedratinib) is a kinase inhibitor with the chemical name N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate. Its empirical formula is C 27 H 36 N 6 O 3 S∙2HCl∙H 2 O and a molecular weight of 615.62.
Overview
11 DESCRIPTION INREBIC (fedratinib) is a kinase inhibitor with the chemical name N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide dihydrochloride monohydrate. Its empirical formula is C 27 H 36 N 6 O 3 S∙2HCl∙H 2 O and a molecular weight of 615.62.
Uses
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 ).
Dosage
2 DOSAGE AND ADMINISTRATION • 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) ].
Side Effects
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 ).
Interactions
7 DRUG INTERACTIONS • Strong CYP3A4 Inhibitors: Reduce INREBIC dose as recommended ( 2.3 , 7.1 ). • Strong and Moderate CYP3A4 Inducers: Avoid use of INREBIC ( 7.1 ). • CYP3A4, CYP2C19, or CYP2D6 Substrates: Dose modifications of substrates drugs may be needed ( 7.2 ). • OCT2 and MATE1/2-K Substrates: Dose modifications of substrate drugs may be needed ( 7.2 ). 7.1 Effect of Other Drugs on INREBIC Strong CYP3A4 Inhibitors Coadministration of INREBIC with a strong CYP3A4 inhibitor increases fedratinib exposure [see Clinical Pharmacology (12.3) ] . Increased exposure may increase the risk of adverse reactions. Consider alternative therapies that do not strongly inhibit CYP3A4 activity.
Warnings
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.
Pregnancy
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.
Storage
16.2 Storage Store below 30°C (86°F).
Frequently Asked Questions
What is Fedratinib Hydrochloride used for?▼
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 ).
What are the side effects of Fedratinib Hydrochloride?▼
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 ).
Can I take Fedratinib Hydrochloride during pregnancy?▼
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.
What are the important warnings for Fedratinib Hydrochloride?▼
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.
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Medical Disclaimer
This drug information is for educational purposes only and should not replace professional medical advice. Drug information is sourced from the FDA National Drug Code Directory and Structured Product Labeling. Always consult with a healthcare provider before starting, stopping, or changing any medication.