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INREBIC is a brand name for Fedratinib, supplied as a capsule. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: INREBIC® (fedratinib) is indicated for: • the treatment of splenomegaly and/or disease related symptoms in adult patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis, including patients who have been previously exposed to…
Verbatim from this product's HC label. Tap a section to expand.
4 Drug-Drug Interactions, Strong CYP3A4 inhibitors; Moderate CYP3A4 inhibitors; Dual CYP2C19 and CYP3A4 moderate inhibitors 07/2024 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed.
RECENT MAJOR LABEL CHANGES ............................................................................... 2 TABLE OF CONTENTS ...................................................................................................... 2 PART I: HEALTH PROFESSIONAL INFORMATION ......................................................
5 1 INDICATIONS ........................................................................................................... 5 2 CONTRAINDICATIONS ...........................................................................................
5 3 SERIOUS WARNINGS AND PRECAUTIONS BOX.............................................. 5 4 DOSAGE AND ADMINISTRATION ........................................................................ 8 5 OVERDOSAGE.........................................................................................................
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). 1 Dosing Considerations • Renal Impairment: No starting dose adjustment is necessary for patients with mild to moderate renal impairment. Due to potential increase of exposure, patients with pre-existing moderate renal impairment require more intensive safety monitoring, and if necessary, dose modifications based on adverse reactions.
In patients with severe renal impairment INREBIC® (fedratinib) Page 6 of 40 (creatinine clearance (CRcl) 15 mL/min to 29 mL/min), reduce the INREBIC dose to 200 mg once daily. • Hepatic Impairment: No starting dose adjustment is necessary for patients with mild to moderate hepatic impairment.
Due to potential increase of exposure, patients with pre-existing moderate hepatic impairment require more intensive safety monitoring, and if necessary, dose modifications based on adverse reactions. INREBIC pharmacokinetics have not been evaluated in patients with severe hepatic impairment.
Avoid use of INREBIC in subjects with severe hepatic impairment (Child-Pugh class C or total bilirubin >3 times ULN and any AST) (see 10 CLINICAL PHARMACOLOGY). 2 Recommended Dose and Dosage Adjustment The recommended dose of INREBIC is 400 mg taken orally once daily for patients with a baseline platelet count of ≥50 x 109/L.
A complete blood count should be obtained prior to starting treatment with INREBIC and during treatment as clinically indicated (see 7 WARNINGS AND PRECAUTIONS, Hematologic). Fedratinib has not been studied in patients with a baseline platelet count less than 50 x 109/L.
Patients receiving treatment with ruxolitinib before the initiation of INREBIC must taper and discontinue ruxolitinib according to the ruxolitinib prescribing information. Modify dose for hematologic and non-hematologic toxicities per Table 1 and Table 2.
Discontinue INREBIC in patients who are unable to tolerate a dose of 200 mg daily. Table 1 Dosage Reductions for Hematologic Toxicities Hematologic Toxicity Dose Reduction Grade 3 Thrombocytopenia with active bleeding or Grade 4 Thrombocytopenia Interrupt INREBIC dose until resolved to Grade ≤ 2 or baseline.
4 Drug-Drug Interactions, Strong CYP3A4 inhibitors; Moderate CYP3A4 inhibitors; Dual CYP2C19 and CYP3A4 moderate inhibitors 07/2024 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed.
RECENT MAJOR LABEL CHANGES ............................................................................... 2 TABLE OF CONTENTS ...................................................................................................... 2 PART I: HEALTH PROFESSIONAL INFORMATION ......................................................
5 1 INDICATIONS ........................................................................................................... 5 2 CONTRAINDICATIONS ...........................................................................................
5 3 SERIOUS WARNINGS AND PRECAUTIONS BOX.............................................. 5 4 DOSAGE AND ADMINISTRATION ........................................................................ 8 5 OVERDOSAGE.........................................................................................................
8 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ............. 8 INREBIC® (fedratinib) Page 3 of 40 7 WARNINGS AND PRECAUTIONS ......................................................................... 12 8 ADVERSE REACTIONS ........................................................................................
16 9 DRUG INTERACTIONS ......................................................................................... 20 10 CLINICAL PHARMACOLOGY .............................................................................. 21 11 STORAGE, STABILITY AND DISPOSAL ............................................................
22 12 SPECIAL HANDLING INSTRUCTIONS ............................................................... 22 PART II: SCIENTIFIC INFORMATION ............................................................................ 23 13 PHARMACEUTICAL INFORMATION ..................................................................
• INREBIC is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
Restart dose at 100 mg daily below the last given dose. Grade 4 Neutropenia Interrupt INREBIC dose until resolved to Grade ≤ 2 or baseline. Restart dose at 100 mg daily below the last given dose. Granulocyte growth factors may be used at the physician’s discretion.
Grade ≥ 3 anemia, transfusion indicated Interrupt INREBIC dose until resolved to Grade ≤ 2 or baseline. Restart dose at 100 mg daily below the last given dose. Consider dose reductions for patients who become transfusion-dependent during treatment with INREBIC.
Table 2 Dosage Reductions for Non-Hematologic Toxicities Adverse Reaction Recommended Action Grade ≥ 3 Nausea, Vomiting, or Diarrhea not responding to supportive measures within 48 hours Interrupt INREBIC dose until resolved to Grade ≤ 1 or baseline.
Restart dose at 100 mg daily below the last given dose. INREBIC® (fedratinib) Page 7 of 40 Grade ≥ 3 ALT, AST, or Bilirubin Interrupt INREBIC dose until resolved to Grade ≤ 1 or baseline. Restart dose at 100 mg daily below the last given dose.
Monitor ALT, AST, and bilirubin (total and direct) every 2 weeks for at least 3 months following the dose reduction. If re-occurrence of a Grade 3 or higher elevation, discontinue treatment with INREBIC. Grade ≥ 3 Other Non-Hematologic Toxicities Interrupt INREBIC dose until resolved to Grade ≤ 1 or baseline.
Restart dose at 100 mg daily below the last given dose. Dose Re-Escalation Following Dose Reduction for Adverse Drug Reactions If the adverse reaction due to INREBIC that resulted in a dose reduction is under effective management with the toxicity resolved for at least 28 days, the dose level may be re-escalated to one dose level higher per month up to the original dose level.
Dose re-escalation is not recommended if the dose reduction was due to a Grade 4 non-hematologic toxicity, Grade ≥ 3 ALT, AST, or total bilirubin elevation, or reoccurrence of a Grade 4 hematologic toxicity. Management of Thiamine Levels and Wernicke’s Encephalopathy (WE) Assess thiamine levels prior to starting INREBIC.
Do not start INREBIC treatment in patients with thiamine deficiency; replete thiamine prior to treatment initiation if thiamine levels are low. While on treatment all patients should receive prophylaxis with daily 100 mg oral thiamine and should have thiamine levels assessed as clinically indicated.
If Wernicke’s encephalopathy is suspected, immediately discontinue treatment with INREBIC and initiate parenteral thiamine treatment. Monitor until symptoms resolve or improve and thiamine levels normalize (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS).
Table 3 Management of Dose Modifications for Thiamine Levels and Wernicke’s Encephalopathy Thiamine Level Recommended Action For thiamine levels below the normal range but greater than or equal to 30 nmol/L without signs or symptoms of WE Interrupt INREBIC treatment.
Dose with daily 100 mg oral thiamine until thiamine levels are restored to normal range. Consider restarting INREBIC when thiamine levels are within normal range. For thiamine levels less than 30 nmol/L without signs or symptoms of WE Interrupt INREBIC treatment.
Immediate treatment with parenteral thiamine at therapeutic dosages until thiamine levels are restored to normal range. Consider restarting INREBIC when thiamine levels are within normal range. For signs or symptoms of WE regardless of thiamine levels Discontinue INREBIC treatment and immediately administer parenteral thiamine at therapeutic dosages.
INREBIC® (fedratinib) Page 8 of 40 Dose Modification with Concomitant Use of Strong CYP3A4 Inhibitors: Avoid strong CYP3A4 inhibitors. If concomitant strong CYP3A4 inhibitors cannot be avoided, reduce INREBIC dose to 200 mg. Patients should be carefully monitored weekly for safety.
In cases where co-administration with a strong CYP3A4 inhibitor is discontinued, increase INREBIC dose […]
23 14 CLINICAL TRIALS ................................................................................................. 23 INREBIC® (fedratinib) Page 4 of 40 15 MICROBIOLOGY....................................................................................................
32 16 NON-CLINICAL TOXICOLOGY […]