INREBIC Dosage & Rx Info | Uses, Side Effects

Inrebic Generic Name & Formulations

Legal Class

General Description

Fedratinib 100mg; caps.

Pharmacological Class

Kinase inhibitor.

How Supplied

Caps—120

Manufacturer

Celgene Corp

Generic Availability

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). In cell models, fedratinib reduced phosphorylation of signal transducer and activator of transcription (STAT3/5) proteins, inhibited cell proliferation, and induced apoptotic cell death.

Inrebic Indications

Indications

Treatment of intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF).

Inrebic Dosage and Administration

Adult

Baseline platelet count ≥50X10⁹/L: 400mg once daily. Given with a high fat meal may reduce nausea/vomiting. Concomitant strong CYP3A4 inhibitors: 200mg once daily; when CYP3A4 inhibitor discontinued: give 300mg once daily for the first 2 weeks, then 400mg once daily as tolerated. Severe renal impairment (CrCl 15–29mL/min): 200mg once daily. Dose modifications for adverse reactions: see full labeling.

Children

Not established.

Inrebic Contraindications

Not Applicable

Inrebic Boxed Warnings

Boxed Warning

Encephalopathy, including Wernicke’s.

Inrebic Warnings/Precautions

Warnings/Precautions

Risk of serious encephalopathy, including Wernicke’s; if suspected, immediately discontinue and initiate parenteral thiamine. Monitor until symptoms resolve and thiamine levels normalize. Do not start in thiamine deficiency; replete thiamine prior to treatment initiation. Risk of anemia, thrombocytopenia. Obtain thiamine levels, CBC with platelets, creatinine, BUN, hepatic panel, amylase, lipase, and nutritional status prior to initiation, during therapy, and as clinically indicated. Consider prophylaxis with anti-emetics (eg, 5-HT₃ antagonists) during therapy. Monitor for serious cardiovascular events, secondary malignancies. Evaluate and treat if thrombosis occurs. Current or past smokers. Severe or pre-existing moderate renal impairment. Severe hepatic impairment: avoid. Pregnancy. Nursing mothers: not recommended (during and for ≥1 month after the last dose).

Inrebic Pharmacokinetics

Absorption

Median time to peak concentrations at steady-state: 3 hours (range: 2 to 4 hours).

Distribution

Apparent volume of distribution at steady-state: 1770 L.
≥92% plasma protein bound.

Metabolism

CYP3A4, CYP2C19.

Elimination

Fecal (77%), renal (5%). Half-life: 114 hours.
Apparent clearance: 13 L/hr.

Inrebic Interactions

Interactions

Potentiated by strong CYP3A4 inhibitors; consider alternatives or reduce Inrebic dose (see Adult). Avoid concomitant strong or moderate CYP3A4 inducers, dual CYP3A4/CYP2C19 inhibitors. Potentiates CYP3A4, CYP2C19, or CYP2D6 substrates; monitor and adjust dose of these substrates. Decreased renal clearance of OCT2 and MATE1/2-K substrates (eg, metformin); monitor and consider dose modifications as needed.

Inrebic Adverse Reactions

Adverse Reactions

Diarrhea, nausea, anemia, vomiting; GI toxicity, hepatic toxicity, amylase/lipase elevation.

Inrebic Clinical Trials

See Literature

Inrebic Note