Fedratinib

INREBIC

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Pronunciation: fed-RA-ti-nib (in-RE-bik)

Fedratinib ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Fedratinib ballicule

Fedratinib INREBIC mascot mnemonic cartoon — Visual mnemonic: Fedratinib mascot
**“Fed-Rat nibbler In Rubik”**
jack → JAK inhibitor

What it isOral JAK2-selective inhibitor with FLT3 activity, for intermediate-2 and high-risk myelofibrosis.

Why this oneIt retains activity in patients who have failed or cannot tolerate ruxolitinib, which was the only prior option in that setting.

What limits itBoxed encephalopathy warning includes Wernicke encephalopathy: check and replete thiamine before and during treatment. Anemia, thrombocytopenia and GI toxicity also occur.

Fedratinib molecular structure (skeletal formula) — Molecular structure: Fedratinib

Fedratinib prescription history

Animated chart of estimated U.S. prescriptions per year, Tyrosine kinase inhibitors (2001–2026). Fedratinib enters in 2019 (estimated).

FDA-approved for

intermediate-2 or high-risk myelofibrosis

Off-label

post-polycythemia vera and post-essential thrombocythemia myelofibrosis

Classes and tags

Clinical profile

Therapeutic safety burden4 / 4

Overdose danger1 / 4

Weight-gain liability1 / 4

Sedation liability0 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryN/A (post-2015 labeling)

Defining liabilityEncephalopathy, myelosuppression and gastrointestinal toxicity

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Serious and fatal encephalopathy including Wernicke's: assess thiamine before starting; do not start if thiamine-deficient (replete first); daily oral thiamine prophylaxis on treatment; if encephalopathy suspected, discontinue immediately and give parenteral thiamine

FDA dosing	Population	Start	Target	Max
Myelofibrosis (baseline platelets >=50 × 10^9/L)	Adults	400 mg QD	400 mg QD	400 mg QD

Renal Severe (CLcr 15–29 mL/min): reduce to 200 mg QD; mild-moderate (CLcr 30–89): no starting-dose change, but moderate impairment needs more intensive monitoring with dose modification as needed

Hepatic Undefined

Adverse-reaction dose modifications: Grade 4 thrombocytopenia/neutropenia or Grade >=3 GI toxicity/LFT elevation — interrupt, restart 100 mg below last dose; recurrent Grade >=3 LFT elevation — discontinue

Instructions

With or without food; high-fat meal may reduce nausea/vomiting
All patients: thiamine 100 mg PO daily prophylaxis; check thiamine at baseline and as indicated
Baseline and periodic: CBC with platelets, creatinine/BUN, hepatic panel, amylase/lipase
Missed dose: take next scheduled dose the following day
Swallowing difficulty/NG tube: disperse capsule contents in ~180 mL Ensure Plus; give within 2 h; flush NG tube with 60 mL water
Taper and discontinue ruxolitinib per its labeling before starting
Strong CYP3A4 inhibitor: reduce to 200 mg QD (on inhibitor stop: 300 mg QD ×2 weeks, then 400 mg QD)
Discontinue if unable to tolerate 200 mg QD

Available strengths

cap 100 mg

Cautions

Encephalopathy including Wernicke's (boxed): thiamine assessment/prophylaxis mandatory
Anemia (Grade 3 new/worsening in 34%) and thrombocytopenia: manage with dose reduction, interruption, or transfusion
GI toxicity (severe diarrhea/nausea/vomiting): antiemetic prophylaxis and antidiarrheals recommended
Hepatic toxicity: dose reduce/interrupt
Amylase/lipase elevation
Uveitis: refer for ophthalmological evaluation if symptoms
Major adverse cardiac events (MACE)
Thrombosis
Secondary malignancies (esp. current/past smokers)
Symptom exacerbation after interruption/discontinuation

Adverse reactions

Diarrhea
Nausea
Anemia
Vomiting

Pregnancy No human data; adverse developmental outcomes in rats below human dose; weigh benefit/risk

Lactation Do not breastfeed during treatment and for at least 1 month after last dose

Cost

Fedratinib (INREBIC)

Strength		#/mo	generic $/mo	CostPlus
100 mg	cap	30 qd		not offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Fedratinib is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

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Self-check

Which vitamin must be checked and repleted with fedratinib?
Thiamine.
Which encephalopathy is boxed for fedratinib?
Wernicke encephalopathy.