Home › NDC Lookup › Ingredients › Fedratinib Hydrochloride › 59572-0720-12
💊image loading
(from DailyMed)

Inrebic Fedratinib Hydrochloride 100 mg Capsule, 120-count

by Celgene Corporation · 120 CAPSULE in 1 BOTTLE, PLASTIC (59572-720-12)
NDC 59572-0720-12
🏷️ FDA NDC (as labeled) 59572-720-12 billing pads the product segment with a zero
Rx only Brand On market Non-controlled
🗂️ Data synced Aug 13, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

🆔 Identity & classification

FDA NDC (as labeled) 59572-720-12
Product NDC 59572-720
11-digit billing NDC 59572072012
NCPDP billing unit EA — each (per item)
RxCUI 2197495, 2197501
UNII UH9J2HBQWJ
Application # NDA212327
SPL Set ID f0f55a2a-4e0c-4cba-8571-03e1424486d7
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2019-08-16
Route ORAL
Dosage form CAPSULE
Substance FEDRATINIB HYDROCHLORIDE
GCN Seq No 080122
GCN 46818
HICL code 045953
Ingredient (HICL) Fedratinib Dihydrochloride
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1Q
Therapeutic class — specific (HIC3) Antineoplastic Systemic Enzyme Inhibitors
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name INREBIC 100 MG CAPSULE
FDB brand name Inrebic
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 59572-720-12 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 59572-0720-12. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Janus-associated kinase (JAK) inhibitors class.

Drug family (ATC) Janus-associated kinase (JAK) inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerCelgene Corporation
Application holderBRISTOL-MYERS SQUIBB CO
FDA applicationNDA212327 (NDA)
Labeler code59572
First marketedAug 2019
Product typeHuman Prescription Drug
Portfolio30 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name INREBIC 100 MG CAPSULE Ingredient Fedratinib Dihydrochloride
📖 What it is MedlinePlus · NLM

Fedratinib is used to treat certain types of myelofibrosis (MF; a cancer of the bone marrow in which the bone marrow is replaced by scar tissue and causes decreased blood cell production). Fedratinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Myelofibrosis is a type of bone marrow cancer where scar tissue builds up in the marrow, disrupting normal blood cell production and often causing an enlarged spleen, fatigue, and...
  • What exactly is myelofibrosis, and why was I prescribed Inrebic for it?
  • This is genuinely important — Inrebic has been linked to a serious, potentially fatal brain condition called Wernicke's encephalopathy, which is caused by a deficiency in thiamine...
  • Why do I have to take a vitamin B1 supplement every day with this medication?
📖 Read our full Fedratinib guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

🧪 Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII 1K09F3G675
    Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
  • UNII 2G86QN327L
    Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
  • UNII 7CV7WJK4UI
    Sodium stearyl fumarate is a synthetic compound made from stearyl alcohol and fumaric acid. It acts as a lubricant and glidant in tablets and capsules, helping ingredients flow smoothly during manufacturing and preventing sticking.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.

6 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $234.52 $28,141.97 / 120 capsules
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Inrebic 100 mgthis 59572-0720-12 Celgene 120 capsules — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

⏳ Availability & generic status

🏛️
2019
First FDA approval
Aug 2019
📍
2026
Currently FDA-listed
7 years listed
🛡️
2039
Latest patent/protection listed
not a guaranteed launch date
🔒No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Sep 2039. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Aug 16, 2019 RLD RS ⏳ ~13 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 10391094 — method of use (U-2607)
US 8138199 — method of use (U-2607)
US 11400092 — method of use (U-3409)
US 7825246 — drug substance
US 7528143 — drug substance
Exclusivity ODE-259
2019 2021 2023 2025 2027 2029 2031 2033 2035 2037 2039
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (5)
PatentTypeUse codeExpires
US 10391094 ↗ Method of use U-2607 Jun 4, 2032
US 8138199 ↗ Method of use U-2607 Jun 30, 2028
US 11400092 ↗ Method of use U-3409 Sep 24, 2039
US 7825246 ↗ Drug substance — Dec 16, 2026
US 7528143 ↗ Drug substance — Nov 16, 2031
FDA exclusivity
CodeWhat it grantsExpires
ODE-259Orphan Drug Exclusivity (7-year)Aug 16, 2026
Common questions
Is there a generic version of INREBIC 100 MG CAPSULE?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for INREBIC 100 MG CAPSULE. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Sep 2039 — an estimate, not a guaranteed launch date.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Inrebic — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Inrebic. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$11.19M
Claims incl. refills
512
Beneficiaries
211
Spend / beneficiary
$53,049.98
Spend / claim
$21,862.40
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Inrebic (this brand).

Top reported reactions

Diarrhoea143
Death139
Nausea118
Fatigue113
Vomiting71
Constipation59
Haemoglobin Decreased54

Reporter sex

0 reports

Serious outcomes

Death189
Life-threatening11
Disabling7
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 282 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
59572-0720-12 You're viewing this 120 CAPSULE in 1 BOTTLE, PLASTIC (59572-720-12) 2019-08-16 Active

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos — Not published for this NDC No photo available yet for this listing.
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 59572-720-12, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 59572-0720-12, written without dashes as 59572072012. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 59572-0720-12, the first segment (59572) is the labeler code FDA assigned to Celgene Corporation; the middle segment (0720) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (12) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Celgene Corporation. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Celgene Corporation is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide
🚨 Boxed Warning 211 words ▾

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. While on treatment all patients should receive prophylaxis with daily oral thiamine and should have thiamine levels assessed as clinically indicated. If encephalopathy is suspected, immediately discontinue INREBIC and initiate parenteral thiamine.

Monitor until symptoms resolve or improve and thiamine levels normalize [see Dosage and Administration (2.6) , Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . WARNING: ENCEPHALOPATHY INCLUDING WERNICKE'S See full prescribing information for complete boxed warning. 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.

While on treatment all patients should receive prophylaxis with daily oral thiamine and should have thiamine levels assessed as clinically indicated. If encephalopathy is suspected, immediately discontinue INREBIC and initiate parenteral thiamine. Monitor until symptoms resolve or improve and thiamine levels normalize.

( 2.6 , 5.1 , 6.1 ).

🎯 Indications and Usage 57 words ▾

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 and Administration ~3 min read ▾

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 ).

2.1Required 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) ].

2.2Recommended Dosage Conduct baseline testing of thiamine (Vitamin B1) levels prior to initiation of INREBIC [see Dosage and Administration (2.7) , Warnings and Precautions (5.1) ] . The recommended dosage of INREBIC is 400 mg taken orally once daily for patients with a baseline platelet count of greater than or equal to 50 × 10 9 /L. Modify the dose for patients using concomitant strong CYP3A4 inhibitors, and in patients with severe renal impairment (creatinine clearance (CL cr ) 15 mL/min to 29 mL/min) [see Dosage and Administration (2.4 , 2.5) ] .

Patients that are on treatment with ruxolitinib before the initiation of INREBIC must taper and discontinue according to the ruxolitinib prescribing information. Administration Information: • INREBIC may be taken with or without food. Administration with a high fat meal may reduce the incidence of nausea and vomiting. • If a dose of INREBIC is missed, the next scheduled dose should be taken the following day. • For patients who have difficulty swallowing capsule(s) whole or those with a nasogastric tube: o Open the capsule(s). o In a glass container, mix the content of the capsule(s) with approximately 180 mL of Ensure ® Plus liquid nutritional supplement [see Clinical Pharmacology (12.3) ] at room temperature [between 20°C to 25°C (68°F to 77°F)]. o Promptly administer the mixture orally or through a nasogastric tube (French size 14 or 16) within 2 hours of preparation. o If using a nasogastric tube, flush it with 60 mL of water after administering the mixture [see Clinical Pharmacology (12.3 )]. o Discard the prepared dose if not given within 2 hours.

2.3Monitoring for Safety Obtain the following blood tests prior to starting treatment with INREBIC, periodically during treatment, and as clinically indicated [see Warnings and Precautions (5.1 , 5.2 , 5.4 , 5.5) ]: • Thiamine (Vitamin B1) level • Complete blood count with platelets • Creatinine and BUN • Hepatic panel • Amylase and lipase

2.4Dose Modifications with Concomitant Use of Strong CYP3A4 Inhibitors Reduce INREBIC dose when administering with strong CYP3A4 inhibitors to 200 mg once daily. In cases where coadministration with a strong CYP3A4 inhibitor is discontinued, INREBIC dosage should be increased to 300 mg once daily during the first two weeks after discontinuation of the CYP3A4 inhibitor, and then to 400 mg once daily thereafter as tolerated [see Drug Interactions (7.1) ] .

2.5Dose Modifications for Severe Renal Impairment Reduce INREBIC dose to 200 mg once daily in patients with severe renal impairment (creatinine clearance (CL cr ) 15 mL/min to 29 mL/min as estimated by Cockcroft-Gault (C-G) equation).

2.6Dose Modifications for Adverse Reactions Modify dose for hematologic and nonhematologic adverse reactions per Table 1 and Table 2. Discontinue INREBIC in patients unable to tolerate a dose of 200 mg daily. See Warnings and Precautions for other mitigating strategies.

Table 1: Dose Modifications for Hematologic Adverse Reactions Hematologic Adverse Reactions Dose Reduction Grade 4 Thrombocytopenia or Grade 3 Thrombocytopenia with active bleeding Interrupt dose until resolved to Grade 2 or lower or baseline. Restart dose at 100 mg daily below the last given dose. Grade 4 Neutropenia Interrupt dose until resolved to Grade 2 or lowe…

💊 Dosage Forms and Strengths 27 words ▾

3 DOSAGE FORMS AND STRENGTHS Capsules: 100 mg, reddish brown, opaque size 0, printed with "FEDR 100 mg" in white ink. Capsules: 100 mg ( 3 ).

⛔ Contraindications 4 words ▾

4 CONTRAINDICATIONS None. None

⚠️ Warnings and Cautions ~3 min read ▾

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 ). • Secondary Malignancies: Monitor for development of secondary malignancies, particularly in patients who are current or past smokers ( 5.9 ). • Symptom Exacerbation Following Interruption or Discontinuation of Treatment: Manage with supportive care and consider resuming treatment with INREBIC ( 5.10 ).

5.1Encephalopathy, Including Wernicke's Serious and fatal encephalopathy, including Wernicke's encephalopathy, has occurred in INREBIC-treated patients. Serious cases were reported in 1.3% (8/608) of patients treated with INREBIC in clinical trials and 0.16% (1/608) of cases were fatal. Wernicke's encephalopathy is a neurologic emergency resulting from thiamine (Vitamin B1) deficiency.

Signs and symptoms of Wernicke's encephalopathy may include ataxia, mental status changes, and ophthalmoplegia (e.g., nystagmus, diplopia). Any change in mental status, confusion, or memory impairment should raise concern for potential encephalopathy, including Wernicke's, and prompt a full evaluation including a neurologic examination, assessment of thiamine levels, and imaging. Assess thiamine levels in all patients prior to starting INREBIC.

Do not start INREBIC in patients with thiamine deficiency. However, if thiamine levels are low, replete thiamine prior to starting treatment. While on treatment all patients should receive prophylaxis with oral thiamine and should have thiamine levels assessed as clinically indicated.

If encephalopathy is suspected, immediately discontinue INREBIC and initiate parenteral thiamine. Monitor until symptoms resolve or improve and thiamine levels normalize [see Dosage and Administration (2.7) and Adverse Reactions (6.1) ] .

5.2Anemia and Thrombocytopenia Treatment with INREBIC can cause anemia and thrombocytopenia. Anemia New or worsening Grade 3 anemia occurred in 34% of INREBIC-treated patients. The median time to onset of the first Grade 3 anemia was approximately 2 months, with 75% of cases occurring within 3 months.

Mean hemoglobin levels reached nadir after 12 to 16 weeks with partial recovery and stabilization after 16 weeks. Red blood cell transfusions were received by 51% of INREBIC-treated patients and permanent discontinuation of INREBIC occurred due to anemia in 1% of patients. Consider dose reduction for patients who become red blood cell transfusion dependent [see Dosage and Administration (2.6) ] .

Thrombocytopenia New or worsening Grade ≥3 thrombocytopenia during the randomized treatment period occurred in 12% of INREBIC-treated patients. The median time to onset of the first Grade 3 thrombocytopenia was approximately 1 month; with 75% of cases occurring within 4 months. Platelet transfusions were received by 3.1% of INREBIC-treated patients.

Permanent discontinuation of treatment due to thrombocytopenia and bleeding that required clinical intervention both occurred in 2.1% of INREBIC-treated patients. Obtain a complete blood count (CBC) at baseline, periodically during treatment, and as clinically indicated. For Grade 3 thrombocytopenia with active bleeding or Grade 4 thrombocytopenia, interrupt INREBIC until resolved to less than or equal to Grade 2 or baseline.

Restart dose at 100 mg daily below the last given dose and monitor platelets as clinically indicated [see Do…

🤒 Adverse Reactions ~3 min read ▾

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) ] • Symptom Exacerbation Following Interruption or Discontinuation of Treatment [see Warnings and Precautions (5.10) ] The most common adverse reactions (≥20%) are diarrhea, nausea, anemia, and vomiting ( 6.1 ).

To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in the WARNINGS AND PRECAUTIONS Section

5.1Encephalopathy, including Wernicke's, reflect exposure to INREBIC as a single agent in 608 patients who received more than one dose (ranging from 30 mg to 800 mg) in Studies JAKARTA, ARD11936, JAKARTA2, ARD12042, ARD12888, TED12037/TED12015, INT12497, and TES13519, of whom 459 were patients with myelofibrosis, including 97 patients previously treated with ruxolitinib. Among the 608 patients receiving INREBIC, the median drug exposure was 37 weeks and the median number of cycles initiated was 9 cycles. Fifty-nine percent of 608 patients were exposed for 6 months or longer and 39% were exposed for 12 months or longer.

Using the dataset described above, the most common adverse reactions in >20% of patients (N=608) were diarrhea, nausea, anemia, vomiting, fatigue, thrombocytopenia, and constipation. JAKARTA Trial The safety of INREBIC was evaluated in the randomized treatment period of the JAKARTA trial [see Clinical Studies (14) ] . Key eligibility criteria included adult patients with intermediate-2 or high-risk primary MF or post-PV MF or post-ET MF with splenomegaly, platelet count ≥50 × 10 9 /L, and no splenectomy.

Patients received INREBIC at 400 mg daily (n=96) or placebo (n=95). Among patients receiving INREBIC, 82% were exposed for more than 6 months and 65% for more than one year. Patients had a median duration of exposure to INREBIC 400 mg daily of 15.5 months compared with placebo where patients were treated for 6 months or until disease progression after which patients were allowed to crossover to active treatment.

The median age of patients who received INREBIC was 65 years (range: 27 to 86 years), 59% were male, 90% were White, 8% were Asian, 1% were Black, 1% were Other, and 92% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Serious adverse reactions occurred in 21% of INREBIC-treated patients. Serious adverse reactions in ≥2% of patients receiving INREBIC 400 mg daily included cardiac failure (5%) and anemia (2%).

Fatal adverse reactions of cardiogenic shock occurred in 1% of patients receiving INREBIC 400 mg daily. Permanent discontinuation due to an adverse reaction occurred in 14% of patients receiving INREBIC. Most frequent reasons for permanent discontinuation in ≥2% of patients receiving INREBIC included cardiac failure (3%), thrombocytopenia, myocardial ischemia, diarrhea, and increased blood creatinine (2% each).

Dosage interruptions due to an adverse reaction during the randomized treatment period occurred in 21% of patients who received INREBIC. Adverse reactions requiring dosage interruption in >3% of patients who receiv…

🔄 Drug Interactions ~2 min read ▾

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 ).

7.1Effect 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.

Alternatively, reduce the dose of INREBIC when administering with a strong CYP3A4 inhibitor [see Dosage and Administration (2.4) ] . Strong and Moderate CYP3A4 Inducers Coadministration of INREBIC with a strong or moderate CYP3A4 inducer can decrease fedratinib exposure [see Clinical Pharmacology (12.3) ] . Decreased exposure may reduce the effectiveness of INREBIC.

Avoid INREBIC with strong and moderate CYP3A4 inducers. Dual CYP3A4 and CYP2C19 Inhibitors Coadministration of INREBIC with a dual CYP3A4 and CYP2C19 inhibitor increases fedratinib exposure [see Clinical Pharmacology (12.3) ] . Increased exposure may increase the risk of adverse reactions.

Due to potential increase of exposure, patients taking concomitant dual CYP3A4 and CYP2C19 inhibitors require more intensive safety monitoring and, if necessary, dose modifications of INREBIC based on adverse reactions [see Dosage and Administration (2.6) ] .

7.2Effect of INREBIC on Other Drugs CYP3A4, CYP2C19, or CYP2D6 Substrate Drugs Coadministration of INREBIC with drugs that are CYP3A4 substrates, CYP2C19 substrates, or CYP2D6 substrates increases the concentrations of these drugs, which may increase the risk of adverse reactions of these drugs [see Clinical Pharmacology (12.3) ] . Monitor for adverse reactions and adjust the dose of drugs that are CYP3A4, CYP2C19, or CYP2D6 substrates as necessary when coadministered with INREBIC. OCT2 and MATE1/2-K Substrate Drugs Coadministration of INREBIC with drugs that are renally excreted via organic cation transporter (OCT2) and multidrug and toxin extrusion (MATE)1/2-K can decrease renal clearance of those drugs [see Clinical Pharmacology (12.3) ] .

Monitor for adverse reactions and consider dose modifications for drugs that are renally excreted via OCT2 or MATE1/2-K (e.g., metformin), as necessary when coadministered with INREBIC.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS • Lactation: Advise not to breastfeed ( 8.2 ).

8.1Pregnancy 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.

The background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal Data In an embryo-fetal development study in pregnant rats, fedratinib administration at a dose of 30 mg/kg/day during organogenesis (gestation days 6 to 17) was associated with adverse developmental outcomes including skeletal variations (such as additional ossification center of neuronal arches). These effects occurred in rats at approximately 0.1 times the clinical exposure based on AUC at the recommended daily dose. At lower doses of 10 mg/kg/day (0.01 times the clinical exposure at the recommended daily dose), fedratinib administered to pregnant rats resulted in maternal toxicity of decreased gestational weight gain.

In an embryo-fetal development study in pregnant rabbits, fedratinib administration during organogenesis (gestation Days 6 to 18) did not produce developmental or maternal toxicity at doses up to the highest dose level tested, 30 mg/kg/day (approximately 0.08 times the clinical exposure at the recommended daily dose). In a separate study, administration of 80 mg/kg/day fedratinib to rabbits resulted in maternal mortality. In a pre- and postnatal study in rats, fedratinib was administered to pregnant female rats at doses of 3, 10, or 30 mg/kg/day from Day 6 of gestation through Day 20 of lactation, with weaning on Day 21.

A slight decrease in maternal body weight gain during gestation occurred at 30 mg/kg/day. The offspring from the high dose (30 mg/kg) had decreased body weight preweaning in both sexes and postweaning through the maturation phase in males. These effects occurred at exposures approximately 0.1 times the clinical exposure at the recommended daily dose.

8.2Lactation Risk Summary There are no data on the presence of fedratinib or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise patients not to breastfeed during treatment with INREBIC, and for at least 1 month after the last dose.

8.4Pediatric Use The safety and effectiveness of INREBIC in pediatric patients have not been established.

8.5Geriatric Use Of the total number of patients with myelofibrosis who received an INREBIC dose of 400 mg in the clinical studies, 47.3% were greater than 65 years of age and 12.3% were greater than 75 years of age. No overall differences in safety or effectiveness of INREBIC were observed between these patients and younger patients.

8.6Renal Impairment Reduce INREBIC dose when administered to patients with severe renal impairment (CL cr 15 mL/min to 29 mL/min by Cockcroft-Gault) [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] . No modification of the starting dose is recommended for patients with mild to moderate renal impairment (CL cr 30 mL/min to 89 mL/min by Cockcroft-Gault). Due to potential increase of exposure, patients with preexisting moderate renal impairment require more intensive safety monitoring, and if necess…

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy 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.

The background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal Data In an embryo-fetal development study in pregnant rats, fedratinib administration at a dose of 30 mg/kg/day during organogenesis (gestation days 6 to 17) was associated with adverse developmental outcomes including skeletal variations (such as additional ossification center of neuronal arches). These effects occurred in rats at approximately 0.1 times the clinical exposure based on AUC at the recommended daily dose. At lower doses of 10 mg/kg/day (0.01 times the clinical exposure at the recommended daily dose), fedratinib administered to pregnant rats resulted in maternal toxicity of decreased gestational weight gain.

In an embryo-fetal development study in pregnant rabbits, fedratinib administration during organogenesis (gestation Days 6 to 18) did not produce developmental or maternal toxicity at doses up to the highest dose level tested, 30 mg/kg/day (approximately 0.08 times the clinical exposure at the recommended daily dose). In a separate study, administration of 80 mg/kg/day fedratinib to rabbits resulted in maternal mortality. In a pre- and postnatal study in rats, fedratinib was administered to pregnant female rats at doses of 3, 10, or 30 mg/kg/day from Day 6 of gestation through Day 20 of lactation, with weaning on Day 21.

A slight decrease in maternal body weight gain during gestation occurred at 30 mg/kg/day. The offspring from the high dose (30 mg/kg) had decreased body weight preweaning in both sexes and postweaning through the maturation phase in males. These effects occurred at exposures approximately 0.1 times the clinical exposure at the recommended daily dose.

🧒 Pediatric Use 16 words ▾

8.4Pediatric Use The safety and effectiveness of INREBIC in pediatric patients have not been established.

🧓 Geriatric Use 57 words ▾

8.5Geriatric Use Of the total number of patients with myelofibrosis who received an INREBIC dose of 400 mg in the clinical studies, 47.3% were greater than 65 years of age and 12.3% were greater than 75 years of age. No overall differences in safety or effectiveness of INREBIC were observed between these patients and younger patients.

🆘 Overdosage 18 words ▾

10 OVERDOSAGE Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism 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). Fedratinib is a JAK2-selective inhibitor with higher inhibitory activity for JAK2 over family members JAK1, JAK3 and TYK2. Abnormal activation of JAK2 is associated with myeloproliferative neoplasms (MPNs), including myelofibrosis and polycythemia vera.

In cell models expressing mutationally active JAK2 V617F or FLT3 ITD , fedratinib reduced phosphorylation of signal transducer and activator of transcription (STAT3/5) proteins, inhibited cell proliferation, and induced apoptotic cell death. In mouse models of JAK2 V617F -driven myeloproliferative disease, fedratinib blocked phosphorylation of STAT3/5, and improved survival, white blood cell counts, hematocrit, splenomegaly, and fibrosis.

12.2Pharmacodynamics Fedratinib inhibited cytokine-induced STAT3 phosphorylation in whole blood from patients with myelofibrosis. The inhibition of STAT3 phosphorylation was maximal approximately 2 hours after the first dose, with values returning to near baseline at 24 hours. After daily administration of fedratinib, levels of inhibition at steady state PK were similar to the maximal inhibition reached after the first dose of 300 (0.75 times the recommended dose), 400 or 500 mg (1.25 times the recommended dose) of fedratinib.

Cardiac Electrophysiology The potential for QTc prolongation with fedratinib was evaluated in 31 patients with solid tumors. No large mean increase in the QTc interval (>20 ms) was detected with daily dosing of fedratinib 500 mg (1.25 times the recommended dose) for 14 days.

12.3Pharmacokinetics INREBIC at 300 mg to 500 mg once daily (0.75 to 1.25 times the recommended dose) results in a dose proportional increase in geometric mean fedratinib peak concentrations (C max ) and the area under the plasma concentration time curve over the dosing interval (AUC tau ). The mean steady state levels are achieved within 15 days of daily dosing. The mean accumulation ratio ranged between 3- to 4-fold.

At the dose of 400 mg once daily, the geometric mean (coefficient of variation, %CV) fedratinib C max is 1804 ng/mL (49%) and AUC tau is 26870 ng.hr/mL (43%) in patients with myelofibrosis. Absorption Following 400 mg once daily, fedratinib median time to peak concentrations (T max ) at steady-state is 3 hours (range: 2 to 4 hours). Following the administration of a single 400 mg dose of fedratinib delivered orally or via nasogastric tube with contents from four 100-mg capsules dispersed in approximately 180 mL nutritional supplement (Ensure ® Plus), the systemic exposures of fedratinib are similar.

Effect of Food A low-fat, low-calorie (total 162 calories: 6% from fat, 78% from carbohydrate and 16% from protein) or a high-fat, high-calorie (total 815 calories: 52% from fat, 33% from carbohydrate and 15% from protein) meal increased area under the curve over time to infinity (AUC inf ) up to 24% and C max up to 14% of a single 500 mg dose (1.25 times the recommended dose) of fedratinib. Distribution The apparent volume of distribution of fedratinib at steady-state is 1770 L in patients with myelofibrosis at 400 mg once daily dose.

Fedratinib is 92% or greater bound to human plasma proteins. Elimination Fedratinib pharmacokinetics is characterized by a biphasic disposition with an effective half-life of 41 hours, a terminal half-life of approximately 114 hours, and apparent clearance (CL/F) (%CV) of 13 L/hr (51%) in patients with myelofibrosis. Metabolism Fedratinib is metabolized by CYP3A4, CYP2C19, and flavin-containing monooxygenase 3 (FMO3).

Fedratinib accounts for approximately 80% of total circulating drug in plasma after oral administration. Excretion Following a single oral dose of radiolabeled fedratinib, 77% (23% unchanged) of the administered dose was excreted in feces and 5% (3% unchanged) was eliminated in…

🧬 Mechanism of Action 119 words ▾

12.1Mechanism 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). Fedratinib is a JAK2-selective inhibitor with higher inhibitory activity for JAK2 over family members JAK1, JAK3 and TYK2. Abnormal activation of JAK2 is associated with myeloproliferative neoplasms (MPNs), including myelofibrosis and polycythemia vera.

In cell models expressing mutationally active JAK2 V617F or FLT3 ITD , fedratinib reduced phosphorylation of signal transducer and activator of transcription (STAT3/5) proteins, inhibited cell proliferation, and induced apoptotic cell death. In mouse models of JAK2 V617F -driven myeloproliferative disease, fedratinib blocked phosphorylation of STAT3/5, and improved survival, white blood cell counts, hematocrit, splenomegaly, and fibrosis.

📦 How Supplied / Storage and Handling 40 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied INREBIC (fedratinib) 100 mg capsules: Reddish brown, opaque, size 0 capsule, printed with "FEDR 100 mg" in white ink. • Bottles of 120 capsules (NDC 59572-720-12)

16.2Storage Store below 30°C (86°F).

📦 Storage and Handling 6 words ▾

16.2Storage Store below 30°C (86°F).

📋 Description 117 words ▾

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. Fedratinib exhibits pH-dependent aqueous solubility; it is freely soluble in the acidic condition (>100 mg/mL at pH 1) and practically insoluble in the neutral condition (4 mcg/mL at pH 7.4).

The chemical structure is: INREBIC (fedratinib) is available as 100-mg (equivalent to 117.3 mg of fedratinib dihydrochloride monohydrate) hard gelatin capsules for oral administration. Each capsule contains inactive ingredients of silicified microcrystalline cellulose and sodium stearyl fumarate. The capsule shell contains gelatin, red iron oxide, titanium dioxide and white ink. inrebic-chem-structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Discuss the following with patients prior to and during treatment with INREBIC. Encephalopathy, including Wernicke's Advise patients that serious and fatal encephalopathy, including Wernicke's, has occurred in patients taking INREBIC.

Wernicke's encephalopathy is a neurological emergency resulting from acute thiamine (Vitamin B1) deficiency. Advise patients of the need to monitor thiamine levels [see Dosage and Administration (2.1 , 2.3 , 2.7) , and Warnings and Precautions (5.1) ] . Instruct patients that they should receive prophylaxis with thiamine 100 mg orally daily while taking INREBIC [see Dosage and Administration (2.7) ] .

Advise patients to seek emergency medical attention for any change in mental status such as confusion, drowsiness or memory impairment, cerebellar abnormalities such as ataxia, and ophthalmic abnormalities such as diplopia and nystagmus. Advise patients to contact their healthcare provider right away if they experience nausea, vomiting, diarrhea, and weight loss unresponsive to treatment resulting in malnutrition and lower thiamine levels, which may lead to Wernicke's encephalopathy [see Boxed Warning and Warnings and Precautions (5.1) ].

Anemia and Thrombocytopenia Advise patients that INREBIC is associated with anemia and thrombocytopenia, and of the need to monitor complete blood counts before and during treatment [see Warnings and Precautions (5.2) ] . Symptom Exacerbation Following Interruption or Discontinuation of Treatment with INREBIC Inform patients that after discontinuation of treatment, signs and symptoms from myeloproliferative neoplasms may return. Instruct patients not to interrupt or discontinue INREBIC therapy without consulting their healthcare provider [see Warnings and Precautions (5.10) ] Gastrointestinal Toxicity Advise patients to contact their healthcare provider if they experience intractable diarrhea, nausea, or vomiting.

Prescribers should advise patients of the potential complications of severe diarrhea, nausea, or vomiting [see Warnings and Precautions (5.3) ]. Hepatic Toxicity Advise patients that INREBIC may increase liver enzymes and of the need to monitor liver enzyme levels [see Warnings and Precautions (5.4) ]. Amylase and Lipase Elevation Advise patients that INREBIC may increase amylase and lipase and of the need to monitor amylase and lipase [see Warnings and Precautions (5.5) ].

Uveitis Advise patients that INREBIC can cause uveitis and to contact their healthcare provider if they experience any symptoms, including eye pain, redness, photophobia, floaters, and decreased vision [see Warnings and Precautions (5.6) ]. Major Adverse Cardiac Events (MACE) Advise patients that events of major adverse cardiac events (MACE) including myocardial infarction, stroke, and cardiovascular death, have been reported in clinical studies with another JAK-inhibitor used to treat rheumatoid arthritis, a condition for which INREBIC is not indicated.

Advise patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions (5.6) ] . Thrombosis Advise patients that events of DVT and PE have been reported in clinical studies with another JAK-inhibitor used to treat rheumatoid arthritis, a condition for which INREBIC is not indicated. Advise patients to tell their healthcare provider if they develop any signs or symptoms of a DVT or PE [see Warnings and Precautions (5.7) ] .

Secondary Malignancies Advise patients, especially current or past smokers and patients with a known secondary malignancy (other than a successfully treated NMSC), that lymphoma and other malignancies (excluding NMSC) have been reported in clinical studies with another JAK-inhibitor used to treat rheumatoid arthritis, a condition for which INREBIC is not indicated…

💬 Medication Guide ~3 min read ▾

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 3/2026 MEDICATION GUIDE INREBIC ® (inn-REH-bik) (fedratinib) capsules, for oral use What is the most important information I should know about INREBIC?

INREBIC may cause serious side effects, including: • Encephalopathy (including Wernicke's encephalopathy). A serious and sometimes fatal neurological problem called encephalopathy (including Wernicke's encephalopathy) has happened in some people who take INREBIC. Wernicke’s encephalopathy is a neurologic emergency that can happen if you do not have enough Vitamin B1 (thiamine) in your body.

Your healthcare provider will do a blood test to check your Vitamin B1 level and treat you with Vitamin B1 if your level is too low before starting treatment with INREBIC. Your healthcare provider may also check your Vitamin B1 level during treatment with INREBIC. You should take a Vitamin B1 supplement (100 mg of thiamine) daily during treatment with INREBIC.

Your healthcare provider may tell you to stop taking INREBIC if you develop side effects during treatment with INREBIC. Get emergency medical help right away if you develop the following: o confusion, memory problems or drowsiness o problems with balance and movement, such as difficulty walking o eye problems, such as double or blurred vision or abnormal eye movements Call your healthcare provider right away if you experience diarrhea, nausea, vomiting, and weight loss that does not get better with treatment. See “What are the possible side effects of INREBIC” for more information about side effects .

What is INREBIC? INREBIC is a prescription medicine used to treat adults with certain types of myelofibrosis (MF). It is not known if INREBIC is safe and effective in children.

Before taking INREBIC, tell your healthcare provider about all your medical conditions, including if you: • have low Vitamin B1 (thiamine) levels • have low red blood cell or platelet counts • have or have had liver problems • have or have had kidney problems • are a current or past smoker • have had a blood clot, heart attack, other heart problems, or stroke • have or have had any other cancer • are pregnant or plan to become pregnant. It is not known if INREBIC may harm your unborn baby. • are breastfeeding or plan to breastfeed.

It is not known if INREBIC passes into your breast milk. You should not breastfeed during treatment with INREBIC and for at least 1 month after your last dose. Talk to your healthcare provider about the best way to feed your baby during treatment with INREBIC.

Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking INREBIC with certain other medicines may cause side effects from INREBIC or from the other medicine and may affect the way that INREBIC works. Know the medicines you take.

Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I take INREBIC? • Take INREBIC exactly as your healthcare provider tells you to. • Do not change your dose or stop taking INREBIC unless your healthcare provider tells you to. If you stop treatment with INREBIC, symptoms of your condition may return.

See “What are the possible side effects of INREBIC?” • Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with INREBIC if you develop side effects. • Take INREBIC 1 time each day. • Take INREBIC with or without food. Taking INREBIC with a high fat meal may help to reduce nausea and vomiting symptoms. • Take Vitamin B1 (thiamine 100 mg) by mouth daily to prevent low Vitamin B1 levels during treatment with INREBIC. • If you miss a dose of INREBIC, skip the missed dose and take your usual dose the next day at your regularly scheduled time.

Do not take 2 doses to make up for the missed dose. • If you cannot swallow INREBIC capsules whole or have a nasogastric tube, the capsu…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
← 59572-0711-01 · Celgene 59572-0730-07 · Celgene →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.