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Onureg azacitidine 300 mg Tablet, Film Coated, 14-count — NDC 59572-0740-14 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Onureg azacitidine 300 mg Tablet, Film Coated, 14-count — NDC 59572-740-14 (Billing 59572-0740-14)

by Celgene Corporation · 14 TABLET, FILM COATED in 1 BOTTLE

This is a package of 14 tablets of Onureg azacitidine 300 mg Tablet, Film Coated from Celgene Corporation, no longer marketed (first marketed Sep 2020), no longer in the FDA NDC Directory.

NDC 59572-0740-14
🏷️ FDA NDC (as labeled) 59572-740-14 billing pads the product segment with a zero
This package
Contains14-count Pack sizes2 compare ↓
Product page 59572-0740-07 Also comes in: 7 tablets 59572-740-07
Rx only Brand Discontinued Non-controlled ⚠ Discontinued by firm ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Jul 24, 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

NDC database record

One package, one record: these facts belong to NDC 59572-740-14 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
59572 labeler · 740 product · 14 package
Listing certified through
Dec 31, 2027
Billing quantity
14 EA per package
Barcode (UPC-A, from the NDC)
3 5957274014 3
FDA record last changed
Jul 24, 2026
⚠️
Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 59572-740-14
Product NDC 59572-740
11-digit billing NDC 59572074014
NCPDP billing unit EA — each (per item)
RxCUI 2396764, 2396770, 2396772, 2396774
UNII M801H13NRU
Application # NDA214120
SPL Set ID 0e95e33f-8aba-4f19-b332-2416580d358b
Established class (EPC) Nucleoside Metabolic Inhibitor
Mechanism of action Nucleic Acid Synthesis Inhibitors
DEA schedule Non-controlled
Marketing category NDA
Marketing status Discontinued
FDA listing status Discontinued by firm
Marketing start 2020-09-01
Route ORAL
Dosage form TABLET, FILM COATED
Substance AZACITIDINE

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 21300003000330
GPI class Onureg
GCN Seq No 081434
GCN 48540
HICL code 026361
Ingredient (HICL) Azacitidine
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1B
Therapeutic class — specific (HIC3) Antineoplastic - Antimetabolites
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name ONUREG 300 MG TABLET
FDB brand name Onureg
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 081434
  • GCN: 48540
  • GPI-14 (Medi-Span): 21300003000330
  • HICL (First Databank): 026361
  • AHFS class code: 10:00.00.00
  • RxCUI (RxNorm): 2396764
Why two NDCs? The FDA registers this code as 59572-740-14 — 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 → 59572-0740-14. 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 Nucleoside Metabolic Inhibitor class.

Pharmacologic class Nucleoside Metabolic Inhibitor
Drug family (ATC) Pyrimidine analogues
How it works Nucleic Acid Synthesis 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.

Clinical

Label name ONUREG 300 MG TABLET Ingredient Azacitidine
📗 Our plain-language guide HelloPharmacist
  • Yes, azacitidine is a type of cancer treatment, though it works a bit differently from traditional chemotherapy. Instead of just killing cancer cells outright, it also reprograms h...
  • What exactly is azacitidine treating — is it chemotherapy?
  • They contain the same active ingredient, but you absolutely cannot swap one for the other. Onureg tablets and the injectable forms are approved for completely different conditions,...
  • Can I take the Onureg tablet instead of getting injections — they're the same drug, right?
📖 Read our full Azacitidine 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.

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 · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Try another pack size: 7 tablets
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.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
59572-0740-07 59572-740-07 Main listing 7 TABLET, FILM COATED in 1 BLISTER PACK 2020-12-18 — Active
59572-0740-14 You're viewing this 14 TABLET, FILM COATED in 1 BOTTLE 2020-09-01 — Discontinued by firm

You're viewing the largest of 2 pack sizes for this product.

This pack shows little to no recent Medicaid volume — the 7 tablets pack carries most fills. See all packs ↓

Pack size FAQ

What quantity is in this package?
This is a 14-count package — 14 tablet, film coated in 1 bottle.
How does this package differ from NDC 59572-0740-07?
Both are Onureg azacitidine 300 mg Tablet, Film Coated — the drug itself is identical. This page's package is the 14-count one, while NDC 59572-0740-07 is the 7 tablets package.
What NDC number is used to bill for this package of Onureg azacitidine 300 mg Tablet, Film Coated?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Onureg 300 mgthis 59572-0740-14 Celgene 14 tablets — — Discontinued —
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

🏛️
2020
First FDA approval
Sep 2020
📍
2026
Currently FDA-listed
6 years listed
🛡️
2030
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 Jun 2030. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Sep 1, 2020 RLD RS ⏳ ~3.7 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 8846628 — method of use (U-2950)
US 8846628 — method of use (U-2950)
US 12053482 — method of use (U-2950)
US 12053482 — method of use (U-2950)
US 11571436 — drug product
US 11571436 — drug product
Exclusivity ODE-320
Exclusivity ODE-320
2020 2022 2024 2026 2028 2030
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 (6)
PatentTypeUse codeExpires
US 8846628 ↗ Method of use U-2950 Jun 3, 2030
US 8846628 ↗ Method of use U-2950 Jun 3, 2030
US 12053482 ↗ Method of use U-2950 May 14, 2029
US 12053482 ↗ Method of use U-2950 May 14, 2029
US 11571436 ↗ Drug product — May 14, 2029
US 11571436 ↗ Drug product — May 14, 2029
FDA exclusivity
CodeWhat it grantsExpires
ODE-320Orphan Drug Exclusivity (7-year)Sep 1, 2027
ODE-320Orphan Drug Exclusivity (7-year)Sep 1, 2027
Common questions
Is there a generic version of ONUREG 300 MG TABLET?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for ONUREG 300 MG TABLET. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Jun 2030 — 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.

What it looks like

Color Pink / Brown
ShapeOval
ImprintONU;300
Size17 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

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.

🧪 Avoiding an ingredient? See Azacitidine inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

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.

Manufacturer & labeler

LabelerCelgene Corporation
Application holderBRISTOL MYERS SQUIBB CO
FDA applicationNDA214120 (NDA)
Labeler code59572
First marketedSep 2020
Product typeHuman Prescription Drug
Portfolio30 products on file

More NDCs from Celgene Corporation labeler code 59572

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.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📚 References 📄 Patient Package Insert 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 93 words ▾

1 INDICATIONS AND USAGE ONUREG is indicated for continued treatment of adult patients with acute myeloid leukemia who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and are not able to complete intensive curative therapy. ONUREG is a nucleoside metabolic inhibitor indicated for continued treatment of adult patients with acute myeloid leukemia who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and are not able to complete intensive curative therapy ( 1 ).

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION • Do not substitute ONUREG for intravenous or subcutaneous azacitidine. The indications and dosing regimen for ONUREG differ from that of intravenous or subcutaneous azacitidine ( 2.1 , 5.1 ). • Administer ONUREG 300 mg orally once daily on Days 1 through 14 of each 28-day cycle ( 2.2 ). • Administer an antiemetic before each dose for at least the first 2 cycles ( 2.2 ).

2.1Important Administration Information Do not substitute ONUREG for intravenous or subcutaneous azacitidine. The indications and dosing regimen for ONUREG differ from that of intravenous or subcutaneous azacitidine [see Warnings and Precautions (5.1) ].

2.2Recommended Dosage The recommended dosage of ONUREG is 300 mg orally once daily with or without food on Days 1 through 14 of each 28-day cycle. Continue ONUREG until disease progression or unacceptable toxicity. Administer an antiemetic 30 minutes prior to each dose of ONUREG for the first 2 cycles. Antiemetic prophylaxis may be omitted after 2 cycles if there has been no nausea and vomiting. If the absolute neutrophil count (ANC) is less than

0.5Gi/L on Day 1 of a cycle, do not administer ONUREG. Delay the start of the cycle until the ANC is

0.5Gi/L or more. Instruct patients on the following: • Swallow tablets whole. Do not cut, crush, or chew the tablets. • Take a dose about the same time each day. • If a dose of ONUREG is missed, or not taken at the usual time, take the dose as soon as possible on the same day, and resume the normal schedule the following day.

Do not take 2 doses on the same day. • If a dose is vomited, do not take another dose on the same day. Resume the normal schedule the following day. ONUREG is a hazardous drug.

Follow applicable special handling and disposal procedures. 1

2.3Monitoring and Dosage Modifications for Adverse Reactions Monitor complete blood count every other week for the first 2 cycles and prior to the start of each cycle thereafter. Increase monitoring to every other week for the 2 cycles after any dose reduction for myelosuppression. The recommended dosage modifications for adverse reactions are provided in Table 1.

Table 1: Recommended Dosage Modifications for Adverse Reactions Adverse Reaction Severity Recommended Dosage Modification Myelosuppression [see Warnings and Precautions (5.2) ] Neutrophils less than

0.5Gi/L on Cycle Day 1 • Interrupt treatment. Resume at the same dose once neutrophils return to

0.5Gi/L or higher. Neutrophils less than 1 Gi/L with fever at anytime First Occurrence • Interrupt treatment. Resume at the same dose once neutrophils return to 1 Gi/L or higher.

Occurrence in 2 Consecutive Cycles • Interrupt treatment. After neutrophils return to 1 Gi/L or higher, resume at reduced dose of 200 mg. • If a patient continues to experience febrile neutropenia after dose reduction, reduce the treatment duration by 7 days. • If febrile neutropenia reoccurs after dose and schedule reduction, discontinue ONUREG. Platelets less than 50 Gi/L with bleeding First Occurrence • Interrupt dose.

Resume at the same dose once platelets return to 50 Gi/L or higher. Occurrence in 2 Consecutive Cycles • Interrupt dose. After platelets return to 50 Gi/L or higher, resume at reduced dose of 200 mg. • If a patient continues to experience thrombocytopenia with bleeding after dose reduction, reduce the treatment duration by 7 days. • If thrombocytopenia with bleeding reoccurs after dose and schedule reduction, discontinue ONUREG.

Gastrointestinal Toxicity [see Adverse Reactions (6.1) ] Grade 3 or 4 Nausea or Vomiting • Interrupt dose. Resume at the same dose once toxicity has resolved to Grade 1 or lower. • If toxicity reoccurs, interrupt dose until resolved to Grade 1 or lower. Resume at reduced dose of 200 mg. • If a patient continues to experience the toxicity after dose reduction, reduce the treatment duration by 7 days. • If the toxicity continues or reoccurs after dose and schedule reduction, discontinue ONUREG.

Grade 3 or 4 Diarr… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 53 words ▾

3 DOSAGE FORMS AND STRENGTHS Tablets: • 200 mg, pink, oval, film-coated tablet with debossed "200" on one side and "ONU" on the other side. • 300 mg, brown, oval, film-coated tablet with debossed "300" on one side and "ONU" on the other side. Tablets: 200 mg and 300 mg ( 3 ).

⛔ Contraindications 37 words ▾

4 CONTRAINDICATIONS ONUREG is contraindicated in patients with known severe hypersensitivity to azacitidine or its components [see Adverse Reactions (6.2) , Description (11) ] . History of severe hypersensitivity to azacitidine or its components ( 4 ).

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS • Risks of Substitution with Other Azacitidine Products : Do not substitute ONUREG for intravenous or subcutaneous azacitidine ( 2.1 , 5.1 ). • Myelosuppression : Monitor complete blood counts every other week for the first 2 cycles and prior to the start of each cycle thereafter. Increase monitoring to every other week for the 2 cycles after any dose reduction. Withhold and then resume at same or reduced dose or discontinue ONUREG based on severity ( 2.3 , 5.2 ). • Embryo-Fetal Toxicity : Can cause fetal harm.

Advise patients of the potential risk to a fetus and use of effective contraception ( 5.4 , 8.1 , 8.3 ).

5.1Risks of Substitution with Other Azacitidine Products Due to substantial differences in the pharmacokinetic parameters [see Clinical Pharmacology (12.3) ] , the recommended dose and schedule for ONUREG are different from those for the intravenous or subcutaneous azacitidine products. Treatment of patients using intravenous or subcutaneous azacitidine at the recommended dosage of ONUREG may result in a fatal adverse reaction. Treatment of patients using ONUREG at the doses recommended for intravenous or subcutaneous azacitidine may not be effective.

Do not substitute ONUREG for intravenous or subcutaneous azacitidine [see Dosage and Administration (2.1) ] .

5.2Myelosuppression New or worsening Grade 3 or 4 neutropenia and thrombocytopenia occurred in 49% and 22% of patients who received ONUREG, respectively. Febrile neutropenia occurred in 12% , and sepsis was reported in 6%, including 1 fatal case . A dose reduction was required for 7% and 2% of patients due to neutropenia and thrombocytopenia, respectively.

Less than 1% of patients discontinued ONUREG due to either neutropenia or thrombocytopenia. Monitor complete blood counts and modify the dosage as recommended [see Dosage and Administration (2.2 , 2.3) ]. Provide standard supportive care, including hematopoietic growth factors, if myelosuppression occurs.

5.3Increased Early Mortality in Patients with Myelodysplastic Syndromes In AZA-MDS-003 (NCT01566695), 216 patients with red blood cell transfusion-dependent anemia and thrombocytopenia due to myelodysplastic syndromes were randomized to ONUREG or placebo. One-hundred and seven patients received a median of 5 cycles of ONUREG 300 mg daily for 21 days of a 28-day cycle. Enrollment was discontinued early due to a higher incidence of early fatal and/or serious adverse reactions in patients who received ONUREG compared with placebo.

The most frequent fatal adverse reaction was sepsis. The safety and effectiveness of ONUREG for treatment of myelodysplastic syndromes have not been established. Treatment of patients with myelodysplastic syndromes with ONUREG is not recommended outside of controlled trials.

5.4Embryo-Fetal Toxicity Based on the mechanism of action and findings in animals, ONUREG can cause fetal harm when administered to a pregnant woman. Azacitidine administered to pregnant rats via a single intraperitoneal dose less than the recommended human daily dose of oral azacitidine on a mg/m 2 basis caused fetal death and anomalies. Advise pregnant women of the potential risk to a fetus.

Advise females of reproductive potential to use effective contraception during treatment with ONUREG and for at least 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with ONUREG and for at least 3 months after the last dose [see Use in Specific Populations (8.1 , 8.3) ] .

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Myelosuppression [see Warnings and Precautions (5.2) ] The most common adverse reactions (≥ 10%) are nausea, vomiting, diarrhea, fatigue/asthenia, constipation, upper respiratory tract infection, pneumonia, abdominal pain, arthralgia, decreased appetite, febrile neutropenia, dizziness, skin infection, and pain in extremity. To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb Company 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. Acute Myeloid Leukemia The safety of ONUREG was evaluated in QUAZAR [see Clinical Studies (14) ] . Patients received ONUREG 300 mg (N=236) or placebo (N=233) orally once daily on Days 1 through 14 of each 28-day cycle.

Among patients who received ONUREG, 71% were exposed for 6 months or longer, and 49% were exposed for greater than one year. The median duration of exposure to ONUREG was 11.6 months (range: 0.5 to 74.3 months) and the median number of cycles was 12 (range: 1 to 82 cycles). Serious adverse reactions occurred in 15% of patients who received ONUREG.

Serious adverse reactions in ≥ 2% of patients who received ONUREG were pneumonia (8%) and febrile neutropenia (7%). One fatal adverse reaction (sepsis) occurred in a patient who received ONUREG. Permanent discontinuation of ONUREG due to an adverse reaction occurred in 8% of patients.

Adverse reactions which resulted in permanent discontinuation of ONUREG in > 1% of patients included nausea (2.1%), diarrhea (1.7%), and vomiting (1.3%). Interruptions of ONUREG due to an adverse reaction occurred in 35% of patients. Adverse reactions which required an interruption of ONUREG in > 5% of patients included neutropenia (20%), thrombocytopenia (8%), and nausea (6%).

Dose reductions of ONUREG due to an adverse reaction occurred in 14% of patients. Adverse reactions which required a dose reduction in > 1% of patients included neutropenia (6%), diarrhea (3.4%), thrombocytopenia (1.7%), and nausea (1.7%). The most common (≥ 10%) adverse reactions were nausea, vomiting, diarrhea, fatigue/asthenia, constipation, upper respiratory tract infection, pneumonia, abdominal pain, arthralgia, decreased appetite, febrile neutropenia, dizziness, skin infection, and pain in extremity.

Table 2 summarizes the adverse reactions in QUAZAR. Table 2: Adverse Reactions (≥ 5%) in Patients with AML Who Received ONUREG with a Difference Between Arms of > 2% Compared to Placebo in QUAZAR Adverse Reaction ONUREG (N=236) Placebo (N=233) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) a Grouped term includes abdominal pain, abdominal pain upper, abdominal discomfort, and gastrointestinal pain. b Grouped term includes fatigue and asthenia. c Broad scope term includes acute sinusitis, adenoviral upper respiratory infection, chronic tonsillitis, influenza, nasopharyngitis, pharyngitis, rhinitis, sinusitis, sinusitis fungal, tonsillitis, tracheitis, upper respiratory tract infection, upper respiratory tract infection bacterial, viral pharyngitis, viral rhinitis, viral upper respiratory tract infection. d Broad scope term includes influenza, pneumonia, respiratory tract infection, respiratory tract infection viral, bronchopulmonary aspergillosis, lung infection, Staphylococcal infection, atypical pneumonia, lower respiratory tract infection, lung abscess, Pneumocystis jirovecii pneumonia, pneumonia bacterial, pneumonia fungal, Pseudomonas infection, hemoptysis, productive cough, pleural effusion, atelectasis, pleuritic pain, rales, Enterobacter test positive, and Hemophilus test positive.

Gastrointestinal disorders Nausea 65 3 24… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

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

8.1Pregnancy Risk Summary Based on its mechanism of action [see Clinical Pharmacology (12.1) ] and findings in animals, ONUREG can cause fetal harm when administered to a pregnant woman. There are no available data on ONUREG use in pregnant women to evaluate for a drug-associated risk. Azacitidine was teratogenic and caused embryo-fetal lethality in animals at doses less than the recommended human daily dose of oral azacitidine on a mg/m 2 basis (see Data ) .

Advise pregnant women of the potential risk to the fetus. The estimated background of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

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 No reproductive or developmental toxicity studies have been conducted with oral azacitidine. Early embryotoxicity studies in mice revealed a 44% frequency of intrauterine embryonal death (increased resorption) after a single intraperitoneal injection of 6 mg/m 2 azacitidine (at doses less than the recommended human daily dose of oral azacitidine on a mg/m 2 basis) on gestation Day 10.

Developmental abnormalities in the brain have been detected in mice given azacitidine on or before gestation Day 15 at doses of approximately 3 to 12 mg/m 2 (at doses less than the recommended human daily dose on a mg/m 2 basis). In rats, azacitidine was clearly embryotoxic when given an intraperitoneal injection on gestation Days 4 to 8 (postimplantation) at a dose of 6 mg/m 2 (at doses less than the recommended human daily dose on a mg/m 2 basis), although treatment in the preimplantation period (on gestation Days 1 to 3) had no adverse effect on the embryos.

Azacitidine caused multiple fetal abnormalities in rats after a single intraperitoneal dose of 3 to 12 mg/m 2 (at doses less than the recommended human daily dose on a mg/m 2 basis) given on gestation Days 9, 10, 11, or 12. In this study, azacitidine caused fetal death when administered at 3 to 12 mg/m 2 on gestation Days 9 and 10; average live animals per litter was reduced to 9% of control at the highest dose on gestation Day 9. Fetal anomalies included: CNS anomalies (exencephaly/encephalocele), limb anomalies (micromelia, club foot, syndactyly, oligodactyly), and others (micrognathia, gastroschisis, edema, and rib abnormalities).

8.2Lactation Risk Summary There are no data regarding the presence of azacitidine in human milk or the effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with ONUREG and for 1 week after the last dose.

8.3Females and Males of Reproductive Potential ONUREG can cause embryo-fetal harm when administered to pregnant women [see Use in Specific Populations (8.1) ] . Pregnancy Testing Pregnancy testing is recommended for females of reproductive potential before starting ONUREG. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with ONUREG and for at least 6 months after the last dose.

Males Advise males with female partners of reproductive potential to use effective contraception during treatment with ONUREG and for at least 3 months after the last dose. Infertility Based on animal data, ONUREG may impair male or female fertility [see Nonclinical Toxicology (13.1) ] .

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

8.5Geriatric Use Of the 238 patients in QUAZAR who received ONUREG, 72% were 65 years of age or older, while 12% were 75 years of age or older. No overall differences in safety or effectiveness of ONUREG were observed between these patients… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary Based on its mechanism of action [see Clinical Pharmacology (12.1) ] and findings in animals, ONUREG can cause fetal harm when administered to a pregnant woman. There are no available data on ONUREG use in pregnant women to evaluate for a drug-associated risk. Azacitidine was teratogenic and caused embryo-fetal lethality in animals at doses less than the recommended human daily dose of oral azacitidine on a mg/m 2 basis (see Data ) .

Advise pregnant women of the potential risk to the fetus. The estimated background of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

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 No reproductive or developmental toxicity studies have been conducted with oral azacitidine. Early embryotoxicity studies in mice revealed a 44% frequency of intrauterine embryonal death (increased resorption) after a single intraperitoneal injection of 6 mg/m 2 azacitidine (at doses less than the recommended human daily dose of oral azacitidine on a mg/m 2 basis) on gestation Day 10.

Developmental abnormalities in the brain have been detected in mice given azacitidine on or before gestation Day 15 at doses of approximately 3 to 12 mg/m 2 (at doses less than the recommended human daily dose on a mg/m 2 basis). In rats, azacitidine was clearly embryotoxic when given an intraperitoneal injection on gestation Days 4 to 8 (postimplantation) at a dose of 6 mg/m 2 (at doses less than the recommended human daily dose on a mg/m 2 basis), although treatment in the preimplantation period (on gestation Days 1 to 3) had no adverse effect on the embryos.

Azacitidine caused multiple fetal abnormalities in rats after a single intraperitoneal dose of 3 to 12 mg/m 2 (at doses less than the recommended human daily dose on a mg/m 2 basis) given on gestation Days 9, 10, 11, or 12. In this study, azacitidine caused fetal death when administered at 3 to 12 mg/m 2 on gestation Days 9 and 10; average live animals per litter was reduced to 9% of control at the highest dose on gestation Day 9. Fetal anomalies included: CNS anomalies (exencephaly/encephalocele), limb anomalies (micromelia, club foot, syndactyly, oligodactyly), and others (micrognathia, gastroschisis, edema, and rib abnormalities).

🧒 Pediatric Use 16 words ▾

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

🧓 Geriatric Use 46 words ▾

8.5Geriatric Use Of the 238 patients in QUAZAR who received ONUREG, 72% were 65 years of age or older, while 12% were 75 years of age or older. No overall differences in safety or effectiveness of ONUREG were observed between these patients and younger patients.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Azacitidine is a pyrimidine nucleoside analog of cytidine that inhibits DNA/RNA methyltransferases. Azacitidine is incorporated into DNA and RNA following cellular uptake and enzymatic biotransformation to nucleotide triphosphates. Incorporation of azacitidine into the DNA of cancer cells in vitro, including acute myeloid leukemia cells, inhibited DNA methyltransferases, reduced DNA methylation and altered gene expression, including re-expression of genes regulating tumor suppression and cell differentiation.

Incorporation of azacitidine into the RNA of cancer cells, including leukemic cells, inhibited RNA methyltransferases, reduced RNA methylation, decreased RNA stability and decreased protein synthesis. Antileukemic activity of azacitidine was demonstrated by reduction of cell viability and induction of apoptosis in AML cell lines in vitro. Azacitidine decreased tumor burden and increased survival in leukemic tumor models in vivo.

12.2Pharmacodynamics Greater reduction in global DNA methylation was observed with higher azacitidine plasma exposure in patients with AML administered ONUREG for 14 days of a 28-day cycle.

12.3Pharmacokinetics The systemic exposure of azacitidine is approximately dose proportional over the dose range of 120 mg to 600 mg once daily of ONUREG (0.4 to 2 times the recommended dosage). Following a single 300 mg dose of ONUREG, the mean (coefficient of variation [CV%]) C max of azacitidine was 145 ng/mL (64%) and the mean AUC of azacitidine was 242 ng h/mL (65%). No accumulation was observed following ONUREG 300 mg once daily.

Absorption The mean oral bioavailability is approximately 11% relative to subcutaneous administration. The median time to peak plasma concentration of azacitidine is 1 hour. Effect of Food A high-fat, high-calorie meal (approximately 800 to 1000 calories, 50% fat) did not affect AUC 0-INF and decreased C max by 21%.

Distribution The mean (CV%) apparent volume of distribution (V z /F) of azacitidine is 881 L (67%). The in vitro serum protein binding of azacitidine is approximately 6% to 12%. The blood-to-plasma ratio is approximately 0.3.

Elimination The mean (CV%) terminal half-life is approximately 0.5 hours (27%) and the apparent clearance (CL/F) is 1240 L/hour (64%). Metabolism Azacitidine undergoes spontaneous hydrolysis and deamination mediated by cytidine deaminase. Excretion Following the administration of ONUREG 300 mg orally once daily, < 2% of the dose was recovered unchanged in the urine.

Specific Populations Age (46 years to 93 years), sex, body weight (39.3 kg to 129 kg), mild to moderate hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin 1 to 3 × ULN and any AST), and mild to moderate renal impairment (CLcr 30 to 89 mL/min) have no clinically meaningful effect on the pharmacokinetics of oral azacitidine. The effects of race/ethnicity, severe hepatic impairment (total bilirubin > 3 × ULN and any AST), and severe renal impairment (CLcr 15 to 29 mL/min) on the pharmacokinetics of oral azacitidine is unknown.

Severe renal impairment increased azacitidine exposure by approximately 70% after a single or 41% after multiple subcutaneous daily administration. Drug Interaction Studies Effect of Gastric Acid Reducing Agents on Azacitidine: Coadministration of omeprazole (a proton pump inhibitor) with ONUREG increased azacitidine AUC 0-INF by 19% and had no effect on C max . In Vitro Studies Cytochrome P450 (CYP) Enzymes: Azacitidine does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, or CYP2E1 at clinically relevant concentrations.

Azacitidine is not an inducer of CYP1A2, CYP2C19, or CYP3A. Transporter Systems: Azacitidine is not a substrate of P-glycoprotein (P-gp). Azacitidine does not inhibit P-gp, breast cancer resistance protein (BCRP), organic anion transporters (OAT) OAT1 and OAT3, organic anion transporting polypeptides (OATP) OATP1B1 and OATP1B3, or organic cation transp… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 127 words ▾

12.1Mechanism of Action Azacitidine is a pyrimidine nucleoside analog of cytidine that inhibits DNA/RNA methyltransferases. Azacitidine is incorporated into DNA and RNA following cellular uptake and enzymatic biotransformation to nucleotide triphosphates. Incorporation of azacitidine into the DNA of cancer cells in vitro, including acute myeloid leukemia cells, inhibited DNA methyltransferases, reduced DNA methylation and altered gene expression, including re-expression of genes regulating tumor suppression and cell differentiation.

Incorporation of azacitidine into the RNA of cancer cells, including leukemic cells, inhibited RNA methyltransferases, reduced RNA methylation, decreased RNA stability and decreased protein synthesis. Antileukemic activity of azacitidine was demonstrated by reduction of cell viability and induction of apoptosis in AML cell lines in vitro. Azacitidine decreased tumor burden and increased survival in leukemic tumor models in vivo.

📦 How Supplied / Storage and Handling 166 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied ONUREG tablets are available as: • 200 mg: pink, oval, film-coated tablets with debossed "200" on one side and "ONU" on the other side. • 300 mg: brown, oval, film-coated tablets with debossed "300" on one side and "ONU" on the other side. Table 6 lists the package configurations and strengths. Table 6: ONUREG Package Configurations and NDC Numbers Package Configuration Tablet Strength NDC Number One blister card containing 7 tablets 200 mg 59572-730-07 One blister card containing 7 tablets 300 mg 59572-740-07 Storage • Store blisters at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Store in the original aluminum-aluminum blisters. Handling and Disposal ONUREG is a hazardous drug. Follow applicable special handling and disposal procedures.

1 If powder comes in contact with skin, immediately and thoroughly wash with soap and water. If powder comes in contact with mucous membranes, immediately flush the area with water.

📦 Storage and Handling 76 words ▾

Storage • Store blisters at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Store in the original aluminum-aluminum blisters.

Handling and Disposal ONUREG is a hazardous drug. Follow applicable special handling and disposal procedures. 1 If powder comes in contact with skin, immediately and thoroughly wash with soap and water. If powder comes in contact with mucous membranes, immediately flush the area with water.

📋 Description 143 words ▾

11 DESCRIPTION Azacitidine is a nucleoside metabolic inhibitor with a molecular formula of C 8 H 12 N 4 O 5 and a molecular weight of 244 g/mol. The chemical name is: 4-amino-1-β-D-ribofuranosyl-s-triazin-2(1H)-one and the chemical structural is: Azacitidine is a white to off-white solid. Azacitidine was found to be soluble in aqueous media across a pH range from 1.0 to 7.0.

ONUREG (azacitidine) is supplied as film-coated tablets containing 200 mg or 300 mg of azacitidine for oral use. Each core tablet contains the following inactive ingredients: croscarmellose sodium, magnesium stearate, mannitol, and silicified microcrystalline cellulose. The 200 and 300 mg tablet coating contains hypromellose, lactose monohydrate, polyethylene glycol, titanium dioxide, and triacetin.

In addition, the 200 mg tablet coating contains iron oxide red and the 300 mg tablet coating contains black iron oxide, iron oxide red, and iron oxide yellow. onureg-chem-structure

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Myelosuppression Advise patients of the risk of myelosuppression with ONUREG and of the need to monitor complete blood counts before and during treatment [see Warnings and Precautions (5.2) ] . Infection Advise patients of the risk of infections, including sepsis, with ONUREG and to report any symptoms of infection to their healthcare provider as soon as possible [see Adverse Reactions (6.1) ] .

Gastrointestinal Toxicity Advise patients of the risk of gastrointestinal toxicity with ONUREG and of the potential need to use anti-emetic or anti-diarrheal medications during treatment [see Adverse Reactions (6.1) ]. Embryo-Fetal Toxicity Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1) ] .

Advise females of reproductive potential to use effective contraception during treatment with ONUREG and for at least 6 months after the last dose [see Use in Specific Populations (8.3) ] . Advise males with female partners of reproductive potential to use effective contraception during treatment with ONUREG and for at least 3 months after the last dose [see Use in Specific Populations (8.3) ] . Lactation Advise women not to breastfeed during treatment with ONUREG and for 1 week after the last dose [see Use in Specific Populations (8.2) ] .

Administration Advise patients to take ONUREG with or without food at about the same time each day and how to make up a missed or vomited dose. Advise patients to swallow tablets whole. Advise patients not to cut, crush, or chew the tablets [see Dosage and Administration (2.2) ] .

Storage Instructions Advise patients to keep ONUREG in the original container (blisters).

🧬 Pharmacokinetics ~2 min read ▾

12.3Pharmacokinetics The systemic exposure of azacitidine is approximately dose proportional over the dose range of 120 mg to 600 mg once daily of ONUREG (0.4 to 2 times the recommended dosage). Following a single 300 mg dose of ONUREG, the mean (coefficient of variation [CV%]) C max of azacitidine was 145 ng/mL (64%) and the mean AUC of azacitidine was 242 ng h/mL (65%). No accumulation was observed following ONUREG 300 mg once daily.

Absorption The mean oral bioavailability is approximately 11% relative to subcutaneous administration. The median time to peak plasma concentration of azacitidine is 1 hour. Effect of Food A high-fat, high-calorie meal (approximately 800 to 1000 calories, 50% fat) did not affect AUC 0-INF and decreased C max by 21%.

Distribution The mean (CV%) apparent volume of distribution (V z /F) of azacitidine is 881 L (67%). The in vitro serum protein binding of azacitidine is approximately 6% to 12%. The blood-to-plasma ratio is approximately 0.3.

Elimination The mean (CV%) terminal half-life is approximately 0.5 hours (27%) and the apparent clearance (CL/F) is 1240 L/hour (64%). Metabolism Azacitidine undergoes spontaneous hydrolysis and deamination mediated by cytidine deaminase. Excretion Following the administration of ONUREG 300 mg orally once daily, < 2% of the dose was recovered unchanged in the urine.

Specific Populations Age (46 years to 93 years), sex, body weight (39.3 kg to 129 kg), mild to moderate hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin 1 to 3 × ULN and any AST), and mild to moderate renal impairment (CLcr 30 to 89 mL/min) have no clinically meaningful effect on the pharmacokinetics of oral azacitidine. The effects of race/ethnicity, severe hepatic impairment (total bilirubin > 3 × ULN and any AST), and severe renal impairment (CLcr 15 to 29 mL/min) on the pharmacokinetics of oral azacitidine is unknown.

Severe renal impairment increased azacitidine exposure by approximately 70% after a single or 41% after multiple subcutaneous daily administration. Drug Interaction Studies Effect of Gastric Acid Reducing Agents on Azacitidine: Coadministration of omeprazole (a proton pump inhibitor) with ONUREG increased azacitidine AUC 0-INF by 19% and had no effect on C max . In Vitro Studies Cytochrome P450 (CYP) Enzymes: Azacitidine does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, or CYP2E1 at clinically relevant concentrations.

Azacitidine is not an inducer of CYP1A2, CYP2C19, or CYP3A. Transporter Systems: Azacitidine is not a substrate of P-glycoprotein (P-gp). Azacitidine does not inhibit P-gp, breast cancer resistance protein (BCRP), organic anion transporters (OAT) OAT1 and OAT3, organic anion transporting polypeptides (OATP) OATP1B1 and OATP1B3, or organic cation transporter (OCT) OCT2 at clinically relevant concentrations.

🧬 Pharmacodynamics 28 words ▾

12.2Pharmacodynamics Greater reduction in global DNA methylation was observed with higher azacitidine plasma exposure in patients with AML administered ONUREG for 14 days of a 28-day cycle.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES The efficacy of ONUREG was evaluated in QUAZAR (NCT01757535), a multicenter, randomized, double-blind, placebo-controlled study. Eligible patients were ages 55 years or older, had AML, and were within 4 months of achieving first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) with intensive induction chemotherapy. Patients may have received consolidation (see Table 4 ).

Patients were excluded if they were candidates for hematopoietic stem cell transplantation at the time of screening. A total of 472 patients who completed induction with or without consolidation therapy were randomized 1:1 to receive ONUREG 300 mg (n=238) or placebo (n=234) orally on Days 1 through 14 of each 28-day cycle. Randomization was stratified by age at time of induction therapy (55 to 64 vs. ≥ 65 years), cytogenetic risk category at time of induction therapy (intermediate risk vs. poor risk), prior history of MDS/CMML (yes vs. no), and received consolidation therapy following induction therapy (yes vs. no).

Baseline demographic and disease characteristics are shown in Table 4. Table 4: Baseline Demographics and Disease-Related Characteristics in QUAZAR Parameter ONUREG (N=238) Placebo (N=234) AML=Acute Myeloid Leukemia, MDS=Myelodysplastic Syndrome, CMML=Chronic Myelomonocytic Leukemia, ECOG=Eastern Cooperative Oncology Group, CR=Morphologic Complete Remission, CRi=Morphologic complete remission with incomplete blood count recovery. 1 Intermediate risk was defined as normal cytogenetics +8, t(9;11), or Other undefined.

2 Poor risk was defined as Complex (≥ 3 abnormalities): -5; 5q-; -7; 7q-; 11q23 - non t(9;11); inv(3); t(3;3); t(6;9); or t(9;22). Source for Intermediate and Poor Risk: National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for Acute Myeloid Leukemia. National Comprehensive Cancer Network website.

Available at http://www.nccn.org/professionals/physician_gls/PDF/aml.pdf. Accessed 01 Mar 2011. Age (years) Median (Min, Max) 68.0 (55, 86) 68.0 (55, 82) Age Category, n (%) < 65 years 66 (28) 68 (29) 65 years to < 75 years 144 (61) 142 (61) ≥ 75 years 28 (12) 24 (10) Sex, n (%) Male 118 (50) 127 (54) Female 120 (50) 107 (46) Race, n (%) White 216 (91) 197 (84) Black or African American 2 (1) 6 (3) Asian 6 (3) 20 (9) Other 12 (5) 11 (5) Not Collected or Reported 2 (1) 0 (0) ECOG Performance Status, n (%) 0 116 (49) 111 (47) 1 101 (42) 106 (45) 2 21 (9) 15 (6) 3 0 (0) 2 (1) Cytogenetic Risk Status at Diagnosis, n (%) Intermediate Risk 1 203 (85) 203 (87) Poor Risk 2 35 (15) 31 (13) Initial AML Classification, n (%) AML with recurrent genetic abnormalities 39 (16) 46 (20) AML with myelodysplasia-related changes 49 (21) 42 (18) Therapy related myeloid neoplasms 2 (1) 0 (0) AML not otherwise specified 148 (62) 145 (62) Missing 0 (0) 1 (< 1) Type of AML, n (%) Primary (de novo) 213 (89) 216 (92) Secondary 25 (11) 18 (8) Induction Response CR 187 (79) 197 (84) CRi 51 (21) 37 (16) Consolidation following induction therapy None 52 (22) 42 (18) 1 cycle 110 (46) 102 (44) 2 cycles 70 (29) 77 (33) 3 cycles 6 (3) 13 (6) Disease status at study baseline CR 185 (78) 181 (77) CRi 44 (18) 38 (16) Not in CR or CRi 9 (4) 13 (6) Not Reported 0 2 (1) The efficacy of ONUREG was established on the basis of overall survival (OS).

The trial demonstrated a statistically significant improvement in OS for patients randomized to ONUREG compared to placebo. A subgroup analysis showed consistency in the OS benefit for patients in either CR or CRi. The efficacy results are summarized in Table 5 and Figure 1.

Table 5: Efficacy Results (ITT Population) in QUAZAR ONUREG (N=238) Placebo (N=234) 1 The hazard ratio is from a Cox proportional hazards model stratified by age (55 to 64 vs. ≥65 years), cytogenetic risk category at time of induction therapy (intermediate risk vs. poor risk), and received consolidation therapy (yes vs. no). The p-value is two-sided from a log-rank test stratified by the… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility The potential carcinogenicity of azacitidine was evaluated in mice and rats. Azacitidine induced tumors of the hematopoietic system in female mice at 2.2 mg/kg (6.6 mg/m 2 , approximately 4% of the recommended human daily dose of oral azacitidine on a mg/m 2 basis) administered intraperitoneal 3 times per week for 52 weeks. An increased incidence of tumors in the lymphoreticular system, lung, mammary gland, and skin was seen in mice treated with intraperitoneal azacitidine at 2 mg/kg (6 mg/m 2 , approximately 3% of the recommended human daily dose of oral azacitidine on a mg/m 2 basis) once a week for 50 weeks.

A tumorigenicity study in rats dosed twice weekly at 15 or 60 mg/m 2 (approximately 8% to 32% of the recommended human daily dose of oral azacitidine on a mg/m 2 basis) revealed an increased incidence of testicular tumors compared with controls. The mutagenic and clastogenic potential of azacitidine was tested in in vitro bacterial systems Salmonella typhimurium strains TA100 and several strains of trpE8, Escherichia coli strains WP14 Pro, WP3103P, WP3104P, and CC103; in an in vitro forward gene mutation assay in mouse lymphoma cells and human lymphoblast cells; and in an in vitro micronucleus assay in mouse L5178Y lymphoma cells and Syrian hamster embryo cells.

Azacitidine was mutagenic in bacterial and mammalian cell systems. The clastogenic effect of azacitidine was shown by the induction of micronuclei in L5178Y mouse cells and Syrian hamster embryo cells. Administration of azacitidine by intraperitoneal injection to male mice at 9.9 mg/m 2 (at doses less than the recommended human daily dose on a mg/m 2 basis) daily for 3 days prior to mating with untreated female mice resulted in decreased fertility and loss of offspring during subsequent embryonic and postnatal development.

Treatment of male rats 3 times per week for 11 or 16 weeks at doses of 15 to 30 mg/m 2 (at doses less than the recommended human daily dose on a mg/m 2 basis) resulted in decreased weight of the testes and epididymides, decreased sperm counts accompanied by decreased pregnancy rates, and increased loss of embryos in mated females. In a related study, male rats treated for 16 weeks at 24 mg/m 2 resulted in an increase in abnormal embryos in mated females when examined on Day 2 of gestation.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~2 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility The potential carcinogenicity of azacitidine was evaluated in mice and rats. Azacitidine induced tumors of the hematopoietic system in female mice at 2.2 mg/kg (6.6 mg/m 2 , approximately 4% of the recommended human daily dose of oral azacitidine on a mg/m 2 basis) administered intraperitoneal 3 times per week for 52 weeks. An increased incidence of tumors in the lymphoreticular system, lung, mammary gland, and skin was seen in mice treated with intraperitoneal azacitidine at 2 mg/kg (6 mg/m 2 , approximately 3% of the recommended human daily dose of oral azacitidine on a mg/m 2 basis) once a week for 50 weeks.

A tumorigenicity study in rats dosed twice weekly at 15 or 60 mg/m 2 (approximately 8% to 32% of the recommended human daily dose of oral azacitidine on a mg/m 2 basis) revealed an increased incidence of testicular tumors compared with controls. The mutagenic and clastogenic potential of azacitidine was tested in in vitro bacterial systems Salmonella typhimurium strains TA100 and several strains of trpE8, Escherichia coli strains WP14 Pro, WP3103P, WP3104P, and CC103; in an in vitro forward gene mutation assay in mouse lymphoma cells and human lymphoblast cells; and in an in vitro micronucleus assay in mouse L5178Y lymphoma cells and Syrian hamster embryo cells.

Azacitidine was mutagenic in bacterial and mammalian cell systems. The clastogenic effect of azacitidine was shown by the induction of micronuclei in L5178Y mouse cells and Syrian hamster embryo cells. Administration of azacitidine by intraperitoneal injection to male mice at 9.9 mg/m 2 (at doses less than the recommended human daily dose on a mg/m 2 basis) daily for 3 days prior to mating with untreated female mice resulted in decreased fertility and loss of offspring during subsequent embryonic and postnatal development.

Treatment of male rats 3 times per week for 11 or 16 weeks at doses of 15 to 30 mg/m 2 (at doses less than the recommended human daily dose on a mg/m 2 basis) resulted in decreased weight of the testes and epididymides, decreased sperm counts accompanied by decreased pregnancy rates, and increased loss of embryos in mated females. In a related study, male rats treated for 16 weeks at 24 mg/m 2 resulted in an increase in abnormal embryos in mated females when examined on Day 2 of gestation.

📚 References 9 words ▾

15 REFERENCES 1. "OSHA Hazardous Drugs." OSHA . http://www.osha.gov/SLTC/hazardousdrugs/index.html

📄 Patient Package Insert ~3 min read ▾

Patient Package Insert Patient Information ONUREG ® (on-u-reg) (azacitidine) tablets, for oral use What is ONUREG? ONUREG is a prescription medicine used for continued treatment of adults with acute myeloid leukemia (AML) who: • had a first complete remission (CR) following intensive induction chemotherapy with or without recovery of your blood cell counts, and • who are not able to complete intensive curative therapy. It is not known if ONUREG is safe and effective in children under 18 years of age.

Do not take ONUREG if you: • are allergic to azacitidine or any of the ingredients in ONUREG. See the end of this leaflet for a complete list of ingredients in ONUREG. Before taking ONUREG, tell your healthcare provider about all of your medical conditions, including if you: • have kidney or liver problems. • are pregnant or plan to become pregnant.

ONUREG can harm your unborn baby. Females who are able to become pregnant: o Your healthcare provider should perform a pregnancy test before you start treatment with ONUREG. o You should use effective birth control (contraception) during treatment and for at least 6 months after your last dose of ONUREG. o Tell your healthcare provider right away if you become pregnant during treatment with ONUREG. Males with a female sexual partner who can become pregnant: o You should use effective birth control (contraception) during treatment and for at least 3 months after your last dose of ONUREG. • are breastfeeding or plan to breastfeed.

It is not known if ONUREG passes into your breast milk. Do not breastfeed during treatment and for 1 week after your last dose of ONUREG. Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I take ONUREG? • Take ONUREG exactly as your healthcare provider tells you to take it. • Your healthcare provider will prescribe an anti-nausea medicine for you to take to help prevent nausea and vomiting during your treatment with ONUREG. o Take the anti-nausea medicine 30 minutes before each dose of ONUREG. o Your healthcare provider may decide to stop the anti-nausea medicine after your second cycle of ONUREG, if you do not have any nausea or vomiting. • Take ONUREG by mouth 1 time each day beginning on Day 1 through Day 14 of each 28-day cycle. • Take ONUREG with or without food at about the same time each day. • Swallow ONUREG tablets whole.

Do not cut, crush, or chew the tablets. • If the powder from ONUREG tablets comes in contact with your skin, wash the area well right away with soap and water. • If the powder from ONUREG tablets comes in contact with your eyes or mouth (mucous membranes), flush the area right away with water. • If you miss a dose of ONUREG, or if you do not take your dose at the usual time, take the dose as soon as possible that day. Take your next dose at the regular time the next day. Do not take 2 doses on the same day to make up for a missed dose. • If you vomit after taking a dose of ONUREG, do not take another dose on the same day.

Take your next dose at the regular time the next day. What are the possible side effects of ONUREG? ONUREG can cause serious side effects, including: • New or worsening low white blood cell counts (neutropenia).

New or worsening low white blood cell counts can be severe during treatment with ONUREG. If your white blood cell counts become very low, you are at increased risk for infections, including a severe infection of the blood called sepsis that can lead to death. Your healthcare provider will check your white blood cell counts before and during treatment with ONUREG.

Your healthcare provider may prescribe a medicine to help increase your white blood cell count if needed. Tell your healthcare provider right away if you get any of the following symptoms: o fever o chills o body aches o shortness of breath o fast heartbeat o feeling very tired or weak o unusual headaches o lightheadedness or dizziness o… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 7 words ▾

Warnings and Precautions ( 5.2 ) 04/2026

📄 Package Label / Principal Display Panel 98 words ▾

PRINCIPAL DISPLAY PANEL - 200 mg Blister Pack Carton NDC 59572-730-07 Rx only ONUREG™ (azacitidine) tablets 200 mg Each tablet contains 200 mg of azacitidine. Swallow tablets whole. Do not cut, crush, or chew the tablets. One Blister Card Containing 7 Tablets Bristol Myers Squibb CAUTION: Hazardous Agent onureg-200-carton

PRINCIPAL DISPLAY PANEL - 300 mg Blister Pack Carton NDC 59572-740-07 Rx only ONUREG™ (azacitidine) tablets 300 mg Each tablet contains 200 mg of azacitidine. Swallow tablets whole. Do not cut, crush, or chew the tablets. One Blister Card Containing 7 Tablets Bristol Myers Squibb CAUTION: Hazardous Agent onureg-300-carton

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
7 tablets59572-0740-07 148 Rx · $3,712,174
14 tablets this page59572-0740-14 No Medicaid data
Drug total (last 4 qtrs): 148 Rx · 2,002 units · $3,712,174 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

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

Medicare Part D (outpatient prescription) spending for Onureg — 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 Onureg. 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
$21.19M
Claims incl. refills
919
Beneficiaries
396
Spend / beneficiary
$53,510.70
Spend / claim
$23,057.93
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 ONUREG (this brand).

Top reported reactions

Febrile Neutropenia2,002
Death1,939
Myelosuppression1,504
Neutropenia1,382
Acute Myeloid Leukaemia1,313
Pneumonia1,070
Pyrexia1,011

Age at onset

Neonate16
Infant30
Child110
Adolescent90
Adult1,532
Elderly2,610

Reporter sex

18,868 reports
Male · 60%
Female · 40%
Unknown · 0%

Serious outcomes

Hospitalization8,401
Death6,106
Life-threatening1,821
Disabling270
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 2,812 942
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.

About this NDC listing & data coverage

Finished prescription product No longer marketed (per FDA listing data)
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 ✓ Available
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is 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.
What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
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 form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 7 tablets (59572-0740-07). Each has its own NDC and its own page — see the package list near the top of this page.
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.
← 59572-0730-07 · Celgene 59572-0775-01 · 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.