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Nerlynx neratinib 40 mg Tablet, 133-count — NDC 70437-0240-33 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Nerlynx neratinib 40 mg Tablet, 133-count — NDC 70437-240-33 (Billing 70437-0240-33)

by Puma Biotechnology, Inc. · 1 BOTTLE in 1 BOX / 133 TABLET in 1 BOTTLE

This is a package of 133 tablets of Nerlynx neratinib 40 mg Tablet from Puma Biotechnology, Inc., marketed since Jul 2017 and currently FDA-listed.

NDC 70437-0240-33
🏷️ FDA NDC (as labeled) 70437-240-33 billing pads the product segment with a zero
This package
Contains133-count Medicaid pays$133.15 / unit · 12 mo Per package$17,709.55 / 133 tablets · Medicaid Pack sizes3 compare ↓
Also priced by: Part D plans $138.63/unit — full pricing hub ↓
Product page 70437-0240-18 Also comes in: 126 tablets 70437-240-26 180 tablets 70437-240-18
Rx only Brand On market Non-controlled ⇄ 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 70437-240-33 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
70437 labeler · 240 product · 33 package
Package marketed since
Jul 17, 2017
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Billing quantity
133 EA per package
Barcode (UPC)
0370437240332, 0370437240264
Medicaid fills, this package
96 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 70437-240-33
Product NDC 70437-240
11-digit billing NDC 70437024033
NCPDP billing unit EA — each (per item)
RxCUI 1940648, 1940654
UNII 9RM7XY23ZS
UPC 0370437240332, 0370437240264
Application # NDA208051
SPL Set ID d1e41dcf-e82a-47c2-a0ad-6c6eef621834
Established class (EPC) Kinase Inhibitor
Mechanism of action Kinase Inhibitors; P-Glycoprotein Inhibitors
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2017-07-17
Route ORAL
Dosage form TABLET
Substance NERATINIB MALEATE ANHYDROUS

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

GPI-14 21533035100320
GCN Seq No 077566
GCN 43613
HICL code 044421
Ingredient (HICL) Neratinib Maleate
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 NERLYNX 40 MG TABLET
FDB brand name Nerlynx
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 077566
  • GCN: 43613
  • GPI-14 (Medi-Span): 21533035100320
  • HICL (First Databank): 044421
  • AHFS class code: 10:00.00.00
  • RxCUI (RxNorm): 1940648
Why two NDCs? The FDA registers this code as 70437-240-33 — 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 → 70437-0240-33. 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 Kinase Inhibitor class.

Pharmacologic class Kinase Inhibitor
Drug family (ATC) Human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors
How it works Kinase Inhibitors, P-Glycoprotein 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 NERLYNX 40 MG TABLET Ingredient Neratinib Maleate
📗 Our plain-language guide HelloPharmacist
  • Neratinib (Nerlynx) treats HER2-positive breast cancer in adults. On its own, it's used after trastuzumab-based therapy for early-stage disease. With capecitabine, it's used for ad...
  • Don't double up. Skip the missed dose and take your next one at the usual time. Try to take it with food at about the same time each day.
  • What happens if I miss a dose of Neratinib?
  • Diarrhea is very common, so planning ahead matters. Your team will likely have you start loperamide with your first dose, or build up the dose over two weeks. Call them if diarrhea...
📖 Read our full Neratinib 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 $133.15 $17,709.55 / 133 tablets
Medicare drug plans payPart D · Q2 2026 $138.63 $18,438.42 / 133 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
70437-0240-18 70437-240-18 Main listing 1 BOTTLE in 1 BOX / 180 TABLET in 1 BOTTLE 2017-07-17 — Active
70437-0240-26 70437-240-26 1 BOTTLE in 1 BOX / 126 TABLET in 1 BOTTLE 2017-07-17 — Active
70437-0240-33 You're viewing this 1 BOTTLE in 1 BOX / 133 TABLET in 1 BOTTLE 2017-07-17 — Active

This pack accounts for about 10% of this product's recent Medicaid fills; most go to a different pack size. See all packs ↓

Pack size FAQ

What quantity is in this package?
This is a 133-count package — 1 bottle in 1 box / 133 tablet in 1 bottle.
How does this package differ from NDC 70437-0240-26?
Both are Nerlynx neratinib 40 mg Tablet — the drug itself is identical. This page's package is the 133-count one, while NDC 70437-0240-26 is the 126 tablets package.
What NDC number is used to bill for this package of Nerlynx neratinib 40 mg Tablet?
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
Nerlynx 40 mgthis 70437-0240-33 Puma 133 tablets — — 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

🏛️
2017
First FDA approval
Jul 2017
📍
2026
Currently FDA-listed
9 years listed
🛡️
2031
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 Jul 2031. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Jul 17, 2017 RLD RS ⏳ ~4.8 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 8518446 — method of use (U-2043)
US 10035788 — method of use (U-2043)
US 8790708 — method of use (U-2043)
US 9211291 — method of use (U-2043)
US 9630946 — method of use (U-2043)
US 8790708 — method of use (U-3097)
US 8790708 — method of use (U-3047)
US 9211291 — method of use (U-3097)
US 8518446 — method of use (U-3097)
US 8518446 — method of use (U-3047)
US 9139558 — method of use (U-3097)
US 9139558 — method of use (U-3047)
US 9630946 — method of use (U-3047)
US 9630946 — method of use (U-3097)
US 10035788 — method of use (U-3047)
US 10035788 — method of use (U-3097)
US 9265784 — method of use (U-3047)
US 8669273 — method of use (U-3047)
US 9139558 — method of use (U-2043)
US 7399865 — drug substance
2017 2019 2021 2023 2025 2027 2029 2031
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 (20)
PatentTypeUse codeExpires
US 8518446 ↗ Method of use U-2043 Nov 20, 2030
US 10035788 ↗ Method of use U-2043 Oct 15, 2028
US 8790708 ↗ Method of use U-2043 Nov 5, 2030
US 9211291 ↗ Method of use U-2043 Mar 24, 2030
US 9630946 ↗ Method of use U-2043 Oct 15, 2028
US 8790708 ↗ Method of use U-3097 Nov 5, 2030
US 8790708 ↗ Method of use U-3047 Nov 5, 2030
US 9211291 ↗ Method of use U-3097 Mar 24, 2030
US 8518446 ↗ Method of use U-3097 Nov 20, 2030
US 8518446 ↗ Method of use U-3047 Nov 20, 2030
US 9139558 ↗ Method of use U-3097 Oct 15, 2028
US 9139558 ↗ Method of use U-3047 Oct 15, 2028
US 9630946 ↗ Method of use U-3047 Oct 15, 2028
US 9630946 ↗ Method of use U-3097 Oct 15, 2028
US 10035788 ↗ Method of use U-3047 Oct 15, 2028
US 10035788 ↗ Method of use U-3097 Oct 15, 2028
US 9265784 ↗ Method of use U-3047 Aug 4, 2029
US 8669273 ↗ Method of use U-3047 Jul 18, 2031
US 9139558 ↗ Method of use U-2043 Oct 15, 2028
US 7399865 ↗ Drug substance — Dec 29, 2030
Common questions
Is there a generic version of NERLYNX 40 MG TABLET?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for NERLYNX 40 MG TABLET. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Jul 2031 — 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 red
ShapeOval
ImprintW104
Size11 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 Neratinib 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.

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

  • UNII 2S7830E561
    Crospovidone is a synthetic polymer derived from povidone. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the active ingredient can be absorbed.
  • 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 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII 3OWL53L36A
    A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
  • 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 3WJQ0SDW1A
    Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
  • UNII 532B59J990
    Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
  • UNII FZ989GH94E
    Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
  • 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 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
  • 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.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

12 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.

Manufacturer & labeler

LabelerPuma Biotechnology, Inc.
Application holderPUMA BIOTECHNOLOGY INC
FDA applicationNDA208051 (NDA)
Labeler code70437
First marketedJul 2017
Product typeHuman Prescription Drug
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 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 163 words ▾

1 INDICATIONS AND USAGE NERLYNX is a kinase inhibitor indicated: As a single agent, for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer, to follow adjuvant trastuzumab-based therapy. ( 1.1 ) In combination with capecitabine, for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting. ( 1.2 )

1.1Extended Adjuvant Treatment of Early-Stage Breast Cancer NERLYNX as a single agent is indicated for the extended adjuvant treatment of adult patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer, to follow adjuvant trastuzumab based therapy [see Clinical Studies ( 14.1 )] .

1.2Advanced or Metastatic Breast Cancer NERLYNX in combination with capecitabine is indicated for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting [see Clinical Studies ( 14.2 )] .

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Premedication for diarrhea: When not using dose escalation, initiate loperamide with the first dose of NERLYNX and continue during the first 56 days of treatment. After day 56, use loperamide to maintain 1–2 bowel movements per day. ( 2.1 , 2.2 ) Extended adjuvant treatment of early-stage breast cancer: 240 mg (6 tablets) given orally once daily, with food, continuously until disease recurrence or for up to one year.

( 2.2 ) Advanced or metastatic breast cancer: 240 mg (6 tablets) given orally once daily with food on Days 1–21 of a 21-day cycle plus capecitabine (750 mg/m 2 given orally twice daily) on Days 1–14 of a 21-day cycle until disease progression or unacceptable toxicities. ( 2.2 ) Dose escalation: A two-week dose escalation for NERLYNX may also be initiated. ( 2.2 ) Dose interruptions and/or dose reductions are recommended based on individual safety and tolerability.

( 2.3 ) Hepatic impairment: Reduce starting dose to 80 mg in patients with severe hepatic impairment. ( 2.4 )

2.1Premedication for Diarrhea When not using dose escalation [see Dosage and Administration ( 2.2 )], administer antidiarrheal prophylaxis during the first 56 days of treatment and initiate with the first dose of NERLYNX [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )] . Instruct patients to take loperamide as directed in Table 1 . Titrate loperamide to 1–2 bowel movements per day.

Table 1: Loperamide Prophylaxis Time on NERLYNX Loperamide Dose and Frequency Weeks 1–2 (days 1–14) 4 mg three times daily Weeks 3–8 (days 15–56) 4 mg twice daily Weeks 9–Discontinuation of NERLYNX 4 mg as needed, not to exceed 16 mg per day; titrate dosing to achieve 1–2 bowel movements per day If diarrhea occurs despite prophylaxis, treat with additional antidiarrheals, fluids and electrolytes as clinically indicated. NERLYNX dose interruptions and dose reductions may also be required to manage diarrhea [see Dosage and Administration ( 2.3 )] .

2.2Recommended Dose and Schedule Extended Adjuvant Treatment of Early-Stage Breast Cancer The recommended dose of NERLYNX is 240 mg (six tablets) given orally once daily, with food, continuously until disease recurrence or for up to one year. Advanced or Metastatic Breast Cancer The recommended dose of NERLYNX is 240 mg (six tablets) given orally once daily with food on Days 1–21 of a 21-day cycle plus capecitabine (750 mg/m 2 given orally twice daily) on Days 1–14 of a 21-day cycle until disease progression or unacceptable toxicities.

Dose Escalation A two-week dose escalation for NERLYNX may be considered instead of starting at the 240 mg daily dose for patients with early-stage breast cancer and metastatic breast cancer, as described in Table 2 [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )] . Table 2: NERLYNX Dose Escalation and Treatment Schedule Time on NERLYNX NERLYNX Dose Week 1 (days 1–7) 120 mg daily (three 40 mg tablets) Week 2 (days 8–14) 160 mg daily (four 40 mg tablets) Week 3 and onwards 240 mg daily (six 40 mg tablets, recommended dose) If diarrhea occurs, treat with antidiarrheal medications, fluids, and electrolytes as clinically indicated.

NERLYNX dose interruptions and dose reductions may also be required to manage diarrhea [see Dosage and Administration ( 2.3 )] . Administration Instructions Instruct patients to take NERLYNX at approximately the same time every day. NERLYNX tablets should be swallowed whole (tablets should not be chewed, crushed, or split prior to swallowing).

If a patient misses a dose, do not replace missed dose, and instruct the patient to resume NERLYNX with the next scheduled daily dose.

2.3Dosage Modifications for Adverse Reactions NERLYNX dose modification is recommended based on individual safety and tolerability. Management of some adverse reactions may require dose interruption and/or dose reduction as shown in Table 3 to Table 6 . Discontinue NERLYNX for patients with adverse reactions that fail to recover t… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 39 words ▾

3 DOSAGE FORMS AND STRENGTHS Tablets: 40 mg neratinib (equivalent to 48.31 mg of neratinib maleate). Film-coated, red, oval shaped and debossed with 'W104' on one side and plain on the other side. Tablets: 40 mg. ( 3 )

⛔ Contraindications 7 words ▾

4 CONTRAINDICATIONS None. None. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Diarrhea: Manage diarrhea through either NERLYNX dose escalation or loperamide prophylaxis ( 2.1 , 2.2 ). If diarrhea occurs despite recommended prophylaxis, treat with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe and/or persistent diarrhea.

Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade ≥2 diarrhea that occurs after maximal dose reduction. ( 2.3 , 5.1 ) Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. Withhold NERLYNX in patients experiencing Grade 3 liver abnormalities and permanently discontinue NERLYNX in patients experiencing Grade 4 liver abnormalities.

( 2.3 , 5.2 ) Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 )

5.1Diarrhea Severe diarrhea and sequelae, such as dehydration, hypotension, and renal failure occurred during treatment with NERLYNX. Diarrhea was reported in 95% of NERLYNX-treated patients in ExteNET, a randomized placebo-controlled trial in the extended adjuvant setting who were not required to receive antidiarrheal prophylaxis. In the NERLYNX arm, Grade 3 diarrhea occurred in 40% and Grade 4 diarrhea occurred in 0.1% of patients.

The majority of patients (93%) had diarrhea in the first month of treatment, the median time to first onset of Grade ≥3 diarrhea was 8 days (range, 1–350), and the median cumulative duration of Grade ≥3 diarrhea was 5 days (range, 1–139) [see Adverse Reactions ( 6.1 )] . Diarrhea was reported in 83% of NERLYNX plus capecitabine treated patients in NALA, a randomized placebo-controlled trial in the metastatic breast cancer setting who were required to receive anti-diarrheal prophylaxis in the first 21-day cycle. The majority of patients (70%) had diarrhea in the first 21 days of treatment, the median time to first onset of Grade ≥3 diarrhea was 11 days (range, 2–728) and the median cumulative duration of Grade ≥3 diarrhea was 3 days (range, 1–21).

In the NERLYNX plus capecitabine arm, Grade 3 diarrhea occurred in 24% of patients [see Adverse Reactions ( 6.1 )] . Antidiarrheal prophylaxis has been shown to lower the incidence and severity of diarrhea. Instruct patients to initiate antidiarrheal prophylaxis with loperamide along with the first dose of NERLYNX and continue during the first 56 days of treatment; after day 56, titrate dose to achieve 1–2 bowel movements per day and not to exceed 16 mg loperamide per day [see Dosage and Administration ( 2.1 )] .

Consider adding other agents to loperamide as clinically indicated [see Adverse Reactions ( 6.1 )] . Alternatively, a 2-week NERLYNX dose escalation approach prior to initiation of the recommended treatment regimen with NERLYNX can also be considered for diarrhea management [see Dosage and Administration ( 2.2 )]. For patients who used NERLYNX dose escalation, the median time to first onset of Grade ≥3 diarrhea was 45 days (range, 15–132) and the median cumulative duration of Grade ≥3 diarrhea was 2.5 days (range, 1–6).

Grade 3 diarrhea occurred in 13% of patients who used NERLYNX dose escalation [see Adverse Reactions ( 6.1 )]. Monitor patients for diarrhea and treat with additional antidiarrheals as needed. When severe diarrhea with dehydration occurs, administer fluid and electrolytes as needed, interrupt NERLYNX, and reduce subsequent doses [see Dosage and Administration ( 2.3 )] .

Perform stool cultures as clinically indicated to exclude infectious causes of Grade 3 or 4 diarrhea or diarrhea of any grade with complicating features (dehydration, fever, neutropenia).

5.2Hepatotoxicity NERLYNX has been associated with hepatotoxicity characterized by increased liver enzymes. In ExteNET, 10% of patients experienced an alanine aminotransferase (ALT) increase ≥2× ULN, 5% of pati… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Diarrhea [see Warnings and Precautions ( 5.1 )] Hepatotoxicity [see Warnings and Precautions ( 5.2 )] The most common adverse reactions (reported in ≥5% of patients) were: NERLYNX as a single agent: diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increased, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased, and urinary tract infection.

( 6 ) NERLYNX in combination with capecitabine: diarrhea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, weight decreased, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract infection, abdominal distention, renal impairment, and muscle spasms. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) 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. Extended Adjuvant Treatment of Early-Stage Breast Cancer ExteNET The data described below reflect the safety data of NERLYNX as a single agent in ExteNET, a multicenter, randomized, double-blind, placebo-controlled study of NERLYNX within 2 years after completion of adjuvant treatment with trastuzumab-based therapy in women with HER2-positive early-stage breast cancer.

Patients who received NERLYNX in this trial were not required to receive any prophylaxis with antidiarrheal agents to prevent the NERLYNX-related diarrhea. Patients were treated with 240 mg of NERLYNX given orally once daily with food, continuously until disease recurrence or for up to one year. The median duration of treatment was 11.6 months in the NERLYNX arm and 11.8 months in the placebo arm.

The median age was 52 years (60% were ≥50 years old, 12% were ≥65 years old); 81% were Caucasian, 3% Black or African American, 14% Asian, and 3% other. A total of 1408 patients were treated with NERLYNX. NERLYNX dose reduction due to an adverse reaction of any grade occurred in 31% of patients receiving NERLYNX compared to 2.6% of patients receiving placebo.

Permanent discontinuation due to any adverse reaction was reported in 28% of NERLYNX-treated patients. The most common adverse reaction leading to discontinuation was diarrhea, accounting for 17% of NERLYNX-treated patients. The most common adverse reactions (≥5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increased, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased, and urinary tract infection.

The most frequently reported Grade 3 or 4 adverse reactions were diarrhea, vomiting, nausea, and abdominal pain. Serious adverse reactions in the NERLYNX arm included diarrhea (1.6%), vomiting (0.9%), dehydration (0.6%), cellulitis (0.4%), renal failure (0.4%), erysipelas (0.4%), ALT increased (0.3%), AST increased (0.3%), nausea (0.3%), fatigue (0.2%), and abdominal pain (0.2%). Table 7 summarizes the adverse reactions in ExteNET.

Table 7: Adverse Reactions Reported in ≥2% of NERLYNX-Treated Patients in ExteNET * Includes abdominal pain, abdominal pain upper, and abdominal pain lower † Includes stomatitis, aphthous stomatitis, mouth ulceration, oral mucosal blistering, mucosal inflammation, oropharyngeal pain, oral pain, glossodynia, glossitis, and cheilitis ‡ Includes rash, rash erythematous, rash follicular, rash generalized, rash pruritic, rash pustular, rash maculo-papular, rash papular, dermatitis, dermatitis acneiform, and toxic skin eruption § Includes nail disorder, paronychia, onychoclasis, nail discoloration,… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors. Separate NERLYNX by at least 2 hours before or 10 hours after H 2 -receptor antagonists. Or separate NERLYNX by at least 3 hours after antacids.

( 2.5 , 7.1 ) Strong CYP3A4 inhibitors: Avoid concomitant use. ( 7.1 ) P-gp and moderate CYP3A4 dual inhibitors: Avoid concomitant use. ( 7.1 ) Strong or moderate CYP3A4 inducers: Avoid concomitant use.

( 7.1 ) Certain P-gp substrates: Monitor for adverse reactions of P-gp substrates for which minimal concentration change may lead to serious adverse reactions when used concomitantly with NERLYNX. ( 7.2 )

7.1Effect of Other Drugs on NERLYNX Table 10 includes drug interactions that affect the pharmacokinetics of neratinib. Table 10: Drug Interactions that Affect NERLYNX AUC=Area Under Curve; C max =Maximum Concentration Gastric Acid Reducing Agents Clinical Impact Concomitant use of NERLYNX with a proton pump inhibitor (PPI), H 2 -receptor antagonist, or antacid may decrease neratinib AUC [see Clinical Pharmacology ( 12.3 )], which may reduce NERLYNX activity. Prevention or Management [see Dosage and Administration ( 2.5 )] Avoid concomitant use of PPIs.

Separate administration of NERLYNX at least 2 hours before or 10 hours after the H 2 -receptor antagonist dose. Separate administration of NERLYNX by at least 3 hours after antacids. Strong CYP3A4 Inhibitors Clinical Impact Concomitant use of NERLYNX with a strong CYP3A4 inhibitor increased neratinib C max and AUC [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of NERLYNX toxicity.

Prevention or Management Avoid concomitant use of NERLYNX with strong CYP3A4 inhibitors. P-gp and Moderate CYP3A4 Dual Inhibitors Clinical Impact Concomitant use of NERLYNX with a P-gp and moderate CYP3A4 dual inhibitor may increase neratinib C max and AUC [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of NERLYNX toxicity. Prevention or Management Avoid concomitant use of NERLYNX with P-gp and moderate CYP3A4 dual inhibitors.

Strong or Moderate CYP3A4 Inducers Clinical Impact Concomitant use of NERLYNX with a strong CYP3A4 inducer reduced neratinib C max and AUC [see Clinical Pharmacology ( 12.3 )] , which may reduce NERLYNX activity. Prevention or Management Avoid concomitant use of NERLYNX with strong or moderate CYP3A4 inducers.

7.2Effect of NERLYNX on Other Drugs Certain P-glycoprotein (P-gp) Substrates Concomitant use of NERLYNX increased concentrations of a P-gp substrate [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of adverse reactions of these substrates. Monitor for adverse reactions of certain P-gp substrates for which minimal concentration changes may lead to serious adverse reactions.

👥 Use in Specific Populations ~3 min read ▾

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

8.1Pregnancy Risk Summary Based on findings from animal studies and the mechanism of action, NERLYNX can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of neratinib to pregnant rabbits during organogenesis resulted in abortions, embryo-fetal death and fetal abnormalities in rabbits at maternal exposures (AUC) approximately 0.2 times exposures in patients at the recommended dose ( see Data ).

Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk of major birth defects is 2%–4% and of miscarriage is 15%–20% of clinically recognized pregnancies in the U.S. general population.

Data Animal Data In a fertility and early embryonic development study in female rats, neratinib was administered orally for 15 days before mating to Day 7 of pregnancy, which did not cause embryonic toxicity at doses up to 12 mg/kg/day in the presence of maternal toxicity. A dose of 12 mg/kg/day in rats is approximately 0.5 times the maximum recommended dose of 240 mg/day in patients on a mg/m 2 basis. In an embryo-fetal development study in rats, pregnant animals received oral doses of neratinib up to 15 mg/kg/day during the period of organogenesis.

No effects on embryo-fetal development or survival were observed. Maternal toxicity was evident at 15 mg/kg/day (approximately 0.6 times the AUC in patients receiving the maximum recommended dose of 240 mg/day). In an embryo-fetal development study in rabbits, pregnant animals received oral doses of neratinib up to 9 mg/kg/day during the period of organogenesis.

Administration of neratinib at doses ≥6 mg/kg/day resulted in maternal toxicity, abortions, and embryo-fetal death (increased resorptions). Neratinib administration resulted in increased incidence of fetal gross external (domed head), soft tissue (dilation of the brain ventricles and ventricular septal defect), and skeletal (misshapen anterior fontanelles and enlarged anterior and/or posterior fontanelles) abnormalities at ≥3 mg/kg/day. The AUC (0-t) at 6 mg/kg/day and 9 mg/kg/day in rabbits were approximately 0.5 and 0.8 times, respectively, the AUCs in patients receiving the maximum recommended dose of 240 mg/day.

In a peri- and postnatal development study in rats, oral administration of neratinib from gestation day 7 until lactation day 20 resulted in maternal toxicity at ≥10 mg/kg/day (approximately 0.4 times the maximum recommended dose of 240 mg/day in patients on a mg/m 2 basis) including decreased body weights, body weight gains, and food consumption. Effects on long-term memory were observed in male offspring at maternal doses ≥5 mg/kg/day (approximately 0.2 times the maximum recommended dose of 240 mg/day in patients on a mg/m 2 basis).

8.2Lactation Risk Summary No data are available regarding the presence of neratinib or its metabolites in human milk or its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in breastfed infants from NERLYNX, advise lactating women not to breastfeed while taking NERLYNX and for at least 1 month after the last dose.

8.3Females and Males of Reproductive Potential Pregnancy Based on animal studies, NERLYNX can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Females of reproductive potential should have a pregnancy test prior to starting treatment with NERLYNX. Contraception Females Based on animal studies, NERLYNX can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] .

Advise females of reproductive potential to use effective contraception during treatment with NERLYNX and for… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary Based on findings from animal studies and the mechanism of action, NERLYNX can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of neratinib to pregnant rabbits during organogenesis resulted in abortions, embryo-fetal death and fetal abnormalities in rabbits at maternal exposures (AUC) approximately 0.2 times exposures in patients at the recommended dose ( see Data ).

Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk of major birth defects is 2%–4% and of miscarriage is 15%–20% of clinically recognized pregnancies in the U.S. general population.

Data Animal Data In a fertility and early embryonic development study in female rats, neratinib was administered orally for 15 days before mating to Day 7 of pregnancy, which did not cause embryonic toxicity at doses up to 12 mg/kg/day in the presence of maternal toxicity. A dose of 12 mg/kg/day in rats is approximately 0.5 times the maximum recommended dose of 240 mg/day in patients on a mg/m 2 basis. In an embryo-fetal development study in rats, pregnant animals received oral doses of neratinib up to 15 mg/kg/day during the period of organogenesis.

No effects on embryo-fetal development or survival were observed. Maternal toxicity was evident at 15 mg/kg/day (approximately 0.6 times the AUC in patients receiving the maximum recommended dose of 240 mg/day). In an embryo-fetal development study in rabbits, pregnant animals received oral doses of neratinib up to 9 mg/kg/day during the period of organogenesis.

Administration of neratinib at doses ≥6 mg/kg/day resulted in maternal toxicity, abortions, and embryo-fetal death (increased resorptions). Neratinib administration resulted in increased incidence of fetal gross external (domed head), soft tissue (dilation of the brain ventricles and ventricular septal defect), and skeletal (misshapen anterior fontanelles and enlarged anterior and/or posterior fontanelles) abnormalities at ≥3 mg/kg/day. The AUC (0-t) at 6 mg/kg/day and 9 mg/kg/day in rabbits were approximately 0.5 and 0.8 times, respectively, the AUCs in patients receiving the maximum recommended dose of 240 mg/day.

In a peri- and postnatal development study in rats, oral administration of neratinib from gestation day 7 until lactation day 20 resulted in maternal toxicity at ≥10 mg/kg/day (approximately 0.4 times the maximum recommended dose of 240 mg/day in patients on a mg/m 2 basis) including decreased body weights, body weight gains, and food consumption. Effects on long-term memory were observed in male offspring at maternal doses ≥5 mg/kg/day (approximately 0.2 times the maximum recommended dose of 240 mg/day in patients on a mg/m 2 basis).

🧒 Pediatric Use 16 words ▾

8.4Pediatric Use The safety and efficacy of NERLYNX in pediatric patients has not been established.

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use In the ExteNET trial, in the NERLYNX arm; 1236 patients were <65 years, 172 patients were ≥65 years, of whom 25 patients were 75 years or older. There was a higher frequency of treatment discontinuations due to adverse reactions in the ≥65 years age group than in the <65 years age group; in the NERLYNX arm, the percentages were 45% compared with 25%, respectively, and in the placebo arm 6% and 5%, respectively. The incidence of serious adverse reactions in the NERLYNX arm vs placebo arm was 7% vs 6% (<65 years old) and 10% vs 8% (≥65 years old).

The serious adverse reactions most frequently reported in the ≥65 years old group were vomiting (2.3%), diarrhea (1.7%), renal failure (1.7%), and dehydration (1.2%). In the NALA trial, in the NERLYNX plus capecitabine arm; 242 patients were <65 years, 61 patients were ≥65 years, of whom 12 patients were 75 years or older. The incidence of serious adverse reactions in the NERLYNX plus capecitabine arm in the ≥65 years age group was 36% and in the <65 years age group was 34%.

The serious adverse reactions most frequently reported in the ≥65 years age group were diarrhea (16%), acute kidney injury (8%), and dehydration (7%). No overall differences in effectiveness were observed between patients ≥65 years old and patients <65 years old.

🆘 Overdosage 78 words ▾

10 OVERDOSAGE There is no specific antidote, and the benefit of hemodialysis in the treatment of NERLYNX overdose is unknown. In the event of an overdose, administration should be withheld and general supportive measures undertaken. In the clinical trial setting, a limited number of patients reported overdose.

The adverse reactions experienced by these patients were diarrhea, nausea, vomiting, and dehydration. The frequency and severity of gastrointestinal disorders (diarrhea, abdominal pain, nausea, and vomiting) appear to be dose related.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Neratinib is an intracellular kinase inhibitor that irreversibly binds to epidermal growth factor receptor (EGFR), HER2, and HER4. In vitro , neratinib reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signaling pathways, and showed antitumor activity in EGFR and/or HER2 expressing carcinoma cell lines. Neratinib human metabolites M3, M6, M7 and M11 inhibited the activity of EGFR, HER2, and HER4 in vitro.

In vivo , oral administration of neratinib inhibited tumor growth in mouse xenograft models with tumor cell lines expressing HER2 and EGFR.

12.2Pharmacodynamics Neratinib exposure-response relationships and the time course of pharmacodynamic response are unknown. Cardiac Electrophysiology The effect of NERLYNX on the QTc interval was evaluated in a randomized, placebo, and positive-controlled, double-blind, single-dose, crossover study in 60 healthy subjects. At 140% the therapeutic exposures of NERLYNX, there was no clinically relevant effect on the QTc interval.

12.3Pharmacokinetics Neratinib AUC increases in less than dose proportional manner over a daily dose range of 40 to 400 mg (0.17 to 1.7 times the maximum approved recommended dosage). Absorption Peak concentrations of neratinib and major active metabolites M3, M6 and M7 are reached in the range of 2 to 8 hours after oral administration. Effect of Food A high-fat meal (approximately 55% fat, 31% carbohydrate, and 14% protein) increased neratinib C max and AUC inf by 70% (90% CI: 1.1–2.7) and 120% (90% CI: 1.4–3.5), respectively, in healthy subjects compared to fasting conditions.

A standard breakfast (approximately 50% carbohydrate, 35% fat, and 15% protein) increased the C max and AUC inf by 20% (90% CI: 0.97–1.42) and 10% (90% CI: 1.02–1.24), respectively, in healthy subjects [see Dosage and Administration ( 2.2 )] . Distribution The mean (%CV) apparent volume of distribution at steady state (V ss /F) was 6433 (19%) L in patients. In vitro protein binding of neratinib was greater than 99%, predominantly to serum albumin and alpha-1 acid glycoprotein, and was independent of concentration.

Elimination The mean (%CV) plasma half-life of neratinib, M3, M6, and M7 was 14.6 (38%), 21.6 (77%), 13.8 (50%) and 10.4 (33%) hours, respectively, in healthy subjects. The mean elimination half-life of neratinib ranged from 7 to 17 hours following a single oral dose in patients. The mean (%CV) CL/F after first dose and at steady state (day 21) were 216 (34%) and 281 (40%) L/hour, respectively, in patients.

Metabolism Neratinib is metabolized primarily in the liver by CYP3A4 and to a lesser extent by flavin-containing monooxygenase (FMO). Neratinib represents the most prominent component in plasma. The systemic exposures (AUC) of the active metabolites M3, M6, M7 and M11 were 15%, 33%, 22%, and 4% of the systemic neratinib exposure, respectively, at steady state in healthy subjects.

Excretion After oral administration of radiolabeled neratinib 200 mg (0.83 times of maximum approved recommended dosage), fecal excretion accounted for approximately 97% and urinary excretion accounted for 1.1% of the total dose. Sixty-one percent of the excreted radioactivity was recovered within 96 hours and 98% was recovered after 10 days. Specific Populations Age, sex, race, and renal function do not have a clinically significant effect on neratinib pharmacokinetics.

Patients With Hepatic Impairment Neratinib exposures in patients with mild (Child Pugh A) and moderate hepatic impairment (Child Pugh B) were similar to that in healthy subjects with normal hepatic function. Neratinib C max and AUC increased by 173% and 181%, respectively, in patients with severe hepatic impairment (Child Pugh C) as compared to subjects with normal hepatic function [see Dosage and Administration ( 2.4 ) and Use in Specific Populations ( 8.6 )] . Drug Interaction Studies Clinical Studies and Model-Informed Approaches Gastric Acid Reducing Agents: Concom… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 89 words ▾

12.1Mechanism of Action Neratinib is an intracellular kinase inhibitor that irreversibly binds to epidermal growth factor receptor (EGFR), HER2, and HER4. In vitro , neratinib reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signaling pathways, and showed antitumor activity in EGFR and/or HER2 expressing carcinoma cell lines. Neratinib human metabolites M3, M6, M7 and M11 inhibited the activity of EGFR, HER2, and HER4 in vitro.

In vivo , oral administration of neratinib inhibited tumor growth in mouse xenograft models with tumor cell lines expressing HER2 and EGFR.

📦 How Supplied / Storage and Handling 75 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING NERLYNX 40 mg film-coated tablets are red, oval shaped and debossed with 'W104' on one side and plain on the other side. NERLYNX is available in: Bottles of 180 tablets: NDC 70437-240-18 Bottles of 133 tablets: NDC 70437-240-33 Bottles of 126 tablets: NDC 70437-240-26 Store at controlled room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] .

📋 Description 161 words ▾

11 DESCRIPTION NERLYNX (neratinib) immediate release, film-coated tablets for oral administration contain 40 mg of neratinib, equivalent to 48.31 mg neratinib maleate. Neratinib is a member of the 4-anilino quinolidine class of protein kinase inhibitors. The molecular formula for neratinib maleate is C 30 H 29 ClN 6 O 3 •C 4 H 4 O 4 and the molecular weight is 673.11 Daltons.

The chemical name is (E)-N-{4-[3-chloro-4-(pyridin-2-yl methoxy)anilino]-3-cyano-7-ethoxyquinolin-6-yl}-4-(dimethylamino)but-2-enamide maleate, and its structural formula is: Neratinib maleate is an off-white to yellow powder with pK a s of 7.65 and 4.66. The solubility of neratinib maleate increases dramatically as neratinib becomes protonated at acidic pH. Neratinib maleate is sparingly soluble at pH 1.2 (32.90 mg/mL) and insoluble at approximately pH 5.0 and above (0.08 mg/mL or less).

Inactive ingredients: Tablet Core: colloidal silicon dioxide, mannitol, microcrystalline cellulose, crospovidone, povidone, magnesium stearate, and purified water. Coating: red film coat: polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and iron oxide red. Structural Formula

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information ). Diarrhea Inform patients that NERLYNX has been associated with diarrhea, which may be severe in some cases. When not using dose escalation, instruct patients to initiate antidiarrheal prophylaxis with the first dose of NERLYNX.

When using dose escalation, instruct patients to initiate 2 weeks of lower dose NERLYNX prior to receiving the recommended full dose of NERLYNX. Instruct patients to maintain 1–2 bowel movements per day and on how to use antidiarrheal treatment regimens. Advise patients to inform their healthcare provider immediately if severe (≥Grade 3) diarrhea or diarrhea associated with weakness, dizziness, or fever occurs during treatment with NERLYNX [see Dosage and Administration ( 2.1 , 2.2 ) and Warnings and Precautions ( 5.1 )] .

Hepatotoxicity Inform patients that NERLYNX has been associated with hepatotoxicity which may be severe in some cases. Inform patients that they should report signs and symptoms of liver dysfunction to their healthcare provider immediately [see Warnings and Precautions ( 5.2 )] . Embryo-Fetal Toxicity Advise females to inform their healthcare provider if they are pregnant or become pregnant.

Inform female patients of the risk to a fetus and potential loss of the pregnancy [see Use in Specific Populations ( 8.1 )] . Advise females of reproductive potential to use effective contraception during treatment and for 1 month after receiving the last dose of NERLYNX [see Warnings and Precautions ( 5.3 ) and Use in Specific Populations ( 8.1 , 8.3 )] . Advise lactating women not to breastfeed during treatment with NERLYNX and for at least 1 month after the last dose [see Use in Specific Populations ( 8.2 )] .

Drug Interactions NERLYNX may interact with many drugs; therefore, advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products [see Dosage and Administration ( 2.5 ) and Clinical Pharmacology ( 12.3 )] . NERLYNX may interact with gastric acid reducing agents. Advise patients to avoid concomitant use of proton pump inhibitors.

When patients require gastric acid reducing agents, use an H 2 -receptor antagonist or antacid. Advise patients to separate the dosing of NERLYNX by 3 hours after antacid medicine, and to take NERLYNX at least 2 hours before or 10 hours after a H 2 -receptor antagonist [see Dosage and Administration ( 2.5 ) and Drug Interactions ( 7.1 )] . NERLYNX may interact with grapefruit.

Advise patients to avoid taking NERLYNX with grapefruit products [see Drug Interactions ( 7.1 )] . Dosing and Administration For patients undergoing extended adjuvant treatment for early-stage breast cancer, instruct patients to take NERLYNX with food at approximately the same time each day consecutively until disease recurrence or for up to one year. For patients undergoing treatment for metastatic breast cancer, instruct patients to take NERLYNX with food on days 1–21 of a 21-day cycle, with capecitabine on Days 1–14 of a 21-day cycle until disease progression or unacceptable toxicities.

If a patient misses a dose, instruct the patient not to replace the missed dose, and to resume NERLYNX with the next scheduled daily dose [see Dosage and Administration ( 2.2 )] . Manufactured for Puma Biotechnology, Inc. 10880 Wilshire Blvd., Suite 1700 Los Angeles, CA 90024-4106 ©2025, Puma Biotechnology, Inc.

All Rights Reserved.

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Neratinib AUC increases in less than dose proportional manner over a daily dose range of 40 to 400 mg (0.17 to 1.7 times the maximum approved recommended dosage). Absorption Peak concentrations of neratinib and major active metabolites M3, M6 and M7 are reached in the range of 2 to 8 hours after oral administration. Effect of Food A high-fat meal (approximately 55% fat, 31% carbohydrate, and 14% protein) increased neratinib C max and AUC inf by 70% (90% CI: 1.1–2.7) and 120% (90% CI: 1.4–3.5), respectively, in healthy subjects compared to fasting conditions.

A standard breakfast (approximately 50% carbohydrate, 35% fat, and 15% protein) increased the C max and AUC inf by 20% (90% CI: 0.97–1.42) and 10% (90% CI: 1.02–1.24), respectively, in healthy subjects [see Dosage and Administration ( 2.2 )] . Distribution The mean (%CV) apparent volume of distribution at steady state (V ss /F) was 6433 (19%) L in patients. In vitro protein binding of neratinib was greater than 99%, predominantly to serum albumin and alpha-1 acid glycoprotein, and was independent of concentration.

Elimination The mean (%CV) plasma half-life of neratinib, M3, M6, and M7 was 14.6 (38%), 21.6 (77%), 13.8 (50%) and 10.4 (33%) hours, respectively, in healthy subjects. The mean elimination half-life of neratinib ranged from 7 to 17 hours following a single oral dose in patients. The mean (%CV) CL/F after first dose and at steady state (day 21) were 216 (34%) and 281 (40%) L/hour, respectively, in patients.

Metabolism Neratinib is metabolized primarily in the liver by CYP3A4 and to a lesser extent by flavin-containing monooxygenase (FMO). Neratinib represents the most prominent component in plasma. The systemic exposures (AUC) of the active metabolites M3, M6, M7 and M11 were 15%, 33%, 22%, and 4% of the systemic neratinib exposure, respectively, at steady state in healthy subjects.

Excretion After oral administration of radiolabeled neratinib 200 mg (0.83 times of maximum approved recommended dosage), fecal excretion accounted for approximately 97% and urinary excretion accounted for 1.1% of the total dose. Sixty-one percent of the excreted radioactivity was recovered within 96 hours and 98% was recovered after 10 days. Specific Populations Age, sex, race, and renal function do not have a clinically significant effect on neratinib pharmacokinetics.

Patients With Hepatic Impairment Neratinib exposures in patients with mild (Child Pugh A) and moderate hepatic impairment (Child Pugh B) were similar to that in healthy subjects with normal hepatic function. Neratinib C max and AUC increased by 173% and 181%, respectively, in patients with severe hepatic impairment (Child Pugh C) as compared to subjects with normal hepatic function [see Dosage and Administration ( 2.4 ) and Use in Specific Populations ( 8.6 )] . Drug Interaction Studies Clinical Studies and Model-Informed Approaches Gastric Acid Reducing Agents: Concomitant use with lansoprazole (proton pump inhibitor) decreased neratinib C max by 71% and AUC by 65%.

When NERLYNX was administered 2 hours after ranitidine (H 2 receptor antagonist), the neratinib C max was reduced by 57% and AUC by 48%. When NERLYNX was administered 2 hours prior to ranitidine, neratinib C max was reduced by 44% and AUC by 32% [see Dosage and Administration ( 2.5 ) and Drug Interactions ( 7.1 )] . Strong CYP3A4 Inhibitors: Concomitant use of ketoconazole (strong inhibitor of CYP3A4 and P-gp inhibitor) increased neratinib C max by 221% and AUC by 381% [see Drug Interactions ( 7.1 )] .

P-gp and moderate CYP3A4 Dual Inhibitors: Verapamil (moderate CYP3A4 and P-gp dual inhibitor) increased the C max and AUC of neratinib by 203% and 299%, respectively [see Drug Interactions ( 7.1 )] . Moderate CYP3A4 Inhibitors: Fluconazole (moderate CYP3A4 inhibitor) increased the C max and AUC of neratinib by 30% and 68%, respectively. Strong and Moderate CYP3A4 Inducers: Concomitant use of rifampin (strong CYP3A4 inducer) decreased n… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 57 words ▾

12.2Pharmacodynamics Neratinib exposure-response relationships and the time course of pharmacodynamic response are unknown. Cardiac Electrophysiology The effect of NERLYNX on the QTc interval was evaluated in a randomized, placebo, and positive-controlled, double-blind, single-dose, crossover study in 60 healthy subjects. At 140% the therapeutic exposures of NERLYNX, there was no clinically relevant effect on the QTc interval.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Extended Adjuvant Treatment of Early-Stage Breast Cancer The safety and efficacy of NERLYNX were investigated in the ExteNET trial (NCT00878709), a multicenter, randomized, double-blind, placebo-controlled study of NERLYNX after adjuvant treatment with a trastuzumab based therapy in women with HER2-positive breast cancer. A total of 2840 patients with early-stage (Stage 1 to 3c) HER2-positive breast cancer within two years of completing treatment with adjuvant trastuzumab was randomized to receive either NERLYNX (n=1420) or placebo (n=1420).

Randomization was stratified by the following factors: hormone receptor status, nodal status (0, 1–3, vs 4 or more positive nodes) and whether trastuzumab was given sequentially versus concurrently with chemotherapy. NERLYNX 240 mg or placebo was given orally once daily for one year. The major efficacy outcome measure was invasive disease-free survival (iDFS) defined as the time between the date of randomization to the first occurrence of invasive recurrence (local/regional, ipsilateral, or contralateral breast cancer), distant recurrence, or death from any cause, with 2 years and 28 days of follow-up.

Patient demographics and tumor characteristics were generally balanced between treatment arms. Patients had a median age of 52 years (range 23 to 83) and 12% of patients were 65 or older. The majority of patients were White (81%), and most patients (99.7%) had an ECOG performance status of 0 or 1.

Fifty-seven percent (57%) of patients had hormone receptor positive disease (defined as ER-positive and/or PR-positive), 24% were node negative, 47% had one to three positive nodes and 30% had four or more positive nodes. Ten percent (10%) of patients had Stage I disease, 41% had Stage II disease and 31% had Stage III disease. The majority of patients (81%) were enrolled within one year of completion of trastuzumab treatment.

Median time from the last adjuvant trastuzumab treatment to randomization was 4.4 months in the NERLYNX arm versus 4.6 months in the placebo arm. Median duration of treatment was 11.6 months in the NERLYNX arm vs 11.8 months in the placebo arm. The efficacy results from the ExteNET trial are summarized in Table 11 and Figure 1 .

Table 11: Efficacy iDFS Results for the ITT Population CI= Confidence Interval; HR=Hazard Ratio; iDFS=Invasive Disease Free-Survival; ITT=Intent to Treat * Kaplan-Meier estimate † Stratified by prior trastuzumab (concurrent vs sequential), nodal status (0–3 positive nodes vs ≥4 positive nodes), and ER/PR status (positive vs negative) ‡ Stratified log-rank test Number of Events/Total N (%) iDFS at 24 months,* % (95% CI) Stratified † HR (95% CI) P-value ‡ NERLYNX Placebo NERLYNX Placebo 67/1420 (4.7) 106/1420 (7.5) 94.2 (92.6, 95.4) 91.9 (90.2, 93.2) 0.66 (0.49, 0.90) 0.008 Figure 1: iDFS in the ExteNET Trial - ITT Population CI=Confidence Interval; iDFS=Invasive Disease Free-Survival; ITT=Intent to Treat Table 12: Subgroup Analyses* CI=Confidence Interval; HR=Hazard Ratio * Exploratory analyses without adjusting multiple comparisons † Kaplan-Meier estimate Population Number of Events/Total N (%) iDFS at 24 Months, † % (95% CI) Unstratified HR (95% CI) NERLYNX Placebo NERLYNX Placebo Hormone Receptor Status Positive 29/816 (3.6) 63/815 (7.7) 95.6 (93.8, 96.9) 91.5 (89.2, 93.3) 0.49 (0.31, 0.75) Negative 38/604 (6.3) 43/605 (7.1) 92.2 (89.4, 94.3) 92.4 (89.8, 94.3) 0.93 (0.60, 1.43) Nodal Status Negative 7/335 (2.1) 11/336 (3.3) 97.2 (94.1, 98.7) 96.5 (93.7, 98.0) 0.72 (0.26, 1.83) 1–3 Positive Nodes 31/664 (4.7) 47/664 (7.1) 94.4 (92.2, 96.1) 92.4 (90.0, 94.2) 0.68 (0.43, 1.07) ≥4 Positive Nodes 29/421 (6.9) 48/420 (11.4) 91.4 (87.9, 94.0) 87.3 (83.4, 90.2) 0.62 (0.39, 0.97) Prior Trastuzumab Concurrent 49/884 (5.5) 66/886 (7.4) 93.2 (91.0, 94.8) 92.0 (89.9, 93.7) 0.80 (0.55, 1.16) Sequential 18/536 (3.4) 40/534 (7.5) 95.8 (93.4, 97.3) 91.6 (88.7, 93.8) 0.46 (0.26, 0.78) Completion of Prior Trastuzumab ≤1 Year 58/1152 (5.0) 95/11… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 209 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility A two-year carcinogenicity study was conducted in rats at oral neratinib doses of 1, 3, and 10 mg/kg/day. Neratinib was not carcinogenic in male and female rats at exposure levels >25 times the AUC in patients receiving the maximum recommended dose of 240 mg/day. Neratinib was not carcinogenic in a 26-week study in Tg.rasH2 transgenic mice when administered daily by oral gavage at doses up to 50 mg/kg/day in males and 125 mg/kg/day in females.

Neratinib was not mutagenic in an in vitro bacterial reverse mutation (AMES) assay or clastogenic in an in vitro human lymphocyte chromosomal aberration assay or an in vivo rat bone marrow micronucleus assay. In a fertility study in rats, neratinib administration up to 12 mg/kg/day (approximately 0.5 times the maximum recommended dose of 240 mg/day in patients on a mg/m 2 basis) caused no effects on mating or the ability of animals to become pregnant. In repeat-dose toxicity studies in dogs with oral administration of neratinib daily for up to 39 weeks, tubular hypoplasia of the testes was observed at ≥0.5 mg/kg/day.

This finding was observed at AUCs that were approximately 0.4 times the AUC in patients at the maximum recommended dose of 240 mg.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 206 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility A two-year carcinogenicity study was conducted in rats at oral neratinib doses of 1, 3, and 10 mg/kg/day. Neratinib was not carcinogenic in male and female rats at exposure levels >25 times the AUC in patients receiving the maximum recommended dose of 240 mg/day. Neratinib was not carcinogenic in a 26-week study in Tg.rasH2 transgenic mice when administered daily by oral gavage at doses up to 50 mg/kg/day in males and 125 mg/kg/day in females.

Neratinib was not mutagenic in an in vitro bacterial reverse mutation (AMES) assay or clastogenic in an in vitro human lymphocyte chromosomal aberration assay or an in vivo rat bone marrow micronucleus assay. In a fertility study in rats, neratinib administration up to 12 mg/kg/day (approximately 0.5 times the maximum recommended dose of 240 mg/day in patients on a mg/m 2 basis) caused no effects on mating or the ability of animals to become pregnant. In repeat-dose toxicity studies in dogs with oral administration of neratinib daily for up to 39 weeks, tubular hypoplasia of the testes was observed at ≥0.5 mg/kg/day.

This finding was observed at AUCs that were approximately 0.4 times the AUC in patients at the maximum recommended dose of 240 mg.

📄 Patient Package Insert ~3 min read ▾

This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 12/2025 PATIENT INFORMATION NERLYNX ® (ner links) (neratinib) tablets What is the most important information I should know about NERLYNX?

NERLYNX may cause serious side effects, including: Diarrhea. Diarrhea is a common side effect of NERLYNX, but it can also be severe. Diarrhea may lead to loss of too much body salts and fluid, which can cause dehydration.

Your healthcare provider will prescribe NERLYNX in one of two ways to help manage diarrhea: Full dose of NERLYNX: Your healthcare provider will prescribe the antidiarrheal medicine loperamide for you during your first 2 months (56 days) of treatment with NERLYNX and then as needed. Your healthcare provider will tell you exactly how much and how often to take this medicine. If you are prescribed the full dose of NERLYNX from the start of your treatment, be sure that your healthcare provider also prescribes antidiarrheals with NERLYNX.

You should start taking loperamide with your first dose of NERLYNX. After 2 months (56 days) of treatment with NERLYNX, follow your healthcare provider's instructions about taking loperamide as needed to control diarrhea. A lower starting dose of NERLYNX: Your healthcare provider will start you on a lower dose of NERLYNX for the first 2 weeks of treatment and then increase you to a full dose NERLYNX regimen.

Tell your healthcare provider right away if you develop diarrhea. You may be prescribed loperamide as needed. To help prevent or reduce diarrhea during treatment with NERLYNX: Your healthcare provider may also need to give you additional antidiarrheals, fluids, and electrolytes to manage diarrhea when you start treatment with NERLYNX.

Follow your healthcare provider's instructions on how to take antidiarrheal medicines. Always take antidiarrheals exactly as your healthcare provider tells you. While taking antidiarrheals, you and your healthcare provider should try to keep the number of bowel movements that you have at 1 or 2 bowel movements each day.

Tell your healthcare provider if you have more than 2 bowel movements in 1 day, or you have diarrhea that does not go away. Call your healthcare provider right away if you have severe diarrhea or if you have diarrhea along with weakness, dizziness, or fever. Your healthcare provider may change your dose of NERLYNX, temporarily stop, or completely stop NERLYNX if needed to manage your diarrhea.

See " What are the possible side effects of NERLYNX? " for more information about side effects. What is NERLYNX? NERLYNX is a prescription medicine used alone to treat adults with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer and who have previously been treated with trastuzumab-based therapy.

NERLYNX is also used with a medicine called capecitabine to treat adults with HER2-positive breast cancer that has spread to other parts of the body (metastatic) and who have received 2 or more anti-HER2 therapy medicines for metastatic breast cancer. It is not known if NERLYNX is safe and effective in children. Before taking NERLYNX, tell your healthcare provider about all of your medical conditions, including if you: have liver problems.

You may need a lower dose of NERLYNX. are pregnant or plan to become pregnant. NERLYNX can harm your unborn baby. If you are a female who can become pregnant: Your healthcare provider should do a pregnancy test before you start taking NERLYNX.

You should use effective birth control (contraception) during treatment and for at least 1 month after your last dose of NERLYNX. Talk with your healthcare provider about forms of birth control that you can use during this time. Tell your healthcare provider right away if you become pregnant during treatment with NERLYNX.

Males with female partners who can become pregnant should use effective birth control during treatment and for 3 months after the last dose of NERLYNX. are breastfeeding or plan to breastfeed. I… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 215 words ▾

Principal Display Panel - Nerlynx 180 Tablets Carton Label NDC 70437-240-18 nerlynx™ (neratinib) tablets 40 mg Each film-coated tablet contains 40 mg neratinib equivalent to 48.31 mg neratinib maleate. 180 tablets Rx only Principal Display Panel - Nerlynx 180 Tablets Carton Label

Principal Display Panel - Nerlynx 180 Tablets Bottle Label NDC 70437-240-18 nerlynx™ (neratinib) tablets 40 mg Rx only 180 tablets Principal Display Panel - Nerlynx 180 Tablets Bottle Label

Principal Display Panel - Nerlynx 126 Tablets Carton Label NDC 70437-240-26 nerlynx™ (neratinib) tablets 40 mg Each film-coated tablet contains 40 mg neratinib equivalent to 48.31 mg neratinib maleate. 126 tablets Rx only Principal Display Panel - Nerlynx 126 Tablets Carton Label

Principal Display Panel - Nerlynx 126 Tablets Bottle Label NDC 70437-240-26 nerlynx™ (neratinib) tablets 40 mg Rx only 126 tablets Principal Display Panel - Nerlynx 126 Tablets Bottle Label

Principal Display Panel - Nerlynx 133 Tablets Carton Label NDC 70437-240-33 nerlynx ® (neratinib) tablets 40 mg Each film-coated tablet contains 40 mg neratinib equivalent to 48.31 mg neratinib maleate. 133 tablets Rx only Principal Display Panel - Nerlynx 133 Tablets Carton Label

Principal Display Panel - Nerlynx 133 Tablets Bottle Label NDC 70437-240-33 nerlynx ® (neratinib) tablets 40 mg Rx only 133 tablets Principal Display Panel - Nerlynx 133 Tablets Bottle Label

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

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
96
Units reimbursed last 4 qtrs
12.5K
Gross reimbursed last 4 qtrs
$1.66M
Avg / prescription
$17,314.25
Avg / unit
$133.15
Latest quarter Q1 2026
40Rx
Fee-for-service vs managed care ⓘ
100% FFS
Fee-for-service · 96 Rx Managed care · 0 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: no data reported NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: 12,483 units · 32.0 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
32.032.0
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 California 32.0 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

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.
180 tablets70437-0240-18 856 Rx · $17,646,355
133 tablets this page70437-0240-33 96 Rx · $1,662,168
126 tablets70437-0240-26 No Medicaid data
Drug total (last 4 qtrs): 952 Rx · 146,678 units · $19,308,523 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 Nerlynx — 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 Nerlynx. 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
$15.03M
Claims incl. refills
766
Beneficiaries
363
Spend / beneficiary
$41,412.94
Spend / claim
$19,625.19
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.

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 ✓ Available
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) ✓ Available
“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 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.
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 Puma Biotechnology, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 2 other package presentations of this same product, including 126 tablets (70437-0240-26), 180 tablets (70437-0240-18). 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?
Puma Biotechnology, Inc. 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.
← 70436-0232-50 · Slate 70440-0001-01 · Mentha →
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.