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Gilotrif afatinib 40 mg Tablet, Film Coated, 30-count — NDC 00597-0138-95 package photo

Gilotrif afatinib 40 mg Tablet, Film Coated, 30-count

by Boehringer Ingelheim Pharmaceuticals, Inc. · 1 BOTTLE in 1 CARTON (0597-0138-95) / 30 TABLET, FILM COATED in 1 BOTTLE
NDC 00597-0138-95
🏷️ FDA NDC (as labeled) 0597-0138-95 billing pads the labeler segment with a zero
This package
Contains30-count Pack sizes2 compare ↓
Also priced by: Part D plans $396.91/unit — full pricing hub ↓
Also comes in: 30 tablets 00597-0138-30
Rx only Brand On market Non-controlled
🗂️ Data synced 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

🆔 Identity & classification

FDA NDC (as labeled) 0597-0138-95
Product NDC 0597-0138
11-digit billing NDC 00597013895
RxCUI 1430446, 1430449, 1430451, 1430453, 1430455, 1430457
UNII 41UD74L59M
Application # NDA201292
SPL Set ID fd638e5e-8032-e7ca-0179-95e96ab5d387
Established class (EPC) Kinase Inhibitor
Mechanism of action Protein Kinase Inhibitors
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2013-07-12
Route ORAL
Dosage form TABLET, FILM COATED
Substance AFATINIB
GPI-14 21360006100340
GPI class Gilotrif
GCN Seq No 071231
GCN 34958
HICL code 040478
Ingredient (HICL) Afatinib Dimaleate
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 GILOTRIF 40 MG TABLET
FDB brand name Gilotrif
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 0597-0138-95 — a 4-4-2 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 labeler segment → 00597-0138-95. 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) Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
How it works Protein Kinase Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerBoehringer Ingelheim Pharmaceuticals, Inc.
Application holderBOEHRINGER INGELHEIM
FDA applicationNDA201292 (NDA)
Labeler code00597
First marketedJul 2013
Product typeHuman Prescription Drug
Portfolio65 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name GILOTRIF 40 MG TABLET Ingredient Afatinib Dimaleate
📖 What it is MedlinePlus · NLM

Afatinib is used to treat certain types of non-small cell lung cancer that has spread to nearby tissues or to other parts of the body. Afatinib is in a class of medications called kinase inhibitors. It works by blocking the action of a certain naturally occurring substance that may be needed to help cancer cells multiply.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Gilotrif targets a specific type of lung cancer called metastatic non-small cell lung cancer, or NSCLC. Depending on which situation applies to you, it's either being used because...
  • What exactly is Gilotrif treating in my lungs?
  • Yes — this is really important. You need to take Gilotrif on an empty stomach every time. That means at least 1 hour before eating, or at least 2 hours after a meal. A high-fat mea...
  • Does it matter when I take my tablet or whether I eat first?
📖 Read our full Afatinib 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.

💊 What it looks like

Color White / Blue
ShapeRound
ImprintT40
Size1 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.

A current SPL was checked, but it does not contain a structured or narrative inactive-ingredient list for this product. This does not mean the product has no inactive ingredients.
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.

💲 Pricing

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

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $396.91 $11,907.32 / 30 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.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Gilotrif 40 mgthis 00597-0138-95 Boehringer 30 tablets — AB FDA listed —
About this product: this is the brand-name version. Some generic versions are approved by the FDA, but we could not confirm current pharmacy availability from our pricing/market data.
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

🏛️
2013
First FDA approval
Jul 2013
📍
2026
Currently FDA-listed
13 years listed
🛡️
2031
Latest patent/protection listed
not a guaranteed launch date
🔒Generic approved by FDA, but pharmacy availability is not confirmed

The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Jan 2031. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Jul 12, 2013 AB TE-rated RLD RS ⏳ ~4.3 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 9539258 — method of use (U-1950)
US 9539258 — method of use (U-1950)
US 9539258 — method of use (U-1950)
US 8545884 — drug product
US 8426586 — drug substance
US 8545884 — drug product
US 8426586 — drug substance
US RE43431 — drug substance
US 8545884 — drug product
US 10004743 — drug product
US RE43431 — drug substance
US 10004743 — drug product
US 8426586 — drug substance
US RE43431 — drug substance
US 10004743 — drug product
US 8545884*PED — drug product
US 8545884*PED — drug product
US 8545884*PED — drug product
US 8426586*PED — drug product
US RE43431*PED — drug product
US RE43431*PED — drug product
US 8426586*PED — drug product
US RE43431*PED — drug product
US 8426586*PED — drug product
US 10004743*PED — drug product
US 10004743*PED — drug product
US 10004743*PED — drug product
US 9539258*PED — drug product
US 9539258*PED — drug product
US 9539258*PED — drug product
2013 2015 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 (30)
PatentTypeUse codeExpires
US 9539258 ↗ Method of use U-1950 Nov 9, 2026
US 9539258 ↗ Method of use U-1950 Nov 9, 2026
US 9539258 ↗ Method of use U-1950 Nov 9, 2026
US 8545884 ↗ Drug product — Dec 19, 2029
US 8426586 ↗ Drug substance — Oct 10, 2029
US 8545884 ↗ Drug product — Dec 19, 2029
US 8426586 ↗ Drug substance — Oct 10, 2029
US RE43431 ↗ Drug substance — Jan 13, 2026
US 8545884 ↗ Drug product — Dec 19, 2029
US 10004743 ↗ Drug product — Jul 5, 2030
US RE43431 ↗ Drug substance — Jan 13, 2026
US 10004743 ↗ Drug product — Jul 5, 2030
US 8426586 ↗ Drug substance — Oct 10, 2029
US RE43431 ↗ Drug substance — Jan 13, 2026
US 10004743 ↗ Drug product — Jul 5, 2030
US 8545884*PED ↗ Drug product — Jun 19, 2030
US 8545884*PED ↗ Drug product — Jun 19, 2030
US 8545884*PED ↗ Drug product — Jun 19, 2030
US 8426586*PED ↗ Drug product — Apr 10, 2030
US RE43431*PED ↗ Drug product — Jul 13, 2026
US RE43431*PED ↗ Drug product — Jul 13, 2026
US 8426586*PED ↗ Drug product — Apr 10, 2030
US RE43431*PED ↗ Drug product — Jul 13, 2026
US 8426586*PED ↗ Drug product — Apr 10, 2030
US 10004743*PED ↗ Drug product — Jan 5, 2031
US 10004743*PED ↗ Drug product — Jan 5, 2031
US 10004743*PED ↗ Drug product — Jan 5, 2031
US 9539258*PED ↗ Drug product — May 9, 2027
US 9539258*PED ↗ Drug product — May 9, 2027
US 9539258*PED ↗ Drug product — May 9, 2027
Common questions
Is there a generic version of GILOTRIF 40 MG TABLET?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for GILOTRIF 40 MG TABLET. See the alternatives section for substitutable, lower-cost products.
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.

💊 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.
30 tablets00597-0138-30 12 Rx · $188,795
30 tablets this page00597-0138-95 No Medicaid data
Drug total (last 4 qtrs): 12 Rx · 480 units · $188,795 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 Gilotrif — 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 Gilotrif. 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
$17.1M
Claims incl. refills
1.4K
Beneficiaries
615
Spend / beneficiary
$27,809.16
Spend / claim
$11,819.37
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 Gilotrif (this brand).

Top reported reactions

Diarrhoea2,121
Malignant Neoplasm Progression1,691
Rash884
Death518
Nausea486
Stomatitis485
Decreased Appetite450

Age at onset

Neonate1
Infant1
Child2
Adolescent2
Adult488
Elderly620

Reporter sex

6,587 reports
Male · 38%
Female · 62%
Unknown · 0%

Serious outcomes

Death1,464
Life-threatening237
Reports over time (by year) — tap or hover for the count & year
2020 2022 2024 2026 582 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
00597-0138-30 1 BOTTLE in 1 CARTON (0597-0138-30) / 30 TABLET, FILM COATED in 1 BOTTLE 2013-08-08 Active
00597-0138-95 You're viewing this 1 BOTTLE in 1 CARTON (0597-0138-95) / 30 TABLET, FILM COATED in 1 BOTTLE 2013-08-08 Active

Pack size FAQ

What quantity is in NDC 00597-0138-95?
NDC 00597-0138-95 is a 30-count package — 1 bottle in 1 carton / 30 tablet, film coated in 1 bottle.
What is the difference between NDC 00597-0138-95 and NDC 00597-0138-30?
Both are Gilotrif afatinib 40 mg Tablet, Film Coated — the drug itself is identical. NDC 00597-0138-95 is the 30-count package, while NDC 00597-0138-30 is the 30 tablets package.
What NDC number is used to bill for this package of Gilotrif afatinib 40 mg Tablet, Film Coated?
Bill NDC 00597-0138-95 — the 11-digit billing format is 00597013895. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

🧭 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) — 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.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 0597-0138-95, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 00597-0138-95, written without dashes as 00597013895. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 00597-0138-95, the first segment (00597) is the labeler code FDA assigned to Boehringer Ingelheim Pharmaceuticals, Inc.; the middle segment (0138) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (95) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Boehringer Ingelheim Pharmaceuticals, 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 1 other package presentation of this same product, including 30 tablets (00597-0138-30). 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?
Boehringer Ingelheim Pharmaceuticals, 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.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage 182 words ▾

1 INDICATIONS AND USAGE GILOTRIF is a kinase inhibitor indicated for: First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test ( 1.1 ) Limitations of Use : Safety and efficacy of GILOTRIF were not established in patients whose tumors have resistant EGFR mutations ( 1.1 ) Treatment of patients with metastatic, squamous NSCLC progressing after platinum-based chemotherapy ( 1.2 )

1.1EGFR Mutation-Positive, Metastatic Non-Small Cell Lung Cancer GILOTRIF is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test [see Dosage and Administration (2.1) , Clinical Pharmacology (12.1) , Clinical Studies (14.1) ]. Limitations of Use : The safety and efficacy of GILOTRIF have not been established in patients whose tumors have resistant EGFR mutations [see Clinical Studies (14.1) ].

1.2Previously Treated, Metastatic Squamous NSCLC GILOTRIF is indicated for the treatment of patients with metastatic squamous NSCLC progressing after platinum-based chemotherapy .

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION Recommended dosage : 40 mg orally once daily ( 2.2 ) Renal impairment : 30 mg orally once daily in patients with severe renal impairment ( 2.4 , 8.6 , 12.3 ) Instruct patients to take GILOTRIF at least 1 hour before or 2 hours after a meal ( 2.2 )

2.1Patient Selection for Non-Resistant EGFR Mutation-Positive Metastatic NSCLC Select patients for first-line treatment of metastatic NSCLC with GILOTRIF based on the presence of non-resistant EGFR mutations in tumor specimens [see Clinical Pharmacology (12.1) , Clinical Studies (14.1) ]. Information on FDA-approved tests for the detection of EGFR mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics .

2.2Recommended Dosage The recommended dosage of GILOTRIF is 40 mg orally once daily until disease progression or no longer tolerated by the patient. Take GILOTRIF at least 1 hour before or 2 hours after a meal. Do not take a missed dose within 12 hours of the next dose.

2.3Dosage Modifications for Adverse Reactions Withhold GILOTRIF for: Grade* 3 or higher adverse reactions Diarrhea of Grade 2 persisting for 2 or more consecutive days while taking anti-diarrheal medication [see Warnings and Precautions (5.1) ] Cutaneous reactions of Grade 2 that are prolonged (lasting more than 7 days) or intolerable [see Warnings and Precautions (5.2) ] * National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v

3.0Resume treatment when the adverse reaction fully resolves, returns to baseline, or improves to Grade 1. Reinstitute GILOTRIF at a reduced dose, i.e., 10 mg per day less than the dose at which the adverse reaction occurred. Permanently discontinue GILOTRIF for: Life-threatening bullous, blistering, or exfoliating skin lesions [see Warnings and Precautions (5.2) ] Confirmed interstitial lung disease (ILD) [see Warnings and Precautions (5.3) ] Severe drug-induced hepatic impairment [see Warnings and Precautions (5.4) ] Gastrointestinal perforation [see Warnings and Precautions (5.5) ] Persistent ulcerative keratitis [see Warnings and Precautions (5.6) ] Symptomatic left ventricular dysfunction [see Adverse Reactions (6.1) ] Severe or intolerable adverse reaction occurring at a dose of 20 mg per day

2.4Dosage Modification for Pre-Existing Severe Renal Impairment The recommended dosage of GILOTRIF in patients with pre-existing severe renal impairment (estimated glomerular filtration rate [eGFR*] 15 to 29 mL/min /1.73 m 2 ) is 30 mg orally once daily [see Use in Specific Populations (8.6) , Clinical Pharmacology (12.3) ] . * Use the Modification of Diet in Renal Disease [MDRD] formula to estimate eGFR.

2.5Dosage Modifications for Drug Interactions P-glycoprotein Inhibitors Reduce GILOTRIF daily dose by 10 mg if not tolerated for patients who require therapy with a P-glycoprotein (P-gp) inhibitor. Resume the previous dose after discontinuation of the P-gp inhibitor as tolerated [see Drug Interactions (7) , Clinical Pharmacology (12.3) ] . P-glycoprotein Inducers Increase GILOTRIF daily dose by 10 mg as tolerated for patients who require chronic therapy with a P-gp inducer.

Resume the previous dose 2 to 3 days after discontinuation of the P-gp inducer [see Drug Interactions (7) , Clinical Pharmacology (12.3) ].

💊 Dosage Forms and Strengths 100 words ▾

3 DOSAGE FORMS AND STRENGTHS GILOTRIF is available as: 40 mg tablets: light blue, film-coated, round, biconvex, bevel-edged tablets debossed with "T40" on one side and the Boehringer Ingelheim company symbol on the other side. 30 mg tablets: dark blue, film-coated, round, biconvex, bevel-edged tablets debossed with "T30" on one side and the Boehringer Ingelheim company symbol on the other side. 20 mg tablets: white to slightly yellowish, film-coated, round, biconvex, bevel-edged tablets debossed with "T20" on one side and the Boehringer Ingelheim company symbol on the other side.

Tablets: 40 mg, 30 mg, and 20 mg ( 3 )

⛔ Contraindications 7 words ▾

4 CONTRAINDICATIONS None. None. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Diarrhea : Diarrhea may result in dehydration and renal failure. Withhold GILOTRIF for severe and prolonged diarrhea not responsive to anti-diarrheal agents. ( 2.3 , 5.1 ) Bullous and exfoliative skin disorders : Severe bullous, blistering, and exfoliating lesions occurred in 0.2% of patients.

Discontinue for life-threatening cutaneous reactions. Withhold GILOTRIF for severe and prolonged cutaneous reactions. ( 2.3 , 5.2 ) Interstitial lung disease (ILD) : Occurs in 1.6% of patients.

Withhold GILOTRIF for acute onset or worsening of pulmonary symptoms. Discontinue GILOTRIF if ILD is diagnosed. ( 2.3 , 5.3 ) Hepatic toxicity : Fatal hepatic impairment occurs in 0.2% of patients.

Monitor with periodic liver testing. Withhold or discontinue GILOTRIF for severe or worsening liver tests. ( 2.3 , 5.4 ) Gastrointestinal perforation : Occurs in 0.2% of patients.

Permanently discontinue GILOTRIF in patients who develop gastrointestinal perforation. ( 2.3 , 5.5 ) Keratitis : Occurs in 0.7% of patients. Withhold GILOTRIF for keratitis evaluation.

Withhold or discontinue GILOTRIF for confirmed ulcerative keratitis. ( 2.3 , 5.6 ) Embryo-fetal toxicity : Can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to the fetus and to use effective contraception.

( 5.7 )

5.1Diarrhea Diarrhea has resulted in dehydration with or without renal impairment across the clinical experience; some cases were fatal. Grade 3-4 diarrhea occurred in 697 (16%) of the 4257 patients who received GILOTRIF across 44 clinical trials. In LUX-Lung 3, diarrhea occurred in 96% of patients treated with GILOTRIF (n=229), of which 15% were Grade 3 in severity and occurred within the first 6 weeks .

Renal impairment as a consequence of diarrhea occurred in 6% of patients treated with GILOTRIF, of which 1.3% were Grade 3. In LUX-Lung 8, diarrhea occurred in 75% of patients treated with GILOTRIF (n=392), of which 10% were Grade 3 in severity and 0.8% were Grade 4 in severity . Renal impairment as a consequence of diarrhea occurred in 7% of patients treated with GILOTRIF, of which 2% were Grade 3 [see Adverse Reactions (6.1) ].

For patients who develop prolonged Grade 2 diarrhea lasting more than 48 hours or greater than or equal to Grade 3 diarrhea, withhold GILOTRIF until diarrhea resolves to Grade 1 or less and resume GILOTRIF with appropriate dose reduction [see Dosage and Administration (2.3) ]. Provide patients with an anti-diarrheal agent (e.g., loperamide) for self-administration at the onset of diarrhea and instruct patients to continue anti-diarrheal therapy until loose bowel movements cease for 12 hours.

5.2Bullous and Exfoliative Skin Disorders Grade 3 cutaneous reactions characterized by bullous, blistering, and exfoliating skin lesions, occurred in 0.2% of the 4257 patients who received GILOTRIF across clinical trials . In LUX-Lung 3, the overall incidence of cutaneous reactions consisting of rash, erythema, and acneiform rash was 90%, and the incidence of Grade 3 cutaneous reactions was 16%. In addition, the incidence of Grade 1-3 palmar-plantar erythrodysesthesia syndrome was 7%.

In LUX-Lung 8, the overall incidence of cutaneous reactions consisting of rash, erythema, and acneiform rash was 70%, and the incidence of Grade 3 cutaneous reactions was 7%. In addition, the incidence of Grade 1-3 palmar-plantar erythrodysesthesia syndrome was 1.5% [see Adverse Reactions (6.1) ] . Discontinue GILOTRIF in patients who develop life-threatening bullous, blistering, or exfoliating skin lesions .

For patients who develop prolonged Grade 2 cutaneous adverse reactions lasting more than 7 days, intolerable Grade 2 cutaneous reactions, or Grade 3 cutaneous reactions, withhold GILOTRIF until the adverse reaction resolves to Grade 1 or less and resume GILOTRIF with appropriate dose reduction [see Dosage and Administration (2.3) ] . Postmarketing cases consistent wit…

🤒 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) ] Bullous and Exfoliative Skin Disorders [see Warnings and Precautions (5.2) ] Interstitial Lung Disease [see Warnings and Precautions (5.3) ] Hepatic Toxicity [see Warnings and Precautions (5.4) ] Gastrointestinal Perforation [see Warnings and Precautions (5.5) ] Keratitis [see Warnings and Precautions (5.6) ] Most common adverse reactions (≥20%) were diarrhea, rash/acneiform dermatitis, stomatitis, paronychia, dry skin, decreased appetite, nausea, vomiting, pruritus ( 6.1 ).

To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at (800) 542-6257 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in the Warnings and Precautions section reflect exposure to GILOTRIF for clinically significant adverse reactions in 4257 patients enrolled in LUX-Lung 3 (n=229) and LUX-Lung 8 (n=392), and 3636 patients with cancer enrolled in 42 studies of GILOTRIF administered alone or in combination with other anti-neoplastic drugs at GILOTRIF doses ranging from 10-70 mg daily or at doses 10-160 mg in other regimens.

The mean exposure was 5.5 months. The population included patients with various cancers, the most common of which were NSCLC, breast, colorectal, brain, and head and neck. The data described below reflect exposure to GILOTRIF as a single agent in LUX-Lung 3, a randomized, active-controlled trial conducted in patients with EGFR mutation-positive, metastatic NSCLC, and in LUX-Lung 8, a randomized, active-controlled trial in patients with metastatic squamous NSCLC progressing after platinum-based chemotherapy.

EGFR Mutation-Positive Metastatic NSCLC The safety of GILOTRIF was evaluated in 229 EGFR-tyrosine kinase inhibitor-naïve patients with EGFR mutation-positive, metastatic non-squamous NSCLC enrolled in a randomized (2:1), multicenter, open-label trial (LUX-Lung 3). Patients received either GILOTRIF 40 mg daily until documented disease progression or intolerance to the therapy or pemetrexed 500 mg/m² followed after 30 minutes by cisplatin 75 mg/m² every three weeks for a maximum of six treatment courses. The median exposure was 11 months for patients treated with GILOTRIF and 3.4 months for patients treated with pemetrexed/cisplatin.

The overall trial population had a median age of 61 years; 61% of patients in the GILOTRIF arm and 60% of patients in the pemetrexed/cisplatin arm were younger than 65 years. A total of 64% of patients on GILOTRIF and 67% of pemetrexed/cisplatin patients were female. More than two-thirds of patients were from Asia (GILOTRIF 70%; pemetrexed/cisplatin 72%).

Serious adverse reactions were reported in 29% of patients treated with GILOTRIF. The most frequent serious adverse reactions reported in patients treated with GILOTRIF were diarrhea (6.6%); vomiting (4.8%); and dyspnea, fatigue, and hypokalemia (1.7% each). Fatal adverse reactions in GILOTRIF-treated patients in LUX-Lung 3 included pulmonary toxicity/ILD-like adverse reactions (1.3%), sepsis (0.43%), and pneumonia (0.43%).

Dose reductions due to adverse reactions were required in 57% of GILOTRIF-treated patients. The most frequent adverse reactions that led to dose reduction in the patients treated with GILOTRIF were diarrhea (20%), rash/acne (19%), paronychia (14%), and stomatitis (10%). Discontinuation of therapy in GILOTRIF-treated patients for adverse reactions was 14.0%.

The most frequent adverse reactions that led to discontinuation in GILOTRIF-treated patients were diarrhea (1.3%), ILD (0.9%), and paronychia (0.9%). Clinical trials of GILOTRIF excluded…

🔄 Drug Interactions 153 words ▾

7 DRUG INTERACTIONS P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. Reduce GILOTRIF by 10 mg per day if not tolerated. ( 2.5 , 7 ) P-gp Inducers : Co-administration of chronic P-gp inducers orally can decrease afatinib exposure.

Increase GILOTRIF by 10 mg per day as tolerated. ( 2.5 , 7 ) Effect of P-glycoprotein (P-gp) Inhibitors and Inducers Concomitant taking of P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) with GILOTRIF can increase exposure to afatinib [see Clinical Pharmacology (12.3) ]. Reduce GILOTRIF daily dose as recommended [see Dosage and Administration (2.5) ].

Concomitant taking of P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital, and St. John's wort) with GILOTRIF can decrease exposure to afatinib [see Clinical Pharmacology (12.3) ]. Increase GILOTRIF daily dose as recommended [see Dosage and Administration (2.5) ].

👥 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 its mechanism of action [see Clinical Pharmacology (12.1) ] , GILOTRIF can cause fetal harm when administered to a pregnant woman. There are no available data on the use of GILOTRIF in pregnant women. Administration of afatinib to pregnant rabbits during organogenesis at exposures approximately 0.2 times the exposure in humans at the recommended dose of 40 mg daily resulted in embryotoxicity and, in rabbits showing maternal toxicity, increased abortions at late gestational stages (see Data ) .

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

Data Animal Data In an embryo-fetal development study in rabbits, administration of afatinib to pregnant animals at doses of 5 mg/kg (approximately 0.2 times the exposure by AUC at the recommended human dose of 40 mg daily) or greater during the period of organogenesis caused increased post-implantation loss, and in animals showing maternal toxicity, abortion at late gestational stages. In the same study, at the high dose level of 10 mg/kg (approximately 0.7 times the exposure by AUC at the recommended human dose of 40 mg daily), there were reduced fetal weights, and increases in the incidence of runts, as well as visceral and dermal variations.

In an embryo-fetal development study in rats, there were skeletal alterations consisting of incomplete or delayed ossifications and reduced fetal weight at a dose of 16 mg/kg (approximately twice the exposure based on AUC at the recommended human dose of 40 mg daily).

8.2Lactation Risk Summary There are no data on the presence of afatinib in human milk or its effects on the breastfed infant or on milk production. Afatinib was present in the milk of lactating rats (see Data ) . Because of the potential for serious adverse reactions in breastfed infants from GILOTRIF, advise women not to breastfeed during treatment with GILOTRIF and for 2 weeks after the final dose.

Data Afatinib was present in the milk of lactating rats at concentrations 80 and 150 times higher than those found in plasma at 1 and 6 hours after administration.

8.3Females and Males of Reproductive Potential Contraception Females GILOTRIF can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with GILOTRIF and for at least 2 weeks after the last dose of GILOTRIF [see Use in Specific Populations (8.1) , Clinical Pharmacology (12.3) ]. Infertility Based on results from an animal fertility study, GILOTRIF may reduce fertility in females and males of reproductive potential.

It is not known if the effects on fertility are reversible [see Nonclinical Toxicology (13.1) ].

8.4Pediatric Use Safety and effectiveness of GILOTRIF in pediatric patients have not been established. The safety and efficacy of afatinib were assessed, but not established, in a single-arm, open-label, multicenter trial [NCT02372006] which included 37 pediatric patients 2 to <17 years of age with recurrent/refractory solid tumors with known ErbB pathway deregulation who received 80% of the adult dose per body surface area. No new safety signals were observed in pediatric patients in this trial.

In these 37 patients, the pharmacokinetic parameters were within range of values in adults.

8.5Geriatric Use LUX-Lung 3 did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In LUX-Lung 8, 53% of the 398 patients randomized to receive afatinib were 65 years of age or older and 11% were 75 years or older. In an exploratory subgr…

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , GILOTRIF can cause fetal harm when administered to a pregnant woman. There are no available data on the use of GILOTRIF in pregnant women. Administration of afatinib to pregnant rabbits during organogenesis at exposures approximately 0.2 times the exposure in humans at the recommended dose of 40 mg daily resulted in embryotoxicity and, in rabbits showing maternal toxicity, increased abortions at late gestational stages (see Data ) .

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

Data Animal Data In an embryo-fetal development study in rabbits, administration of afatinib to pregnant animals at doses of 5 mg/kg (approximately 0.2 times the exposure by AUC at the recommended human dose of 40 mg daily) or greater during the period of organogenesis caused increased post-implantation loss, and in animals showing maternal toxicity, abortion at late gestational stages. In the same study, at the high dose level of 10 mg/kg (approximately 0.7 times the exposure by AUC at the recommended human dose of 40 mg daily), there were reduced fetal weights, and increases in the incidence of runts, as well as visceral and dermal variations.

In an embryo-fetal development study in rats, there were skeletal alterations consisting of incomplete or delayed ossifications and reduced fetal weight at a dose of 16 mg/kg (approximately twice the exposure based on AUC at the recommended human dose of 40 mg daily).

🧒 Pediatric Use 90 words ▾

8.4Pediatric Use Safety and effectiveness of GILOTRIF in pediatric patients have not been established. The safety and efficacy of afatinib were assessed, but not established, in a single-arm, open-label, multicenter trial [NCT02372006] which included 37 pediatric patients 2 to <17 years of age with recurrent/refractory solid tumors with known ErbB pathway deregulation who received 80% of the adult dose per body surface area. No new safety signals were observed in pediatric patients in this trial.

In these 37 patients, the pharmacokinetic parameters were within range of values in adults.

🧓 Geriatric Use 108 words ▾

8.5Geriatric Use LUX-Lung 3 did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In LUX-Lung 8, 53% of the 398 patients randomized to receive afatinib were 65 years of age or older and 11% were 75 years or older. In an exploratory subgroup analysis of LUX-Lung 8, the hazard ratio for overall survival (OS) in patients less than 65 years old was 0.68 (95% CI: 0.55, 0.85) and in patients 65 years or older was 0.95 (95% CI: 0.76, 1.19).

No overall differences in safety were observed between patients 65 years and older and younger patients.

🆘 Overdosage 45 words ▾

10 OVERDOSAGE Overdose was reported in 2 healthy adolescents each of whom ingested 360 mg of GILOTRIF (as part of a mixed-drug ingestion) resulting in nausea, vomiting, asthenia, dizziness, headache, abdominal pain, and elevated amylase [<1.5 times upper limit of normal (ULN)]. Both subjects recovered.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Afatinib covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signaling. Certain mutations in EGFR, including non-resistant mutations in its kinase domain, can result in increased autophosphorylation of the receptor, leading to receptor activation, sometimes in the absence of ligand binding, and can support cell proliferation in NSCLC. Non-resistant mutations are defined as those occurring in exons constituting the kinase domain of EGFR that lead to increased receptor activation and where efficacy is predicted by 1) clinically meaningful tumor shrinkage with the recommended dose of afatinib and/or 2) inhibition of cellular proliferation or EGFR tyrosine kinase phosphorylation at concentrations of afatinib sustainable at the recommended dosage according to validated methods.

The most commonly found of these mutations are exon 21 L858R substitutions and exon 19 deletions. Afatinib demonstrated inhibition of autophosphorylation and/or in vitro proliferation of cell lines expressing wild-type EGFR and in those expressing selected EGFR exon 19 deletion mutations, exon 21 L858R mutations, or other less common non-resistant mutations, at afatinib concentrations achieved in patients. In addition, afatinib inhibited in vitro proliferation of cell lines overexpressing HER2.

Treatment with afatinib resulted in inhibition of tumor growth in nude mice implanted with tumors either overexpressing wild type EGFR or HER2 or in an EGFR L858R/T790M double mutant model.

12.2Pharmacodynamics Cardiac Electrophysiology The effect of multiple doses of GILOTRIF (50 mg once daily) on the QTc interval was evaluated in an open-label, single-arm study in patients with relapsed or refractory solid tumors. No large changes in the mean QTc interval (i.e., >20 ms) were detected in the study.

12.3Pharmacokinetics Absorption Following oral administration of GILOTRIF tablets, time to peak afatinib plasma concentrations (T max ) is 2 to 5 hours. Maximum concentration (C max ) and area under the concentration-time curve from time zero to infinity (AUC 0-INF ) values increased slightly more than dose proportional in the range of 20 to 50 mg. The geometric mean relative bioavailability of 20 mg GILOTRIF tablets was 92% as compared to an oral solution.

Steady-state plasma concentrations are achieved within 8 days of repeat dosing of GILOTRIF resulting in an accumulation of 2.8-fold for AUC and 2.1-fold for C max . Effect of Food A high-fat meal decreased C max by 50% and AUC 0-INF by 39% relative to the fasted condition [see Dosage and Administration (2.2) ] . Distribution In vitro binding of afatinib to human plasma proteins is approximately 95%.

Elimination The elimination half-life of afatinib is 37 hours after repeat dosing in cancer patients. Metabolism Covalent adducts to proteins are the major circulating metabolites of afatinib and enzymatic metabolism of afatinib is minimal. The metabolites formed by CYP450-dependent reactions were approximately 9% of the total metabolic turnover in sandwich-cultured human hepatocytes.

Approximately 2% of the afatinib dose was metabolized by FMO3; the CYP3A4-dependent N-demethylation was not detected. Excretion In humans, excretion of afatinib is primarily via the feces (85%) with 4% recovered in the urine following a single oral dose of [ 14 C]-labeled afatinib solution. The parent compound accounted for 88% of the recovered dose.

Specific Populations Based on the population pharmacokinetic analysis, weight, gender, age, and race do not have a clinically important effect on exposure of afatinib. Patients with Renal Impairment A pharmacokinetic study was conducted in 14 subjects with normal (eGFR ≥90 mL/min/1.73 m 2 ) renal function, 8 subjects with moderate (eGFR 30 to 59 mL/min/1.73 m 2 ) and 8 subjects with severe (eGFR 15 to 29 mL/min/1.73…

🧬 Mechanism of Action ~1 min read ▾

12.1Mechanism of Action Afatinib covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signaling. Certain mutations in EGFR, including non-resistant mutations in its kinase domain, can result in increased autophosphorylation of the receptor, leading to receptor activation, sometimes in the absence of ligand binding, and can support cell proliferation in NSCLC. Non-resistant mutations are defined as those occurring in exons constituting the kinase domain of EGFR that lead to increased receptor activation and where efficacy is predicted by 1) clinically meaningful tumor shrinkage with the recommended dose of afatinib and/or 2) inhibition of cellular proliferation or EGFR tyrosine kinase phosphorylation at concentrations of afatinib sustainable at the recommended dosage according to validated methods.

The most commonly found of these mutations are exon 21 L858R substitutions and exon 19 deletions. Afatinib demonstrated inhibition of autophosphorylation and/or in vitro proliferation of cell lines expressing wild-type EGFR and in those expressing selected EGFR exon 19 deletion mutations, exon 21 L858R mutations, or other less common non-resistant mutations, at afatinib concentrations achieved in patients. In addition, afatinib inhibited in vitro proliferation of cell lines overexpressing HER2.

Treatment with afatinib resulted in inhibition of tumor growth in nude mice implanted with tumors either overexpressing wild type EGFR or HER2 or in an EGFR L858R/T790M double mutant model.

📦 How Supplied / Storage and Handling 150 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING GILOTRIF tablets are available as follows: 40 mg: light blue, film-coated, round, biconvex, bevel-edged tablets debossed with "T40" on one side and the Boehringer Ingelheim company symbol on the other side. Unit of use bottles of 30 NDC: 0597-0138-30 30 mg: dark blue, film-coated, round, biconvex, bevel-edged tablets debossed with "T30" on one side and the Boehringer Ingelheim company symbol on the other side. Unit of use bottles of 30 NDC: 0597-0137-30 20 mg: white to slightly yellowish, film-coated, round, biconvex, bevel-edged tablets debossed with "T20" on one side and the Boehringer Ingelheim company symbol on the other side.

Unit of use bottles of 30 NDC: 0597-0141-30 Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense medication in the original container to protect from exposure to high humidity and light.

📦 Storage and Handling 38 words ▾

Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense medication in the original container to protect from exposure to high humidity and light.

📋 Description 146 words ▾

11 DESCRIPTION GILOTRIF tablets contain afatinib, a tyrosine kinase inhibitor which is a 4-anilinoquinazoline. Afatinib is presented as the dimaleate salt, with the chemical name 2-butenamide, N -[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3 S )-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethylamino)-,(2 E )-, (2 Z )-2-butenedioate (1:2). Its structural formula is: Afatinib dimaleate is a white to brownish yellow powder, water soluble and hygroscopic, with an empirical formula of C 32 H 33 ClFN 5 O 11 , and a molecular weight of 718.1 g/mol.

GILOTRIF tablets for oral administration are available in 40 mg, 30 mg, or 20 mg of afatinib (equivalent to 59.12 mg, 44.34 mg, or 29.56 mg afatinib dimaleate, respectively). The inactive ingredients of GILOTRIF are the following: Tablet Core: lactose monohydrate, microcrystalline cellulose, crospovidone, colloidal silicon dioxide, magnesium stearate and Coating: hypromellose, polyethylene glycol, titanium dioxide, talc, polysorbate 80, FD&C Blue No. 2 (40 mg and 30 mg tablets only).

Chemical Structure

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Diarrhea Advise patients that diarrhea occurs in nearly all patients who receive GILOTRIF. Inform patients that diarrhea may result in dehydration and renal impairment if not treated.

Advise patients to notify their physician if diarrhea develops and to seek medical attention promptly for severe or persistent diarrhea [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ]. Bullous and Exfoliative Skin Disorders Advise patients to minimize sun exposure with protective clothing and use of sunscreen while taking GILOTRIF [see Warnings and Precautions (5.2) ]. Interstitial Lung Disease Advise patients to immediately report any new or worsening lung symptoms, or any combination of the following symptoms: trouble breathing or shortness of breath, cough, fever [see Warnings and Precautions (5.3) ].

Hepatic Toxicity Advise patients that they will need to undergo liver function monitoring periodically. Advise patients to immediately report any symptoms of a liver problem [e.g., skin or the whites of eyes turn yellow, urine turns dark or brown (tea colored), pain on the right side of stomach, bleeds or bruises more easily than normal, lethargy] [see Warnings and Precautions (5.4) ]. Gastrointestinal Perforation Advise patients that GILOTRIF can increase the risk of gastrointestinal perforation and to seek immediate medical attention for severe abdominal pain [see Warnings and Precautions (5.5) ] .

Keratitis Advise patients to immediately report eye problems (e.g., eye pain, swelling, redness, blurred vision, or other vision changes) [see Warnings and Precautions (5.6) ]. Left Ventricular Dysfunction Advise patients to contact a healthcare professional immediately for any of the following: new onset or worsening shortness of breath or exercise intolerance, cough, fatigue, swelling of the ankles/legs, palpitations, or sudden weight gain [see Dosage and Administration (2.3) and Adverse Reactions (6.1) ]. Instructions for Taking GILOTRIF Advise patients to take GILOTRIF on an empty stomach at least 1 hour before or 2 hours after eating [see Dosage and Administration (2.2) ].

Advise patients not to take a missed dose within 12 hours of the next dose. Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential that GILOTRIF can result in fetal harm. Advise female patients to contact their healthcare provider with a known or suspected pregnancy .

Advise females of reproductive potential to use effective contraception during treatment with GILOTRIF and for at least 2 weeks after the last dose of GILOTRIF [see Use in Specific Populations (8.1 , 8.3) ]. Lactation Advise women not to breastfeed during treatment with GILOTRIF and for 2 weeks after the last dose of GILOTRIF [see Use in Specific Populations (8.2) ]. Infertility Advise females and males of reproductive potential of the potential for reduced fertility from GILOTRIF [see Use in Specific Populations (8.3) ] .

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
← 00597-0137-30 · Boehringer 00597-0140-30 · Boehringer →
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