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Xalkori CRIZOTINIB 50 mg Capsule, Coated Pellets, 60-count — NDC 00069-0507-60 package photo

Xalkori CRIZOTINIB 50 mg Capsule, Coated Pellets, 60-count

by Pfizer Laboratories Div Pfizer Inc · 60 CAPSULE, COATED PELLETS in 1 BOTTLE (0069-0507-60)
NDC 00069-0507-60
🏷️ FDA NDC (as labeled) 0069-0507-60 billing pads the labeler segment with a zero
Rx only Brand On market Non-controlled
🗂️ Data synced Sep 10, 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) 0069-0507-60
Product NDC 0069-0507
11-digit billing NDC 00069050760
NCPDP billing unit EA — each (per item)
RxCUI 1148498, 1148502, 1148504, 1148506, 2670166, 2670170, 2670172, 2670174,
UNII 53AH36668S
UPC 0300698140201, 0300690507606, 0300690251608, 0300691500606 +1 more
Application # NDA217581
SPL Set ID 2a51b0de-47d6-455e-a94c-d2c737b04ff7
Established class (EPC) Kinase Inhibitor
Mechanism of action Cytochrome P450 3A Inhibitors; Receptor Tyrosine Kinase Inhibitors; Cytochrome P450 2B6 Inhibitors; P-Glycoprotein Inhibitors; Organic Cation Transporter 1 Inhibitors; Organic Cation Transporter 2 Inhibitors
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2023-11-20
Route ORAL
Dosage form CAPSULE, COATED PELLETS
Substance CRIZOTINIB
GPI-14 21530517006830
GCN Seq No 085523
GCN 55028
HICL code 037916
Ingredient (HICL) Crizotinib
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 XALKORI 50 MG PELLET
FDB brand name Xalkori
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 0069-0507-60 — 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 → 00069-0507-60. 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) Anaplastic lymphoma kinase (ALK) inhibitors
How it works Receptor Tyrosine Kinase Inhibitors, Cytochrome P450 2B6 Inhibitors, P-Glycoprotein Inhibitors, Organic Cation Transporter 2 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

LabelerPfizer Laboratories Div Pfizer Inc
Application holderPF PRISM CV
FDA applicationNDA217581 (NDA)
Labeler code00069
First marketedNov 2023
Product typeHuman Prescription Drug
Portfolio242 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 XALKORI 50 MG PELLET Ingredient Crizotinib
📗 Our plain-language guide HelloPharmacist
  • Crizotinib (Xalkori) targets cancers that carry specific gene changes — called ALK or ROS1 alterations — that drive tumor growth. It's approved for certain adults with metastatic n...
  • What exactly does crizotinib treat, and how do I know if it's right for me?
  • You can take Xalkori capsules with or without food — it's flexible. A high-fat meal does slightly reduce how much gets absorbed, but the effect is modest and the label allows eithe...
  • Does it matter if I take Xalkori with food or on an empty stomach?
📖 Read our full Crizotinib 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 Pink / White / Blue / Gray
ShapeCapsule
ImprintPfizer;CRZ;20
Size15 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.

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

  • UNII XM0M87F357
    A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
  • UNII 2G86QN327L
    Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
  • UNII 230OU9XXE4
    A waxy substance made from glycerin and stearic acid that acts as an emulsifier to blend oily and watery ingredients together. It also helps thicken and stabilize the medicine's texture.
  • UNII 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
  • UNII C9H2L21V7U
    A fat derived from coconut or palm oil containing shorter fatty acid chains. It serves as a solvent and carrier to help dissolve or suspend active ingredients, improving absorption and stability in liquid formulations.
  • UNII TUF2IVW3M2
    Poloxamer 407 is a synthetic polymer made from ethylene oxide and propylene oxide. In medicines, it acts as a thickener, emulsifier, and solubilizer to help mix ingredients and create the right texture.
  • 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 2KR89I4H1Y
    Stearyl alcohol is a waxy, fatty substance derived from natural oils or made synthetically. It acts as an emulsifier and thickener in medicines, helping mix ingredients together and give the product the right texture.
  • UNII C151H8M554
    A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
  • 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.

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

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

Inactive ingredient FAQ

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

💲 Pricing

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

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $94.76 $5,685.72 / 60 capsules
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Xalkori 50 mgthis 00069-0507-60 Pfizer 60 capsules — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

⏳ Availability & generic status

🏛️
2023
First FDA approval
Sep 2023
📍
2026
Currently FDA-listed
3 years listed
🛡️
2029
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 Nov 2029. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Sep 7, 2023 RLD RS ⏳ ~3.1 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 7825137 — method of use (U-3057)
US 7825137 — method of use (U-3403)
US 7825137 — method of use (U-3058)
US 7825137 — method of use (U-3057)
US 7825137 — method of use (U-3058)
US 7825137 — method of use (U-3403)
US 7825137 — method of use (U-3403)
US 7825137 — method of use (U-3057)
US 7825137 — method of use (U-3058)
US 7858643 — drug substance
US 7858643 — drug substance
US 7858643 — drug substance
US 8217057 — drug substance
US 8217057 — drug substance
US 8217057 — drug substance
2023 2025 2027 2029
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 (15)
PatentTypeUse codeExpires
US 7825137 ↗ Method of use U-3057 May 12, 2027
US 7825137 ↗ Method of use U-3403 May 12, 2027
US 7825137 ↗ Method of use U-3058 May 12, 2027
US 7825137 ↗ Method of use U-3057 May 12, 2027
US 7825137 ↗ Method of use U-3058 May 12, 2027
US 7825137 ↗ Method of use U-3403 May 12, 2027
US 7825137 ↗ Method of use U-3403 May 12, 2027
US 7825137 ↗ Method of use U-3057 May 12, 2027
US 7825137 ↗ Method of use U-3058 May 12, 2027
US 7858643 ↗ Drug substance — Oct 8, 2029
US 7858643 ↗ Drug substance — Oct 8, 2029
US 7858643 ↗ Drug substance — Oct 8, 2029
US 8217057 ↗ Drug substance — Nov 6, 2029
US 8217057 ↗ Drug substance — Nov 6, 2029
US 8217057 ↗ Drug substance — Nov 6, 2029
Common questions
Is there a generic version of XALKORI 50 MG PELLET?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for XALKORI 50 MG PELLET. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Nov 2029 — an estimate, not a guaranteed launch date.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

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

Medicare Part D (outpatient prescription) spending for Xalkori — the program that covers self-administered drugs. 2 manufacturers.
⚠️ 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 Xalkori. 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
$14.98M
Claims incl. refills
732
Beneficiaries
297
Spend / beneficiary
$50,446.84
Spend / claim
$20,468.18
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.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
00069-0507-60 You're viewing this 60 CAPSULE, COATED PELLETS in 1 BOTTLE (0069-0507-60) 2023-11-20 Active

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ 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) — 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 0069-0507-60, 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: 00069-0507-60, written without dashes as 00069050760. 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 00069-0507-60, the first segment (00069) is the labeler code FDA assigned to Pfizer Laboratories Div Pfizer Inc; the middle segment (0507) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (60) 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 Pfizer Laboratories Div Pfizer Inc. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Pfizer Laboratories Div Pfizer 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 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide
🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE XALKORI is a kinase inhibitor indicated for the treatment of • adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test. ( 1.1 , 2.1 ) • pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive. ( 1.2 , 2.3 ) o Limitations of Use: The safety and efficacy of XALKORI have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL. • adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive.

( 1.3 , 2.3 )

1.1ALK- or ROS1-Positive Metastatic Non-Small Cell Lung Cancer XALKORI is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test [see Dosage and Administration (2.1) ] .

1.2Relapsed or Refractory, Systemic ALK-Positive Anaplastic Large Cell Lymphoma XALKORI is indicated for the treatment of pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive . Limitations of Use : The safety and efficacy of XALKORI have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL.

1.3Unresectable, Recurrent, or Refractory ALK-Positive Inflammatory Myofibroblastic Tumor XALKORI is indicated for the treatment of adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION • Metastatic NSCLC: The recommended dosage is 250 mg orally twice daily. ( 2.3 ) • Systemic ALCL: The recommended dosage is 280 mg/m 2 orally twice daily based on body surface area. ( 2.3 ) • Unresectable IMT: o Adult: The recommended dosage is 250 mg orally twice daily.

( 2.3 ) o Pediatric: The recommended dosage is 280 mg/m 2 orally twice daily based on body surface area. ( 2.3 ) • See full prescribing information for dosage adjustments by indication for patients with moderate or severe hepatic impairment or severe renal impairment. ( 2.7 , 2.8 )

2.1Patient Selection Select patients for the treatment of metastatic NSCLC with XALKORI based on the presence of ALK or ROS1 positivity in tumor specimens [see Clinical Studies (14.1 , 14.2 , 14.3) ] . Information on FDA-approved tests for the detection of ALK and ROS1 rearrangements in NSCLC is available at http://www.fda.gov/companiondiagnostics .

2.2Recommended Testing During Treatment with XALKORI • Monitor liver function tests, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin, every 2 weeks during the first 2 months of treatment, then once a month, and as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop increased transaminases [see Warnings and Precautions (5.1) ] . • Monitor complete blood counts including differential weekly for the first month of therapy and then at least monthly, with more frequent monitoring if Grade 3 or 4 abnormalities, fever, or infection occur [see Adverse Reactions (6.1) ] . • For pediatric and young adult patients with ALCL or pediatric patients with IMT, obtain baseline and follow-up ophthalmologic examinations including retinal examination within 1 month of starting XALKORI and every 3 months thereafter [see Warnings and Precautions (5.5) ] .

2.3Recommended Dosage The recommended dosage of XALKORI is provided in Table 1. Table 1. Recommended Dosage of XALKORI Indication Recommended Dosage of XALKORI ALK- or ROS1-Positive Metastatic NSCLC Adults : 250 mg orally twice daily Relapsed or Refractory, Systemic ALK-Positive ALCL Pediatric Patients and Young Adults : 280 mg/m 2 orally twice daily See Table 2 for Recommended Dosage based on body surface area for pediatric patients and young adults with ALCL for the capsules and oral pellets.

Unresectable, Recurrent, or Refractory ALK-Positive IMT Adults : 250 mg orally twice daily Pediatric Patients : 280 mg/m 2 orally twice daily See Table 3 for Recommended Dosage based on body surface area for pediatric patients with IMT for the capsules and oral pellets. Recommended Dosage for Adult Patients with ALK- or ROS1-Positive Metastatic NSCLC • The recommended dosage for adult patients with ALK- or ROS1-positive metastatic NSCLC is XALKORI capsules 250 mg orally, twice daily, with or without food until disease progression or unacceptable toxicity occurs. • For adults who cannot swallow capsules, the recommended dosage of XALKORI pellets is 250 mg (2 x 50 mg + 1 x 150 mg) orally, twice daily, with or without food until disease progression or unacceptable toxicity occurs.

Recommended Dosage for Pediatric and Young Adult Patients with ALK-Positive ALCL • The recommended dosage for pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic ALK-positive ALCL is based on body surface area (BSA) and is provided in Table 2. • Administer XALKORI capsules or pellets orally, twice daily, with or without food until disease progression or unacceptable toxicity occurs. Table 2 provides the dosage based on body surface area (BSA) for XALKORI capsules or pellets.

Table 2. Recommended XALKORI Dosage for Pediatric Patients 1 Year of Age and Older and Young Adults With ALK-Positive ALCL Using Either XALKORI Capsules or Pellets Body Surface Area (BSA) Recommended XALKORI Dosage to Achieve 280 mg/m 2 Twice Daily…

💊 Dosage Forms and Strengths 163 words ▾

3 DOSAGE FORMS AND STRENGTHS Capsules: • 200 mg: hard gelatin capsule, size 1, white opaque body and pink opaque cap, with "Pfizer" on the cap and "CRZ 200" on the body. • 250 mg: hard gelatin capsule, size 0, pink opaque cap and body, with "Pfizer" on the cap and "CRZ 250" on the body. Oral Pellets: • 20 mg: hard gelatin capsule, size 4, white opaque body and light blue opaque cap, printed with black ink “Pfizer” on the cap and “CRZ 20” on the body. • 50 mg: hard gelatin capsule, size 3, light gray opaque body and gray opaque cap, printed with black ink “Pfizer” on the cap and “CRZ 50” on the body. • 150 mg: hard gelatin capsule, size 0, light blue opaque body and cap, printed with black ink “Pfizer” on the cap and “CRZ 150” on the body.

Capsules: 200 mg, 250 mg ( 3 ) Oral pellets: 20 mg, 50 mg, 150 mg (3)

⛔ Contraindications 7 words ▾

4 CONTRAINDICATIONS None. None. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Hepatotoxicity: Fatal hepatotoxicity has occurred. Monitor with periodic liver testing. Temporarily suspend, dose reduce, or permanently discontinue XALKORI.

( 2.2 , 2.6 , 5.1 ) • Interstitial Lung Disease (ILD)/Pneumonitis: Permanently discontinue in patients with ILD/pneumonitis. ( 2.6 , 5.2 ) • QT Interval Prolongation: Monitor electrocardiograms and electrolytes in patients who have a history of or predisposition for QTc prolongation, or who are taking medications that prolong QT. Temporarily suspend, dose reduce, or permanently discontinue XALKORI.

( 2.6 , 5.3 ) • Bradycardia: XALKORI can cause bradycardia. Monitor heart rate and blood pressure regularly. Temporarily suspend, dose reduce, or permanently discontinue XALKORI.

( 2.6 , 5.4 ) • Severe Visual Loss: XALKORI can cause visual changes including severe visual loss. Monitor and evaluate for ocular toxicity throughout treatment. Discontinue XALKORI in patients with severe visual loss.

( 2.2 , 2.6 , 5.5 ) • Gastrointestinal Toxicity in Pediatric and Young Adult Patients with ALCL or Pediatric Patients with IMT: XALKORI can cause severe nausea, vomiting, diarrhea, and stomatitis. Provide standard antiemetic and antidiarrheal agents. Temporarily suspend, dose reduce, or permanently discontinue XALKORI.

( 2.6 , 5.6 ) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception. ( 5.7 , 8.1 , 8.3 )

5.1Hepatotoxicity Drug-induced hepatotoxicity with fatal outcome occurred in 0.1% of the 1719 patients treated with XALKORI for NSCLC across clinical trials [see Adverse Reactions (6.1) ] . Concurrent elevations in ALT or AST ≥3 times the ULN and total bilirubin ≥2 times the ULN, with normal alkaline phosphatase, occurred in <1% of patients treated with XALKORI. Increased ALT or AST >5 times the ULN occurred in 11% and 6% of patients, respectively.

One percent (1.0%) of patients required permanent discontinuation due to elevated transaminases. Increased transaminases generally occurred within the first 2 months of treatment. In Study ADVL0912, of 121 patients ages 1 to ≤21 years treated with XALKORI for relapsed or refractory tumors including ALCL and IMT, 71% and 79% had increases of AST and ALT, respectively, with increased ALT or AST >5 times the ULN in 6% each.

Of the 26 patients with ALCL treated with XALKORI, 65% and 81% had increases of AST and ALT, respectively, with increases >5 times the ULN in 4% each. Of the 14 pediatric patients with IMT treated with XALKORI, 71% had increases of AST and 71% had increases of ALT. In Study A8081013, of the 7 adult patients with IMT treated with XALKORI, 57% and 43% had increases of AST and ALT, respectively.

Monitor liver function tests, including ALT, AST, and total bilirubin, every 2 weeks during the first 2 months of treatment, then once a month, and as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop increased transaminases. Withhold, reduce dose, or permanently discontinue XALKORI for hepatotoxicity as recommended [see Dosage and Administration (2.6) ] .

5.2Interstitial Lung Disease/Pneumonitis Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur in patients treated with XALKORI. Across clinical trials in patients with NSCLC (n=1719), 2.9% of XALKORI-treated patients had ILD of any grade, 1% had Grade 3 or 4 ILD, and 0.5% had fatal ILD [see Adverse Reactions (6.1) ] . Interstitial lung disease generally occurred within 3 months after the initiation of XALKORI.

In Study ADVL0912, among 121 patients ages 1 to ≤21 years with relapsed or refractory tumors, including ALCL and IMT, ILD occurred in 0.8% of patients. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. Exclude other potential causes of ILD/pneumonitis, and permanently discontinue XALKORI…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Hepatotoxicity [see Warnings and Precautions (5.1) ] • Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.2) ] • QT Interval Prolongation [see Warnings and Precautions (5.3) ] • Bradycardia [see Warnings and Precautions (5.4) ] • Severe Visual Loss [see Warnings and Precautions (5.5) ] • Gastrointestinal Toxicity in Pediatric and Young Adult Patients with ALCL or Pediatric Patients with IMT [see Warnings and Precautions (5.6) ] The most common adverse reactions (≥25%) in adult patients with NSCLC are vision disorders, nausea, diarrhea, vomiting, edema, constipation, elevated transaminases, fatigue, decreased appetite, upper respiratory infection, dizziness, and neuropathy.

( 6.1 ) The most common adverse reactions (≥35%) in patients with ALCL are diarrhea, vomiting, nausea, vision disorder, headache, musculoskeletal pain, stomatitis, fatigue, decreased appetite, pyrexia, abdominal pain, cough, and pruritus. Grade 3–4 laboratory abnormalities (≥15%) are neutropenia, lymphopenia, and thrombocytopenia. ( 6.1 ) The most common adverse reactions (≥35%) in adult patients with IMT are vision disorders, nausea, and edema.

( 6.1 ) The most common adverse reactions (≥35%) in pediatric patients with IMT are vomiting, nausea, diarrhea, abdominal pain, rash, vision disorder, upper respiratory tract infection, cough, pyrexia, musculoskeletal pain, fatigue, edema, constipation, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 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 clinical practice. The data in the Warnings and Precautions reflect exposure to XALKORI in 1719 patients with NSCLC who received XALKORI 250 mg twice daily enrolled on Studies 1 (including an additional 109 patients who crossed over from the control arm), 2, 3, a single-arm trial (n=1063) of ALK-positive NSCLC, and an additional ALK-positive NSCLC expansion cohort of a dose finding study (n=154).

The data also reflect exposure to XALKORI in 121 patients ages 1 to ≤21 years with relapsed or refractory tumors, including 26 patients with systemic ALCL and 14 pediatric patients with IMT, in a single-arm trial (Study ADVL0912). The data are also described for 7 adult patients with IMT treated with XALKORI in a single-arm trial (Study A8081013). ALK- or ROS1-Positive Metastatic NSCLC The data described below is based primarily on 343 patients with ALK-positive metastatic NSCLC who received XALKORI 250 mg orally twice daily from 2 open-label, randomized, active-controlled trials (Studies 1 and 2).

The safety of XALKORI was also evaluated in 50 patients with ROS1-positive metastatic NSCLC from a single-arm study (Study 3). The most common adverse reactions (≥25%) of XALKORI in patients with NSCLC are vision disorders, nausea, diarrhea, vomiting, edema, constipation, elevated transaminases, fatigue, decreased appetite, upper respiratory infection, dizziness, and neuropathy. Previously Untreated ALK-Positive Metastatic NSCLC - Study 1 (PROFILE 1014) The data in Table 9 are derived from 340 patients with ALK-positive metastatic NSCLC who had not received previous systemic treatment for advanced disease who received treatment in a randomized, multicenter, open-label, active-controlled trial (Study 1).

Patients in the XALKORI arm (n=171) received XALKORI 250 mg orally twice daily until documented disease progression, intolerance to therapy, or the investigator determined that the patient was no longer experiencing clinical benefit. A total of 169 patients in the chemotherapy arm received pemetrexed 500 mg/m 2 with cisp…

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS • Strong CYP3A Inhibitors: Avoid concomitant use. ( 2.9 , 7.1 ) • Strong CYP3A Inducers: Avoid concomitant use. ( 7.1 ) • CYP3A Substrates: Avoid concomitant use with CYP3A substrates, where minimal concentration changes may lead to serious adverse reactions. ( 7.2 )

7.1Effect of Other Drugs on XALKORI Strong or Moderate CYP3A Inhibitors Concomitant use of crizotinib with strong CYP3A inhibitors increases crizotinib plasma concentrations [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions of XALKORI. Avoid concomitant use of strong CYP3A inhibitors. If concomitant use of strong CYP3A inhibitors is unavoidable, reduce the XALKORI dosage [see Dosage and Administration (2.9) ] .

Avoid grapefruit or grapefruit juice which may also increase plasma concentrations of crizotinib. Use caution with concomitant use of moderate CYP3A inhibitors. Strong CYP3A Inducers Concomitant use of crizotinib with strong CYP3A inducers decreases crizotinib plasma concentrations [see Clinical Pharmacology (12.3) ] , which may decrease the efficacy of XALKORI.

Avoid concomitant use of strong CYP3A inducers.

7.2Effect of XALKORI on Other Drugs CYP3A Substrates Concomitant use of crizotinib increases plasma concentrations of CYP3A substrates [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions of these substrates. Avoid concomitant use of XALKORI with CYP3A substrates where minimal concentration changes may lead to serious adverse reactions. If concomitant use of XALKORI is unavoidable, decrease the CYP3A substrate dosage in accordance with approved product labeling.

7.3Drugs That Prolong the QT Interval XALKORI can prolong the QT/QTc interval. Avoid concomitant use of XALKORI with drugs that prolong the QT interval [see Warnings and Precautions (5.3) , Clinical Pharmacology (12.2) ] .

7.4Drugs That Cause Bradycardia XALKORI can cause bradycardia. Avoid concomitant use of XALKORI with drugs that cause bradycardia (e.g., beta-blockers, non-dihydropyridine calcium channel blockers, clonidine, and digoxin) [see Warnings and Precautions (5.4) ] .

👥 Use in Specific Populations ~3 min read ▾

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

8.1Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, XALKORI can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of XALKORI in pregnant women. In animal reproduction studies, oral administration of crizotinib to pregnant rats during organogenesis at exposures similar to those expected with the maximum recommended human dose resulted in embryotoxicity and fetotoxicity (see Data ) .

Advise pregnant women of the potential risk to a fetus. 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 Crizotinib was administered to pregnant rats and rabbits during organogenesis to study the effects on embryo-fetal development.

Postimplantation loss was increased at doses ≥50 mg/kg/day (approximately 0.6 times the recommended human dose based on AUC) in rats. No teratogenic effects were observed in rats at doses up to the maternally toxic dose of 200 mg/kg/day (approximately 2.7 times the recommended human dose based on AUC) or in rabbits at doses of up to 60 mg/kg/day (approximately 1.6 times the recommended human dose based on AUC), though fetal body weights were reduced at these doses.

8.2Lactation Risk Summary There is no information regarding the presence of crizotinib or its metabolites in human milk, or the effects on the breastfed child or on milk production. Because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with XALKORI and for 45 days after the last dose.

8.3Females and Males of Reproductive Potential Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating XALKORI [see Use in Specific Population (8.1) ]. Contraception XALKORI can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Females Advise females of reproductive potential to use effective contraception during treatment with XALKORI and for 45 days after the last dose.

Males Because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use condoms during treatment with XALKORI and for 90 days after the last dose [see Nonclinical Toxicology (13.1) ]. Infertility Based on reproductive organ findings in animals, XALKORI may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Nonclinical Toxicology (13.1) ].

8.4Pediatric Use The safety and effectiveness of XALKORI have been established in pediatric patients 1 year of age and older with relapsed or refractory, systemic ALK-positive ALCL or with unresectable, recurrent, or refractory ALK-positive IMT [see Adverse Reactions (6.1) , Clinical Studies (14.2 , 14.3) ] . The safety and effectiveness have not been established in pediatric patients younger than 1 year of age with ALCL or with IMT, or in any pediatric patients with NSCLC. In a study that evaluated XALKORI in combination with chemotherapy in pediatric patients with newly diagnosed ALCL (Study ANHL12P1; NCT01979536), 13 of 66 (20%) patients had a Grade 2 or higher thromboembolic event, including pulmonary embolism in 6%.

The safety and effectiveness of XALKORI in combination with chemotherapy have not been established in patients with newly diagnosed ALCL. Juvenile Animal Toxicity Data Decreased bone formation in growing long bones was observed in immature rats at 150 mg/kg/day following once daily dosing for 28 days (approximately 5.4 times the recommended human dose based on AUC). Other toxicities of potential concern to pediatric patients have not been evaluated in juvenile animals.

8.5 Geriatric Use Of the total number of patients wi…

🤰 Pregnancy 214 words ▾

8.1Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, XALKORI can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of XALKORI in pregnant women. In animal reproduction studies, oral administration of crizotinib to pregnant rats during organogenesis at exposures similar to those expected with the maximum recommended human dose resulted in embryotoxicity and fetotoxicity (see Data ) .

Advise pregnant women of the potential risk to a fetus. 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 Crizotinib was administered to pregnant rats and rabbits during organogenesis to study the effects on embryo-fetal development.

Postimplantation loss was increased at doses ≥50 mg/kg/day (approximately 0.6 times the recommended human dose based on AUC) in rats. No teratogenic effects were observed in rats at doses up to the maternally toxic dose of 200 mg/kg/day (approximately 2.7 times the recommended human dose based on AUC) or in rabbits at doses of up to 60 mg/kg/day (approximately 1.6 times the recommended human dose based on AUC), though fetal body weights were reduced at these doses.

🧒 Pediatric Use 186 words ▾

8.4Pediatric Use The safety and effectiveness of XALKORI have been established in pediatric patients 1 year of age and older with relapsed or refractory, systemic ALK-positive ALCL or with unresectable, recurrent, or refractory ALK-positive IMT [see Adverse Reactions (6.1) , Clinical Studies (14.2 , 14.3) ] . The safety and effectiveness have not been established in pediatric patients younger than 1 year of age with ALCL or with IMT, or in any pediatric patients with NSCLC. In a study that evaluated XALKORI in combination with chemotherapy in pediatric patients with newly diagnosed ALCL (Study ANHL12P1; NCT01979536), 13 of 66 (20%) patients had a Grade 2 or higher thromboembolic event, including pulmonary embolism in 6%.

The safety and effectiveness of XALKORI in combination with chemotherapy have not been established in patients with newly diagnosed ALCL. Juvenile Animal Toxicity Data Decreased bone formation in growing long bones was observed in immature rats at 150 mg/kg/day following once daily dosing for 28 days (approximately 5.4 times the recommended human dose based on AUC). Other toxicities of potential concern to pediatric patients have not been evaluated in juvenile animals.

🧓 Geriatric Use 78 words ▾

8.5Geriatric Use Of the total number of patients with ALK-positive metastatic NSCLC in clinical studies of XALKORI (n=1669), 16% were 65 years or older and 3.8% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients. Clinical studies of XALKORI in patients with ROS1-positive metastatic NSCLC did not include sufficient numbers of patients age 65 years and older to determine whether they respond differently from younger patients.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), ROS1 (c-ros), and Recepteur d'Origine Nantais (RON). Translocations can affect the ALK gene resulting in the expression of oncogenic fusion proteins. The formation of ALK fusion proteins results in activation and dysregulation of the gene's expression and signaling which can contribute to increased cell proliferation and survival in tumors expressing these proteins.

Crizotinib demonstrated concentration-dependent inhibition of ALK, ROS1, and c-Met phosphorylation in cell-based assays using tumor cell lines and demonstrated antitumor activity in mice bearing tumor xenografts that expressed echinoderm microtubule-associated protein-like 4 (EML4)- or nucleophosmin (NPM)-ALK fusion proteins or c-Met. In vitro, crizotinib induced apoptosis and inhibited proliferation and ALK-mediated signaling in ALCL-derived cell lines (containing NPM-ALK) at clinically achievable exposures. In vivo data obtained in an ALCL-derived mouse model showed complete regression of the tumor at a dose of 100 mg/kg once daily.

12.2Pharmacodynamics Cardiac Electrophysiology In an ECG substudy conducted in 52 patients with ALK-positive NSCLC, the maximum mean QTcF (corrected QT by the Fridericia method) change from baseline was 12.3 ms (2-sided 90% upper CI: 19.5 ms) following administration of XALKORI 250 mg orally twice daily. An exposure-QT analysis suggested a crizotinib plasma concentration-dependent increase in QTcF [see Warnings and Precautions (5.3) ] .

12.3Pharmacokinetics Following XALKORI 250 mg capsules twice daily, steady-state was reached within 15 days with a median accumulation ratio of 4.8. Steady-state minimum concentration (C min.ss ) and AUC increased in a greater than dose-proportional manner over the dose range of 200 mg to 300 mg twice daily (0.8 to 1.2 times the approved recommended dosage). Absorption A single crizotinib capsule dose was absorbed with median time to achieve peak concentration (T max ) of 4 to 6 hours, and the mean absolute bioavailability of 43% (range: 32% to 66%).

The oral pellets had a comparable crizotinib bioavailability compared with the capsules. Effect of Food A high-fat meal, reduced AUC 0-INF and maximum plasma concentration (C max ) of crizotinib each by 14% for the capsule formulation; reduced AUC 0-INF and C max of crizotinib by 15% and 23%, respectively, for the pellet formulation as compared to those under fasted conditions. Distribution The geometric mean volume of distribution (V ss ) of crizotinib was 1772 L following a single intravenous dose.

Protein binding of crizotinib is 91% and is independent of drug concentration in vitro. Crizotinib is a substrate for P-glycoprotein (P-gp) in vitro. The blood-to-plasma concentration ratio is approximately 1.

Elimination The mean apparent plasma terminal half-life of crizotinib was 42 hours following single doses of crizotinib in patients. The mean apparent clearance (CL/F) of crizotinib was lower at steady-state (60 L/h) after 250 mg twice daily than after a single 250 mg oral dose (100 L/h). Metabolism Crizotinib is predominantly metabolized by CYP3A.

Excretion Following administration of a single oral 250 mg dose of radiolabeled crizotinib dose to healthy subjects, 63% (53% as unchanged) of the administered dose was recovered in feces and 22% (2.3% as unchanged) in urine. Specific Populations No clinically significant difference in crizotinib pharmacokinetics were observed based on age, sex, or ethnicity (Asian, non-Asian). For patients <18 years of age, body weight has a significant effect on the pharmacokinetics of crizotinib, with lower crizotinib exposures observed in patients with higher body weight.

Pediatric Patients In pediatric patients, crizotinib steady-state exposure increased proportionally with dose over the dose range of 165 mg/m 2 to 280 mg/m 2 orally twice daily. At a do…

🧬 Mechanism of Action 156 words ▾

12.1Mechanism of Action Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), ROS1 (c-ros), and Recepteur d'Origine Nantais (RON). Translocations can affect the ALK gene resulting in the expression of oncogenic fusion proteins. The formation of ALK fusion proteins results in activation and dysregulation of the gene's expression and signaling which can contribute to increased cell proliferation and survival in tumors expressing these proteins.

Crizotinib demonstrated concentration-dependent inhibition of ALK, ROS1, and c-Met phosphorylation in cell-based assays using tumor cell lines and demonstrated antitumor activity in mice bearing tumor xenografts that expressed echinoderm microtubule-associated protein-like 4 (EML4)- or nucleophosmin (NPM)-ALK fusion proteins or c-Met. In vitro, crizotinib induced apoptosis and inhibited proliferation and ALK-mediated signaling in ALCL-derived cell lines (containing NPM-ALK) at clinically achievable exposures. In vivo data obtained in an ALCL-derived mouse model showed complete regression of the tumor at a dose of 100 mg/kg once daily.

📦 How Supplied / Storage and Handling ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Capsules: • 200 mg capsules Hard gelatin capsule with pink opaque cap and white opaque body, printed with black ink "Pfizer" on the cap, "CRZ 200" on the body; available in: Bottles of 60 capsules: NDC 0069-8141-20 • 250 mg capsules Hard gelatin capsule with pink opaque cap and body, printed with black ink "Pfizer" on the cap, "CRZ 250" on the body; available in: Bottles of 60 capsules: NDC 0069-8140-20 Store at room temperature 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Oral Pellets: • 20 mg oral pellets Hard gelatin capsule, size 4, light blue opaque cap and white opaque body, printed with black ink “Pfizer” on the cap, “CRZ 20” on the body; available in: Bottles of 60 capsules: NDC 0069-0251-60 • 50 mg oral pellets Hard gelatin capsule, size 3, gray opaque cap and light gray opaque body, printed with black ink “Pfizer” on the cap, “CRZ 50” on the body; available in: Bottles of 60 capsules: NDC 0069-0507-60 • 150 mg oral pellets Hard gelatin capsule, size 0, light blue opaque cap and body, printed with black ink “Pfizer” on the cap, “CRZ 150” on the body; available in: Bottles of 60 capsules: NDC 0069-1500-60 Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

📋 Description ~1 min read ▾

11 DESCRIPTION Crizotinib is a kinase inhibitor. The molecular formula for crizotinib is C 21 H 22 Cl 2 FN 5 O and the molecular weight is 450.34 daltons. Crizotinib is described chemically as ( R )-3-[1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1 H -pyrazol-4-yl]pyridin-2-amine.

The chemical structure of crizotinib is shown below: Crizotinib is a white to pale-yellow powder with a pKa of 9.4 (piperidinium cation) and 5.6 (pyridinium cation). The solubility of crizotinib in aqueous media decreases over the range pH 1.6 to pH 8.2 from greater than 10 mg/mL to less than 0.1 mg/mL. The log of the distribution coefficient (octanol/water) at pH 7.4 is 1.65.

Capsules: XALKORI (crizotinib) capsules for oral administration are supplied as printed hard-shell capsules containing 250 mg or 200 mg of crizotinib together with colloidal silicon dioxide, microcrystalline cellulose, anhydrous dibasic calcium phosphate, sodium starch glycolate, magnesium stearate, and hard gelatin capsule shells as inactive ingredients. The pink opaque capsule shell components contain gelatin, titanium dioxide, and red iron oxide. The white opaque capsule shell components contain gelatin and titanium dioxide.

The printing ink contains shellac, propylene glycol, strong ammonia solution, potassium hydroxide, and black iron oxide. Oral Pellets: XALKORI (crizotinib) oral pellets for oral administration are supplied as 20 mg, 50 mg, 150 mg of crizotinib contained in hard gelatin capsules. The inactive ingredients in the uncoated pellets are poloxamer and stearyl alcohol.

The film-coating consists of hypromellose, glyceryl monostearate, medium chain triglycerides, polyethylene glycol/macrogol, sucrose, and talc. Chemical Structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide; Instructions for Use). Hepatotoxicity Inform patients to immediately report symptoms of hepatotoxicity [see Warnings and Precautions (5.1) ] . Interstitial Lung Disease (Pneumonitis) Advise patients to immediately report any new or worsening pulmonary symptoms [see Warnings and Precautions (5.2) ].

Bradycardia Advise patients to report any symptoms of bradycardia and to inform their healthcare provider about the use of any heart or blood pressure medications [see Warnings and Precautions (5.4) ]. Severe Visual Loss Inform patients of the potential risk of severe visual loss and to immediately contact their healthcare provider if they develop severe visual loss. Inform patients that visual changes such as perceived flashes of light, blurry vision, light sensitivity, and floaters are commonly reported adverse reactions and may occur while driving or operating machinery.

The onset of visual disorders most commonly occurs during the first week of treatment [see Warnings and Precautions (5.5) , Adverse Reactions (6) ] . Gastrointestinal Toxicity in Pediatric and Young Adult Patients with ALCL or Pediatric Patients with IMT Inform patients with ALCL or pediatric patients with IMT of the risk of severe nausea, vomiting, diarrhea, and stomatitis. Advise patients to immediately inform their healthcare provider of problems with swallowing, vomiting, or diarrhea [see Warnings and Precautions (5.6) ].

Drug Interactions Inform patients to avoid grapefruit or grapefruit juice while taking XALKORI. Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products [see Drug Interactions (7) ] . Photosensitivity Inform patients of the signs and symptoms of photosensitivity.

Advise patients to avoid prolonged sun exposure and to use sunscreen or protective clothing during treatment with XALKORI [see Adverse Reactions (6.1) ] . Dosage and Administration Advise patients to take XALKORI with or without food. If a patient misses a dose, advise the patient to take it as soon as remembered unless it is less than 6 hours until the next dose, in which case, advise the patient not to take the missed dose.

If a patient vomits after taking a dose of XALKORI, advise the patient not to take an extra dose, but to take the next dose at the regular time [see Dosage and Administration (2.4) ] . Capsules: Advise patients to swallow XALKORI capsules whole [see Dosage and Administration (2.4) ] . Oral Pellets: Inform patient or caregiver to open the encapsulated XALKORI oral pellets and administer the oral pellets directly in the patient’s mouth or with a consumer-supplied oral dosing aid, for example a spoon or medicine cup.

Advise patient or caregiver that the oral pellets are not to be chewed and to give a sufficient amount of water after pellets are administered to ensure all oral pellets are swallowed [see Dosage and Administration (2.4) ] . Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.7) , Use in Specific Populations (8.1) ] . Females and Males of Reproductive Potential Advise females of reproductive potential to use effective contraception during treatment with XALKORI and for 45 days after the last dose [see Use in Specific Populations (8.3) ] .

Advise male patients with female partners of reproductive potential to use condoms during treatment with XALKORI and for 90 days after the last dose [see Use in Specific Populations (8.3) , Nonclinical Toxicology (13.1) ] . Lactation Advise females not to breastfeed during treatment with XALKORI and for 45 days after the last dose [see Use in Specific Populations (8.2) ] . Infertility Advise females and males of reproductive poten…

💬 Medication Guide ~3 min read ▾

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: Sep 2023 MEDICATION GUIDE XALKORI ® (zal-KOR-ee) (crizotinib) capsules XALKORI ® (zal-KOR-ee) (crizotinib) oral pellets What is the most important information I should know about XALKORI?

XALKORI may cause serious side effects, including: • Liver problems. XALKORI may cause life-threatening liver injury that may lead to death. Your healthcare provider should do blood tests to check your liver every 2 weeks during the first 2 months of treatment with XALKORI, then 1 time a month and as recommended by your healthcare provider during treatment.

Tell your healthcare provider right away if you develop any of the following new or worsening symptoms: o yellowing of your skin or the white part of your eyes o severe tiredness o dark or brown (tea color) urine o nausea or vomiting o decreased appetite o pain on the right side of your stomach o bleed or bruise more easily than normal o itching • Lung problems (pneumonitis). XALKORI may cause life-threatening lung problems that may lead to death. Symptoms may be similar to those symptoms from lung cancer.

Tell your healthcare provider right away if you have any new or worsening symptoms, including: o trouble breathing or shortness of breath o cough with or without mucous o fever • Heart problems. XALKORI may cause very slow, very fast, or abnormal heartbeats. Your healthcare provider may check your pulse rate and blood pressure regularly during treatment with XALKORI.

Tell your healthcare provider right away if you feel dizzy or faint or have abnormal heartbeats. Tell your healthcare provider if you take any heart or blood pressure medicines. • Severe vision problems. Vision problems are common with XALKORI.

These problems usually happen within 1 week of starting treatment with XALKORI. Vision problems with XALKORI can be severe and may cause partial or complete loss of vision in one or both eyes. Your healthcare provider may hold or permanently stop your treatment with XALKORI and refer you to an eye specialist if any vision problems develop during treatment with XALKORI.

Tell your healthcare provider right away if you have any new vision problems, loss of vision or any change in vision, including: o double vision o seeing flashes of light o blurry vision o light hurting your eyes o new or increased floaters In addition, for children or young adults taking XALKORI to treat anaplastic large cell lymphoma (ALCL) or children taking XALKORI to treat inflammatory myofibroblastic tumor (IMT): Your healthcare provider may refer you to an eye specialist before starting XALKORI, and within 1 month of starting XALKORI to check for vision problems.

You should have an eye examination every 3 months during treatment with XALKORI and more often if there are any new vision problems. • Severe stomach, intestine, and mouth (gastrointestinal) problems in children or young adults with ALCL or children with IMT. XALKORI may cause severe diarrhea, nausea, vomiting, or mouth sores. Tell your healthcare provider right away if problems with swallowing, vomiting, or diarrhea develop during treatment with XALKORI. o Your healthcare provider may give medicines as needed to prevent or treat diarrhea, nausea, and vomiting. o Your healthcare provider may recommend drinking more fluids or may prescribe electrolyte supplements or other kinds of nutritional support if severe symptoms develop.

See " What are possible side effects of XALKORI? " for more information about side effects. What is XALKORI? XALKORI is a prescription medicine that is used to treat: • adults with non-small cell lung cancer (NSCLC) that has spread to other parts of the body and is caused by a defect in either a gene called ALK (anaplastic lymphoma kinase) or a gene called ROS1. • children 1 year of age and older and young adults with ALCL when your ALCL with a defect in a gene called ALK has returned or you have tried a treatment and it did not work or is no…

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