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VITRAKVI LAROTRECTINIB 20 mg/mL Solution, Concentrate, 100 mL — NDC 50419-0392-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

VITRAKVI LAROTRECTINIB 20 mg/mL Solution, Concentrate, 100 mL — NDC 50419-392-01 (Billing 50419-0392-01)

by Bayer HealthCare Pharmaceuticals Inc. · 100 mL in 1 BOTTLE

This is a package of 100 mL of VITRAKVI LAROTRECTINIB 20 mg/mL Solution, Concentrate from Bayer HealthCare Pharmaceuticals Inc., marketed since Jul 2019 and currently FDA-listed. It is this product's only package size.

NDC 50419-0392-01
🏷️ FDA NDC (as labeled) 50419-392-01 billing pads the product segment with a zero
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

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

NDC database record

One package, one record: these facts belong to NDC 50419-392-01 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
50419 labeler · 392 product · 01 package
Package marketed since
Jul 26, 2019
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Billing quantity
100 mL per package
Barcode (UPC-A, from the NDC)
3 5041939201 3
FDA record last changed
Jul 24, 2026
Past resolved recalls for this product (1)
Class I · Nov 6, 2023 · Terminated — Microbial Contamination of Non-Sterile Products: microbial contamination identified as Penicillium brevicompactum observed during routine ongoing stability testing (Bayer Healthcare Pharmaceuticals Inc.) · FDA recall D-0145-2024

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 50419-392-01
Product NDC 50419-392
11-digit billing NDC 50419039201
NCPDP billing unit ML — per mL (volume)
RxCUI 2105633, 2105645, 2105649, 2105653, 2105655, 2105657
UNII PF9462I9HX
Application # NDA211710
SPL Set ID 0c8ca614-58b2-4aa4-83d3-0387a8f782fd
Established class (EPC) Kinase Inhibitor
Mechanism of action Tropomyosin Receptor Kinases Inhibitors
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2019-07-26
Route OROPHARYNGEAL
Dosage form SOLUTION, CONCENTRATE
Substance LAROTRECTINIB

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

GPI-14 21533835202020
GPI class Vitrakvi
GCN Seq No 079308
GCN 45789
HICL code 045494
Ingredient (HICL) Larotrectinib Sulfate
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 VITRAKVI 20 MG/ML SOLUTION
FDB brand name Vitrakvi
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 079308
  • GCN: 45789
  • GPI-14 (Medi-Span): 21533835202020
  • HICL (First Databank): 045494
  • AHFS class code: 10:00.00.00
  • RxCUI (RxNorm): 2105633
Why two NDCs? The FDA registers this code as 50419-392-01 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 50419-0392-01. 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) Other protein kinase inhibitors
How it works Tropomyosin Receptor Kinases Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name VITRAKVI 20 MG/ML SOLUTION Ingredient Larotrectinib Sulfate
📗 Our plain-language guide HelloPharmacist
  • Vitrakvi (larotrectinib) is a targeted cancer medicine — it doesn't treat cancer by location (like 'lung cancer' or 'breast cancer') but by a specific genetic change in your tumor...
  • What exactly is Vitrakvi and why did my doctor prescribe it for me?
  • You can take Vitrakvi with or without food — your choice. However, you should avoid grapefruit and grapefruit juice entirely while on this medicine. Grapefruit interferes with the...
  • Can I eat before taking Vitrakvi, and is grapefruit okay?
📖 Read our full Larotrectinib guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

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

Price systemPer mLPer 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 $191.80 $19,180.02 / 100 ml
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
50419-0392-01 You're viewing this Main listing 100 mL in 1 BOTTLE 2019-07-26 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Vitrakvi 20 mg/mLthis 50419-0392-01 Bayer 100 ml — — FDA listed —
Vitrakvi 20 mg/mL 50419-0393-03 Bayer 2 bottles — — FDA listed —
Vitrakvi 20 mg/mL 71777-0392-01 Loxo 100 ml — — 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

🏛️
2018
First FDA approval
Nov 2018
📍
2026
Currently FDA-listed
8 years listed
🛡️
2037
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 May 2037. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Nov 26, 2018 RLD RS ⏳ ~10.6 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 10047097 — method of use (U-2474)
US 8865698 — method of use (U-2469)
US 10005783 — method of use (U-2472)
US 10045991 — method of use (U-2473)
US 9782414 — method of use (U-2471)
US 9447104 — method of use (U-2470)
US 11484535 — method of use (U-2470)
US 11191766 — method of use (U-2471)
US 11337967 — method of use (U-4123)
US 11974998 — method of use (U-4124)
US 9676783 — method of use (U-2469)
US 10774085 — method of use (U-2470)
US 10799505 — drug substance
US 8513263 — drug substance
US 10668072 — drug product
US 10137127 — drug product
US 10172861 — drug substance
US 9127013 — drug substance
2018 2020 2022 2024 2026 2028 2030 2032 2034 2036
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 (18)
PatentTypeUse codeExpires
US 10047097 ↗ Method of use U-2474 Oct 21, 2029
US 8865698 ↗ Method of use U-2469 Oct 21, 2029
US 10005783 ↗ Method of use U-2472 Oct 21, 2029
US 10045991 ↗ Method of use U-2473 Apr 4, 2037
US 9782414 ↗ Method of use U-2471 Nov 16, 2035
US 9447104 ↗ Method of use U-2470 Oct 21, 2029
US 11484535 ↗ Method of use U-2470 Apr 4, 2037
US 11191766 ↗ Method of use U-2471 Apr 4, 2037
US 11337967 ↗ Method of use U-4123 May 16, 2037
US 11974998 ↗ Method of use U-4124 May 16, 2037
US 9676783 ↗ Method of use U-2469 Oct 21, 2029
US 10774085 ↗ Method of use U-2470 Oct 21, 2029
US 10799505 ↗ Drug substance — Aug 15, 2036
US 8513263 ↗ Drug substance — Dec 23, 2029
US 10668072 ↗ Drug product — Apr 4, 2037
US 10137127 ↗ Drug product — Apr 4, 2037
US 10172861 ↗ Drug substance — Nov 16, 2035
US 9127013 ↗ Drug substance — Oct 21, 2029
Common questions
Is there a generic version of VITRAKVI 20 MG/ML SOLUTION?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for VITRAKVI 20 MG/ML SOLUTION. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until May 2037 — an estimate, not a guaranteed launch date.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

What it looks like

Color White / white / yellow
ShapeCapsule
ImprintBAYER;100mg
Size22 mm
ScoringNot scored
FlavorStrawberry
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 8W6Q67R6NX
    Adrabetadex is a chemically modified sugar-like compound that acts as a solubilizer, helping poorly soluble drugs dissolve better in liquid medicines. It's used in injectable and oral formulations to improve drug stability and absorption.
  • UNII 2968PHW8QP
    A weak organic acid derived from citrus fruits or made through fermentation. It works as a buffer to control pH, a preservative to extend shelf life, and a flavoring agent in medications.
  • UNII PDC6A3C0OX
    Glycerin is a clear, thick liquid derived from plant oils or fats. It acts as a humectant to retain moisture, a sweetener, and a solvent in medications.
  • UNII A2I8C7HI9T
    Methylparaben is a preservative derived from benzoic acid that prevents growth of bacteria, fungi, and mold in medicines. It extends the product's shelf life and maintains safety during storage.
  • UNII 1VPU26JZZ4
    Potassium sorbate is a salt derived from sorbic acid, a naturally occurring preservative. It prevents growth of mold, yeast, and some bacteria, extending the medicine's shelf life.
  • UNII 6DC9Q167V3
    Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
  • UNII SE337SVY37
    A mineral salt used as a buffer to help maintain the medicine's pH level and prevent breakdown of active ingredients. It also acts as a thickening agent in liquid formulations.
  • UNII 506T60A25R
    Sorbitol is a natural sugar alcohol derived from glucose. It serves as a sweetener, humectant, and bulking agent in medications to improve taste and help maintain moisture in the product.
  • 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 B22547B95K
    A salt derived from citric acid that helps maintain the proper acid-base balance in the medicine. It's used as a buffer to keep the product stable and at the right pH level.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

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.

Manufacturer & labeler

LabelerBayer HealthCare Pharmaceuticals Inc.
Application holderBAYER HEALTHCARE PHARMACEUTICALS INC
FDA applicationNDA211710 (NDA)
Labeler code50419
First marketedJul 2019
Product typeHuman Prescription Drug
Portfolio62 products on file

More NDCs from Bayer HealthCare Pharmaceuticals Inc. labeler code 50419

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. 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 📦 Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage 150 words ▾

1 INDICATIONS AND USAGE VITRAKVI is indicated for the treatment of adult and pediatric patients with solid tumors that: have a neurotrophic receptor tyrosine kinase ( NTRK ) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. Select patients for therapy based on an FDA-approved test [see Dosage and Administration (2.1) ]. VITRAKVI is a kinase inhibitor indicated for the treatment of adult and pediatric patients with solid tumors that: have a neurotrophic receptor tyrosine kinase ( NTRK ) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment.

Select patients for therapy based on an FDA-approved test. ( 1 , 2.1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Select patients for treatment with VITRAKVI based on the presence of a NTRK gene fusion ( 2.1 , 14 ). Recommended Dosage in Adult and Pediatric Patients with Body Surface Area of 1 Meter-Squared or greater: 100 mg orally twice daily ( 2.2 ) Recommended Dosage in Pediatric Patients with Body Surface Area of Less Than 1 Meter-Squared: 100 mg/m 2 orally twice daily ( 2.2 )

2.1Patient Selection Select patients for treatment with VITRAKVI based on the presence of a NTRK gene fusion in tumor specimens [see Clinical Studies (14) ] . In patients with secretory breast cancer, mammary analogue secretory cancer (MASC), congenital mesoblastic nephroma (CMN), or infantile fibrosarcoma, consider treatment without confirmation of NTRK rearrangements in tumor specimens. Information on FDA-approved tests is available at http://www.fda.gov/companiondiagnostics.

2.2Recommended Dosage Recommended Dosage in Adult and Pediatric Patients with Body Surface Area of 1 Meter-Squared or greater The recommended dosage of VITRAKVI is 100 mg orally twice daily, with or without food, until disease progression or until unacceptable toxicity. Recommended Dosage in Pediatric Patients with Body Surface Area Less Than 1 Meter-Squared The recommended dosage of VITRAKVI is 100 mg/m 2 orally twice daily, with or without food, until disease progression or until unacceptable toxicity.

2.3Dosage Modifications for Adverse Reactions For Grade 2 and higher liver function test abnormalities, refer to Section 2.4, Table 2, Dosage Modifications for Hepatotoxicity. For all other Grade 3 or 4 adverse reactions: Withhold VITRAKVI until adverse reaction resolves or improves to baseline or Grade 1. Resume at the next dosage modification if resolution occurs within 4 weeks.

Permanently discontinue VITRAKVI if an adverse reaction does not resolve within 4 weeks. The recommended dosage reductions for VITRAKVI for adverse reactions are provided in Table 1. Table 1 Recommended Dosage Reductions for VITRAKVI for Adverse Reactions Dosage Reduction Adult and Pediatric Patients with Body Surface Area of 1 m 2 or Greater Pediatric Patients with Body Surface Area Less Than 1 m 2 First 75 mg orally twice daily 75 mg/m 2 orally twice daily Second 50 mg orally twice daily 50 mg/m 2 orally twice daily Third 100 mg orally once daily 25 mg/m 2 orally twice daily Pediatric patients on 25 mg/m 2 orally twice daily should remain on this dosage even if body surface area becomes greater than 1 m 2 during the treatment.

Maximum dose should be 25 mg/m 2 orally twice daily at the third dosage modification. Permanently discontinue VITRAKVI in patients who are unable to tolerate VITRAKVI after three dose modifications.

2.4Dosage Modifications for Hepatotoxicity The recommended dosage modifications for VITRAKVI liver function test abnormalities are provided in Table 2. For CTCAE Grade 2 ALT and/or AST elevation, monitor liver function frequently as clinically indicated, to establish whether a dose interruption or reduction is required [see Warnings and Precautions (5.3) ] . Table 2 Recommended Dosage Modifications for VITRAKVI for Hepatotoxicity Severity Grading defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version

4.03Dosage Modification ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal AST or ALT ≥ 5 × ULN with bilirubin ≤ 2 × ULN [see Warnings and Precautions (5.3) ] Withhold VITRAKVI until recovery to ≤ Grade 1 or return to baseline. Resume VITRAKVI at the next lower dose level. Permanently discontinue if a Grade 4 AST and/or ALT elevation occurs after resuming VITRAKVI.

AST or ALT > 3 × ULN with total bilirubin > 2 × ULN in the absence of alternative causes Permanently discontinue VITRAKVI.

2.5Dosage Modifications for Coadministration with Strong CYP3A4 Inhibitors Avoid coadministration of strong CYP3A4 inhibitors with VITRAKVI. If coadministration of a strong CYP3A4 inhibitor…

💊 Dosage Forms and Strengths 143 words ▾

3 DOSAGE FORMS AND STRENGTHS Capsules: 25 mg, 100 mg ( 3 ) Oral Solution: 20 mg/mL ( 3 ) Capsules 25 mg: white opaque hard gelatin capsule, size 2, with blue printing of "BAYER" cross and "25 mg" on body of capsules. 25 mg larotrectinib is equivalent to 30.7 mg larotrectinib sulfate. 100 mg: white opaque hard gelatin capsule, size 0, with blue printing of "BAYER" cross and "100 mg" on body of capsule.

100 mg larotrectinib is equivalent to 123 mg larotrectinib sulfate. Oral Solution packaged in one bottle containing 100 mL 20 mg/mL: clear yellow to orange solution. 20 mg/mL larotrectinib is equivalent to 24.6 mg/mL larotrectinib sulfate.

Oral Solution packaged in two bottles each containing 50 mL 20 mg/mL: colorless to yellow or orange or red or brownish solution. 20 mg/mL larotrectinib is equivalent to 24.6 mg/mL larotrectinib sulfate.

⛔ Contraindications 7 words ▾

4 CONTRAINDICATIONS None. None. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Central Nervous System (CNS) Effects: Advise patients and caretakers of the risk of CNS adverse reactions including dizziness, cognitive impairment, mood disorders, and sleep disturbances. Advise patients not to drive or operate hazardous machinery if experiencing neurotoxicity. Withhold and modify dosage, or permanently discontinue VITRAKVI based on severity.

( 2.3 , 5.1 ) Skeletal Fractures: Promptly evaluate patients with signs or symptoms of fractures. ( 5.2 ) Hepatotoxicity: Obtain liver function tests (ALT, AST, ALP and bilirubin) before initiation of VITRAKVI and every 2 weeks during the first 2 months of treatment, then monthly thereafter or as clinically indicated. Temporarily withhold, reduce dose, or permanently discontinue VITRAKVI based on severity.

( 2.4 , 5.3 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females with reproductive potential of potential risk to the fetus and to use effective contraception. ( 5.4 , 8.3 )

5.1Central Nervous System Effects Central nervous system (CNS) adverse reactions occurred in patients receiving VITRAKVI, including dizziness, cognitive impairment, mood disorders, and sleep disturbances. In patients who received VITRAKVI (n=444), all grades CNS effects including cognitive impairment, mood disorders, dizziness and sleep disorders were observed in 40.3% with Grades 3-4 in 3.8% of patients. Cognitive impairment occurred in 11% of patients.

The median time to onset of cognitive impairment was 6 months (range: 2 days to 56 months). Cognitive impairment occurring in ≥ 1% of patients included memory impairment (4.1%), disturbance in attention (3.6%), confusional state (2.3%), cognitive disorder (1.6%), delirium (1.4%), and hallucination (1.1%). Grade 3 cognitive adverse reactions occurred in 1.8% of patients and Grade 4 cognitive adverse reactions in 0.2% of patients.

Among the 49 patients with cognitive impairment, 6% required a dose modification, and 18% required dose interruption. Mood disorders occurred in 14% of patients. The median time to onset of mood disorders was 3.3 months (range: 1 day to 65 months).

Mood disorders occurring in ≥ 1% of patients included anxiety (5%), agitation (3.2%), depression (3.2%), irritability (2.3%), and restlessness (1.1%). Grade 3 mood disorders occurred in 0.9% of patients. Among the 63 patients who experienced mood disorders, no patient required a dose modification, and 1.6% required dose interruption.

Dizziness occurred in 22% of patients, and Grade 3 dizziness occurred in 0.9% of patients. Among the 96 patients who experienced dizziness, 6% of patients required a dose modification, and 5% required dose interruption. Sleep disturbances occurred in 12% of patients.

Sleep disturbances included insomnia (9%), somnolence (3.4%), and sleep disorder (0.5%). Grade 3 sleep disturbances occurred in 0.2% of patients. Among the 54 patients who experienced sleep disturbances, no patient required a dose modification, and 3.7% required dose interruption.

Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity.

If withheld, modify the VITRAKVI dosage when resumed [see Dosage and Administration (2.3) ] .

5.2Skeletal Fractures Skeletal fractures can occur in patients taking VITRAKVI. Among 444 patients who received VITRAKVI across clinical trials, fractures occurred in 7% of patients; 6% of 290 adult patients and 10% of 154 pediatric patients. Median time to first fracture was 13 months (range 27 days to 73 months) in patients followed per fracture.

The most common fractures were of the rib (1.4%), fibula, foot, or wrist (0.7% each). Most fractures were associated with minimal or moderate trauma. Some fractures were associated with radiologic abnormalities suggestive of local tumor involvement.

VITRAKVI treatment was interrupted due to fractur…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Central Nervous System Effects [see Warnings and Precautions (5.1) ] Skeletal Fractures [see Warnings and Precautions (5.2) ] Hepatotoxicity [see Warnings and Precautions (5.3) ] The most common (≥ 20%) adverse reactions, including laboratory abnormalities, with VITRAKVI were increased AST, increased ALT, anemia, hypoalbuminemia, musculoskeletal pain, increased alkaline phosphatase, leukopenia, lymphopenia, neutropenia, hypocalcemia, fatigue, vomiting, cough, constipation, pyrexia, diarrhea, nausea, abdominal pain, dizziness, and rash ( 6 ).

To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-842-2937 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trial 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. Unless noted, data in WARNINGS AND PRECAUTIONS and below reflects exposure to VITRAKVI in 444 patients, including 62% patients exposed for greater than 6 months, 44% patients exposed for greater than 1 year, and 30% patients exposed for greater than 2 years.

VITRAKVI was studied in one adult dose-finding trial [LOXO-TRK-14001 (n = 75)], one pediatric dose-finding trial [SCOUT (n = 154)], and one single arm trial [NAVIGATE (n = 215)]. All patients had an unresectable or metastatic solid tumor and no satisfactory alternative treatment options or disease progression following treatment. Across these 444 patients, the median age was 44 years (range: 18 days to 90 years); 35% were younger than 18 years; 53% were female; 59% were White, 24% were Asian and, 4% were Black; and 7% were Hispanic/Latino.

Most adults (91%) received VITRAKVI 100 mg orally twice daily and 91% of pediatrics (< 18 years) received VITRAKVI 100 mg/m 2 twice daily up to a maximum dose of 100 mg twice daily. The dose ranged from 50 mg daily to 200 mg twice daily in adults and 9.6 mg/m 2 twice daily to 120 mg/m 2 twice daily in pediatrics [see Use in Specific Populations (8.4) ] . The most common serious adverse reactions (≥ 2%) were pneumonia, pyrexia, and dyspnea.

Grade 3 or 4 adverse reactions occurred in 60% of patients; adverse reactions leading to dose interruption or modification occurred in 45% and 11% of patients, respectively, and 12% permanently discontinued VITRAKVI for adverse reactions. The most common adverse reactions (1% each) that resulted in permanent discontinuation of VITRAKVI were increased ALT and increased AST. The most common adverse reactions (≥ 3%) resulting in dose interruption were increased ALT (6%), increased AST (5%), neutrophil count decreased (4.7%), pyrexia (4.3%), and vomiting (3.2%).

Most (64%) adverse reactions leading to dose interruption occurred during the first three months of exposure. The most common adverse reactions (≥ 20%), including laboratory abnormalities, in order of decreasing frequency were increased AST, increased ALT, anemia, hypoalbuminemia, musculoskeletal pain, increased alkaline phosphatase, leukopenia, lymphopenia, neutropenia, hypocalcemia, fatigue, vomiting, cough, constipation, pyrexia, diarrhea, nausea, abdominal pain, dizziness, and rash. Adverse reactions of VITRAKVI occurring in ≥ 10% of patients and laboratory abnormalities worsening from baseline in ≥ 20% of patients are summarized in Table 3 and Table 4, respectively.

Table 3 Adverse Reactions Occurring in ≥ 10% of Patients Treated with VITRAKVI Adverse Reaction The adverse reaction identifies a composite term: VITRAKVI N = 444 All Grades National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 4.03. (%) Grade 3-4 Grade 4 adverse reaction: 1 of cognitive impairment, 1 of pyrexia. (%) Musculoskeletal and Connective Tissue Musc…

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors: Avoid coadministration of strong CYP3A4 inhibitors with VITRAKVI. If coadministration cannot be avoided, reduce the VITRAKVI dose. ( 2.5 , 7.1 ) Moderate CYP3A4 Inhibitors: Monitor for adverse reactions more frequently in patients coadministered a moderate CYP3A4 inhibitor with VITRAKVI and reduce the VITRAKVI dosage based on severity of adverse reactions.

( 7.1 ) Strong CYP3A4 Inducers: Avoid coadministration of strong CYP3A4 inducers with VITRAKVI. If coadministration cannot be avoided, increase the VITRAKVI dose. ( 2.6 , 7.1 ) Moderate CYP3A4 Inducers: Increase the VITRAKVI dose.

( 2.6 , 7.1 ) Sensitive CYP3A4 Substrates: Avoid coadministration of sensitive CYP3A4 substrates with VITRAKVI. ( 7.2 )

7.1Effects of Other Drugs on VITRAKVI Strong and Moderate CYP3A4 Inhibitors Coadministration of VITRAKVI with a strong or moderate CYP3A4 inhibitor may increase larotrectinib plasma concentrations, which may result in a higher incidence of adverse reactions [see Clinical Pharmacology (12.3) ]. Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors, including grapefruit or grapefruit juice. If coadministration of strong CYP3A4 inhibitors cannot be avoided, modify VITRAKVI dose as recommended [see Dosage and Administration (2.5) ] .

In patients coadministered a moderate CYP3A4 inhibitor with VITRAKVI, monitor for adverse reactions more frequently and reduce the VITRAKVI dosage based on the severity of emergent adverse reactions [see Dosage and Administration (2.3) ] . Strong and Moderate CYP3A4 Inducers Coadministration of VITRAKVI with a strong or moderate CYP3A4 inducer may decrease larotrectinib plasma concentrations, which may decrease the efficacy of VITRAKVI [see Clinical Pharmacology (12.3) ]. Avoid coadministration of VITRAKVI with strong CYP3A4 inducers, including St.

John's wort. If coadministration of strong CYP3A4 inducers cannot be avoided, modify VITRAKVI dose as recommended. For coadministration with moderate CYP3A4 inducers, modify VITRAKVI dose as recommended [see Dosage and Administration (2.6) ].

7.2Effects of VITRAKVI on Other Drugs Sensitive CYP3A4 Substrates Coadministration of VITRAKVI with sensitive CYP3A4 substrates may increase their plasma concentrations, which may increase the incidence or severity of adverse reactions [see Clinical Pharmacology (12.3) ] . Avoid coadministration of VITRAKVI with sensitive CYP3A4 substrates. If coadministration of these sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) Hepatic Impairment: Reduce the starting dose of VITRAKVI in patients with moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment. ( 2.7 , 8.7 )

8.1Pregnancy Risk Summary Based on literature reports in human subjects with congenital mutations leading to changes in TRK signaling, findings from animal studies, and its mechanism of action [see Clinical Pharmacology (12.1) ] , VITRAKVI can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on VITRAKVI use in pregnant women. Administration of larotrectinib to pregnant rats and rabbits during the period of organogenesis resulted in malformations at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily (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 Human Data Published reports of individuals with congenital mutations in TRK pathway proteins suggest that decreases in TRK-mediated signaling are correlated with obesity, developmental delays, cognitive impairment, insensitivity to pain, and anhidrosis.

Animal Data Larotrectinib crosses the placenta in animals. Larotrectinib did not result in embryolethality at maternally toxic doses [up to 40 times the human exposure based on area under the curve (AUC) at the clinical dose of 100 mg twice daily] in embryo-fetal development studies in pregnant rats dosed during the period of organogenesis; however, larotrectinib was associated with fetal anasarca in rats from dams treated at twice-daily doses of 40 mg/kg [11 times the human exposure (AUC) at the clinical dose of 100 mg twice daily].

In pregnant rabbits, larotrectinib administration was associated with omphalocele at twice-daily doses of 15 mg/kg (0.7 times the human exposure at the clinical dose of 100 mg twice daily).

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

8.3Females and Males of Reproductive Potential Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating VITRAKVI [see Use in Specific Populations (8.1) ]. Contraception VITRAKVI can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ]. Females Advise female patients of reproductive potential to use effective contraception during treatment with VITRAKVI and for 1 week after the last dose.

Males Advise males with female partners of reproductive potential to use effective contraception during treatment with VITRAKVI and for 1 week after the last dose. Infertility Females Based on histopathological findings in the reproductive tracts of female rats in a 1-month repeated-dose study, VITRAKVI may reduce fertility [See Nonclinical Toxicology (13.1) ].

8.4Pediatric Use The safety and effectiveness of VITRAKVI in pediatric patients was established based upon data from three multicenter, open-label, single-arm clinical trials in adult or pediatric patients. [see Adverse Reactions (6.1) , Clinical Studies (14) ]. The efficacy of VITRAKVI was evaluated in 131 pediatric patients and is described in the Clinical Studies section [see Clinical Studies (14) ] . The safety of VITRAKVI was evaluated in 154 pediatric patients who received VITRAKVI.

Of these 154 patients, 31% were <1 month to < 2 years (n = 47), 49% were 2 years to < 12 years (n = 75), and 21% were 12 years to < 18 years (n = 32); 25% had metastatic disease, 44% had loc…

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Based on literature reports in human subjects with congenital mutations leading to changes in TRK signaling, findings from animal studies, and its mechanism of action [see Clinical Pharmacology (12.1) ] , VITRAKVI can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on VITRAKVI use in pregnant women. Administration of larotrectinib to pregnant rats and rabbits during the period of organogenesis resulted in malformations at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily (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 Human Data Published reports of individuals with congenital mutations in TRK pathway proteins suggest that decreases in TRK-mediated signaling are correlated with obesity, developmental delays, cognitive impairment, insensitivity to pain, and anhidrosis.

Animal Data Larotrectinib crosses the placenta in animals. Larotrectinib did not result in embryolethality at maternally toxic doses [up to 40 times the human exposure based on area under the curve (AUC) at the clinical dose of 100 mg twice daily] in embryo-fetal development studies in pregnant rats dosed during the period of organogenesis; however, larotrectinib was associated with fetal anasarca in rats from dams treated at twice-daily doses of 40 mg/kg [11 times the human exposure (AUC) at the clinical dose of 100 mg twice daily].

In pregnant rabbits, larotrectinib administration was associated with omphalocele at twice-daily doses of 15 mg/kg (0.7 times the human exposure at the clinical dose of 100 mg twice daily).

🧒 Pediatric Use ~3 min read ▾

8.4Pediatric Use The safety and effectiveness of VITRAKVI in pediatric patients was established based upon data from three multicenter, open-label, single-arm clinical trials in adult or pediatric patients. [see Adverse Reactions (6.1) , Clinical Studies (14) ]. The efficacy of VITRAKVI was evaluated in 131 pediatric patients and is described in the Clinical Studies section [see Clinical Studies (14) ] . The safety of VITRAKVI was evaluated in 154 pediatric patients who received VITRAKVI.

Of these 154 patients, 31% were <1 month to < 2 years (n = 47), 49% were 2 years to < 12 years (n = 75), and 21% were 12 years to < 18 years (n = 32); 25% had metastatic disease, 44% had locally advanced disease, and 31% had primary CNS; and 82% had received prior treatment for their cancer, including surgery, radiotherapy, or systemic therapy, including radioactive iodine therapy (RAI). The most common cancers were infantile fibrosarcoma (32%), primary CNS tumors (31%), soft tissue sarcoma (27%), and thyroid cancer (4%).

The median duration of exposure was 14.8 months (range: 0.4 months to 87.4 months). Due to the small number of pediatric and adult patients, the single arm design of clinical studies of VITRAKVI, and confounding factors such as differences in susceptibility to infections between pediatric and adult patients, it is not possible to determine whether differences in the incidence of adverse reactions to VITRAKVI are related to patient age or other factors. Adverse reactions occurring more frequently (at least a 10% increase in per-patient incidence) in pediatric patients compared to adult patients were vomiting (51% versus 18%), pyrexia (47% versus 15%), cough (36% versus 23%), diarrhea (34% versus 21%), upper respiratory tract infection (33% versus 10%), headache (25% versus 13%), nasopharyngitis (20% versus 7%), nasal congestion (18% versus 7%), gastroenteritis (13% versus 2%), and rhinitis (12% versus 0%).

Laboratory abnormalities occurring more frequently (at least a 10% increase in per-patient incidence) in pediatric patients compared to adult patients were AST increased (75% versus 55% in adults), ALT increased (69% versus 57% in adults), neutrophil count decrease (59% versus 20% in adults), leukocyte count decrease (46% versus 32% in adults), hyperkalemia (39% versus 16%), glucose decrease (29% versus 13% in adults), and lymphocyte increase (25% versus 1%). Three of the 154 pediatric patients discontinued VITRAKVI due to an adverse reaction associated with a laboratory abnormality (1 patient with Grade 3 increased ALT and 2 patients with Grade 3 decreased neutrophil count).

The pharmacokinetics of VITRAKVI in the pediatric population were similar to those seen in adults [see Clinical Pharmacology (12.3) ]. Juvenile Animal Toxicity Data Larotrectinib was administered in a juvenile toxicity study in rats at twice daily doses of 0.2, 2 and 7.5 mg/kg from postnatal day (PND) 7 to 27 and at twice daily doses of 0.6, 6 and 22.5mg/kg between PND 28 and 70. The dosing period was equivalent to human pediatric populations from newborn to adulthood.

The doses of 2/6 mg/kg twice daily [approximately 0.7 times the human exposure (AUC) at the clinical dose of 100 mg twice daily] and 7.5/22.5 mg/kg twice daily (approximately 4 times the human exposure at the clinical dose of 100 mg twice daily) resulted in mortality between PND 9 to 99; a definitive cause of death was not identified in the majority of cases. The main findings were transient central nervous system-related signs including head flick, tremor, and circling in both sexes. An increase in the number of errors in a maze swim test occurred in females at exposures of approximately 4 times the human exposure (AUC) at the clinical dose of 100 mg twice daily.

Decreased growth and delays in sexual development occurred in the mid- and high-dose groups. Mating was normal in treated animals, but a reduction in pregnancy rate occurred at the high-dose of 7.5/22.5 mg/kg twice daily (appr…

🧓 Geriatric Use 54 words ▾

8.5Geriatric Use Of 444 patients in the overall safety population who received VITRAKVI, 20% of patients were ≥ 65 years of age and 6% of patients were ≥ 75 years of age. No overall differences in safety or effectiveness of VITRAKVI were observed between patients 65 years and older and younger adult patients.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Larotrectinib is an inhibitor of the tropomyosin receptor kinases (TRK), TRKA, TRKB, and TRKC. In a broad panel of purified enzyme assays, larotrectinib inhibited TRKA, TRKB, and TRKC with IC 50 values between 5-11 nM. One other kinase TNK2 was inhibited at approximately 100-fold higher concentration.

TRKA, B, and C are encoded by the genes NTRK1, NTRK2, and NTRK3. Chromosomal rearrangements involving in-frame fusions of these genes with various partners can result in constitutively-activated chimeric TRK fusion proteins that can act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines. In in vitro and in vivo tumor models, larotrectinib demonstrated anti-tumor activity in cells with constitutive activation of TRK proteins resulting from gene fusions, deletion of a protein regulatory domain, or in cells with TRK protein overexpression.

Larotrectinib had minimal activity in cell lines with point mutations in the TRKA kinase domain, including the clinically identified acquired resistance mutation, G595R. Point mutations in the TRKC kinase domain with clinically identified acquired resistance to larotrectinib include G623R, G696A, and F617L.

12.2Pharmacodynamics Cardiac Electrophysiology At a dose 9-fold higher than the recommended adult dose, VITRAKVI does not prolong QTc intervals to any clinically relevant extent.

12.3Pharmacokinetics The pharmacokinetics of larotrectinib were studied in healthy subjects and adult and pediatric patients with locally advanced or metastatic solid tumors. In healthy subjects who received a single dose of VITRAKVI capsules, systemic exposure (C max and AUC) of larotrectinib was dose proportional over the dose range of 100 mg to 400 mg (1 to 4 times the recommended adult dose) and slightly greater than proportional at doses of 600 mg to 900 mg (6 to 9 times the recommended adult dose). In adult patients who received VITRAKVI capsules 100 mg twice daily in Study LOXO-TRK-14001, peak plasma levels (C max ) of larotrectinib were achieved at approximately 1 hour after dosing and steady-state was reached within 3 days.

Mean steady-state larotrectinib [coefficient of variation (CV%)] for C max was 788 (81%) ng/mL and AUC 0-24hr was 4351 (97%) ng*h/mL. Absorption The mean absolute bioavailability of VITRAKVI capsules was 34% (range: 32% to 37%). In healthy subjects, the AUC of VITRAKVI oral solution was similar to that of the capsules and the C max was 36% higher with the oral solution.

Effect of Food The AUC of larotrectinib was similar and the C max was reduced by 35% after oral administration of a single 100 mg capsule of VITRAKVI to healthy subjects taken with a high-fat meal (approximately 900 calories, 58 grams carbohydrate, 56 grams fat and 43 grams protein) compared to the C max and AUC in the fasted state. Distribution The mean (CV%) volume of distribution (V ss ) of larotrectinib is 48 (38%) L following intravenous administration of larotrectinib in healthy subjects. Larotrectinib is 70% bound to human plasma proteins in vitro and binding is independent of drug concentrations.

The blood-to-plasma concentration ratio is 0.9. Elimination The mean (CV%) clearance (CL/F) of larotrectinib is 98 (44%) L/h and the half-life is 2.9 hours following oral administration of VITRAKVI in healthy subjects. Metabolism Larotrectinib is metabolized predominantly by CYP3A4.

Following oral administration of a single [ 14 C] radiolabeled 100 mg dose of larotrectinib to healthy subjects, unchanged larotrectinib constituted 19% and an O-linked glucuronide constituted 26% of the major circulating radioactive drug components in plasma. Excretion Following oral administration of a single [ 14 C] radiolabeled 100 mg dose of larotrectinib to healthy subjects, 58% (5% unchanged) of the administered radioactivity was recovered in feces and 39% (20% unchanged) was recovered in urine. Specific Populations Age (range: 28 days to 82 years), sex,…

🧬 Mechanism of Action 177 words ▾

12.1Mechanism of Action Larotrectinib is an inhibitor of the tropomyosin receptor kinases (TRK), TRKA, TRKB, and TRKC. In a broad panel of purified enzyme assays, larotrectinib inhibited TRKA, TRKB, and TRKC with IC 50 values between 5-11 nM. One other kinase TNK2 was inhibited at approximately 100-fold higher concentration.

TRKA, B, and C are encoded by the genes NTRK1, NTRK2, and NTRK3. Chromosomal rearrangements involving in-frame fusions of these genes with various partners can result in constitutively-activated chimeric TRK fusion proteins that can act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines. In in vitro and in vivo tumor models, larotrectinib demonstrated anti-tumor activity in cells with constitutive activation of TRK proteins resulting from gene fusions, deletion of a protein regulatory domain, or in cells with TRK protein overexpression.

Larotrectinib had minimal activity in cell lines with point mutations in the TRKA kinase domain, including the clinically identified acquired resistance mutation, G595R. Point mutations in the TRKC kinase domain with clinically identified acquired resistance to larotrectinib include G623R, G696A, and F617L.

📦 How Supplied / Storage and Handling 170 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Capsules 25 mg: Hard gelatin opaque white capsule size #2 with blue printing of "BAYER" cross and "25 mg" on the body of the capsule. 60 count bottle NDC# 50419-390-01 100 mg: Hard gelatin opaque white capsule size #0 with blue printing of "BAYER" cross and "100 mg" on the body of the capsule. 60 count bottle NDC# 50419-391-01 Store capsules at room temperature 20°C to 25°C (68°F to 77°F); temperature excursions between 15°C and 30°C (59°F to 86°F) are permitted [see USP Controlled Room Temperature].

Oral Solution Packaged in One Bottle Containing 100 mL 20 mg/mL: Clear yellow to orange solution. One bottle containing 100 mL NDC# 50419-392-01 Refrigerate oral solution at 2°C to 8°C (36°F to 46°F). Do not freeze.

Oral Solution Packaged in Two Bottles Each Containing 50 mL 20 mg/mL: Colorless to yellow or orange or red or brownish solution. Two bottles each containing 50 mL NDC# 50419-393-03 Refrigerate oral solution at 2°C to 8°C (36°F to 46°F). Do not freeze.

📦 Storage and Handling 106 words ▾

Store capsules at room temperature 20°C to 25°C (68°F to 77°F); temperature excursions between 15°C and 30°C (59°F to 86°F) are permitted [see USP Controlled Room Temperature]. Oral Solution Packaged in One Bottle Containing 100 mL 20 mg/mL: Clear yellow to orange solution. One bottle containing 100 mL NDC# 50419-392-01 Refrigerate oral solution at 2°C to 8°C (36°F to 46°F).

Do not freeze. Oral Solution Packaged in Two Bottles Each Containing 50 mL 20 mg/mL: Colorless to yellow or orange or red or brownish solution. Two bottles each containing 50 mL NDC# 50419-393-03 Refrigerate oral solution at 2°C to 8°C (36°F to 46°F).

Do not freeze.

📋 Description ~1 min read ▾

11 DESCRIPTION Larotrectinib is a kinase inhibitor. VITRAKVI (larotrectinib) capsules and oral solution are formulated using larotrectinib sulfate. The molecular formula for larotrectinib sulfate is C 21 H 24 F 2 N 6 O 6 S and the molecular weight is 526.51 g/mol for the sulfate salt and 428.44 g/mol for the free base.

The chemical name is (3 S )- N -{5-[(2 R )-2-(2,5-difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-a]pyrimidin-3-yl}-3-hydroxy-1-pyrrolidinecarboxamide sulfate. Larotrectinib sulfate has the following chemical structure: Larotrectinib sulfate is an off-white to pinkish yellow solid that is not hygroscopic. The aqueous solubility of larotrectinib at 37°C is pH dependent (very soluble at pH 1.0 and freely soluble at pH 6.8, according to USP descriptive terms of solubility).

VITRAKVI (larotrectinib) capsules and oral solution are for oral use. Each capsule contains 25 mg or 100 mg larotrectinib (30.7 mg and 123 mg larotrectinib sulfate, respectively) in a hard gelatin capsule. The capsule is composed of gelatin, titanium dioxide, and edible ink.

The oral solution packaged in one bottle containing 100 mL contains 20 mg/mL larotrectinib (24.6 mg/mL larotrectinib sulfate) and the following inactive ingredients: purified water, hydroxypropyl betadex, sucrose, glycerin, sorbitol, citric acid, sodium phosphate, sodium citrate dihydrate, propylene glycol and flavoring. Preserved with methylparaben and potassium sorbate. The oral solution packaged in two bottles each containing 50 mL contains 20 mg/mL larotrectinib (24.6 mg/mL larotrectinib sulfate) and the following inactive ingredients: purified water, hydroxypropyl betadex, sucralose, sodium citrate, strawberry flavor, and citric acid.

Preserved with sodium benzoate. Chemical Structure

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Central Nervous System Effects Advise patients to notify their healthcare provider if they experience new or worsening neurotoxicity. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions [see Warnings and Precautions (5.1) ] .

Skeletal Fractures Inform patients that bone fractures can occur in patients taking VITRAKVI. Advise patients to report symptoms such as pain, changes in mobility, or deformity to their healthcare provider [see Warnings and Precautions (5.2) ]. Hepatotoxicity Advise patients that they will need to undergo laboratory tests to monitor liver function [see Warnings and Precautions (5.3) ] .

Embryo-Fetal Toxicity Advise males and females of reproductive potential of the potential risk to a fetus [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1) ]. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy and to use effective contraception during the treatment with VITRAKVI and for 1 week after the last dose [see Use in Specific Populations (8.3) ] . Advise males with female partners of reproductive potential to use effective contraception during treatment with VITRAKVI and for 1 week after the last dose [see Use in Specific Populations (8.3) ] .

Lactation Advise women not to breastfeed during treatment with VITRAKVI and for 1 week following the last dose [see Use in Specific Populations (8.2) ] . Infertility Advise females of reproductive potential that VITRAKVI may impair fertility [See Nonclinical Toxicology (13.1) ] . Drug Interactions Advise patients and caregivers to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products.

Inform patients to avoid St. John's wort, grapefruit or grapefruit juice while taking VITRAKVI [see Drug Interactions (7.1, 7.2) ].

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

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

Medicare Part D (outpatient prescription) spending for Vitrakvi — 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 Vitrakvi. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$15.28M
Claims incl. refills
382
Beneficiaries
157
Spend / beneficiary
$97,308.99
Spend / claim
$39,993.48
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — 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 form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Bayer HealthCare Pharmaceuticals Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Bayer HealthCare 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.
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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.