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CAPRELSA Vandetanib 300 mg Tablet, Film Coated, 30-count — NDC 58468-7840-03 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

CAPRELSA Vandetanib 300 mg Tablet, Film Coated, 30-count — NDC 58468-7840-3 (Billing 58468-7840-03)

by Genzyme Corporation · 1 BOTTLE, PLASTIC in 1 CARTON / 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

This is a package of 30 tablets of CAPRELSA Vandetanib 300 mg Tablet, Film Coated from Genzyme Corporation, marketed since Jul 2011 and currently FDA-listed. It is this product's only package size.

NDC 58468-7840-03
🏷️ FDA NDC (as labeled) 58468-7840-3 billing pads the package segment with a zero
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

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

NDC database record

One package, one record: these facts belong to NDC 58468-7840-3 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
58468 labeler · 7840 product · 3 package
Package marketed since
Jul 25, 2011
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Billing quantity
30 EA per package
Barcode (UPC-A, from the NDC)
3 5846878403 2
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 58468-7840-3
Product NDC 58468-7840
11-digit billing NDC 58468784003
NCPDP billing unit EA — each (per item)
RxCUI 1098416, 1098418, 1114074, 1114096
UNII YO460OQ37K
Application # NDA022405
SPL Set ID e5721cb8-4185-47b9-bbb3-1c587e558a03
Established class (EPC) Kinase Inhibitor
Mechanism of action Protein Kinase Inhibitors; P-Glycoprotein 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 2011-07-25
Route ORAL
Dosage form TABLET, FILM COATED
Substance VANDETANIB

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

GPI-14 21533085000340
GPI class Caprelsa
GCN Seq No 067291
GCN 29818
HICL code 037531
Ingredient (HICL) Vandetanib
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 CAPRELSA 300 MG TABLET
FDB brand name Caprelsa
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 067291
  • GCN: 29818
  • GPI-14 (Medi-Span): 21533085000340
  • HICL (First Databank): 037531
  • AHFS class code: 10:00.00.00
  • RxCUI (RxNorm): 1098416
Why two NDCs? The FDA registers this code as 58468-7840-3 — a 5-4-1 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 package segment → 58468-7840-03. 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 Protein Kinase 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.

Clinical

Label name CAPRELSA 300 MG TABLET Ingredient Vandetanib
📖 What it is MedlinePlus · NLM

Vandetanib is used to treat a certain type of thyroid cancer. Vandetanib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It treats medullary thyroid cancer that is causing symptoms or growing, and that can't be removed by surgery because it is advanced or has spread. If your cancer is slow-growing an...
  • Take one tablet by mouth once a day, with or without food, exactly as prescribed. Don't crush it. If swallowing is hard, your pharmacist can show you how to stir it into plain wate...
  • Vandetanib can lengthen the QT interval, which can lead to a dangerous heart rhythm. ECGs and blood tests for potassium, calcium, magnesium and thyroid hormone catch problems early...
  • Why do I need so many heart tests and blood tests?
📖 Read our full Vandetanib guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

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

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $612.03 $18,361.03 / 30 tablets
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
58468-7840-03 You're viewing this Main listing 1 BOTTLE, PLASTIC in 1 CARTON / 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC 2011-07-25 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Caprelsa 300 mgthis 58468-7840-03 Genzyme 30 tablets — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2011
First FDA approval
Apr 2011
📍
2026
Currently FDA-listed
15 years listed
🛡️
2028
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 Aug 2028. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Apr 6, 2011 RLD RS ⏳ ~1.8 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 8067427 — drug product
US 8067427 — drug product
2011 2013 2015 2017 2019 2021 2023 2025 2027
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 (2)
PatentTypeUse codeExpires
US 8067427 ↗ Drug product — Aug 8, 2028
US 8067427 ↗ Drug product — Aug 8, 2028
Common questions
Is there a generic version of CAPRELSA 300 MG TABLET?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for CAPRELSA 300 MG TABLET. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Aug 2028 — 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
ShapeOval
ImprintZ;300
Size16 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

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

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

  • UNII 68401960MK
    Crospovidone is a synthetic polymer made from polyvinylpyrrolidone. It acts as a disintegrant, helping tablets break apart quickly in the stomach so the medicine dissolves and absorbs into the body.
  • UNII O7TSZ97GEP
    A mineral compound that serves as a filler and binding agent in tablets and capsules. It adds bulk to the medicine and helps hold ingredients together during manufacturing.
  • 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 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII 5655G9Y8AQ
    A synthetic liquid polymer used as a solvent and humectant in medications. It helps dissolve active ingredients, maintain moisture in the formulation, and improve how the medicine flows and is absorbed.
  • UNII FZ989GH94E
    Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
  • UNII 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.

8 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

LabelerGenzyme Corporation
Application holderGENZYME CORP
FDA applicationNDA022405 (NDA)
Labeler code58468
First marketedJul 2011
Product typeHuman Prescription Drug
Portfolio33 products on file

More NDCs from Genzyme Corporation labeler code 58468

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

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📚 References 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 140 words ▾

WARNING: QT PROLONGATION, TORSADES DE POINTES, AND SUDDEN DEATH CAPRELSA can prolong the QT interval. Torsades de pointes and sudden death have occurred in patients receiving CAPRELSA. Do not use CAPRELSA in patients with hypocalcemia, hypokalemia, hypomagnesemia, or long QT syndrome.

Correct hypocalcemia, hypokalemia and/or hypomagnesemia prior to CAPRELSA administration. Monitor electrolytes periodically. Avoid drugs known to prolong the QT interval [see Warnings and Precautions (5.1) ] .

WARNING: QT PROLONGATION, TORSADES DE POINTES, AND SUDDEN DEATH See full prescribing information for complete boxed warning. CAPRELSA can prolong the QT interval. Torsades de pointes and sudden death have occurred in patients receiving CAPRELSA.

Do not use CAPRELSA in patients with hypocalcemia, hypokalemia, hypomagnesemia, or long QT syndrome. Correct hypocalcemia, hypokalemia and/or hypomagnesemia prior to CAPRELSA administration. Monitor electrolytes periodically.

Avoid drugs known to prolong the QT interval ( 5.1 ).

🎯 Indications and Usage 101 words ▾

1 INDICATIONS AND USAGE CAPRELSA is indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease. Use CAPRELSA in patients with indolent, asymptomatic or slowly progressing disease only after careful consideration of the treatment related risks of CAPRELSA. CAPRELSA is a kinase inhibitor indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.

( 1 ) Use CAPRELSA in patients with indolent, asymptomatic or slowly progressing disease only after careful consideration of the treatment related risks of CAPRELSA. ( 1 )

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION The recommended dose of CAPRELSA is 300 mg taken orally once daily until disease progression or unacceptable toxicity occurs. CAPRELSA may be taken with or without food. Do not take a missed dose within 12 hours of the next dose.

Do not crush CAPRELSA tablets. The tablets can be dispersed in 2 ounces of water by stirring for approximately 10 minutes (will not completely dissolve). Do not use other liquids for dispersion.

Swallow immediately after dispersion. Mix any remaining residue with 4 additional ounces of water and swallow. The dispersion can also be administered through nasogastric or gastrostomy tubes.

300 mg once daily. ( 2 ) CAPRELSA may be taken with or without food. ( 2 ) Dosage reduction may be necessary in the event of severe toxicities or QTc interval prolongation.

( 2.1 ) The starting dose is 200 mg in patients with moderate renal impairment. ( 2.1 )

2.1Dosage Adjustment For Adverse Reactions The 300 mg daily dose can be reduced to 200 mg (two 100 mg tablets) and then to 100 mg for Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or greater toxicities. Interrupt CAPRELSA for the following: Corrected QT interval, Fridericia (QTcF) greater than 500 ms: Resume at a reduced dose when the QTcF returns to less than 450 ms. CTCAE Grade 3 or greater toxicity: Resume at a reduced dose when the toxicity resolves or improves to CTCAE Grade 1.

For recurrent toxicities, reduce the dose of CAPRELSA to 100 mg after resolution or improvement to CTCAE Grade 1 severity, if continued treatment is warranted. Adverse events including QT interval prolongation should be monitored closely as they may not resolve fully until approximately three plasma half-lives of the drug. Monitor appropriately [see Warnings and Precautions (5.1) , (5.2) , (5.3) , (5.4) , (5.5) , (5.6) , (5.7) , and (5.9) ] .

For Patients with Renal Impairment Reduce the starting dose to 200 mg in patients with moderate (creatinine clearance ≥30 to <50 mL/min) renal impairment [see Warnings and Precautions (5.12) and Use in Specific Populations (8.6) ] . For Patients with Hepatic Impairment CAPRELSA is not recommended for use in patients with moderate and severe hepatic impairment [see Use in Specific Populations (8.7) ] .

💊 Dosage Forms and Strengths 60 words ▾

3 DOSAGE FORMS AND STRENGTHS CAPRELSA 100 mg tablets are white, round, biconvex, film-coated, and intagliated with 'Z 100' on one side and plain on the reverse side. CAPRELSA 300 mg tablets are white, oval, biconvex, film-coated, and intagliated with 'Z 300' on one side and plain on the reverse side. 100 mg and 300 mg tablets ( 3 )

⛔ Contraindications 30 words ▾

4 CONTRAINDICATIONS Do not use in patients with congenital long QT syndrome [see Boxed Warning ] . Do not use in patients with congenital long QT syndrome. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Prolonged QT interval, torsades de pointes, and sudden death: Monitor electrocardiograms and levels of serum potassium, calcium, magnesium and TSH. Reduce CAPRELSA dose as appropriate. ( 2.1 , 5.1 ) Severe skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome, some fatal.

Discontinue CAPRELSA for severe skin reactions. ( 2.1 , 5.2 ) Interstitial lung disease (ILD), including fatalities: investigate unexplained non-specific respiratory signs and symptoms. Discontinue CAPRELSA for confirmed ILD.

( 2.1 , 5.3 ) Ischemic cerebrovascular events, hemorrhage, heart failure, diarrhea, hypertension, and reversible posterior leukoencephalopathy syndrome: Discontinue or interrupt CAPRELSA. ( 2.1 , 5.4 , 5.5 , 5.6 , 5.7 , 5.9 , 5.10 ) Impaired wound healing: Withhold for at least 1 month prior to elective surgery. Do not administer CAPRELSA for at least 2 weeks following major surgery and until adequate wound healing.

The safety of resumption of treatment with CAPRELSA after resolution of wound healing complications has not been established. ( 5.14 ) Embryo-fetal toxicity: Can cause fetal harm. Advise women of reproductive potential of the potential risk to a fetus and to use effective contraception.

( 5.15 , 8.1 ) Osteonecrosis, including osteonecrosis of the jaw: Withhold CAPRELSA for 1 month prior to scheduled dental surgery and permanently discontinue if osteonecrosis occurs ( 5.16 , 6.2 ).

5.1QT Prolongation and Torsades de Pointes CAPRELSA can prolong the QT interval in a concentration-dependent manner [see Clinical Pharmacology (12.2) ] . Torsades de pointes, ventricular tachycardia and sudden deaths have occurred in patients treated with CAPRELSA. Do not start CAPRELSA treatment in patients whose QTcF interval is greater than 450 ms.

Do not administer CAPRELSA to patients who have a history of Torsades de pointes, congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure. CAPRELSA has not been studied in patients with ventricular arrhythmias or recent myocardial infarction. Vandetanib exposure is increased in patients with impaired renal function.

Reduce the starting dose to 200 mg in patients with moderate renal impairment and monitor QT interval frequently. Obtain an ECG and serum potassium, calcium, magnesium and TSH at baseline, 2 to 4 weeks and 8 to 12 weeks after starting treatment with CAPRELSA, and every 3 months thereafter. Monitor electrolytes and ECGs more frequently in patients who experience diarrhea.

Following any dose reduction for QT prolongation or any dose interruption greater than 2 weeks, conduct QT assessments as described above. Maintain serum potassium levels of 4 mEq/L or higher (within normal range) and maintain serum magnesium and calcium levels within normal ranges to reduce the risk of QT prolongation. Avoid using CAPRELSA with drugs known to prolong the QT interval [see Warnings and Precautions (5.11) and Drug Interactions (7.4) ] .

If such drugs are given to patients already receiving CAPRELSA and no alternative therapy exists, perform ECG monitoring of the QT interval more frequently. Stop CAPRELSA in patients who develop a QTcF greater than 500 ms until the QTcF returns to less than 450 ms. Dosing of CAPRELSA can then be resumed at a reduced dose [see Dosage and Administration (2.1) ] .

5.2Severe Skin Reactions Severe and sometimes fatal skin reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome, have occurred in patients treated with CAPRELSA. Permanently discontinue CAPRELSA for severe skin reactions and refer the patient for urgent medical evaluation. Systemic therapies such as corticosteroids may be required.

Photosensitivity reactions can occur during CAPRELSA treatment and up to 4 months after treatment discontinuation.

5.3Interstitial Lung Disease Interstitial Lung Disease (ILD) or pneumonitis, including fatalities, has occurred in patients treated with CAPRELSA. Consider a diagnosis of IL… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the label: QT Prolongation and Torsades de Pointes [see Boxed Warning , Warnings and Precautions (5.1) ] Severe Skin Reactions [see Warnings and Precautions (5.2) ] Interstitial Lung Disease [see Warnings and Precautions (5.3) ] Ischemic Cerebrovascular Events [see Warnings and Precautions (5.4) ] Hemorrhage [see Warnings and Precautions (5.5) ] Heart Failure [see Warnings and Precautions (5.6) ] Diarrhea [see Warnings and Precautions (5.7) ] Hypothyroidism [see Warnings and Precautions (5.8) ] Hypertension [see Warnings and Precautions (5.9) ] Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions (5.10) ] Renal Failure [see Warnings and Precautions (5.12) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.15) ] Osteonecrosis [see Warnings and Precautions (5.16) ] The most common adverse drug reactions (>20%) seen with CAPRELSA and with a between-arm difference of ≥5 % have been diarrhea/colitis, rash, acneiform dermatitis, hypertension, nausea, headache, upper respiratory tract infections, decreased appetite and abdominal pain.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, Contact Sanofi Genzyme at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Patients with unresectable locally advanced or metastatic medullary thyroid cancer were treated with CAPRELSA 300 mg (n=231) or Placebo (n=99). The population exposed to CAPRELSA was 58% male, 94% white, and had a median age of 50 years.

The data described below reflect a median exposure to CAPRELSA for 607 days. The most commonly reported adverse drug reactions which occurred in >20% of CAPRELSA-treated patients and with a between-arm difference of ≥5% included, in order of decreasing frequency: diarrhea/colitis, rash, acneiform dermatitis, hypertension, nausea, headache, upper respiratory tract infection, decreased appetite, and abdominal pain. Among CAPRELSA-treated patients, dose interruption occurred in 109 (47%) and dose reduction occurred in 83 (36%).

Adverse reactions led to study treatment discontinuation in 28 of 231 patients (12%) receiving CAPRELSA and in 3 of 99 patients (3.0%) receiving placebo. Adverse reactions leading to permanent discontinuation in 2 or more (≥0.9%) patients treated with CAPRELSA were: asthenia (1.7%), rash (1.7%), diarrhea (0.9%), fatigue (0.9%), pyrexia (0.9%), elevated creatinine (0.9%), QT prolongation (0.9%), and hypertension (0.9%). Table 1: Per-Patient Incidence of Selected Adverse Reactions Occurring at a Higher Incidence in CAPRELSA-Treated Patients During Randomized Treatment (Between-Arm Difference of ≥5% [All Grades] CTCAE version 3 was used to grade adverse events. ) System Organ Class CAPRELSA 300 mg Placebo Preferred Term N=231 N=99 All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Gastrointestinal Disorders Diarrhea/Colitis 57 11 27 2 Nausea 33 1 16 0 Abdominal Pain Includes abdominal pain, abdominal pain upper, lower abdominal pain, and abdominal discomfort.

21 3 11 0 Vomiting 15 1 7 0 Dyspepsia 11 0 4 0 Dry Mouth 9 0 3 0 Skin and Cutaneous Disorders Rash Includes rash, rash (erythematous, generalized, macular, maculopapular, papular, pruritic, and exfoliative), dermatitis, dermatitis bullous, generalized erythema, and eczema. 53 5 12 0 Dermatitis Acneiform/Acne 35 1 7 0 Dry Skin 15 0 5 0 Photosensitivity Reaction 13 2 0 0 Pruritus 11 1 4 0 Nail abnormalities Includes nail disorder, nail bed inflammation, nail bed tenderness, paronychia, nail bed infection, and nail infection.

9 0 0 0 Alopecia 8 N/A 0 N/A Vascular Disorders Hypertension/Hypertensive Crisis/Accelerated Hypertension 33 9 5 1 Nervous… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 183 words ▾

7 DRUG INTERACTIONS Avoid the use of strong CYP3A4 inducers because they may decrease CAPRELSA exposure. ( 7.1 ) Avoid the use of agents that prolong the QT interval. ( 5.11 )

7.1Effect of CYP3A4 Inducers on CAPRELSA Rifampicin, a strong CYP3A4 inducer, decreased vandetanib plasma concentrations. Avoid concomitant use of known strong CYP3A4 inducers during CAPRELSA therapy. Avoid concomitant use of St. John's wort because it can decrease vandetanib exposure unpredictably [see Clinical Pharmacology (12.3) ] .

7.2Effect of CAPRELSA on OCT2 Transporter CAPRELSA increased plasma concentrations of metformin that is transported by the organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering CAPRELSA with drugs that are transported by OCT2 [see Clinical Pharmacology (12.3) ] .

7.3Effect of CAPRELSA on Digoxin CAPRELSA increased plasma concentrations of digoxin. Use caution and closely monitor for toxicities when administering CAPRELSA with digoxin [see Clinical Pharmacology (12.3) ] .

7.4Drugs that Prolong the QT Interval Avoid concomitant use of CAPRELSA with agents that may prolong the QT interval [see Warnings and Precautions (5.11) ] .

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary Based on its mechanism of action and findings in animals, CAPRELSA can cause fetal harm when administered to a pregnant woman. There are no available human data on CAPRELSA use in pregnant women to inform a drug-associated risk. Vandetanib is embryotoxic, fetotoxic, and induced fetal malformations in rats at exposures less than or equal to those expected at the recommended human dose of 300 mg/day.

Advise patients 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 In reproductive toxicity studies, administration of vandetanib to female rats prior to mating and through the first week of pregnancy at a dose of 25 mg/kg/day (approximately equal to the human exposure at the 300 mg clinical dose based on C max ), there were increases in pre-implantation loss and post-implantation loss resulting in a reduction in the number of live embryos.

During organogenesis, vandetanib caused an increase in post-implantation loss, including occasional total litter loss at a dose of 25 mg/kg/day. At doses greater than 10 mg/kg/day (approximately 0.4 times the human C max at the 300 mg clinical dose) treatment with vandetanib resulted in increases in late embryofetal death and decreases in fetal birth weight. A no-effect level for malformations was not identified in this study.

Administration of vandetanib at doses greater than or equal to 1 mg/kg/day (approximately 0.03 times the human C max at the 300 mg clinical dose) resulted in dose dependent increases in both malformations of the heart vessels and skeletal variations including delayed ossification of the skull, vertebrae, and sternum, indicating delayed fetal development. In a rat prenatal and postnatal development study, at doses (1 and 10 mg/kg/day) producing mild maternal toxicity during gestation and/or lactation, vandetanib decreased pup survival and reduced postnatal pup growth.

Reduced postnatal pup growth was associated with a delay in physical development.

8.2Lactation Risk Summary There are no data on the presence of vandetanib or its metabolites in human milk, the effects on the breastfed child or on milk production. Vandetanib was present in the milk of lactating rats (see Data ) . Because of the potential for serious adverse reactions from CAPRELSA in breastfed children, advise lactating women not to breastfeed during treatment with CAPRELSA and for 4 months after the last dose.

Data Animal data In nonclinical studies, vandetanib was excreted in rat milk and found in plasma of pups following dosing to lactating rats. Vandetanib transfer in breast milk resulted in relatively constant exposure in pups due to the long half-life of the drug.

8.3Females and Males of Reproductive Potential Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating treatment with CAPRELSA [see Use in Specific Populations (8.1) ] . Contraception CAPRELSA 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 CAPRELSA and for 4 months after the last dose.

Males Advise males with female partners of reproductive potential to use effective contraception during treatment with CAPRELSA and for 4 months after the last dose. Infertility There are no data on the effect of CAPRELSA on human fertility. Results from animal studies indicate that vandetanib can impair male and female fertility [see Nonclinical Toxicology (13.1) ] .

8.4Pediatric Use Safety and efficacy of CAPRELSA in pediatric patients have not been established.

8.5Geriatric Use The MTC study of CAPRELSA did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently compare… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary Based on its mechanism of action and findings in animals, CAPRELSA can cause fetal harm when administered to a pregnant woman. There are no available human data on CAPRELSA use in pregnant women to inform a drug-associated risk. Vandetanib is embryotoxic, fetotoxic, and induced fetal malformations in rats at exposures less than or equal to those expected at the recommended human dose of 300 mg/day.

Advise patients 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 In reproductive toxicity studies, administration of vandetanib to female rats prior to mating and through the first week of pregnancy at a dose of 25 mg/kg/day (approximately equal to the human exposure at the 300 mg clinical dose based on C max ), there were increases in pre-implantation loss and post-implantation loss resulting in a reduction in the number of live embryos.

During organogenesis, vandetanib caused an increase in post-implantation loss, including occasional total litter loss at a dose of 25 mg/kg/day. At doses greater than 10 mg/kg/day (approximately 0.4 times the human C max at the 300 mg clinical dose) treatment with vandetanib resulted in increases in late embryofetal death and decreases in fetal birth weight. A no-effect level for malformations was not identified in this study.

Administration of vandetanib at doses greater than or equal to 1 mg/kg/day (approximately 0.03 times the human C max at the 300 mg clinical dose) resulted in dose dependent increases in both malformations of the heart vessels and skeletal variations including delayed ossification of the skull, vertebrae, and sternum, indicating delayed fetal development. In a rat prenatal and postnatal development study, at doses (1 and 10 mg/kg/day) producing mild maternal toxicity during gestation and/or lactation, vandetanib decreased pup survival and reduced postnatal pup growth.

Reduced postnatal pup growth was associated with a delay in physical development.

🧒 Pediatric Use 15 words ▾

8.4Pediatric Use Safety and efficacy of CAPRELSA in pediatric patients have not been established.

🧓 Geriatric Use 30 words ▾

8.5Geriatric Use The MTC study of CAPRELSA did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently compared to younger patients.

🆘 Overdosage 38 words ▾

10 OVERDOSAGE In the event of an overdose, monitor patients closely for QTc prolongation. Adverse events including QT interval prolongation should be monitored closely as they may not resolve fully until approximately three plasma half-lives of the drug.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action In vitro studies have shown that vandetanib inhibits the tyrosine kinase activity of the EGFR and VEGFR families, RET, BRK, TIE2, and members of the EPH receptor and Src kinase families. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment. In addition, the N-desmethyl metabolite of the drug, representing 7 to 17.1% of vandetanib exposure, has similar inhibitory activity to the parent compound for VEGF receptors (KDR and Flt-1) and EGFR.

In vitro , vandetanib inhibited epidermal growth factor (EGF)-stimulated receptor tyrosine kinase phosphorylation in tumor cells and endothelial cells and VEGF-stimulated tyrosine kinase phosphorylation in endothelial cells. In vivo , vandetanib administration reduced tumor cell-induced angiogenesis, tumor vessel permeability, and inhibited tumor growth and metastasis in mouse models of cancer.

12.2Pharmacodynamics Cardiac Electrophysiology In 231 patients with medullary thyroid cancer randomized to receive CAPRELSA 300 mg once daily in the phase 3 clinical trial. CAPRELSA was associated with sustained plasma concentration-dependent QT prolongation. Based on the exposure-response relationship, the mean (90% CI) QTcF change from baseline (ΔQTcF) was 35 (33–36) ms for the 300 mg dose.

The ΔQTcF remained above 30 ms for the duration of the trial (up to 2 years). In addition, 36% of patients experienced greater than 60 ms increase in ΔQTcF and 4.3% of patients had QTcF greater than 500 ms. Cases of Torsades de pointes and sudden death have occurred [see Boxed Warning and Warnings and Precautions (5.1) , (5.11) ] .

12.3Pharmacokinetics A population pharmacokinetic analysis of CAPRELSA was conducted in 231 patients with MTC following oral administration of 300 mg daily doses. The pharmacokinetics of CAPRELSA at the 300 mg dose in MTC patients are characterized by a mean clearance of approximately

13.2L/h, a mean volume of distribution of approximately 7450 L, and a median plasma half-life of 19 days. Absorption Following oral administration of CAPRELSA, absorption is slow with peak plasma concentrations typically achieved at a median of 6 hours, range 4 to 10 hours, after dosing. Vandetanib accumulates approximately 8-fold on multiple dosing with steady state achieved in approximately 3 months.

Exposure to vandetanib is unaffected by food. Distribution Vandetanib binds to human serum albumin and α1-acid-glycoprotein with in vitro protein binding being approximately 90%. In ex vivo plasma samples from colorectal cancer patients at steady state exposure after 300 mg once daily, the mean percentage protein binding was 94%.

Metabolism Following oral dosing of 14 C-vandetanib, unchanged vandetanib and metabolites vandetanib N-oxide and N-desmethyl vandetanib were detected in plasma, urine and feces. A glucuronide conjugate was seen as a minor metabolite in excreta only. N-desmethyl-vandetanib is primarily produced by CYP3A4 and vandetanib-N-oxide by flavin-containing monooxygenase enzymes FMO1 and FMO3.

N-desmethyl-vandetanib and vandetanib-N-oxide circulate at concentrations of approximately 7–17% and 1.4–2.2%, respectively, of those of vandetanib. Excretion Within a 21-day collection period after a single dose of 14 C-vandetanib, approximately 69% was recovered with 44% in feces and 25% in urine. Excretion of the dose was slow and further excretion beyond 21 days would be expected based on the plasma half-life.

Vandetanib was not a substrate of hOCT2 expressed in HEK293 cells. Vandetanib inhibits the uptake of the selective OCT2 marker substrate 14 C-creatinine by HEK-OCT2 cells, with a mean IC 50 of 2.1 μg/mL. This is higher than vandetanib plasma concentrations (0.81 μg/mL) observed after multiple dosing at 300 mg.

Inhibition of renal excretion of creatinine by vandetanib provides an explanation for in… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 142 words ▾

12.1Mechanism of Action In vitro studies have shown that vandetanib inhibits the tyrosine kinase activity of the EGFR and VEGFR families, RET, BRK, TIE2, and members of the EPH receptor and Src kinase families. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment. In addition, the N-desmethyl metabolite of the drug, representing 7 to 17.1% of vandetanib exposure, has similar inhibitory activity to the parent compound for VEGF receptors (KDR and Flt-1) and EGFR.

In vitro , vandetanib inhibited epidermal growth factor (EGF)-stimulated receptor tyrosine kinase phosphorylation in tumor cells and endothelial cells and VEGF-stimulated tyrosine kinase phosphorylation in endothelial cells. In vivo , vandetanib administration reduced tumor cell-induced angiogenesis, tumor vessel permeability, and inhibited tumor growth and metastasis in mouse models of cancer.

📦 How Supplied / Storage and Handling 82 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING 100 mg Tablets available in bottles containing 30 tablets (NDC 58468-7820-3). 300 mg Tablets available in bottles containing 30 tablets (NDC 58468-7840-3).

16.1Storage and Handling CAPRELSA tablets should be stored at room temperature between 68°F and 77°F (20°C and 25°C); excursions permitted to 59°F–86°F (15°C-30°C) [See USP controlled room temperature]. Procedures for proper handling and disposal of anticancer drugs should be considered. A guideline on this subject has been published. 1 Do not crush CAPRELSA tablets.

📦 Storage and Handling 55 words ▾

16.1Storage and Handling CAPRELSA tablets should be stored at room temperature between 68°F and 77°F (20°C and 25°C); excursions permitted to 59°F–86°F (15°C-30°C) [See USP controlled room temperature]. Procedures for proper handling and disposal of anticancer drugs should be considered. A guideline on this subject has been published. 1 Do not crush CAPRELSA tablets.

📋 Description 114 words ▾

11 DESCRIPTION Vandetanib has the chemical name N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl) methoxy]quinazolin-4-amine. The structural and molecular formulas are: C 22 H 24 BrFN 4 O 2 Vandetanib has a molecular weight of 475.36 g/mol. Vandetanib exhibits pH-dependent solubility, with increased solubility at lower pH.

Vandetanib is practically insoluble in water with a value of 0.008 mg/mL at 25°C (77°F). CAPRELSA tablets for daily oral administration are available in two dosage strengths containing either 100 mg or 300 mg of vandetanib. The tablet cores contain the following inactive ingredients: calcium hydrogen phosphate dihydrate, crospovidone, magnesium stearate, microcrystalline cellulose, and povidone.

The tablet film-coat contains the following inactive ingredients: hypromellose 2910, macrogol 300, and titanium dioxide E171. Chemical Structure

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). QT Prolongation and Torsades de Pointes Advise patients to contact their healthcare provider in the event of syncope, pre-syncopal symptoms, and cardiac palpitations. Advise patients that their healthcare provider will monitor their electrolytes and ECGs during treatment [see Warnings and Precautions (5.1) ] .

Severe Skin Reactions Advise patients to contact their healthcare provider in the event of skin reactions or rash [see Warnings and Precautions (5.2) ] . Interstitial Lung Disease (ILD) Advise patients to contact their health care provider in the event of sudden onset or worsening of breathlessness, persistent cough or fever [see Warnings and Precautions (5.3) ] . Diarrhea Advise patients to contact their healthcare provider in the event of diarrhea [see Warnings and Precautions (5.7) ] .

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) Advise patients to contact their healthcare provider in the event of seizures, headaches, visual disturbances, confusion or difficulty thinking [see Warnings and Precautions (5.10) ] . Impaired Wound Healing Advise patients that CAPRELSA may impair wound healing. Advise patients to inform their healthcare provider of any planned surgical procedure [see Warnings and Precautions (5.14) ] .

Osteonecrosis Advise patients regarding good oral hygiene practices and to have preventive dentistry performed prior to treatment with CAPRELSA and throughout treatment with CAPRELSA and to inform their healthcare provider of any planned dental procedures. Advise patients to immediately contact their healthcare provider for signs or symptoms associated with osteonecrosis [see Warnings and Precautions (5.16) ] . Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus.

Advise females to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment with CAPRELSA [see Use in Specific Populations (8.1) , (8.3) ] . Advise females of reproductive potential to use effective contraception during treatment with CAPRELSA and for 4 months after the last dose [see Use in Specific Populations (8.3) ] . Advise males with female partners of reproductive potential to use effective contraception during treatment with CAPRELSA and for 4 months after the last dose [see Use in Specific Populations (8.3) ] .

Lactation Advise women not to breastfeed during treatment with CAPRELSA and for 4 months after the last dose [see Use in Specific Populations (8.2) ] . Photosensitivity Advise patients to use appropriate sun protection due to the increased susceptibility to sunburn while taking CAPRELSA and for at least 4 months after drug discontinuation [see Warnings and Precautions (5.2) ] . Administration Advise patients that CAPRELSA can be taken with or without food and not to crush CAPRELSA tablets [see Clinical Pharmacology (12.3) ] .

💬 Medication Guide ~3 min read ▾

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 1/2026 MEDICATION GUIDE CAPRELSA ® (kap-rel-sah) (vandetanib) tablets Read this Medication Guide before you start taking CAPRELSA and each time you get a refill.

There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. What is the most important information I should know about CAPRELSA?

CAPRELSA can cause a change in the electrical activity of your heart called QT prolongation , which can cause irregular heartbeats and that may lead to death. You should not take CAPRELSA if you have had a condition called long QT syndrome since birth. Your healthcare provider should perform tests to check the levels of your blood potassium, calcium, magnesium, and thyroid-stimulating hormone (TSH), as well as the electrical activity of your heart with a test called an electrocardiogram (ECG).

You should have these tests: Before starting CAPRELSA Regularly during CAPRELSA treatment: 2 to 4 weeks after starting CAPRELSA 8 to 12 weeks after starting CAPRELSA every 3 months thereafter if your healthcare provider changes your dose of CAPRELSA if you start taking medicine that causes QT prolongation as instructed by your healthcare provider Your healthcare provider may stop your CAPRELSA treatment for a while and restart you at a lower dose if you have QT prolongation. Call your healthcare provider right away if you feel faint, light-headed, or feel your heart beating irregularly during treatment with CAPRELSA.

These may be symptoms related to QT prolongation. See " What are the possible side effects of CAPRELSA? " for more information about side effects. What is CAPRELSA?

CAPRELSA is a prescription medicine used to treat medullary thyroid cancer that cannot be removed by surgery or that has spread to other parts of the body. It takes a long time to get rid of CAPRELSA from your body and you may be at risk for side effects related to CAPRELSA after you have stopped your treatment. It is not known if CAPRELSA is safe and effective in children.

Who should not take CAPRELSA? Do not take CAPRELSA if you have QT prolongation. Before you take CAPRELSA, tell your healthcare provider about all of your medical conditions, including if you: have any heart problems, including a condition called congenital long QT syndrome have an irregular heartbeat take or have stopped taking a medicine that causes QT prolongation have low blood levels of potassium, calcium, or magnesium have high blood levels of thyroid-stimulating hormone have high blood pressure have skin problems have a history of breathing problems have a recent history of coughing up blood or bleeding have diarrhea have liver problems have kidney problems have seizures or are being treated for seizures have weak or soft bone problems (osteonecrosis), including osteonecrosis of the jaw plan to have any surgery, a dental procedure or have had a recent surgery.

You should stop taking CAPRELSA at least 1 month before a planned surgery or dental procedure. See " What are the possible side effects of CAPRELSA? " are pregnant or plan to become pregnant. CAPRELSA can cause harm to your unborn baby.

Tell your healthcare provider if you become pregnant or think you might be pregnant during treatment with CAPRELSA. Females who are able to become pregnant: Your healthcare provider must do a pregnancy test before you begin treatment with CAPRELSA. You must use effective birth control (contraception) during your treatment with CAPRELSA and for 4 months after your last dose of CAPRELSA.

Talk to your healthcare provider about birth control methods that may be used during treatment with CAPRELSA. Males with female partners who are able to become pregnant: You must use effective birth control during treatment with CAPRELSA and for 4 months after your last dose of CAPRELSA. are breastfeeding or plan to breastfeed. It is not known if… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics A population pharmacokinetic analysis of CAPRELSA was conducted in 231 patients with MTC following oral administration of 300 mg daily doses. The pharmacokinetics of CAPRELSA at the 300 mg dose in MTC patients are characterized by a mean clearance of approximately

13.2L/h, a mean volume of distribution of approximately 7450 L, and a median plasma half-life of 19 days. Absorption Following oral administration of CAPRELSA, absorption is slow with peak plasma concentrations typically achieved at a median of 6 hours, range 4 to 10 hours, after dosing. Vandetanib accumulates approximately 8-fold on multiple dosing with steady state achieved in approximately 3 months.

Exposure to vandetanib is unaffected by food. Distribution Vandetanib binds to human serum albumin and α1-acid-glycoprotein with in vitro protein binding being approximately 90%. In ex vivo plasma samples from colorectal cancer patients at steady state exposure after 300 mg once daily, the mean percentage protein binding was 94%.

Metabolism Following oral dosing of 14 C-vandetanib, unchanged vandetanib and metabolites vandetanib N-oxide and N-desmethyl vandetanib were detected in plasma, urine and feces. A glucuronide conjugate was seen as a minor metabolite in excreta only. N-desmethyl-vandetanib is primarily produced by CYP3A4 and vandetanib-N-oxide by flavin-containing monooxygenase enzymes FMO1 and FMO3.

N-desmethyl-vandetanib and vandetanib-N-oxide circulate at concentrations of approximately 7–17% and 1.4–2.2%, respectively, of those of vandetanib. Excretion Within a 21-day collection period after a single dose of 14 C-vandetanib, approximately 69% was recovered with 44% in feces and 25% in urine. Excretion of the dose was slow and further excretion beyond 21 days would be expected based on the plasma half-life.

Vandetanib was not a substrate of hOCT2 expressed in HEK293 cells. Vandetanib inhibits the uptake of the selective OCT2 marker substrate 14 C-creatinine by HEK-OCT2 cells, with a mean IC 50 of 2.1 μg/mL. This is higher than vandetanib plasma concentrations (0.81 μg/mL) observed after multiple dosing at 300 mg.

Inhibition of renal excretion of creatinine by vandetanib provides an explanation for increases in plasma creatinine seen in human subjects receiving vandetanib. Specific Populations Effects of age and gender In a population pharmacokinetic evaluation in cancer patients, no relationship was apparent between oral clearance of vandetanib and patient age or gender. Ethnicity Based on a cross-study comparison in a limited number of patients, Japanese (N=3) and Chinese (N=7) patients had average exposures of vandetanib that were higher than Caucasian (N=7) patients receiving the same dose of CAPRELSA.

Pediatric The pharmacokinetics of vandetanib has not been evaluated in pediatric patients. Effect of renal impairment The pharmacokinetics of vandetanib were evaluated after a single CAPRELSA dose of 800 mg in six subjects with mild (creatinine clearance = 50 to <80 mL/min), eight subjects with moderate (creatinine clearance ≥30 to <50 mL/min), six subjects with severe (creatinine clearance <30 mL/min) renal impairment and ten subjects with normal (creatinine clearance >80 mL/min) renal function. Subjects with mild renal impairment had a comparable mean AUC of vandetanib to that with normal renal function.

In subjects with moderate or severe renal impairment, the average AUC of vandetanib increased by 39% and 41%, respectively, compared to patients with normal renal function [see Dosage and Administration (2.1) , Warnings and Precautions (5.12) and Use in Specific Populations (8.6) ] . Drug Interactions Effect of other drugs on CAPRELSA Strong CYP3A4 inducers: In a cross-over study in 12 healthy volunteers, a single oral 300 mg dose of CAPRELSA was administered alone on day 1 and on day 10 in combination with daily doses of 600 mg of rifampicin (a strong CYP3A4 inducer) given on days 1 to 31.

The coadministration of rifampicin with CA… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 118 words ▾

12.2Pharmacodynamics Cardiac Electrophysiology In 231 patients with medullary thyroid cancer randomized to receive CAPRELSA 300 mg once daily in the phase 3 clinical trial. CAPRELSA was associated with sustained plasma concentration-dependent QT prolongation. Based on the exposure-response relationship, the mean (90% CI) QTcF change from baseline (ΔQTcF) was 35 (33–36) ms for the 300 mg dose.

The ΔQTcF remained above 30 ms for the duration of the trial (up to 2 years). In addition, 36% of patients experienced greater than 60 ms increase in ΔQTcF and 4.3% of patients had QTcF greater than 500 ms. Cases of Torsades de pointes and sudden death have occurred [see Boxed Warning and Warnings and Precautions (5.1) , (5.11) ] .

🔬 Clinical Studies ~2 min read ▾

14 CLINICAL STUDIES

14.1Clinical Trial in Patients with Medullary Thyroid Cancer A double-blind, placebo-controlled study (Study D4200C00058, NCT00410761) randomized patients with unresectable locally advanced or metastatic medullary thyroid cancer to CAPRELSA 300 mg (n=231) versus placebo (n=100). The major efficacy outcome measure was progression-free survival (PFS) with CAPRELSA compared to placebo. Other efficacy outcome measures included evaluation of overall survival (OS) and overall objective response rate (ORR).

Centralized, independent blinded review of the imaging data was used in the assessment of PFS and ORR. Upon objective disease progression based on the investigator's assessment, patients were discontinued from blinded study treatment and given the option to receive open-label CAPRELSA. Forty-seven percent (109/231) of the patients initially randomized to CAPRELSA opted to receive open-label CAPRELSA after disease progression, and 79% (79/100) of the patients initially randomized to placebo opted to receive open-label CAPRELSA after disease progression.

The result of the PFS analysis, based on the central review RECIST assessment, showed a statistically significant improvement in PFS for patients randomized to CAPRELSA (Hazard Ratio (HR) = 0.35; 95% Confidence Interval (CI) = 0.24-0.53; p<0.0001). Analyses in the subgroups of patients who were symptomatic or had progressed within 6 months prior to their enrollment showed similar PFS results (HR = 0.31 95% CI: 0.19, 0.53 for symptomatic patients; HR = 0.41 95% CI: 0.25, 0.66 for patients who had progressed within 6 months prior to enrollment).

Median final OS were similar across both treatment arms. The overall objective response rate (ORR) for patients randomized to CAPRELSA was 44% compared to 1% for patients randomized to placebo. All objective responses were partial responses.

Figure 1: Kaplan-Meier Curves for Progression Free Survival in Study D4200C00058 Table 3: Efficacy Results in Study D4200C00058 Vandetanib 300 mg (N=231) Placebo (N=100) Progression Free Survival Events (%) 59 (26.0) 41 (41.0) Median, months NR Not reached 16.4 (95% CI) (22.6, NE Not estimable ) (8.3, 19.7) Hazard Ratio (95% CI) 0.35 (0.24, 0.53) p-value <0.0001 Overall Survival Deaths (%) 116 (50.2) 52 (52.0) Median, months 81.6 80.4 (95% CI) (64.6, 98.5) (52.5, NE) Hazard Ratio (95% CI) 0.99 (0.72, 1.38) p-value 0.975 Figure 1

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Vandetanib was not carcinogenic in a 2-year study in rats when administered by daily oral gavage at doses of up to 10 mg/kg (0.7 times the human C max at the 300 mg clinical dose), or in the Tg∙RasH2 mouse when administered by daily oral gavage at doses of up to 30 mg/kg (~5 times the human C max at the clinical dose of 300 mg) for 26 weeks. Vandetanib was not mutagenic in vitro in the bacterial reverse mutation (Ames) assay and was not clastogenic in either the in vitro cytogenetic assay using human lymphocytes or in the in vivo rat micronucleus assay.

Based on nonclinical findings, male and female fertility may be impaired by treatment with CAPRELSA. In a fertility study of male rats, vandetanib had no effect on copulation or fertility rate when untreated females were mated with males administered 1, 5, or 20 mg/kg/day of vandetanib (approximately 0.03, 0.22, or 0.40 times, respectively, the human exposure based on area under the curve (AUC) in patients with cancer at the 300 mg clinical dose); however, in the same study there was a slight decrease in the number of live embryos in females mated with males treated at the 20 mg/kg/day dose level and an increase in preimplantation loss in females mated with males administered vandetanib at doses of ≥5 mg/kg/day.

In a female fertility study, there was a trend towards increased estrus cycle irregularity, a slight reduction in pregnancy incidence and an increase in implantation loss. In a one-month repeat-dose toxicity study in rats, there was a decrease in the number of corpora lutea in the ovaries of rats administered 75 mg/kg/day vandetanib (approximately 1.8 times the human exposure based on AUC at the 300 mg clinical dose).

13.2Animal Toxicology and/or Pharmacology In an animal model of wound-healing, mice dosed with vandetanib had reduced skin-breaking strength compared with controls. This suggests that CAPRELSA slows but does not prevent wound healing. The appropriate interval between discontinuation of CAPRELSA and subsequent elective surgery required to avoid the risks of impaired wound healing has not been determined.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~1 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Vandetanib was not carcinogenic in a 2-year study in rats when administered by daily oral gavage at doses of up to 10 mg/kg (0.7 times the human C max at the 300 mg clinical dose), or in the Tg∙RasH2 mouse when administered by daily oral gavage at doses of up to 30 mg/kg (~5 times the human C max at the clinical dose of 300 mg) for 26 weeks. Vandetanib was not mutagenic in vitro in the bacterial reverse mutation (Ames) assay and was not clastogenic in either the in vitro cytogenetic assay using human lymphocytes or in the in vivo rat micronucleus assay.

Based on nonclinical findings, male and female fertility may be impaired by treatment with CAPRELSA. In a fertility study of male rats, vandetanib had no effect on copulation or fertility rate when untreated females were mated with males administered 1, 5, or 20 mg/kg/day of vandetanib (approximately 0.03, 0.22, or 0.40 times, respectively, the human exposure based on area under the curve (AUC) in patients with cancer at the 300 mg clinical dose); however, in the same study there was a slight decrease in the number of live embryos in females mated with males treated at the 20 mg/kg/day dose level and an increase in preimplantation loss in females mated with males administered vandetanib at doses of ≥5 mg/kg/day.

In a female fertility study, there was a trend towards increased estrus cycle irregularity, a slight reduction in pregnancy incidence and an increase in implantation loss. In a one-month repeat-dose toxicity study in rats, there was a decrease in the number of corpora lutea in the ovaries of rats administered 75 mg/kg/day vandetanib (approximately 1.8 times the human exposure based on AUC at the 300 mg clinical dose).

📚 References 9 words ▾

15 REFERENCES OSHA Hazardous Drugs (OSHA Technical Manual). OSHA.

📄 Recent Major Changes 7 words ▾

Warnings and Precautions ( 5.16 ) 05/2025

📄 Package Label / Principal Display Panel 74 words ▾

PRINCIPAL DISPLAY PANEL - 100 mg Tablet Bottle Carton NDC 58468-7820-3 Rx only Caprelsa ® (vandetanib) tablets 100 mg Dispense enclosed medication guide to each patient. 30 Tablets PRINCIPAL DISPLAY PANEL - 100 mg Tablet Bottle Carton

PRINCIPAL DISPLAY PANEL - 300 mg Tablet Bottle Carton NDC 58468-7840-3 Rx only Caprelsa ® (vandetanib) tablets 300 mg Dispense enclosed medication guide to each patient. 30 Tablets PRINCIPAL DISPLAY PANEL - 300 mg Tablet Bottle Carton

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 Caprelsa — 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 Caprelsa. 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
$739.3K
Claims incl. refills
45
Beneficiaries
20
Spend / beneficiary
$36,966.97
Spend / claim
$16,429.77
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for CAPRELSA (this brand).

Top reported reactions

Diarrhoea329
Rash176
Fatigue175
Electrocardiogram Qt Prolonged142
Hypertension115
Nausea111
Acne97

Reporter sex

1,794 reports
Male · 52%
Female · 47%
Unknown · 2%

Serious outcomes

Death161
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 150 39
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

About this NDC listing & data coverage

Finished prescription product
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 Genzyme Corporation. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Genzyme Corporation is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 58468-7820-03 · Genzyme 58498-0123-01 · Olympic →
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.