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WELIREG belzutifan 40 mg Tablet, Film Coated, 90-count — NDC 00006-5331-58 package photo

WELIREG belzutifan 40 mg Tablet, Film Coated, 90-count

by Merck Sharp & Dohme LLC · 1 BOTTLE in 1 CARTON (0006-5331-58) / 90 TABLET, FILM COATED in 1 BOTTLE
NDC 00006-5331-58
🏷️ FDA NDC (as labeled) 0006-5331-58 billing pads the labeler segment with a zero
This package
Contains90-count Pack sizes3 compare ↓
Also priced by: Part D plans $339.48/unit — full pricing hub ↓
Also comes in: 90 tablets 00006-5331-01 90 tablets 00006-5331-59
Rx only Brand On market Non-controlled
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

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

🆔 Identity & classification

FDA NDC (as labeled) 0006-5331-58
Product NDC 0006-5331
11-digit billing NDC 00006533158
RxCUI 2567231, 2567237
UNII 7K28NB895L
UPC 0300065331010
Application # NDA215383
SPL Set ID 13e15ee0-d679-4fa9-9430-e2e2170474da
Established class (EPC) Hypoxia-inducible Factor Inhibitor
Mechanism of action Hypoxia-inducible Factor 2 alpha Inhibitors; Cytochrome P450 3A4 Inducers
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2021-08-13
Route ORAL
Dosage form TABLET, FILM COATED
Substance BELZUTIFAN
GPI-14 21421020000320
GCN Seq No 082589
GCN 50046
HICL code 047546
Ingredient (HICL) Belzutifan
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V16
Therapeutic class — specific (HIC3) Antineoplastic-Hypoxia Inducible Factor (Hif) Inh
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name WELIREG 40 MG TABLET
FDB brand name Welireg
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 0006-5331-58 — a 4-4-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the labeler segment → 00006-5331-58. 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 Hypoxia-inducible Factor Inhibitor class.

Pharmacologic class Hypoxia-inducible Factor Inhibitor
Drug family (ATC) Other antineoplastic agents
How it works Cytochrome P450 3A4 Inducers, Hypoxia-inducible Factor 2 alpha Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerMerck Sharp & Dohme LLC
Application holderMERCK SHARP AND DOHME CORP A SUB OF MERCK AND CO INC
FDA applicationNDA215383 (NDA)
Labeler code00006
First marketedAug 2021
Product typeHuman Prescription Drug
Portfolio112 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name WELIREG 40 MG TABLET Ingredient Belzutifan
📗 Our plain-language guide HelloPharmacist
  • Welireg (belzutifan) is a targeted cancer pill used for a few different conditions. It treats tumors related to VHL disease — a rare genetic condition that causes tumors to grow in...
  • What exactly is Welireg used for — I've never heard of it before.
  • The most common thing people notice is fatigue and anemia — low red blood cell counts — which can start within the first month. You might also get headaches, dizziness, nausea, or...
  • What side effects should I actually expect, and which ones should make me call my doctor?
📖 Read our full Belzutifan guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

💊 What it looks like

Color blue
ShapeOval
Imprint177
Size13 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 Inactive Ingredients / Excipients

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

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

  • UNII M28OL1HH48
    Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
  • UNII 4AQJ3LG584
    A synthetic blue dye combined with aluminum to create a stable colorant. It's used in medicines and supplements to add blue color or create specific shades for product identification and appearance.
  • UNII 6N003M473W
    Hypromellose acetate succinate is a modified cellulose polymer that dissolves in the small intestine. It's used as a coating material to protect the medicine from stomach acid and control where and when the drug is released in the digestive tract.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII 3OWL53L36A
    A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII 3WJQ0SDW1A
    Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
  • UNII 532B59J990
    Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
  • UNII 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.

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

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

Inactive ingredient FAQ

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

💲 Pricing

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

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $339.48 $30,553.39 / 90 tablets
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Welireg 40 mgthis 00006-5331-58 Merck 90 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

🏛️
2021
First FDA approval
Aug 2021
📍
2026
Currently FDA-listed
5 years listed
🛡️
2042
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 Jun 2042. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Aug 13, 2021 RLD RS ⏳ ~15.8 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 RE49948 — drug substance (U-4195)
US 9908845 — drug substance (U-4195)
US 9908845 — drug substance (U-3201)
US RE49948 — drug substance (U-4176)
US 9908845 — drug substance (U-4176)
US RE49948 — drug substance (U-3201)
US 10335388 — method of use (U-4565)
US RE49948 — drug substance (U-4565)
US 9908845 — drug substance (U-4565)
US 12358870 — drug product
Exclusivity I-931
Exclusivity I-968
Exclusivity I-994
Exclusivity NCE
Exclusivity ODE-364
2021 2023 2025 2027 2029 2031 2033 2035 2037 2039 2041
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 (10)
PatentTypeUse codeExpires
US RE49948 ↗ Drug substance U-4195 Sep 5, 2034
US 9908845 ↗ Drug substance U-4195 Sep 5, 2034
US 9908845 ↗ Drug substance U-3201 Sep 5, 2034
US RE49948 ↗ Drug substance U-4176 Sep 5, 2034
US 9908845 ↗ Drug substance U-4176 Sep 5, 2034
US RE49948 ↗ Drug substance U-3201 Sep 5, 2034
US 10335388 ↗ Method of use U-4565 Apr 14, 2036
US RE49948 ↗ Drug substance U-4565 Sep 5, 2034
US 9908845 ↗ Drug substance U-4565 Sep 5, 2034
US 12358870 ↗ Drug product — Jun 30, 2042
FDA exclusivity
CodeWhat it grantsExpires
I-931New indication (3-year)Dec 14, 2026
I-968New indication (3-year)May 14, 2028
I-994New indication (3-year)Jun 12, 2029
NCENew Chemical Entity (5-year)Aug 13, 2026
ODE-364Orphan Drug Exclusivity (7-year)Aug 13, 2028
Common questions
Is there a generic version of WELIREG 40 MG TABLET?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for WELIREG 40 MG TABLET. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Jun 2042 — 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.

💊 Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
90 tablets00006-5331-01 1,047 Rx · $27,646,000
90 tablets this page00006-5331-58 No Medicaid data
90 tablets00006-5331-59 No Medicaid data
Drug total (last 4 qtrs): 1,047 Rx · 82,345 units · $27,646,000 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

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

Medicare Part D (outpatient prescription) spending for Welireg — 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 Welireg. 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
$103.37M
Claims incl. refills
4K
Beneficiaries
1.8K
Spend / beneficiary
$57,909.01
Spend / claim
$25,932.66
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 WELIREG (this brand).

Top reported reactions

Anaemia283
Malignant Neoplasm Progression208
Hypoxia146
Fatigue121
Death73
Dyspnoea63
Diarrhoea61

Age at onset

Child4
Adult299
Elderly220

Reporter sex

1,573 reports
Male · 64%
Female · 36%
Unknown · 0%

Serious outcomes

Hospitalization678
Life-threatening62
Reports over time (by year) — tap or hover for the count & year
2022 2023 2024 2026 315 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
00006-5331-01 90 TABLET, FILM COATED in 1 BOTTLE (0006-5331-01) 2021-08-13 Active
00006-5331-58 You're viewing this 1 BOTTLE in 1 CARTON (0006-5331-58) / 90 TABLET, FILM COATED in 1 BOTTLE 2023-06-21 Active
00006-5331-59 1 BOTTLE in 1 CARTON (0006-5331-59) / 90 TABLET, FILM COATED in 1 BOTTLE 2023-06-21 Active

This pack shows little to no recent Medicaid volume — the 90 tablets pack carries most fills. See all packs ↓

Pack size FAQ

What quantity is in NDC 00006-5331-58?
NDC 00006-5331-58 is a 90-count package — 1 bottle in 1 carton / 90 tablet, film coated in 1 bottle.
What is the difference between NDC 00006-5331-58 and NDC 00006-5331-01?
Both are WELIREG belzutifan 40 mg Tablet, Film Coated — the drug itself is identical. NDC 00006-5331-58 is the 90-count package, while NDC 00006-5331-01 is the 90 tablets package.
What NDC number is used to bill for this package of WELIREG belzutifan 40 mg Tablet, Film Coated?
Bill NDC 00006-5331-58 — the 11-digit billing format is 00006533158. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 0006-5331-58, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 00006-5331-58, written without dashes as 00006533158. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 00006-5331-58, the first segment (00006) is the labeler code FDA assigned to Merck Sharp & Dohme LLC; the middle segment (5331) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (58) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Merck Sharp & Dohme LLC. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 2 other package presentations of this same product, including 90 tablets (00006-5331-01), 90 tablets (00006-5331-59). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Merck Sharp & Dohme LLC is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🚨 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 📦 Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide
🚨 Boxed Warning 115 words ▾

WARNING: EMBRYO-FETAL TOXICITY Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception.

WELIREG can render some hormonal contraceptives ineffective [see Warnings and Precautions (5.3) , Drug Interactions (7.2) , Use in Specific Populations (8.1 , 8.3) ]. WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. Exposure to WELIREG during pregnancy can cause embryo-fetal harm.

Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception. WELIREG can render some hormonal contraceptives ineffective.

( 5.3 , 7.2 , 8.1 , 8.3 )

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE WELIREG is a hypoxia-inducible factor inhibitor indicated: von Hippel-Lindau (VHL) disease for treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. ( 1.1 ) Renal Cell Carcinoma with a Clear Cell Component (ccRCC) in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, for the adjuvant treatment of adult patients with ccRCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

( 1.2 ) as monotherapy, for treatment of adult patients with advanced ccRCC following a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). ( 1.2 ) Pheochromocytoma or Paraganglioma (PPGL) for treatment of adult and pediatric patients 12 years and older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL). ( 1.3 ) 1.1 von Hippel-Lindau (VHL) disease WELIREG is indicated for treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

1.2Renal Cell Carcinoma with a Clear Cell Component (ccRCC) WELIREG, in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, is indicated for the adjuvant treatment of adult patients with ccRCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. WELIREG is indicated for the treatment of adult patients with advanced ccRCC following a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI).

1.3Pheochromocytoma or Paraganglioma (PPGL) WELIREG is indicated for the treatment of adult and pediatric patients 12 years and older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL).

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION The recommended dosage of WELIREG in adult patients is 120 mg administered orally once daily with or without food. ( 2.1 ) The recommended dosage of WELIREG in pediatric patients 12 years and older is based on bodyweight: Patients weighing 40 kg or greater: 120 mg orally once daily Patients weighing less than 40 kg: 80 mg orally once daily

2.1Recommended Dosage The recommended dosages for WELIREG are listed in Table 1. Table 1: Recommended Dosage Indication Recommended WELIREG Dosage Duration of Therapy von Hippel-Lindau Disease 120 mg orally once daily. Until disease progression or unacceptable toxicity.

Adjuvant Treatment of ccRCC 120 mg orally once daily in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph. For the recommended dosage of pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, refer to the respective Prescribing Information. Until disease recurrence or unacceptable toxicity, or up to 54 weeks.

Treatment of Advanced ccRCC 120 mg orally once daily. Until disease progression or unacceptable toxicity. Pheochromocytoma or Paraganglioma Adults: 120 mg orally once daily.

Pediatric patients 12 years and older based on bodyweight: Patients weighing 40 kg or greater: 120 mg orally once daily. Patients weighing less than 40 kg: 80 mg orally once daily. Until disease progression or unacceptable toxicity.

Administration Instructions WELIREG should be taken at the same time each day and may be taken with or without food. Advise patients to swallow tablets whole. Do not chew, crush, or split WELIREG prior to swallowing.

If a dose of WELIREG is missed, it can be taken as soon as possible on the same day. Resume the regular daily dose schedule for WELIREG the next day. Do not take extra tablets to make up for the missed dose.

If vomiting occurs any time after taking WELIREG, do not retake the dose. Take the next dose on the next day.

2.2Dosage Modifications for Adverse Reactions Dosage modifications for WELIREG for adverse reactions are summarized in Table 2 . The recommended dose reductions are: First dose reduction: WELIREG 80 mg orally once daily Second dose reduction: WELIREG 40 mg orally once daily Third dose reduction: Permanently discontinue Table 2: Recommended Dosage Modifications for Adverse Reactions Adverse Reaction Severity Dosage Modification Anemia [see Warnings and Precautions (5.1) ] Adjuvant ccRCC Indication: Hemoglobin <9 g/dL or transfusion indicated Withhold WELIREG until hemoglobin ≥9 g/dL.

Resume WELIREG at the same or reduced dose; or discontinue depending on the severity of anemia. Life-threatening or urgent intervention indicated Withhold WELIREG until hemoglobin ≥9 g/dL. Resume WELIREG at a reduced dose once resolved, or permanently discontinue.

All Other Indications: Hemoglobin <8 g/dL or transfusion indicated Withhold WELIREG until hemoglobin ≥8 g/dL. Resume WELIREG at the same or reduced dose; or discontinue depending on the severity of anemia. Life-threatening or urgent intervention indicated Withhold WELIREG until hemoglobin ≥8g/dL.

Resume WELIREG at a reduced dose once resolved, or permanently discontinue. Hypoxia [see Warnings and Precautions (5.2) ] Decreased oxygen saturation with exercise (e.g., pulse oximeter <88%) Consider withholding WELIREG until resolved. Resume WELIREG at the same dose or at a reduced dose depending on the severity of hypoxia.

Decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO 2 ≤55 mm Hg) or urgent intervention indicated Life-threatening or recurrent symptomatic hypoxia Withhold WELIREG until resolved. Resume WELIREG at reduced dose or discontinue depending on the severity of hypoxia. Permanently discontinue WELIREG.

Other Adverse Reactions [see Adverse Reactions (6) ] Grade 3 Withhold WELIREG until resolved to ≤ Grade 2. Consider resuming WELIREG at a reduced dose (reduce by 40 mg). Permanently discontinue WELIREG upon recurrence of Grade 3.

Grade 4 Permanently discontinue WELIRE…

💊 Dosage Forms and Strengths 30 words ▾

3 DOSAGE FORMS AND STRENGTHS Tablets: 40 mg, blue, oval shaped, film-coated, debossed with “177” on one side and plain on the other side. Tablets: 40 mg ( 3 )

⛔ Contraindications 7 words ▾

4 CONTRAINDICATIONS None. None. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Anemia : Monitor for anemia before initiation of and periodically throughout treatment with WELIREG. Withhold, reduce dose, or permanently discontinue WELIREG based on severity. ( 2.2 , 5.1 ) Hypoxia : Monitor oxygen saturation before initiation of, and periodically throughout, treatment with WELIREG.

For hypoxia at rest, withhold until resolved, resume at reduced dose, or discontinue depending on severity. For life-threatening hypoxia, permanently discontinue WELIREG. ( 2.2 , 5.2 )

5.1Anemia WELIREG can cause severe anemia that can require blood transfusion. Monitor for anemia before initiation of, and periodically throughout, treatment with WELIREG. Transfuse patients as clinically indicated.

Withhold, reduce dose, or permanently discontinue WELIREG based on severity [see Dosage and Administration (2.2) ] . von Hippel-Lindau (VHL) disease In LITESPARK-004, decreased hemoglobin occurred in 93% of patients and 7% had Grade 3 events [see Adverse Reactions (6.1) ] . Median time to onset of anemia was 31 days (range: 1 day to 8.4 months). The safety of erythropoiesis stimulating agents (ESAs) for treatment of anemia in patients with VHL disease treated with WELIREG has not been established.

Randomized controlled trials in patients with cancer receiving myelosuppressive chemotherapy with ESAs have shown that ESAs increased the risks of death and serious cardiovascular reactions, and decreased progression-free survival and/or overall survival. See the prescribing information for ESAs for more information. Renal Cell Carcinoma with a Clear Cell Component (ccRCC) In LITESPARK-005, decreased hemoglobin occurred in 88% of patients and 29% had Grade 3 events [see Adverse Reactions (6.1) ] .

Median time to onset of anemia was 29 days (range: 1 day to 16.6 months). Of the patients with anemia, 22% received transfusions only, 20% of patients received ESAs only and 12% received both transfusion and ESAs. In LITESPARK-022, decreased hemoglobin occurred in 95% of patients and 11% had Grade 3 or higher events [see Adverse Reactions (6.1) ].

Median time to onset of anemia was 42 days (range: 1 day to 11.1 months). Of the patients with anemia, 5% received transfusions only, 8% received ESAs only, and 1.3% received both transfusion and ESAs. Pheochromocytoma or Paraganglioma (PPGL) In LITESPARK-015, anemia occurred in 96% of patients and 22% had Grade 3 events [see Adverse Reactions (6.1) ] .

Median time to onset of anemia was 29 days (range: 1 day to 22.1 months). Of the patients with anemia, 20% received transfusions only, 26% received ESAs only, and 6% received both transfusion and ESAs.

5.2Hypoxia WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization [see Dosage and Administration (2.2) ]. Monitor oxygen saturation before initiation of, and periodically throughout, treatment with WELIREG. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or P a O 2 ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same dose or at a reduced dose.

For decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or urgent intervention indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening hypoxia or for recurrent symptomatic hypoxia, permanently discontinue WELIREG [see Dosage and Administration (2.2) ] . Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider. von Hippel-Lindau (VHL) disease In LITESPARK-004, hypoxia occurred in 1.6% of patients [see Adverse Reactions (6.1) ] .

Renal Cell Carcinoma with a Clear Cell Component (ccRCC) In LITESPARK-005, hypoxia occurred in 15% of patients and 10% had Grade 3 events [see Adverse Reactions (6.1) ] . Of the patients with hypoxia, 69% were treated with oxygen therapy. Median time to onset of hypoxia was 30.5 days (range: 1 day to 21.1 mont…

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed elsewhere in the labeling: Anemia [see Warnings and Precautions (5.1) ] Hypoxia [see Warnings and Precautions (5.2) ] VHL disease : Most common (≥25%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea. ( 6.1 ) ccRCC : Most common (≥25%) adverse reactions for WELIREG, including laboratory abnormalities, in combination with pembrolizumab were decreased hemoglobin, increased alanine aminotransferase (ALT), fatigue, increased aspartate aminotransferase (AST), decreased lymphocytes, and increased alkaline phosphatase.

( 6.1 ) Most common (≥25%) adverse reactions for WELIREG as monotherapy, including laboratory abnormalities were decreased hemoglobin, fatigue, musculoskeletal pain, increased creatinine, decreased lymphocytes, increased ALT, decreased sodium, increased potassium, and increased AST. ( 6.1 ) PPGL : Most common (≥25%) adverse reactions, including laboratory abnormalities were anemia, fatigue, musculoskeletal pain, decreased lymphocytes, increased ALT, increased AST, increased calcium, dyspnea, increased potassium, decreased leukocytes, headache, increased alkaline phosphatase, dizziness, and nausea.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 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. von Hippel-Lindau (VHL) disease LITESPARK-004 The safety of WELIREG was evaluated in an open-label clinical trial (LITESPARK-004) in 61 patients with VHL disease who had at least one measurable solid tumor localized to the kidney [see Clinical Studies (14.1) ] .

Patients received WELIREG 120 mg orally once daily until disease progression or unacceptable toxicity. The median duration of exposure to WELIREG was 68 weeks (range: 8.4 to 104.7 weeks). Serious adverse reactions occurred in 15% of patients who received WELIREG, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each).

Permanent discontinuation of WELIREG due to adverse reactions occurred in 3.3% of patients. Adverse reactions which resulted in permanent discontinuation of WELIREG were dizziness and opioid overdose (1.6% each). Dosage interruptions of WELIREG due to an adverse reaction occurred in 39% of patients.

Adverse reactions which required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness. Dose reductions of WELIREG due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction which required dose reduction was fatigue (7%).

The most common (≥25%) adverse reactions, including laboratory abnormalities, that occurred in patients who received WELIREG were decreased hemoglobin, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea. Table 3 summarizes the adverse reactions reported in patients treated with WELIREG in LITESPARK-004. Table 3: Adverse Reactions Occurring in ≥10% of Patients Who Received WELIREG in LITESPARK-004 Adverse Reaction WELIREG (n=61) All Grades Graded per NCI CTCAE v4.0 (%) Grade 3-4 (%) General Fatigue Includes other related terms 64 5 Nervous system Headache 39 0 Dizziness 38 0 Gastrointestinal Nausea 31 0 Constipation 13 0 Abdominal pain 13 0 Eye Disorders Visual impairment Includes visual impairment, vision blurred, central retinal vein occlusion and retinal detachment 21

3.3Infections Upper respiratory tract infection 21 0 Respiratory, Thoracic and Mediastinal Dyspnea 20

1.6 Muscul…

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS UGT2B17 or CYP2C19 Inhibitors: Monitor for signs and symptoms of anemia and hypoxia and reduce the dosage of WELIREG as recommended. ( 2.2 , 7.1 ) Sensitive CYP3A4 Substrates : Avoid coadministration with WELIREG for which minimal decrease in concentration may lead to reduced efficacy of the substrate. ( 7.2 )

7.1Effects of Other Drugs on WELIREG UGT2B17 or CYP2C19 Inhibitors Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended [see Dosage and Administration (2.2) , Warnings and Precautions (5.1 , 5.2) , Adverse Reactions (6) ] . Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases belzutifan exposure [see Clinical Pharmacology (12.3 , 12.5) ] , which may increase the risk of adverse reactions of WELIREG.

7.2Effect of WELIREG on Other Drugs CYP3A4 Substrates Avoid coadministration of WELIREG with sensitive CYP3A4 substrates, for which minimal decrease in concentration may lead to therapeutic failures of the substrate. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information. Coadministration of WELIREG with CYP3A4 substrates decreases concentrations of CYP3A substrates [see Clinical Pharmacology (12.3) ] , which may reduce the efficacy of these substrates.

The magnitude of this decrease may be more pronounced in patients who are dual UGT2B17 and CYP2C19 poor metabolizers [see Clinical Pharmacology (12.3) ]. Hormonal Contraceptives Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding [see Clinical Pharmacology (12.3) , Use in Specific Populations (8.3) ] .

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation : Advise not to breastfeed. ( 8.2 ) Infertility : May impair fertility in males and females. ( 8.3 )

8.1Pregnancy Risk Summary Based on findings in animal studies, WELIREG can cause fetal harm when administered to a pregnant woman. There are no available data on the use of WELIREG in pregnant women to inform the drug-associated risk. In an animal reproduction study, oral administration of belzutifan to pregnant rats during the period of organogenesis caused embryo-fetal lethality, reduced fetal body weight, and fetal skeletal malformations at maternal exposures ≥0.2 times the human exposure (AUC) at the recommended dose of 120 mg daily ( see Data ).

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

Data Animal Data In a pilot embryo-fetal development study, pregnant rats received oral doses of 6, 60, or 200 mg/kg/day of belzutifan during the period of organogenesis. Belzutifan caused embryo-fetal lethality at doses ≥60 mg/kg/day (approximately 1 time the human exposure at the recommended dose based on AUC). Reduced fetal body weights, fetal rib malformations, and reduced skeletal ossification occurred at doses of 6 and 60 mg/kg/day (approximately ≥0.2 times the human exposure at the recommended dose based on AUC).

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

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

WELIREG can render some hormonal contraceptives ineffective [see Drug Interactions (7.2) ] . Males Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose. Infertility Based on findings in animals, WELIREG may impair fertility in males and females of reproductive potential [see Nonclinical Toxicology (13.1) ] .

The reversibility of the effect on fertility is unknown.

8.4Pediatric Use The safety and effectiveness of WELIREG have been established in pediatric patients aged 12 years and older for the treatment of locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma. Use of WELIREG in pediatric patients aged 12 years and older is supported by evidence from an adequate and well-controlled study of WELIREG in adults with additional pharmacokinetic data demonstrating that belzutifan exposure is predicted to be within range of that observed in adults, and that the course of locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma is sufficiently similar in adults and pediatric patients to allow extrapolation of data in adults to pediatric patients [see Clinical Pharmacology (12.3) , and Clinical Studies (14.3) ] .

The safety and effectiveness of WELIREG have not been established in pediatric patients with VHL or ccRCC, or in pediatric patients younger than 12 years of age with PPGL.

8.5Geriatric Use Of the 61 patients who received WELIREG for VHL in LITESPARK-004, 3.3% were ≥65 years old [see Clinical Studies (14.1) ] Clinical trials of W…

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Based on findings in animal studies, WELIREG can cause fetal harm when administered to a pregnant woman. There are no available data on the use of WELIREG in pregnant women to inform the drug-associated risk. In an animal reproduction study, oral administration of belzutifan to pregnant rats during the period of organogenesis caused embryo-fetal lethality, reduced fetal body weight, and fetal skeletal malformations at maternal exposures ≥0.2 times the human exposure (AUC) at the recommended dose of 120 mg daily ( see Data ).

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

Data Animal Data In a pilot embryo-fetal development study, pregnant rats received oral doses of 6, 60, or 200 mg/kg/day of belzutifan during the period of organogenesis. Belzutifan caused embryo-fetal lethality at doses ≥60 mg/kg/day (approximately 1 time the human exposure at the recommended dose based on AUC). Reduced fetal body weights, fetal rib malformations, and reduced skeletal ossification occurred at doses of 6 and 60 mg/kg/day (approximately ≥0.2 times the human exposure at the recommended dose based on AUC).

🧒 Pediatric Use 147 words ▾

8.4Pediatric Use The safety and effectiveness of WELIREG have been established in pediatric patients aged 12 years and older for the treatment of locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma. Use of WELIREG in pediatric patients aged 12 years and older is supported by evidence from an adequate and well-controlled study of WELIREG in adults with additional pharmacokinetic data demonstrating that belzutifan exposure is predicted to be within range of that observed in adults, and that the course of locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma is sufficiently similar in adults and pediatric patients to allow extrapolation of data in adults to pediatric patients [see Clinical Pharmacology (12.3) , and Clinical Studies (14.3) ] .

The safety and effectiveness of WELIREG have not been established in pediatric patients with VHL or ccRCC, or in pediatric patients younger than 12 years of age with PPGL.

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use Of the 61 patients who received WELIREG for VHL in LITESPARK-004, 3.3% were ≥65 years old [see Clinical Studies (14.1) ] Clinical trials of WELIREG in patients with VHL did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger patients. Of the 915 patients who received WELIREG in combination with pembrolizumab for ccRCC in LITESPARK-022, 30% were ≥65 years old and 5% were ≥75 years old. No overall differences in efficacy or safety were reported between patients who were ≥65 years of age and younger patients.

Dose interruptions of WELIREG occurred in 57% of patients ≥65 years of age and in 49% of younger patients. Dose reductions of WELIREG occurred in 39% of patients ≥65 years of age and in 32% of younger patients. Of the 372 patients who received WELIREG for advanced ccRCC in LITESPARK-005, 62% of patients were younger than 65 years, 28% of patients were 65 to 74 years, and 10% were 75 years and over.

No overall difference in efficacy was reported between patients who were ≥65 years of age and younger patients. Dose interruptions occurred in 48% of patients ≥65 years of age and in 34% of younger patients. Dose reductions occurred in 18% of patients ≥65 years of age and in 10% of younger patients.

Of the 72 patients who received WELIREG for PPGL in LITESPARK-015, 13% were ≥65 years old and 4.2% were ≥75 years old [see Clinical Studies (14.3) ]. Clinical trials of WELIREG in patients with PPGL did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

🆘 Overdosage 51 words ▾

10 OVERDOSAGE There is no specific treatment for WELIREG overdose. In cases of suspected overdose, withhold WELIREG and institute supportive care. Grade 3 hypoxia occurred at dosages of 120 mg twice a day and Grade 4 thrombocytopenia occurred at dosages of 240 mg once daily (approximately 2 times the recommended dosage).

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Belzutifan is an inhibitor of hypoxia-inducible factor 2 alpha (HIF-2α). HIF-2α is a transcription factor that plays a role in oxygen sensing by regulating genes that promote adaptation to hypoxia. Under normal oxygen levels, HIF-2α is targeted for ubiquitin-proteasomal degradation by VHL protein.

Lack of functional VHL protein results in stabilization and accumulation of HIF-2α. Upon stabilization, HIF-2α translocates into the nucleus and interacts with hypoxia-inducible factor 1 beta (HIF-1β) to form a transcriptional complex that induces expression of downstream genes, including genes associated with cellular proliferation, angiogenesis, and tumor growth. Belzutifan binds to HIF-2α, and in conditions of hypoxia or impairment of VHL protein function, belzutifan blocks the HIF-2α-HIF-1β interaction, leading to reduced transcription and expression of HIF-2α target genes.

In vivo, belzutifan demonstrated anti-tumor activity in mouse xenograft models of renal cell carcinoma.

12.2Pharmacodynamics Reductions in plasma levels of erythropoietin (EPO) were observed to be dose- and exposure-dependent at dosages up to 120 mg once daily. The maximum EPO suppression occurred following 2 weeks of consecutive dosing of WELIREG (mean percent decrease from baseline of approximately 60%). Mean EPO levels gradually returned to baseline values after 12 weeks of treatment.

The incidence of Grade 3 anemia increased with higher belzutifan exposure in patients with baseline hemoglobin levels <12 g/dL [see Warnings and Precautions (5.1) ] . Cardiac Electrophysiology At the recommended dosage, WELIREG does not cause large mean increases (i.e., >20 msec) in the QT interval.

12.3Pharmacokinetics The C max and AUC of belzutifan increase proportionally over a dose range of 20 mg to 120 mg (0.17 to 1 times the approved recommended dose). The estimated geometric mean steady-state (CV%) C max is 1.5 μg/mL (45%) and AUC 0-24h is 20 μg•hr/mL (62%). Steady state is reached after approximately 3 days.

Absorption The median T max occurs at 1 to 2 hours after WELIREG administration. Effect of Food A high-fat, high-calorie meal (total calories approximately 1000 kcal, 56 g fat, 55 g carbohydrate, and 31 g protein) delayed T max by approximately 2 hours with no clinically significant effect on C max and AUC of belzutifan. Distribution The estimated mean (CV%) volume of distribution is 119 L (28%) Plasma protein binding of belzutifan is 45%.

The blood-to-plasma concentration ratio of belzutifan is 0.88. Elimination The estimated mean (CV%) clearance is 6 L/hr (58%) and the mean elimination half-life is 14 hrs. Metabolism Belzutifan is primarily metabolized by UGT2B17 and CYP2C19 and to a lesser extent by CYP3A4 [see Clinical Pharmacology (12.5) ] .

Excretion Following a single oral dose of radiolabeled belzutifan, approximately 49.6% of the dose was excreted in urine and 51.7% in feces (primarily as inactive metabolites). Specific Populations Patients who are poor metabolizers of UGT2B17 and CYP2C19 had higher belzutifan AUC [see Clinical Pharmacology (12.5) ] . No clinically significant differences in the pharmacokinetics of belzutifan were observed based on age (15 to 90 years), sex, ethnicity (non-Hispanic, Hispanic), race (White (76%), Black (5%), Asian (15%), Native American, Pacific Islander), or body weight (40 to 166 kg).

Pediatric patients The exposure of belzutifan in pediatric patients 12 years and older is predicted to be within range of that observed in adults at the recommended dosage. Patients with Renal Impairment No clinically significant differences in the mean belzutifan exposure were observed between subjects with normal renal function and those with mild (eGFR 60-89 mL/min) or moderate renal impairment (eGFR 30-59 mL/min) and those with end-stage renal disease (eGFR <15 mL/min) requiring dialysis. Patients with Hepatic Impairment No clinically significant differences in the mean belzutifan expo…

🧬 Mechanism of Action 139 words ▾

12.1Mechanism of Action Belzutifan is an inhibitor of hypoxia-inducible factor 2 alpha (HIF-2α). HIF-2α is a transcription factor that plays a role in oxygen sensing by regulating genes that promote adaptation to hypoxia. Under normal oxygen levels, HIF-2α is targeted for ubiquitin-proteasomal degradation by VHL protein.

Lack of functional VHL protein results in stabilization and accumulation of HIF-2α. Upon stabilization, HIF-2α translocates into the nucleus and interacts with hypoxia-inducible factor 1 beta (HIF-1β) to form a transcriptional complex that induces expression of downstream genes, including genes associated with cellular proliferation, angiogenesis, and tumor growth. Belzutifan binds to HIF-2α, and in conditions of hypoxia or impairment of VHL protein function, belzutifan blocks the HIF-2α-HIF-1β interaction, leading to reduced transcription and expression of HIF-2α target genes.

In vivo, belzutifan demonstrated anti-tumor activity in mouse xenograft models of renal cell carcinoma.

📦 Storage and Handling 76 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied WELIREG tablets are supplied as 40 mg blue, oval shaped, film-coated, debossed with “177” on one side and plain on the other side, available in: bottles of 90 tablets with child-resistant closure: NDC 0006-5331-01. The bottle also contains two desiccant canisters. Do not eat.

Storage and Handling Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

📋 Description 125 words ▾

11 DESCRIPTION Belzutifan is an inhibitor of hypoxia-inducible factor-2α (HIF-2α). The chemical name of belzutifan is 3-[[(1S,2S,3R)-2,3-Difluoro-2,3-dihydro-1-hydroxy-7-(methylsulfonyl)-1H-inden-4-yl]oxy]-5-fluorobenzonitrile. The molecular formula is C 17 H 12 F 3 NO 4 S and the molecular weight is 383.34 Daltons.

The chemical structure is: Belzutifan is a white to light brown powder that is soluble in acetonitrile, dimethoxyethane, and acetone, sparingly soluble in ethyl acetate, very slightly soluble in isopropanol and toluene, and insoluble in water. WELIREG is supplied as blue, film-coated tablets for oral use containing 40 mg of belzutifan together with croscarmellose sodium, hypromellose acetate succinate, magnesium stearate, mannitol, microcrystalline cellulose, and silicon dioxide, as inactive ingredients. In addition, the film-coating contains FD&C Blue #2 aluminum lake, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide. image description

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Anemia Inform patients that WELIREG can cause severe anemia that may require blood transfusions and that red blood cell levels will be monitored routinely during treatment. Advise patients to contact their healthcare provider if the patient experiences any symptoms suggestive of anemia [see Warnings and Precautions (5.1) ] .

Hypoxia Inform patients that WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization; and that oxygen levels will be monitored routinely during treatment. Advise patients to contact their healthcare provider if the patient experiences any symptoms suggestive of hypoxia [see Warnings and Precautions (5.2) ] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the risk to a fetus.

Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose [see Use in Specific Populations (8.3) ] . Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose [see Use in Specific Populations (8.3) ] .

Lactation Advise females not to breastfeed during treatment with WELIREG and for 1 week after the last dose [see Use in Specific Populations (8.2) ] . Infertility Advise male and female patients that WELIREG may impair fertility [see Use in Specific Populations (8.3) ] . Dosage and Administration Instruct patients to take their dose of WELIREG at the same time each day (once daily).

Advise patients WELIREG can be taken with or without food. Each tablet should be swallowed whole [see Dosage and Administration (2.1) ].

💬 Medication Guide ~3 min read ▾

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 06/2026 MEDICATION GUIDE WELIREG ® (Well-ih-reg) (belzutifan) tablets What is the most important information I should know about WELIREG?

WELIREG can cause serious side effects, including: Low red blood cell counts (anemia). Low red blood cell counts can be severe. You may need a blood transfusion if your red blood cell counts drop too low.

Your healthcare provider will do blood tests to check your red blood cell counts before you start and during treatment with WELIREG. Tell your healthcare provider if you get any symptoms of low red blood cell counts, including tiredness, feeling cold, shortness of breath, chest pain, or fast heartbeat. Low oxygen levels in your body.

WELIREG can cause low oxygen levels in your body that can be severe and may require you to stop treatment with WELIREG, receive oxygen therapy, or be hospitalized. Your healthcare provider will monitor your oxygen levels before you start and during treatment with WELIREG. Tell your healthcare provider or get medical help right away if you get symptoms of low oxygen in your body, including shortness of breath or increased heart rate.

Harm to your unborn baby. Treatment with WELIREG during pregnancy can cause harm to your unborn baby. Females who are able to become pregnant: Your healthcare provider will do a pregnancy test before you start treatment with WELIREG.

You should use an effective form of non-hormonal birth control (contraception) during treatment with WELIREG and for 1 week after your last dose. Birth control methods that contain hormones (such as birth control pills, injections, or transdermal system patches) may not work as well during treatment with WELIREG. Talk to your healthcare provider about birth control methods that may be right for you during treatment with WELIREG.

Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with WELIREG. Males with female partners who are able to become pregnant: You should use effective birth control (contraception) during treatment with WELIREG and for 1 week after your last dose. Tell your healthcare provider right away if your partner becomes pregnant or thinks she is pregnant while you are taking WELIREG.

See “What are the possible side effects of WELIREG?” for more information about side effects. What is WELIREG? WELIREG is a prescription medicine used to treat: von Hippel-Lindau (VHL) disease in adults who need treatment for a type of kidney cancer called renal cell carcinoma (RCC), tumors in the brain and spinal cord called central nervous system (CNS) hemangioblastomas, or a type of pancreatic cancer called pancreatic neuroendocrine tumors (pNET), that do not require surgery right away. a type of kidney cancer called renal cell carcinoma with a clear cell component (ccRCC) in adults, with the medicine pembrolizumab or pembrolizumab berahyaluronidase alfa-pmph, who are at intermediate-high or high risk of kidney cancer coming back after surgery to: remove all or part of the kidney, or remove all or part of the kidney and also surgery to remove cancer that has spread to other parts of the body (metastatic lesions). ccRCC in adults that has spread (advanced RCC) following treatment with a programmed death-receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI) cancer medicines. a type of tumor that starts in nerve and hormone making cells (neuroendocrine tumors) called pheochromocytoma or paraganglioma (PPGL) in adults and children 12 years of age and older that have spread to areas near the adrenal glands (locally advanced), or cannot be removed by surgery (unresectable), or that has spread to other parts of the body (metastatic).

It is not known if WELIREG is safe and effective in children with VHL or ccRCC, or in children younger than 12 years of age with PPGL. Before taking…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
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For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.