Hypoxia-inducible Factor InhibitorPrescription OnlyPregnancy Cat. Not classifiedFDA Yes

Welireg

BELZUTIFAN

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 ) Advanced Renal Cell Carcinoma (RCC) for treatment of adult patients with advanced renal cell carcinoma (RCC) with a clea...

Medically reviewed by MedCentralHub Medical Review Board, Licensed Pharmacists & Physicians · May 2026

Brand names:WELIREG

Rx Only

WeliregMedication

Quick Reference

Medicine ClassHypoxia-inducible Factor Inhibitor

FDA ApprovedYes

PregnancyCategory Not classified

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Quick Facts

Active ingredient: BELZUTIFAN
Medicine class: Hypoxia-inducible Factor Inhibitor
Brand names: WELIREG
Availability: Prescription only (Rx)
Pregnancy category: Not classified
Half-life: half-life is 14 hrs
FDA approved: Yes

Welireg (BELZUTIFAN) medication overview

What Is Welireg?

Welireg (BELZUTIFAN) belongs to the Hypoxia-inducible Factor Inhibitor class of medications. It was first approved by the FDA in Yes. This medication requires a prescription from a licensed healthcare provider.

Key Safety Information

•Always follow the dose recommended by your healthcare professional. Taking more than prescribed increases the risk of side effects including serious complications.
•Seek emergency care if you experience signs of an allergic reaction — hives, swelling, difficulty breathing, or rash. Stop the medication and call your doctor immediately.
•Some medications can increase the risk of cardiovascular events. Tell your doctor if you have high blood pressure, a history of heart attack or stroke, or any pre-existing health condition.
•Avoid or limit alcohol while taking Welireg. Do not drink alcohol without first discussing it with your healthcare provider as it may increase adverse effects.
•Take Welireg with food or a full glass of water if stomach upset occurs. Stop use and talk to your doctor if you experience persistent stomach pain or GI symptoms.
•Tell your doctor about all medications, supplements, and vitamins you take. Some combinations significantly increase the risk of harm.

This is a summary only. Always read the full prescribing information and consult your healthcare provider for personalized medical advice.

Uses & Indications

Welireg is prescribed for the following conditions. Some uses are FDA-approved indications; others may be evidence-based off-label uses. Consult your healthcare provider for personalized guidance.

( 1.1 ) Advanced Renal Cell Carcinoma (RCC) for treatment of adult patients with advanced renal cell carcinoma (RCC) with a clear cell component 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.

1.2 Advanced Renal Cell Carcinoma (RCC) WELIREG is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) with a clear cell component 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).

1.3 Pheochromocytoma 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 Guide

The following are general dosing guidelines only. Your actual dose should be determined by your healthcare provider based on your condition, renal/hepatic function, and other medications.

Adult Dosage

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: 120 mg orally once daily Patients weighing < 40 kg: 80 mg orally once daily 2.1 Recommended Dosage The recommended dosage of WELIREG in adult patients is 120 mg administered orally once daily. The recommended dosage of WELIREG in pediatric patients 12 years and older is based on bodyweight: Patients weighing ≥ 40 kg: 120 mg orally once daily Patients weighing < 40 kg: 80 mg orally once daily Continue WELIREG until disease progression or unacceptable toxicity. 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

Available Forms

Available Strengths

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Side Effects

Common

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 ) Advanced RCC : Most common (≥25%) adverse reactions, including laboratory abnormalities were decreased hemoglobin, fatigue, musculoskeletal pain, increased creatinine, decreased lymphocytes, increased alanine aminotransferase, decreased sodium, increased potassium, and increased aspartate aminotransferase.
( 6.1 ) PPGL : Most common (≥25%) adverse reactions, including laboratory abnormalities were anemia, fatigue, musculoskeletal pain, decreased lymphocytes, increased alanine aminotransferase, increased aspartate aminotransferase, 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 .
6.1 Clinical 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.

Serious

5 WARNINGS AND PRECAUTIONS Anemia : Monitor for anemia before initiation of and periodically throughout treatment with WELIREG.
Withhold WELIREG until hemoglobin ≥8g/dL, then resume at the same or reduced dose or discontinue.
For life threatening anemia, or for anemia requiring urgent intervention, withhold WELIREG until hemoglobin ≥8g/dL and resume at a reduced dose or permanently discontinue WELIREG.
( 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.

Rare

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Medicine Interactions

Always inform your healthcare provider and pharmacist about ALL medications you take, including prescriptions, OTC medicines, vitamins, and supplements.

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Warnings & Contraindications

5 WARNINGS AND PRECAUTIONS Anemia : Monitor for anemia before initiation of and periodically throughout treatment with WELIREG. Withhold WELIREG until hemoglobin ≥8g/dL, then resume at the same or reduced dose or discontinue. For life threatening anemia, or for anemia requiring urgent intervention, withhold WELIREG until hemoglobin ≥8g/dL and resume at a reduced dose or permanently discontinue WEL

How Welireg Works

12.1 Mechanism 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 b

Pharmacokinetics

Absorption

Absorption The median T max occurs at 1 to 2 hours after WELIREG administration

Half-Life

half-life is 14 hrs

Metabolism

Metabolism Belzutifan is primarily metabolized by UGT2B17 and CYP2C19 and to a lesser extent by CYP3A4 [see Clinical Pharmacology (12

Excretion

Excretion Following a single oral dose of radiolabeled belzutifan , approximately 49

Pregnancy & Breastfeeding Safety

Not classified

FDA Pregnancy Category Not classified

Consult your healthcare provider.

Full Pregnancy Information

Breastfeeding

Many medications pass into breast milk in varying amounts. Before using Weliregwhile breastfeeding, discuss the benefits and risks with your healthcare provider or pharmacist — they can weigh your dose, your infant's age, and available lactation safety data to find the safest option for you and your baby.

Storage & Handling

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 desicc

Frequently Asked Questions

Sources & References

• FDA Prescribing Information — Official labeling and package insert for Welireg
• U.S. National Library of Medicine — MedlinePlus drug information
• American Hospital Formulary Service (AHFS) — Clinical pharmacology monograph
• PubMed / MEDLINE — View clinical studies

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Medical Disclaimer

The information on this page is for educational purposes only and is not intended as medical advice, diagnosis, or treatment. Always consult your doctor, pharmacist, or qualified healthcare provider before starting, stopping, or changing any medication.