Belzutifan

Belzutifan is a prescription medication used for adults with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors, not requiring immediate surgery.

• Belzutifan is available under the following different brand names: Welireg.

Common side effects of Belzutifan include:

• Decreased hemoglobin,
• Abnormal laboratory results,
• Fatigue,
• Weakness,
• Pale or yellowish skin,
• Irregular heartbeats,
• Shortness of breath,
• Lightheadedness,
• Chest pain,
• Cold hands and feet,
• Headache,
• Nausea,
• Chest pain,
• Muscle cramps,
• Vomiting,
• High blood pressure,
• Swelling or fluid retention,
• Itching,  
• Headache,
• Dizziness,
• Vomiting,
• Excessive hunger and thirst,
• Rapid heartbeat, and
• Vision problems

Serious side effects of Belzutifan include:

• Hives,
• Difficulty breathing,
• Swelling of your face, lips, tongue, or throat,
• Severe dizziness,
• Fatigue,
• Weakness,
• Pale or yellowish skin,
• Irregular heartbeats,
• Shortness of breath,
• Lightheadedness,
• Chest pain,
• Cold hands and feet,
• Headache,
• Coughing,
• Wheezing,
• Confusion, and
• Bluish color of the skin, fingernails, and lips

Rare side effects of Belzutifan include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 40 mg

Von Hippel-Lindau Disease

Adult dosage

• 120 mg orally once a day
• Continue until disease progression or unacceptable toxicity.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Belzutifan has severe interactions with the following drug:
  • mavacamten
• Belzutifan has serious interactions with at least 22 other drugs.
• Belzutifan has moderate interactions with at least 169 other drugs.
• Belzutifan has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Belzutifan?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Belzutifan?”

Cautions

• Fetal harm can occur when administered to pregnant females.
• Anemia
  • Severe anemia may occur.
  • Monitor for anemia before initiation and periodically during treatment.
  • Closely monitor patients who are dual UGT2B17 and CYP2C19 poor metabolizers owing to potential increased systemic exposure that may increase the incidence or severity of anemia.
  • Transfuse patients as clinically indicated.
  • For treated patients who develop anemia, the use of erythropoiesis-stimulating agents (ESAs) is not recommended; ESA safety and effectiveness in treated patients with anemia have not been established.
  • ESAs reported to increase the risk of serious cardiovascular reactions and death in addition to decreasing progression-free survival and/or overall survival in patients with cancer receiving myelosuppressive chemotherapy.
  • See prescribing information for ESAs for more information.
• Hypoxia
  • Hypoxia reported; severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization may occur.
  • Monitor oxygen saturation before initiation and periodically during treatment.
  • Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider.
• Drug interaction overview
  • Substrate of UGT2B17 or CYP2C19
    • Inducer of CYP3A4
    • UGT2B17 or CYP2C19 Inhibitors
    • Monitor for signs and symptoms of anemia and hypoxia and reduce the dose as recommended.
    • UGT2B17 or CYP2C19 inhibitors increase plasma exposure and toxicity of Belzutifan.
  • Sensitive CYP3A4 substrates
    • Avoid coadministration; if unavoidable, increase the sensitive CYP3A4 substrate dosage according to its prescribing information
    • Belzutifan decreases the concentrations and efficacy of CYP3A4 substrates.
    • Magnitude of decreased CYP3A4 substrate efficacy may be more pronounced in patients who are dual UGT2B17 and CYP2C19 poor metabolizers.
  • Hormonal contraceptives
    • Use effective nonhormonal contraception.
    • Coadministration with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding.

Pregnancy and Lactation

• Based on findings in animal studies, fetal harm can occur when administered to pregnant females
• No data are available on use in pregnant females to inform a drug-associated risk
• Contraception
  • Belzutifan can render some hormonal contraceptives ineffective.
  • Females of reproductive potential: Use effective nonhormonal contraception during treatment and for 1 week after the final dose.
  • Male patients with female partners of reproductive potential: Use effective contraception during treatment and for 1 week after the final dose.
• Infertility
  • Therapy may impair fertility in males and females of reproductive potential.
  • Reversibility of the effect on fertility is unknown.
• Lactation
  • There are no data on the presence of Belzutifan or its metabolites in human milk or their effects on breastfed children or milk production.
  • Advise females not to breastfeed during treatment and for 1 week after the final dose.