Belzutifan – Uses, Dosage, Side Effects, Interaction

Belzutifan exerts its therapeutic effects by inhibiting a transcription factor necessary for the growth of solid tumors associated with VHL disease. It is taken once daily at approximately the same time each day, with or without food. Both severe anemia and hypoxia have been observed following therapy with belzutifan, and patients should be monitored closely before and during therapy to ensure patients can be managed as clinically indicated. There are no data regarding the use of erythropoiesis-stimulating agents for the treatment of belzutifan-induced anemia, and as such these therapies should be avoided. Belzutifan may cause embryo-fetal toxicity when administered to pregnant women. Female patients and male patients with female partners of reproductive potential should ensure that an effective form of contraception is used throughout therapy and for one week after the last dose – as belzutifan appears to decrease the efficacy of systemic hormonal contraceptives, patients should be advised to use an additional method of contraception (e.g. condoms) to eliminate the possibility of pregnancy during therapy.

Use in Cancer

Belzutifan is approved to treat adults with:

• Cancers linked to Von Hippel-Lindau disease that require treatment but not immediate surgery, including:
  • Central nervous system hemangioblastoma.
  • Pancreatic neuroendocrine tumors.
  • Renal cell carcinoma.

Belzutifan is also being studied in the treatment of other types of cancer.

Contraindication

The following conditions are contraindicated with this drug. Check with your physician if you have any of the following:

• anemia
• decreased oxygen in the tissues or blood
• pregnancy
• a patient who is producing milk and breastfeeding

Dosage

Strengths: 40 mg

Von Hippel-Lindau Syndrome

• 120 mg orally once daily until disease progression or unacceptable toxicity

Renal Dose Adjustments

• Mild (CrCl 60 to less than 90 mL/min) to moderate (CrCl 30 to less than 60 mL/min) renal dysfunction: No adjustment recommended.
  Severe (CrCl 15 to 30 mL/min) to end-stage renal dysfunction: Data not available

Liver Dose Adjustments

• Mild (total bilirubin upper limit of normal [ULN] or less and aspartate aminotransferase [AST] greater than ULN or total bilirubin greater than 1 to 1.5 x ULN and any AST) hepatic impairment: No adjustment recommended.
  Moderate to severe (total bilirubin greater than 1.5 x ULN and any AST) hepatic impairment: Data not available

Dose Adjustments

Recommended Dose Reductions:

• First dose reduction: 80 mg orally once daily
• Second dose reduction: 40 mg orally once daily
• Third dose reduction: Permanently discontinue therapy.

Dose Modifications for Adverse Reactions:
ANEMIA:

• Hemoglobin less than 9 g/dL or transfusion indicated: Withhold therapy until hemoglobin 9 g/dL or greater; resume at reduced dose or discontinue depending on the severity of anemia
• Life-threatening or urgent intervention indicated: Withhold therapy until hemoglobin 9 g/dL or greater; resume at reduced dose or permanently discontinue

HYPOXIA:

• Decreased oxygen saturation with exercise (e.g., pulse oximeter less than 88%): Consider withholding therapy until resolved; resume at the same dose or at a reduced dose depending on the severity of hypoxia.
• Decreased oxygen saturation at rest (e.g., pulse oximeter less than 88% or partial pressure of oxygen (PaO2) 55 mm Hg or less) or urgent intervention indicated: Withhold therapy until resolved; resume at reduced dose or discontinue depending on the severity of hypoxia

Side Effects

The Most Common

• dizziness
• tiredness
• headache
• nausea
• constipation
• stomach pain
• joint or muscle pain
• vision changes
• weight gain
• fever, cough, shortness of breath, or other signs of infection
• tiredness, feeling cold, pale skin, shortness of breath, chest pain, or fast heartbeat

More common

• Body aches or pain
• chills
• constipation
• difficulty in moving
• ear congestion
• fever
• loss of voice
• muscle aches, cramps, pain, or stiffness
• nausea
• pain in the joints
• sneezing
• sore throat
• stomach pain
• stuffy or runny nose
• swollen joints
• weight increased

Rare

• change in vision
• chest tightness
• confusion
• cough
• difficulty swallowing
• dizziness
• fast heartbeat
• headache
• hives, itching, skin rash
• nervousness
• pale skin
• pounding in the ears
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• seeing flashes or sparks of light
• seeing floating spots before the eyes, or a veil or curtain appearing across part of vision
• trouble breathing
• unusual bleeding or bruising
• unusual tiredness or weakness

Drug Interaction

Pregnancy and Lactation

US FDA pregnancy category Not Assigned

Pregnancy

Do not take belzutifan if you are pregnant, plan to become pregnant, or plan to father a child. You will have to take a pregnancy test before starting treatment. If you are female, you will need to use non-hormonal birth control during your treatment and for 1 week after your final dose.

Lactation

Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during therapy with this drug and for 1 week after.

References