Belzutifan 40 mg tablets contain the active ingredient belzutifan, an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor used in the treatment of certain cancers associated with von Hippel-Lindau (VHL) disease and advanced renal cell carcinoma (RCC).

Belzutifan inhibits HIF-2α, a protein involved in cellular responses to low oxygen levels. In VHL-associated cancers, abnormal HIF signaling can contribute to tumor growth and blood-vessel formation. By inhibiting HIF-2α, belzutifan helps reduce signalling that supports tumor growth and progression.

Adults with von Hippel-Lindau (VHL) disease who require treatment for associated:

• Renal cell carcinoma (RCC)
• Central nervous system (CNS) hemangioblastomas
• Pancreatic neuroendocrine tumors (pNETs)
• When immediate surgery is not required.

Adults with advanced renal cell carcinoma (RCC) with a clear cell component following treatment with a PD-1/PD-L1 inhibitor and a VEGF-TKI.

Belzutifan is a selective HIF-2α inhibitor.

It works by:

• Binding to and inhibiting HIF-2α activity.
• Reducing abnormal HIF-mediated gene signaling.
• Decreasing production of factors that support tumor growth and angiogenesis.
• Inhibiting proliferation of certain VHL-associated tumor cells.
• Helping slow tumor progression.

The medicine is particularly relevant to tumors in which abnormal VHL/HIF-2α signaling contributes to disease progression.

• Belzutifan is taken orally once daily, with or without food.
• The currently labeled recommended dosage is 120 mg once daily, equivalent to three 40 mg tablets, unless the treating physician prescribes a modified dose.
• Swallow tablets whole with water.
• Do not crush, chew, or break the tablets unless specifically instructed by a healthcare professional.
• Take the medicine at approximately the same time each day.
• If a dose is missed, follow the prescribing physician's instructions rather than taking an extra dose.

Serious:

• Anemia
• Hypoxia
• Severe fatigue associated with low hemoglobin
• Serious complications associated with reduced oxygen levels

Belzutifan can significantly decrease hemoglobin levels, so blood counts should be monitored before treatment and periodically during therapy.

Common:

• Decreased hemoglobin (anemia)
• Fatigue
• Musculoskeletal pain
• Increased creatinine
• Decreased lymphocyte count
• Increased ALT
• Decreased sodium
• Increased potassium
• Increased AST
• Headache
• Dizziness
• Nausea
• Increased glucose

The exact frequency and pattern of adverse effects can vary according to the indication and patient population.

Patients should inform their healthcare provider about all prescription medicines, over-the-counter medicines, vitamins, and herbal supplements they are taking.

Belzutifan has clinically important interactions with:

• UGT2B17 inhibitors—may increase belzutifan exposure and the risk of adverse reactions.
• CYP2C19 inhibitors—may increase belzutifan exposure.
• Sensitive CYP3A4 substrates—belzutifan can decrease their concentrations and potentially reduce their effectiveness.
• Hormonal contraceptives—Belzutifan may reduce their effectiveness and increase the risk of contraceptive failure.

Patients receiving UGT2B17 or CYP2C19 inhibitors require monitoring for anemia and hypoxia, with dose modification where appropriate. Sensitive CYP3A4 substrates should generally be avoided where possible.

• Store at 20°C–25°C (68°F–77°F).
• Keep in the original container.
• Protect from excessive heat and moisture.
• Keep out of reach of children.

• Monitor hemoglobin regularly before and during treatment because anemia is one of the most important adverse effects of belzutifan.
• Monitor oxygen saturation before treatment and periodically thereafter.
• Report shortness of breath, unusual fatigue, dizziness, or other symptoms suggestive of hypoxia promptly.
• Pregnancy should be excluded before initiating treatment in females who can become pregnant.
• Use effective non-hormonal contraception during treatment and for 1 week after the final dose.
• Inform your physician about all medicines being taken, particularly medicines affecting UGT2B17, CYP2C19, and CYP3A4.
• Do not discontinue, increase, or reduce the dose without medical supervision.
• Regular blood tests and clinical follow-up are important throughout treatment.