Belzutifan (Welireg) is a hypoxia-inducible factor-2α (HIF-2α) inhibitor that received its first approval in the United States in 2021. It is primarily indicated for the treatment of adult patients with von Hippel-Lindau (VHL) syndrome who have renal cell carcinoma, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors requiring treatment and for whom immediate surgery is not necessary.

Dosage and Administration of Belzutifan (Welireg)

Standard Dosing Regimen

The recommended standard dose of belzutifan is 120 mg orally once daily.

Patients may take the medication at a fixed time each day, and food does not affect its absorption, meaning it can be administered either before or after meals, which offers convenience to patients.

Specific Administration Instructions

Patients must swallow the tablets whole; chewing, crushing, or splitting the tablets is not allowed, to ensure the drug is released in the body at the designed rate.

If a dose is missed on a given day, it should be taken as soon as possible on the same day. The regular dosing schedule should be resumed the next day, and a double dose should not be taken to make up for the missed dose.

If vomiting occurs after taking the medication, no additional dose is needed, and the next scheduled dose should be taken on the following day.

Dose Adjustment of Belzutifan (Welireg)

Dose Adjustment for Anemia

Anemia is one of the most common adverse reactions to belzutifan.

Treatment should be interrupted when the patient's hemoglobin level drops below 9 g/dL or blood transfusion is required.

After the hemoglobin level returns to 9 g/dL or higher, resumption of treatment at a reduced dose may be considered, or permanent discontinuation may be implemented based on the severity of anemia.

In cases of life-threatening anemia or severe anemia requiring emergency intervention, treatment must also be temporarily suspended first; after the indicators recover, treatment may be continued at a reduced dose or permanently discontinued.

Dose Adjustment for Hypoxemia

Blood oxygen saturation should be monitored regularly during treatment.

If a patient experiences decreased blood oxygen levels during physical activity, treatment interruption should be considered until recovery, after which treatment may be continued at the original or reduced dose.

If decreased blood oxygen levels occur at rest or emergency intervention is required, treatment must be suspended; after symptom relief, treatment may be resumed at a reduced dose or permanently discontinued.

For life-threatening or recurrent hypoxemia, belzutifan should be permanently discontinued.

Use in Special Populations

Reproductive-Age Females and Males

Belzutifan has embryo-fetal toxicity and may cause harm to the developing fetus.

The pregnancy status of female patients must be confirmed prior to the initiation of treatment.

Reproductive-age females must use effective non-hormonal contraceptive methods during treatment and for 1 week after the last dose, as this drug may render some hormonal contraceptives ineffective.

Male patients with reproductive-age female partners should also use effective contraceptive measures during treatment and for 1 week after the last dose.

Lactating Females

There are currently no data available regarding whether belzutifan or its metabolites are excreted in human milk.

Given the potential risk of serious adverse reactions in infants, it is recommended that females not breastfeed during treatment and for 1 week after the last dose.

Patients with Hepatic or Renal Impairment

No dose adjustment is required for patients with mild to moderate renal impairment (eGFR 30–89 mL/min/1.73 m²) or mild hepatic impairment.

The safety of this drug in patients with severe renal impairment (eGFR 15–29 mL/min/1.73 m²) and moderate to severe hepatic impairment has not been studied, and caution should be exercised when using it in these populations.