Lucius Version of Belzutifan: Dosage and Administration, Indications, Precautions

Lucius Version of Belzutifan: Dosage and Administration, Indications, Precautions

Indications

Belzutifan is a hypoxia-inducible factor inhibitor indicated for:

Von Hippel-Lindau (VHL) Disease: 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) that do not require immediate surgery.

Advanced Renal Cell Carcinoma (RCC): Treatment of adult patients with advanced RCC following treatment with 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).

Dosage and Administration

The recommended dosage of belzutifan is 120 mg taken orally once daily, with or without food.

Use in Specific Populations

1. Pregnancy

Risk Summary: Based on animal study results, WELIREG (belzutifan) can cause fetal harm when administered to pregnant women. There are no available data on the drug-related risks of WELIREG use in pregnant women. In an animal reproductive study, pregnant rats were given belzutifan orally during the organogenesis period. When maternal exposure was ≥ 0.2 times the human exposure (AUC) at the recommended daily dose of 120 mg, it resulted in embryofetal death, reduced fetal body weight, and fetal skeletal malformations. Inform pregnant women and females of reproductive potential about the potential risk to the fetus. The background risk of major birth defects and miscarriage in the indicated population is unknown. In the general U.S. population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.

Data (Animal Data): In a preliminary embryofetal development study, pregnant rats were given belzutifan at doses of 6, 60, or 200 mg/kg/day orally during the organogenesis period. Belzutifan caused embryofetal death at doses ≥ 60 mg/kg/day (approximately 1 time the human exposure at the recommended dose, based on AUC). At doses of 6 and 60 mg/kg/day (≥ 0.2 times the human exposure at the recommended dose, based on AUC), reduced fetal body weight, fetal rib malformations, and decreased skeletal ossification occurred.

2. Lactation

Risk Summary: There are no data on the presence of belzutifan or its metabolites in human milk, or on their effects on breastfed infants or milk production. Due to the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during WELIREG treatment and for 1 week after the last dose.

3. Females and Males of Reproductive Potential

WELIREG can cause fetal harm when administered to pregnant women.

Pregnancy Testing: Verify the pregnancy status of females of reproductive potential before initiating WELIREG treatment.

Contraception:

Females: Advise females of reproductive potential to use effective non-hormonal contraception during WELIREG treatment and for 1 week after the last dose. WELIREG may reduce the efficacy of some hormonal contraceptives.

Males: Advise males with female partners of reproductive potential to use effective contraception during WELIREG treatment and for 1 week after the last dose.

Infertility: Based on animal study results, WELIREG may impair fertility in males and females of reproductive potential. The reversibility of the effect on fertility is unknown.

4. Pediatric Use

The safety and efficacy of WELIREG in pediatric patients have not been established.

5. Geriatric Use

Of the patients who received WELIREG in Study 004, 3.3% were ≥ 65 years of age. WELIREG clinical trials did not include a sufficient number of patients aged 65 years and older to determine whether their response differs from that of younger patients.

6. Renal Impairment

No dosage adjustment of WELIREG is recommended in patients with mild (estimated eGFR 60-89 mL/min/1.73 m², based on MDRD) or moderate (eGFR 30-59 mL/min/1.73 m²) renal impairment. WELIREG has not been studied in patients with severe renal impairment (eGFR 15-29 mL/min/1.73 m²).

7. Hepatic Impairment

No dosage adjustment of WELIREG is recommended in patients with mild hepatic impairment [total bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN, or total bilirubin > 1-1.5 × ULN and any AST]. WELIREG has not been studied in patients with moderate or severe hepatic impairment (total bilirubin > 1.5 × ULN and any AST).

8. Poor Metabolizers of Both UGT2B17 and CYP2C19

Patients who are poor metabolizers of both UGT2B17 and CYP2C19 have higher belzutifan exposure, which may increase the incidence and severity of WELIREG-associated adverse reactions. Closely monitor patients who are poor metabolizers of both UGT2B17 and CYP2C19 for adverse reactions.

Warnings and Precautions

Anemia

Monitor for anemia before initiating belzutifan and periodically throughout treatment.

Hold belzutifan until hemoglobin ≥ 8 g/dL, then resume at the same or reduced dose, or discontinue.

For life-threatening anemia or anemia requiring urgent intervention, hold belzutifan until hemoglobin ≥ 8 g/dL, then resume at a reduced dose or discontinue permanently.

Hypoxia

Monitor oxygen saturation before initiating belzutifan and periodically throughout treatment.

For hypoxia at rest, hold until resolution, resume at a reduced dose, or discontinue based on severity.

For life-threatening hypoxia, discontinue belzutifan permanently.

Drug Interactions

UGT2B17 or CYP2C19 Inhibitors

Monitor for signs and symptoms of anemia and hypoxia, and reduce the dose of belzutifan as recommended.

Adverse Reactions

VHL Disease: The most common adverse reactions (incidence ≥ 25%), including laboratory abnormalities, are decreased hemoglobin, fatigue, increased creatinine, headache, dizziness, increased blood glucose, and nausea.

Advanced RCC: The most common adverse reactions (incidence ≥ 25%), including laboratory abnormalities, are decreased hemoglobin, fatigue, musculoskeletal pain, increased creatinine, lymphopenia, increased alanine aminotransferase, decreased sodium, increased potassium, and increased aspartate aminotransferase.

Contraindications

No specific contraindications have been identified.

Dosage Form

Tablets.

Storage

Store belzutifan at room temperature between 68°F and 77°F (20°C and 25°C).Belzutifan bottles contain 2 desiccant canisters to help keep the drug dry. Do not consume the desiccant canisters.Keep belzutifan and all medications out of the reach of children.