belzutifan

High Alert

von Hippel-Lindau (VHL) disease in patients who require therapy for associated renal cell carcinoma (RCC), CNS hemangioblastomas, or pancreatic neuroendocrine tumors, but do not require immediate surgery.
Advanced RCC following previous therapy with a programmed death receptor-1 or programmed death-ligand 1 inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor.

Action ⬆ ⬇

Inhibits hypoxia-inducible factor 2 alpha, which inhibits cell proliferation, angiogenesis, and tumor growth.

Therapeutic effects:

Reduction in progression of RCC, CNS hemangioblastomas, or pancreatic neuroendocrine tumors in VHL disease.
Improved progression-free survival in advanced RCC.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Primarily metabolized in the liver via UGT2B17 and the CYP2C19 isoenzyme, and to a lesser extent by the CYP3A4 isoenzyme. The CYP2C19 isoenzyme exhibits genetic polymorphism (2% of White people, 4% of Black people, and 14% of Asians may be poor metabolizers and may have significantly ↑ belzutifan concentrations and an ↑ risk of adverse effects). UGT2B17 also exhibits genetic polymorphism (15% of White people, 6% of Black people, and up to 77% of Asians populations may be poor metabolizers and have significantly ↑ belzutifan concentrations and an ↑ risk of adverse effects). Primarily excreted in the feces (51.7%) as inactive metabolites, with 49.6% excreted in the urine primarily as inactive metabolites.

Half-Life: 14 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–2 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Dual UGT2B17 and CYP2C19 poor metabolizers (↑ incidence or severity of adverse reactions);
Severe renal impairment;
Moderate or severe hepatic impairment;
Rep: Women and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, hypertension

Derm: rash

EENT: blurred vision, retinal detachment

Endo: hypoglycemia

F and E: hyperkalemia, hypocalcemia, hyponatremia

GI: abdominal pain, constipation, ↓appetite, diarrhea, ↑liver enzymes, nausea, vomiting

GU: ↑serum creatinine, ↓fertility

Hemat: anemia, lymphopenia, bleeding

Metab: ↑weight

MS: arthralgia, myalgia

Neuro: dizziness, fatigue, headache

Resp: dyspnea, hypoxia

Interactions ⬆ ⬇

Drug-drug:

UGT2B17 inhibitors may ↑ levels and the risk of toxicity.
CYP2C19 inhibitors may ↑ levels and the risk of toxicity.
May ↓ levels and effectiveness of CYP3A4 substrates, including hormonal contraceptives; avoid concurrent use. If concurrent use unavoidable, ↑ dose of CYP3A4 substrate.

Route/Dosage ⬆ ⬇

PO (Adults ): 120 mg once daily; continue until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Assessment ⬆ ⬇

Monitor oxygen saturation before initiation and periodically during therapy. If hypoxia occurs,withhold until resolved and resume at same or reduced dose or discontinue belzutifan permanently depending on severity.

Lab Test Considerations:

Verify pregnancy status prior to initiation of belzutifan.
- Monitor CBC before and routinely during therapy. May cause anemia. If hemoglobin <8 g/dL or transfusion is indicated,withhold therapy until hemoglobin ≥8 g/dL and resume at same or reduced dose or permanently discontinue belzutifan depending on severity.

Implementation ⬆ ⬇

PO: Administer at the same time each day with or without food. DNC: Swallow tablets whole; do not chew, crush, or split tablets.If dose is missed, take as soon as possible on the same day; resume regular schedule the next day. Do not take extra dose to make up for missed dose.If vomiting occurs at any time after dose taken,do not retake dose; resume regular schedule the next day.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult a health care professional before taking other medications.
Advise patient to report symptoms of hypoxia (change in skin tone, difficulty breathing, ↑ heartbeat, confusion) immediately to a health care professional.
Advise patient to report symptoms of anemia (fatigue, headache, dizziness) to a health care professional.
Rep: Advise females of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Explain embryo-fetal toxicity risk and need for effective nonhormonal contraception during therapy and for 1 wk after the last dose. May impair fertility in all patients of reproductive potential.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇