WELIREG
Clinical safety rating: caution
Comprehensive clinical and safety monograph for WELIREG (WELIREG).
Hypoxia-inducible factor-2α (HIF-2α) inhibitor. Binds to HIF-2α, blocking its heterodimerization with HIF-1β, thereby reducing transcription of genes involved in cell proliferation, angiogenesis, and metabolism associated with tumor growth.
| Metabolism | Primarily metabolized by CYP3A4 and to a minor extent by CYP2C19 and UGT1A9. |
| Excretion | Primarily hepatic metabolism (CYP3A4) with 65% fecal excretion (mostly as metabolites) and 22% renal excretion (mostly unchanged drug). |
| Half-life | Terminal elimination half-life is approximately 14-18 hours in patients; supports once-daily dosing. |
| Protein binding | 99.7% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution is 1.2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 60-70%. |
| Onset of Action | Onset of clinical effect is observed within 2-4 weeks of oral administration. |
| Duration of Action | Duration of action is approximately 24 hours, allowing once-daily dosing; sustained exposure is necessary for continuous HIF-2α inhibition. |
120 mg orally once daily with or without food until disease progression or unacceptable toxicity.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl 15-29 mL/min), reduce dose to 40 mg orally once daily. Not studied in ESRD (CrCl <15 mL/min). |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no dose adjustment. Moderate (Child-Pugh B): reduce dose to 80 mg orally once daily. Severe (Child-Pugh C): reduce dose to 40 mg orally once daily. |
| Pediatric use | Safety and effectiveness not established in pediatric patients; no recommended dose. |
| Geriatric use | No specific dose adjustment required; however, consider age-related renal impairment and monitor for adverse reactions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for WELIREG (WELIREG).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Due to potential for serious adverse reactions, breastfeeding is not recommended during treatment and for at least 1 week after the last dose. M/P ratio unknown. |
| Teratogenic Risk | Welireg (belzutifan) is embryotoxic and teratogenic in animal studies at maternal exposures below the recommended human dose. No human data. First trimester: High risk of major congenital malformations and pregnancy loss. Second and third trimesters: Potential for impaired renal development and fetal hypoxia due to HIF-2α inhibition. Contraindicated in pregnancy. |
■ FDA Black Box Warning
None.
| Serious Effects |
["None."]
| Precautions | ["Anemia: Can cause severe anemia. Monitor hemoglobin before and during treatment.","Hypoxia: May cause hypoxia. Monitor oxygen saturation; dose interruption or reduction may be required.","Hepatotoxicity: Can cause elevated liver enzymes. Monitor liver function tests.","Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of effective contraception."] |
Loading safety data…
| Fetal Monitoring | Verify pregnancy status in females of reproductive potential prior to initiation. Monthly pregnancy testing during treatment and for 1 week after last dose. Monitor fetal growth and amniotic fluid volume by ultrasound if exposure occurs. |
| Fertility Effects | Based on animal studies, may impair female fertility (e.g., disrupted estrous cycles). No data on male fertility; however, HIF-2α inhibition may affect spermatogenesis. Advise patients on potential impact on fertility. |