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Belzutifan can cause severe anemia that can require blood transfusion.
In Study 004, anemia occurred in 90% of patients and 7% had Grade 3 anemia. Median time to onset of anemia was 31 days (range: 1 day to 8.4 months). In another clinical trial [Study 001 (n=58)] in patients with advanced solid tumors who received the same dosage of Belzutifan, anemia occurred in 76% of patients and 28% had Grade 3 anemia.
Monitor for anemia before initiation of, and periodically throughout, treatment with Belzutifan. Closely monitor patients who are dual UGT2B17 and CYP2C19 poor metabolizers due to potential increases in exposure that may increase the incidence or severity of anemia.
Transfuse patients as clinically indicated. For patients with hemoglobin <9g/dL, withhold Belzutifan until ≥9g/dL, then resume at reduced dose or permanently discontinue Belzutifan, depending on the severity of anemia. For life threatening anemia or when urgent intervention is indicated, withhold Belzutifan until hemoglobin ≥9g/dL, then resume at a reduced dose or permanently discontinue Belzutifan.
The use of erythropoiesis stimulating agents (ESAs) for treatment of anemia is not recommended in patients treated with Belzutifan. For patients treated with Belzutifan who develop anemia, the safety and effectiveness for use of ESAs have not been established. Randomized controlled trials in patients with cancer receiving myelosuppressive chemotherapy with ESAs have shown that ESAs increased the risks of death and serious cardiovascular reactions, and decreased progression-free survival and/or overall survival. See the prescribing information for ESAs for more information.
Belzutifan can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization.
In Study 004, hypoxia occurred in 1.6% of patients . In another clinical trial [Study 001 (n=58)] in patients with advanced solid tumors who received the same dosage of Belzutifan, hypoxia occurred in 29% of patients, including Grade 3 hypoxia in 16%.
Monitor oxygen saturation before initiation of, and periodically throughout, treatment with Belzutifan. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg), consider withholding Belzutifan until pulse oximetry with exercise is greater than 88%, then resume at the same dose or at a reduced dose. For decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or urgent intervention indicated, withhold Belzutifan until resolved and resume at a reduced dose or discontinue. For life-threatening hypoxia or for recurrent symptomatic hypoxia, permanently discontinue Belzutifan.
Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider.
Based on findings in animals, WELIREG can cause fetal harm when administered to a pregnant woman. In an animal reproduction study, oral administration of belzutifan to pregnant rats during the period of organogenesis caused embryo-fetal lethality, reduced fetal body weight, and fetal skeletal malformations at maternal exposures ≥0.2 times the human exposures (AUC) at the recommended dose of 120 mg daily.
Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose, since WELIREG can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.
FDA，2021.08
