Welireg

/ MSD

The recommended dose is 120 mg (three 40 mg tablets) administered orally once daily, with or without food. Tablets should be swallowed whole. Treatment should continue until disease progression or unacceptable toxicity occurs.
See prescribing information for full details.

Treatment of adult patients with von Hippel-Lindau (VHL) disease who
require therapy for VHL associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumours (pNET), and for whom localized procedures are unsuitable or undesirable.

Hypersensitivity to the active substance(s) or to any of the excipients.

Anaemia due to decreased erythropoietin
Anaemia occurred very commonly in patients receiving this medical product. Patients should be monitored for anaemia before initiation of and periodically throughout treatment with belzutifan with more frequent monitoring within the first 6 months of treatment. For patients who develop Grade 3 anaemia (Hb < 8 g/dL), belzutifan should be withheld and patients should be treated according to standard medical practice, including ESA administration until resolved to ≤ Grade 2 (Hb ≥ 8 g/dL). For recurrent Grade 3 anaemia, belzutifan should be discontinued. For patients who develop Grade 4 anaemia, the dose of belzutifan should be reduced or permanently discontinued.
Hypoxia
Severe hypoxia may require discontinuation, supplemental oxygen, or
hospitalization.
Patients should be monitored for oxygen saturation with pulse oximetry before initiation of and periodically throughout treatment, with more frequent monitoring within the first 6 months of treatment. In light of the risk of hypoxia, smoking cessation is recommended.
For Grade 2 hypoxia, providing supplemental oxygen and continuing or withholding treatment should be considered. If withheld, belzutifan should be resumed at a reduced dose. For patients who have Grade 3 hypoxia, belzutifan should be withheld, hypoxia treated, and dose reduction should be considered. If Grade 3 hypoxia continues to recur, treatment should be discontinued. For Grade 4 hypoxia, treatment should be permanently discontinued. Patients treated with belzutifan must be given the patient alert card.
Embryo-foetal toxicity
Females of reproductive potential should be advised to use highly effective non-hormonal contraceptive methods during treatment with belzutifan and for 1 week after the last dose, since belzutifan can render some hormonal contraceptives ineffective. Advise male patients and their female partners of reproductive potential to use highly effective contraception during treatment with belzutifan and for 1 week after the last dose. Advise male patients with female partners who are pregnant to use a barrier method of contraception during treatment with belzutifan and 1 week after the last dose.
See prescribing information for full details.

The most common adverse reactions with belzutifan were anaemia (90%), fatigue (71%), dizziness (44%) and nausea (36%). The most common Grade 3 or 4 adverse reactions were anaemia (10%), and fatigue (5%). Serious adverse reactions occurred in 5% of patients who received belzutifan, including anaemia, dyspnoea and hypoxia.
See prescribing information for full details.

Effects of belzutifan on other medicinal products
Coadministration with CYP3A4 substrates, including hormonal contraceptives, decreases concentrations of CYP3A substrates, which may reduce the efficacy of these substrates. The magnitude of this reduction may be more pronounced in patients who are dual UGT2B17 and CYP2C19 poor metabolisers.
Avoid coadministration owith sensitive CYP3A4 substrates, for which minimal decrease in concentration may lead to therapeutic failures of the substrate. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage.
Effects of other medicinal products on belzutifan
Co-administration of belzutifan with inhibitors of UGT2B17 or CYP2C19 increases plasma exposures of belzutifan, which may increase the incidence and severity of adverse reactions of belzutifan. Monitor for anaemia and hypoxia and reduce the dosage of belzutifan as recommended.

Women of child-bearing potential:
Pregnancy Testing The pregnancy status of females of reproductive potential should be verified prior to initiating treatment.
Females of reproductive potential should be advised to use highly effective contraception during treatment with belzutifan and for at least 1 week after the last dose. Use of belzutifan may reduce the efficacy of hormonal contraceptives. Patients using hormonal contraceptives should be advised to use an alternative non-hormonal contraceptive method or have their male partner use a condom during treatment with belzutifan.
Male patients and their female partner of reproductive potential should be advised to use highly effective contraception during male patient treatment with belzutifan and for at least 1 week after the last dose.
Pregnancy: There are no data from the use of belzutifan in pregnant women. Belzutifan is not recommended during pregnancy and in women of childbearing potential not using contraception.
Lactation: It is unknown whether belzutifan or its metabolites are excreted in human milk. A risk to newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with belzutifan and for 1 week after the last dose.
See prescribing information for full details.

There is no specific treatment for belzutifan overdose. In cases of suspected overdose, withhold belzutifan and institute supportive care. The highest dose of belzutifan studied clinically was 240 mg daily (120 mg twice a day or 240 mg once a day). Adverse reactions observed in patients receiving more than 120 mg once a day were generally similar to those observed at other doses except for Grade 3 hypoxia observed at 120 mg twice a day and Grade 4 thrombocytopenia observed at 240 mg once daily.