Welireg

Belzutifan.

WELIREG contains 40 mg of belzutifan.
Belzutifan is an inhibitor of hypoxia-inducible factor-2α (HIF-2α). The chemical name of belzutifan is 3-[[(1S,2S,3R)-2,3-Difluoro-2,3-dihydro-1-hydroxy-7-(methylsulfonyl)-1H-inden-4-yl]oxy]-5-fluorobenzonitrile. The molecular formula is C₁₇H₁₂F₃NO₄S and the molecular weight is 383.34 Daltons.
Belzutifan is a white to light brown powder that is soluble in acetonitrile, dimethoxyethane, and acetone, sparingly soluble in ethyl acetate, very slightly soluble in isopropanol and toluene, and insoluble in water.
Excipients/Inactive Ingredients: WELIREG contains croscarmellose sodium, hypromellose acetate succinate, magnesium stearate, mannitol, microcrystalline cellulose, and silicon dioxide, as inactive ingredients. In addition, the film-coating contains FD&C Blue #2 aluminum lake, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide.

Pharmacology: Mechanism of Action: Belzutifan is an inhibitor of hypoxia-inducible factor 2 alpha (HIF-2α). HIF-2α is a transcription factor that plays a role in oxygen sensing by regulating genes that promote adaptation to hypoxia. Under normal oxygen levels, HIF-2α is targeted for ubiquitin-proteasomal degradation by VHL protein. Lack of functional VHL protein results in stabilization and accumulation of HIF-2α. Upon stabilization, HIF-2α translocates into the nucleus and interacts with hypoxia-inducible factor 1 beta (HIF-1β) to form a transcriptional complex that induces expression of downstream genes, including genes associated with cellular proliferation, angiogenesis, and tumor growth. Belzutifan binds to HIF-2α, and in conditions of hypoxia or impairment of VHL protein function, belzutifan blocks the HIF-2α-HIF-1β interaction, leading to reduced transcription and expression of HIF-2α target genes. In vivo, belzutifan demonstrated anti-tumor activity in mouse xenograft models of renal cell carcinoma.
Pharmacogenomics: Patients who are UGT2B17, CYP2C19, or dual UGT2B17 and CYP2C19 poor metabolizers have 2-, 1.6-, or 3.2-fold higher belzutifan steady state AUC_0-24h (respectively) compared to patients who are UGT2B17 normal (extensive) metabolizers and CYP2C19 non-poor (ultrarapid, rapid, normal, and intermediate) metabolizers [see Dual UGT2B17 and CYP2C19 Poor Metabolizers under Precautions].
UGT2B17 poor metabolizers who are homozygous for the UGT2B17*2 allele have no UGT2B17 enzyme activity. CYP2C19 poor metabolizers (such as *2/*2, *3/*3, *2/*3) have significantly reduced or absent CYP2C19 enzyme activity. Approximately 15% of White, 6% of Black or African American, and up to 77% of certain Asian populations are UGT2B17 poor metabolizers. Approximately 2% of White, 5% of Black or African American, and up to 19% of certain Asian populations are CYP2C19 poor metabolizers. Approximately 0.4% of White, 0.3% of Black or African American, and up to 15% of certain Asian populations are dual UGT2B17 and CYP2C19 poor metabolizers.
Pharmacodynamics: Reductions in plasma levels of erythropoietin (EPO) were observed to be dose- and exposure-dependent at dosages up to 120 mg once daily. The maximum EPO suppression occurred following 2 weeks of consecutive dosing of WELIREG (mean percent decrease from baseline of approximately 60%). Mean EPO levels gradually returned to baseline values after 12 weeks of treatment.
The incidence of Grade 3 anemia increased with higher belzutifan exposure in patients with baseline hemoglobin levels <12 g/dL [see Anemia under Precautions].
Cardiac Electrophysiology: At the recommended dosage, WELIREG does not cause large mean increases (i.e., >20 msec) in the QT interval.
Clinical Studies: The efficacy of WELIREG was evaluated in Study 004 (NCT03401788), an open-label clinical trial in 61 patients with VHL-associated RCC diagnosed based on a VHL germline alteration and with at least one measurable solid tumor localized to the kidney as defined by response evaluation criteria in solid tumors (RECIST) v1.1. Enrolled patients had other VHL-associated tumors including CNS hemangioblastomas and pNET. CNS hemangioblastomas and pNET in these patients were diagnosed based on the presence of at least one measurable solid tumor in brain/spine or pancreas, respectively, as defined by RECIST v1.1 and identified by IRC. The study excluded patients with metastatic disease. Patients received WELIREG 120 mg once daily until progression of disease or unacceptable toxicity.
The study population characteristics were: median age 41 years [range 19-66 years], 3.3% age 65 or older; 53% male; 90% were White, 3.3% were Black or African-American, 1.6% were Asian, and 1.6% were Native Hawaiian or other Pacific Islander; 82% had an ECOG PS of 0, 16% had an ECOG PS of 1, and 1.6% had an ECOG PS of 2; and 84% had VHL Type I Disease. The median diameter of RCC target lesions per central independent review committee (IRC) was 2.2 cm (range 1-6.1). Median time from initial radiographic diagnosis of VHL-associated RCC tumors that led to enrollment on Study 004 to the time of treatment with WELIREG was 17.9 months (range 2.8-96.7). Seventy-seven percent of patients had prior surgical procedures for RCC.
The major efficacy endpoint for the treatment of VHL-associated RCC was overall response rate (ORR) measured by radiology assessment using RECIST v1.1 as assessed by IRC. Additional efficacy endpoints included duration of response (DoR), and time to response (TTR).
Table 1 summarizes the efficacy results for VHL-associated RCC in Study 004. (See Table 1.)

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For VHL-associated RCC, median TTR was 8 months (range 2.7, 19).
Table 2 summarizes the efficacy results for VHL-associated pNET or CNS hemangioblastomas in Study 004. (See Table 2.)

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For VHL-associated CNS hemangioblastomas, TTR was 3.1 months (range 2.5, 11). For VHL-associated pNET, median TTR was 8.1 months (range 2.7, 11).
Decreases in size of CNS hemangioblastoma-associated peri-tumoral cysts and syringes were observed.
Pharmacokinetics: The mean steady-state (CV%) C_max is 1.3 μg/mL (42%) and AUC_0-24h is 16.7 μg·hr/mL (52%) in patients with VHL disease-associated RCC. Steady state is reached after approximately 3 days. C_max and AUC increase proportionally over a dose range of 20 mg to 120 mg (0.17 to 1 times the approved recommended dose).
Absorption: The median T_max occurs at 1 to 2 hours after administration.
Effect of Food: A high-fat, high-calorie meal (total calories approximately 1000 kcal, 56 g fat, 55 g carbohydrate, and 31 g protein) delayed time to reach peak belzutifan concentration by approximately 2 hours, had no clinically meaningful effect on C_max, and had no effect on AUC.
Distribution: The mean (CV%) steady-state volume of distribution is 130 L (35%). Plasma protein binding of belzutifan is 45%. The blood-to-plasma concentration ratio of belzutifan is 0.88.
Elimination: The mean (CV%) clearance is 7.3 L/hr (51%) and the mean elimination half-life is 14 hrs.
Metabolism: Belzutifan is primarily metabolized by UGT2B17 and CYP2C19 and to a lesser extent by CYP3A4 [see Pharmacogenomics as previously mentioned].
Specific Populations: Patients who are poor metabolizers of UGT2B17 and CYP2C19 had higher belzutifan AUC [see Pharmacogenomics as previously mentioned].
There were no clinically significant differences in the pharmacokinetics of belzutifan based on age (19 to 84 years), sex, ethnicity (non-Hispanic, Hispanic), race (White, Black, Asian, Pacific Islander), body weight (42 to 166 kg), mild to moderate renal impairment (eGFR 30-89 mL/min/1.73 m² estimated by MDRD), or mild hepatic impairment (total bilirubin ≤ ULN with AST > ULN or total bilirubin > ULN to 1.5 x ULN with any AST). The effect of severe renal impairment (eGFR 15-29 mL/min/1.73 m²) and moderate to severe hepatic impairment (total bilirubin >1.5 x ULN and any AST) have not been studied.
Drug Interaction Studies: Clinical Studies and Model-Informed Approaches: Effect of Belzutifan on CYP3A Substrates: Co-administration of WELIREG 120 mg once daily with midazolam (a sensitive CYP3A4 substrate) decreased the midazolam AUC by 40% and the C_max by 34%. Midazolam AUC is predicted to decrease up to 70% in patients with higher belzutifan concentrations (e.g., dual poor metabolizers) [see Pharmacogenomics as previously mentioned].
In Vitro Studies: Cytochrome P450 (CYP) Enzymes: Belzutifan does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4.
Belzutifan does not induce CYP1A2 or CYP2B6.
Transporter Systems: Belzutifan is a substrate of P-gp, OATP1B1, and OATP1B3, but is not a substrate of BCRP.
Belzutifan inhibits MATE2K. Belzutifan does not inhibit P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, OCT2, or MATE1.
Toxicology: Nonclinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenicity studies have not been conducted with belzutifan.
Belzutifan was not mutagenic in the in vitro bacterial reverse mutation (Ames) assay. Belzutifan was not clastogenic in either an in vitro micronucleus assay or an in vivo rat bone marrow micronucleus assay.
Fertility studies in animals have not been conducted with belzutifan. In repeat-dose toxicity studies up to 3-month duration, belzutifan-related findings included degeneration/atrophy of testes and hypospermia and cellular debris of the epididymis in rats administered ≥2 mg/kg/day (approximately 0.1 times the human exposure at the recommended dose of 120 mg daily). Findings in testes and epididymis were associated with decreased sperm count and motility and abnormal sperm morphology at ≥6 mg/kg/day (approximately 0.2 times the human exposure at the recommended dose of 120 mg daily) and did not reverse by the end of the recovery period. Belzutifan had no adverse effects on female reproductive organs in repeat-dose toxicity studies up to 3-month duration; however, belzutifan caused embryo-fetal lethality (post-implantation loss) in pregnant rats given oral doses ≥60 mg/kg/day (approximately 1 time the human exposure at the recommended dose based on AUC) during the period of organogenesis [see Pregnancy under Use in Pregnancy & Lactation].

WELIREG is indicated for 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), not requiring immediate surgery.

Recommended Dosage: The recommended dosage of WELIREG is 120 mg administered orally once daily until disease progression or unacceptable toxicity. WELIREG should be taken at the same time each day and may be taken with or without food.
Advise patients to swallow tablets whole. Do not chew, crush, or split WELIREG prior to swallowing.
If a dose of WELIREG is missed, it can be taken as soon as possible on the same day. Resume the regular daily dose schedule for WELIREG the next day. Do not take extra tablets to make up for the missed dose.
If vomiting occurs any time after taking WELIREG, do not retake the dose. Take the next dose on the next day.
Dosage Modifications for Adverse Reactions: Dosage modifications for WELIREG for adverse reactions are summarized in Table 3. (See Table 3.)
The recommended dose reductions are: First dose reduction: WELIREG 80 mg orally once daily.
Second dose reduction: WELIREG 40 mg orally once daily.
Third dose reduction: Permanently discontinue.

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There is no specific treatment for WELIREG overdose. In cases of suspected overdose, withhold WELIREG and institute supportive care. Grade 3 hypoxia occurred at dosages of 120 mg twice a day and Grade 4 thrombocytopenia occurred at dosages of 240 mg once daily (approximately 2 times the recommended dosage).

None.

Embryo-Fetal Toxicity: Exposure to WELIREG during pregnancy can cause embryo-fetal harm.
Verify pregnancy status prior to the initiation of WELIREG.
Advise patients of these risks and the need for effective non-hormonal contraception. WELIREG can render some hormonal contraceptives ineffective [see Embryo-Fetal Toxicity under Precautions; Effect of WELIREG on Other Drugs under Interactions; Pregnancy and Females and Males of Reproductive Potential under Use in Pregnancy & Lactation].

Anemia: WELIREG can cause severe anemia that can require blood transfusion.
In Study 004, anemia occurred in 90% of patients and 7% had Grade 3 anemia [see Clinical Trials Experience under Adverse Reactions]. 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 WELIREG, anemia occurred in 76% of patients and 28% had Grade 3 anemia.
Monitor for anemia before initiation of, and periodically throughout, treatment with WELIREG. 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 [see Pharmacology: Pharmacogenomics under Actions].
Transfuse patients as clinically indicated. For patients with hemoglobin <9 g/dL, withhold WELIREG until ≥9 g/dL, then resume at reduced dose or permanently discontinue WELIREG, depending on the severity of anemia. For life-threatening anemia or when urgent intervention is indicated, withhold WELIREG until hemoglobin ≥9 g/dL, then resume at a reduced dose or permanently discontinue WELIREG [see Dosage Modifications for Adverse Reactions under Dosage & Administration].
The use of erythropoiesis stimulating agents (ESAs) for treatment of anemia is not recommended in patients treated with WELIREG. For patients treated with WELIREG 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.
Hypoxia: WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization [see Dosage Modifications for Adverse Reactions under Dosage & Administration].
In Study 004, hypoxia occurred in 1.6% of patients [see Clinical Trials Experience under Adverse Reactions]. In another clinical trial [Study 001 (n=58)] in patients with advanced solid tumors who received the same dosage of WELIREG, hypoxia occurred in 29% of patients, including Grade 3 hypoxia in 16%.
Monitor oxygen saturation before initiation of, and periodically throughout, treatment with WELIREG. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or PaO₂ ≤55 mmHg), consider withholding WELIREG 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 mmHg) or urgent intervention indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening hypoxia or for recurrent symptomatic hypoxia, permanently discontinue WELIREG [see Dosage Modifications for Adverse Reactions under Dosage & Administration].
Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider.
Embryo-Fetal Toxicity: 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 [see Effect of WELIREG on Other Drugs under Interactions]. 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 [see Pregnancy and Females and Males of Reproductive Potential under Use in Pregnancy & Lactation].
Renal Impairment: No dosage modification of WELIREG is recommended in patients with mild (eGFR 60-89 mL/min/1.73 m² estimated by MDRD) and moderate (eGFR 30-59 mL/min/1.73 m²) renal impairment [see Pharmacology: Pharmacokinetics under Actions]. WELIREG has not been studied in patients with severe (eGFR 15-29 mL/min/1.73 m²) renal impairment.
Hepatic Impairment: No dosage modification of WELIREG is recommended in patients with mild [total bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN or total bilirubin >1 to 1.5 x ULN and any AST] hepatic impairment. WELIREG has not been studied in patients with moderate or severe hepatic impairment (total bilirubin >1.5 x ULN and any AST) [see Pharmacology: Pharmacokinetics under Actions].
Dual UGT2B17 and CYP2C19 Poor Metabolizers: Patients who are dual UGT2B17 and CYP2C19 poor metabolizers have higher belzutifan exposures, which may increase the incidence and severity of adverse reactions of WELIREG. Closely monitor for adverse reactions in patients who are dual UGT2B17 and CYP2C19 poor metabolizers [see as previously mentioned; Adverse Reactions; Pharmacology: Pharmacogenomics under Actions].
Use in Children: Safety and effectiveness of WELIREG have not been established in pediatric patients.
Use in the Elderly: Of the patients who received WELIREG in Study 004, 3.3% were ≥65 years old [see Pharmacology: Pharmacodynamics: Clinical Studies under Actions]. Clinical trials of WELIREG did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger patients.

Pregnancy: Risk Summary: Based on findings in animal studies, WELIREG can cause fetal harm when administered to a pregnant woman. There are no available data on the use of WELIREG in pregnant women to inform the drug-associated risk. 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 exposure (AUC) at the recommended dose of 120 mg daily (see Data as follows). Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data: Animal Data: In a pilot embryo-fetal development study, pregnant rats received oral doses of 6, 60, or 200 mg/kg/day of belzutifan during the period of organogenesis. Belzutifan caused embryo-fetal lethality at doses ≥60 mg/kg/day (approximately 1 time the human exposure at the recommended dose based on AUC). Reduced fetal body weights, fetal rib malformations, and reduced skeletal ossification occurred at doses of 6 and 60 mg/kg/day (approximately ≥0.2 times the human exposure at the recommended dose based on AUC).
Lactation: Risk Summary: There are no data on the presence of belzutifan or its metabolites in human milk or their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose.
Females and Males of Reproductive Potential: WELIREG can cause fetal harm when administered to a pregnant woman [see Pregnancy as previously mentioned].
Pregnancy Testing: Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG.
Contraception: Females: Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective [see Effect of WELIREG on Other Drugs under Interactions].
Males: Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.
Infertility: Based on findings in animals, WELIREG may impair fertility in males and females of reproductive potential [see Pharmacology: Toxicology: Nonclinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility under Actions]. The reversibility of the effect on fertility is unknown.

The following clinically significant adverse reactions are discussed in Precautions: Anemia; Hypoxia.
Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of WELIREG was evaluated in an open-label clinical trial (Study 004) in 61 patients with VHL disease who had at least one measurable solid tumor localized to the kidney [see Pharmacology: Pharmacodynamics: Clinical Studies under Actions]. Patients received WELIREG 120 mg orally once daily. The median duration of exposure to WELIREG was 68 weeks (range: 8.4 to 104.7 weeks).
Serious adverse reactions occurred in 15% of patients who received WELIREG, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each).
Permanent discontinuation of WELIREG due to adverse reactions occurred in 3.3% of patients. Adverse reactions which resulted in permanent discontinuation of WELIREG were dizziness and opioid overdose (1.6% each).
Dosage interruptions of WELIREG due to an adverse reaction occurred in 39% of patients. Adverse reactions which required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness.
Dose reductions of WELIREG due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction which required dose reduction was fatigue (7%).
The most common (≥25%) adverse reactions, including laboratory abnormalities, that occurred in patients who received WELIREG were decreased hemoglobin, anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea.
Table 4 summarizes the adverse reactions reported in patients treated with WELIREG in Study 004. (See Table 4.)

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Table 5 summarizes the laboratory abnormalities in Study 004. (See Table 5.)

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Other Clinical Trials Experience: In Study 001 (NCT02974738), a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose in which the median age of enrollment was 62.5 years (range 39-75) and the median number of prior therapies for cancer was 3 (range 1-9), the following additional adverse reactions have been reported following administration of WELIREG at the recommended dosage: edema, cough, musculoskeletal pain, vomiting, diarrhea, and dehydration.

Effects of Other Drugs on WELIREG: UGT2B17 or CYP2C19 Inhibitors: Co-administration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan [see Pharmacology: Pharmacokinetics and Pharmacogenomics under Actions], which may increase the incidence and severity of adverse reactions of WELIREG. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended [see Dosage Modifications for Adverse Reactions under Dosage & Administration; Anemia and Hypoxia under Precautions; Adverse Reactions].
Effect of WELIREG on Other Drugs: Sensitive CYP3A4 Substrates: Co-administration of WELIREG with CYP3A4 substrates decreases concentrations of CYP3A substrates [see Pharmacology: Pharmacokinetics under Actions], which may reduce the efficacy of these substrates. The magnitude of this decrease may be more pronounced in patients who are dual UGT2B17 and CYP2C19 poor metabolizers [see Pharmacology: Pharmacokinetics under Actions]. Avoid co-administration of WELIREG with sensitive CYP3A4 substrates, for which minimal decrease in concentration may lead to therapeutic failures of the substrate. If co-administration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information.
Hormonal Contraceptives: Co-administration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding [see Pharmacology: Pharmacokinetics under Actions; Females and Males of Reproductive Potential under Use in Pregnancy & Lactation].

Store at or below 30°C.

Advise the patient to read the patient labeling (Medication Guide).
Anemia: Inform patients that WELIREG can cause severe anemia that may require blood transfusions and that red blood cell levels will be monitored routinely during treatment. Advise patients to contact their healthcare provider if the patient experiences any symptoms suggestive of anemia [see Anemia under Precautions].
Hypoxia: Inform patients that WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization; and that oxygen levels will be monitored routinely during treatment. Advise patients to contact their healthcare provider if the patient experiences any symptoms suggestive of hypoxia [see Hypoxia under Precautions].
Embryo-Fetal Toxicity: Advise pregnant women and females of reproductive potential of the risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Embryo-Fetal Toxicity under Precautions; Pregnancy under Use in Pregnancy & Lactation].
Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose [see Females and Males of Reproductive Potential under Use in Pregnancy & Lactation].
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 [see Females and Males of Reproductive Potential under Use in Pregnancy & Lactation].
Lactation: Advise females not to breastfeed during treatment with WELIREG and for 1 week after the last dose [see Lactation under Use in Pregnancy & Lactation].
Infertility: Advise male and female patients that WELIREG may impair fertility [see Females and Males of Reproductive Potential under Use in Pregnancy & Lactation].
Dosage and Administration: Instruct patients to take their dose of WELIREG at the same time each day (once daily). Advise patients that WELIREG can be taken with or without food. Each tablet should be swallowed whole [see Recommended Dosage under Dosage & Administration].

Targeted Cancer Therapy

L01XX74 - belzutifan ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.

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