Belzutifan is an orally active, small molecule inhibitor of hypoxia-inducible factor (HIF)-2alpha (HIF-2a), with potential antineoplastic activity. Upon oral administration, belzutifan binds to and blocks the function of HIF-2alpha, thereby preventing HIF-2alpha heterodimerization and its subsequent binding to DNA. This results in decreased transcription and expression of HIF-2alpha downstream target genes, many of which regulate hypoxic signaling. This inhibits cell growth and survival of HIF-2alpha-expressing tumor cells. HIF-2alpha, the alpha subunit for the heterodimeric transcription factor HIF-2, is overexpressed in many cancers and promotes tumorigenesis.
Belzutifan is an inhibitor of hypoxia-inducible factor 2α (HIF-2α) used in the treatment of von Hippel-Lindau (VHL) disease-associated cancers. The HIF-2α protein was first identified in the 1990s by researchers at UT Southwestern Medical Center as a key player in the growth of certain cancers. Initially considered to be undruggable, a binding pocket was eventually discovered in the HIF-2α molecule which allowed for compounds to bind and inhibit these proteins. This discovery led to the initial development of belzutifan (at the time called PT2977), which was further developed by a spin-off company named Peloton Pharmaceuticals (which itself was eventually acquired by Merck in 2019). Belzutifan inhibits the complexation of HIF-2α with another transcription factor, HIF-1β, a necessary step in its activation – by preventing the formation of this complex, belzutifan can slow or stop the growth of VHL-associated tumors. Belzutifan received FDA approval for the treatment of select VHL-associated cancers on August 13, 2021.
Mechanism of Action
Hypoxia-inducible factor 2α (HIF-2α) is a transcription factor that aids in oxygen sensing by regulating genes that promote adaptation to hypoxia. In healthy patients, when oxygen levels are normal, HIF-2α is broken down via ubiquitin-proteasomal degradation by von-Hippel Lindau (VHL) proteins. In the presence of hypoxia, HIF-2α translocates into cell nuclei and forms a transcriptional complex with hypoxia-inducible factor 1β (HIF-1β) – this complex then induces the expression of downstream genes associated with cellular proliferation and angiogenesis. Patients with von-Hippel Lindau (VHL) disease lack functional VHL proteins, leading to an accumulation of HIF-2α, and this accumulation is what drives the growth of VHL-associated tumors. Belzutifan is an inhibitor of HIF-2α that prevents its complexation with HIF-1β in conditions of hypoxia or impaired VHL protein function, thereby reducing the expression of HIF-2α target genes and slowing/stopping the growth of VHL-associated tumors.
Belzutifan exerts its therapeutic effects by inhibiting a transcription factor necessary for the growth of solid tumors associated with VHL disease. It is taken once daily at approximately the same time each day, with or without food. Both severe anemia and hypoxia have been observed following therapy with belzutifan, and patients should be monitored closely before and during therapy to ensure patients can be managed as clinically indicated. There are no data regarding the use of erythropoiesis-stimulating agents for the treatment of belzutifan-induced anemia, and as such these therapies should be avoided. Belzutifan may cause embryo-fetal toxicity when administered to pregnant women. Female patients and male patients with female partners of reproductive potential should ensure that an effective form of contraception is used throughout therapy and for one week after the last dose – as belzutifan appears to decrease the efficacy of systemic hormonal contraceptives, patients should be advised to use an additional method of contraception (e.g. condoms) to eliminate the possibility of pregnancy during therapy.
Indications
Belzutifan is indicated for the 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), who do not require immediate surgery.
- Cancers linked to Von Hippel-Lindau disease that require treatment but not immediate surgery, including:
- Central nervous system hemangioblastoma.
- Pancreatic neuroendocrine tumors
- Renal cell carcinoma.
- Hemangioblastoma
- Pancreatic Neuroendocrine Cancer
- Renal Cell Carcinoma
Use in Cancer
Belzutifan is approved to treat adults with:
- Cancers linked to Von Hippel-Lindau disease that require treatment but not immediate surgery, including:
- Central nervous system hemangioblastoma.
- Pancreatic neuroendocrine tumors.
- Renal cell carcinoma.
Belzutifan is also being studied in the treatment of other types of cancer.
Contraindication
The following conditions are contraindicated with this drug. Check with your physician if you have any of the following:
- anemia
- decreased oxygen in the tissues or blood
- pregnancy
- a patient who is producing milk and breastfeeding
Dosage
Strengths: 40 mg
Von Hippel-Lindau Syndrome
- 120 mg orally once daily until disease progression or unacceptable toxicity
Renal Dose Adjustments
- Mild (CrCl 60 to less than 90 mL/min) to moderate (CrCl 30 to less than 60 mL/min) renal dysfunction: No adjustment recommended.
Severe (CrCl 15 to 30 mL/min) to end-stage renal dysfunction: Data not available
Liver Dose Adjustments
- Mild (total bilirubin upper limit of normal [ULN] or less and aspartate aminotransferase [AST] greater than ULN or total bilirubin greater than 1 to 1.5 x ULN and any AST) hepatic impairment: No adjustment recommended.
Moderate to severe (total bilirubin greater than 1.5 x ULN and any AST) hepatic impairment: Data not available
Dose Adjustments
Recommended Dose Reductions:
- First dose reduction: 80 mg orally once daily
- Second dose reduction: 40 mg orally once daily
- Third dose reduction: Permanently discontinue therapy.
Dose Modifications for Adverse Reactions:
ANEMIA:
- Hemoglobin less than 9 g/dL or transfusion indicated: Withhold therapy until hemoglobin 9 g/dL or greater; resume at reduced dose or discontinue depending on the severity of anemia
- Life-threatening or urgent intervention indicated: Withhold therapy until hemoglobin 9 g/dL or greater; resume at reduced dose or permanently discontinue
HYPOXIA:
- Decreased oxygen saturation with exercise (e.g., pulse oximeter less than 88%): Consider withholding therapy until resolved; resume at the same dose or at a reduced dose depending on the severity of hypoxia.
- Decreased oxygen saturation at rest (e.g., pulse oximeter less than 88% or partial pressure of oxygen (PaO2) 55 mm Hg or less) or urgent intervention indicated: Withhold therapy until resolved; resume at reduced dose or discontinue depending on the severity of hypoxia
Side Effects
The Most Common
- dizziness
- tiredness
- headache
- nausea
- constipation
- stomach pain
- joint or muscle pain
- vision changes
- weight gain
- fever, cough, shortness of breath, or other signs of infection
- tiredness, feeling cold, pale skin, shortness of breath, chest pain, or fast heartbeat
More common
- Body aches or pain
- chills
- constipation
- difficulty in moving
- ear congestion
- fever
- loss of voice
- muscle aches, cramps, pain, or stiffness
- nausea
- pain in the joints
- sneezing
- sore throat
- stomach pain
- stuffy or runny nose
- swollen joints
- weight increased
Rare
- change in vision
- chest tightness
- confusion
- cough
- difficulty swallowing
- dizziness
- fast heartbeat
- headache
- hives, itching, skin rash
- nervousness
- pale skin
- pounding in the ears
- puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
- seeing flashes or sparks of light
- seeing floating spots before the eyes, or a veil or curtain appearing across part of vision
- trouble breathing
- unusual bleeding or bruising
- unusual tiredness or weakness
Drug Interaction
DRUG | INTERACTION |
---|---|
Abatacept | The metabolism of Belzutifan can be increased when combined with Abatacept. |
Abemaciclib | The serum concentration of Abemaciclib can be decreased when it is combined with Belzutifan. |
Abiraterone | The serum concentration of Belzutifan can be increased when it is combined with Abiraterone. |
Abrocitinib | The metabolism of Belzutifan can be decreased when combined with Abrocitinib. |
Acalabrutinib | The serum concentration of Acalabrutinib can be decreased when it is combined with Belzutifan. |
Acenocoumarol | The serum concentration of Acenocoumarol can be decreased when it is combined with Belzutifan. |
Adalimumab | The metabolism of Belzutifan can be increased when combined with Adalimumab. |
Albendazole | The metabolism of Belzutifan can be decreased when combined with Albendazole. |
Alectinib | The serum concentration of Alectinib can be decreased when it is combined with Belzutifan. |
Alpelisib | The serum concentration of Alpelisib can be decreased when it is combined with Belzutifan. |
Aminophenazone | The serum concentration of Belzutifan can be increased when it is combined with Aminophenazone. |
Aminophylline | The serum concentration of Aminophylline can be decreased when it is combined with Belzutifan. |
Amiodarone | The serum concentration of Amiodarone can be decreased when it is combined with Belzutifan. |
Amitriptyline | The serum concentration of Belzutifan can be increased when it is combined with Amitriptyline. |
Amprenavir | The serum concentration of Belzutifan can be increased when it is combined with Amprenavir. |
Anakinra | The metabolism of Belzutifan can be increased when combined with Anakinra. |
Antipyrine | The serum concentration of Belzutifan can be increased when it is combined with Antipyrine. |
Apalutamide | The serum concentration of Belzutifan can be increased when it is combined with Apalutamide. |
Apixaban | The metabolism of Belzutifan can be decreased when combined with Apixaban. |
Apremilast | The metabolism of Belzutifan can be increased when combined with Apremilast. |
Aprepitant | The serum concentration of Belzutifan can be increased when it is combined with Aprepitant. |
Armodafinil | The serum concentration of Belzutifan can be increased when it is combined with Armodafinil. |
Artemether | The metabolism of Belzutifan can be decreased when combined with Artemether. |
Artenimol | The serum concentration of Belzutifan can be increased when it is combined with Artenimol. |
Articaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Articaine. |
Asciminib | The metabolism of Belzutifan can be decreased when combined with Asciminib. |
Astemizole | The serum concentration of Astemizole can be decreased when it is combined with Belzutifan. |
Axitinib | The serum concentration of Axitinib can be decreased when it is combined with Belzutifan. |
Azelastine | The serum concentration of Belzutifan can be increased when it is combined with Azelastine. |
Benzocaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Benzocaine. |
Benzyl alcohol | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Benzyl alcohol. |
Bicalutamide | The serum concentration of Bicalutamide can be decreased when it is combined with Belzutifan. |
Bimekizumab | The metabolism of Belzutifan can be increased when combined with Bimekizumab. |
Bortezomib | The serum concentration of Bortezomib can be decreased when it is combined with Belzutifan. |
Bosutinib | The serum concentration of Bosutinib can be decreased when it is combined with Belzutifan. |
Brentuximab vedotin | The serum concentration of Brentuximab vedotin can be decreased when it is combined with Belzutifan. |
Brigatinib | The serum concentration of Brigatinib can be decreased when it is combined with Belzutifan. |
Bupivacaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Bupivacaine. |
Buprenorphine | The serum concentration of Belzutifan can be increased when it is combined with Buprenorphine. |
Busulfan | The serum concentration of Busulfan can be decreased when it is combined with Belzutifan. |
Butacaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Butacaine. |
Butamben | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Butamben. |
Cabazitaxel | The serum concentration of Cabazitaxel can be decreased when it is combined with Belzutifan. |
Cabergoline | The serum concentration of Cabergoline can be decreased when it is combined with Belzutifan. |
Canakinumab | The metabolism of Belzutifan can be increased when combined with Canakinumab. |
Cannabidiol | The serum concentration of Belzutifan can be increased when it is combined with Cannabidiol. |
Capsaicin | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Capsaicin. |
Carbamazepine | The serum concentration of Carbamazepine can be decreased when it is combined with Belzutifan. |
Carisoprodol | The metabolism of Belzutifan can be decreased when combined with Carisoprodol. |
Cenobamate | The serum concentration of Belzutifan can be increased when it is combined with Cenobamate. |
Ceritinib | The serum concentration of Ceritinib can be decreased when it is combined with Belzutifan. |
Certolizumab pegol | The metabolism of Belzutifan can be increased when combined with Certolizumab pegol. |
Chloramphenicol | The serum concentration of Belzutifan can be increased when it is combined with Chloramphenicol. |
Chloroprocaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Chloroprocaine. |
Cimetidine | The serum concentration of Belzutifan can be increased when it is combined with Cimetidine. |
Cinchocaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Cinchocaine. |
Citalopram | The serum concentration of Belzutifan can be increased when it is combined with Citalopram. |
Clevidipine | The serum concentration of Belzutifan can be increased when it is combined with Clevidipine. |
Clobazam | The metabolism of Belzutifan can be decreased when combined with Clobazam. |
Clomipramine | The serum concentration of Clomipramine can be decreased when it is combined with Belzutifan. |
Clonidine | The serum concentration of Clonidine can be decreased when it is combined with Belzutifan. |
Clopidogrel | The metabolism of Belzutifan can be decreased when combined with Clopidogrel. |
Clozapine | The serum concentration of Belzutifan can be increased when it is combined with Clozapine. |
Cobimetinib | The serum concentration of Cobimetinib can be decreased when it is combined with Belzutifan. |
Cocaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Cocaine. |
Conivaptan | The serum concentration of Conivaptan can be decreased when it is combined with Belzutifan. |
Copanlisib | The serum concentration of Copanlisib can be decreased when it is combined with Belzutifan. |
Crizotinib | The serum concentration of Crizotinib can be decreased when it is combined with Belzutifan. |
Cyclophosphamide | The serum concentration of Cyclophosphamide can be decreased when it is combined with Belzutifan. |
Cyclosporine | The serum concentration of Cyclosporine can be decreased when it is combined with Belzutifan. |
Cyproterone acetate | The therapeutic efficacy of Cyproterone acetate can be decreased when used in combination with Belzutifan. |
Dabrafenib | The serum concentration of Dabrafenib can be decreased when it is combined with Belzutifan. |
Dacomitinib | The serum concentration of Dacomitinib can be decreased when it is combined with Belzutifan. |
Darbepoetin alfa | The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Belzutifan. |
Dasatinib | The serum concentration of Dasatinib can be decreased when it is combined with Belzutifan. |
Delavirdine | The serum concentration of Belzutifan can be increased when it is combined with Delavirdine. |
Desogestrel | The therapeutic efficacy of Desogestrel can be decreased when used in combination with Belzutifan. |
Dexlansoprazole | The metabolism of Belzutifan can be decreased when combined with Dexlansoprazole. |
Diazepam | The serum concentration of Belzutifan can be increased when it is combined with Diazepam. |
Dienogest | The therapeutic efficacy of Dienogest can be decreased when used in combination with Belzutifan. |
Diethylstilbestrol | The therapeutic efficacy of Diethylstilbestrol can be decreased when used in combination with Belzutifan. |
Digitoxin | The serum concentration of Digitoxin can be decreased when it is combined with Belzutifan. |
Dihydroergotamine | The serum concentration of Dihydroergotamine can be decreased when it is combined with Belzutifan. |
Dimethyl sulfoxide | The serum concentration of Belzutifan can be increased when it is combined with Dimethyl sulfoxide. |
Diphenhydramine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Diphenhydramine. |
Docetaxel | The serum concentration of Docetaxel can be decreased when it is combined with Belzutifan. |
Dofetilide | The serum concentration of Dofetilide can be decreased when it is combined with Belzutifan. |
Dosulepin | The serum concentration of Belzutifan can be increased when it is combined with Dosulepin. |
Doxazosin | The metabolism of Belzutifan can be decreased when combined with Doxazosin. |
Doxepin | The metabolism of Belzutifan can be decreased when combined with Doxepin. |
Doxorubicin | The serum concentration of Doxorubicin can be decreased when it is combined with Belzutifan. |
Dronabinol | The metabolism of Belzutifan can be decreased when combined with Dronabinol. |
Dronedarone | The serum concentration of Dronedarone can be decreased when it is combined with Belzutifan. |
Drospirenone | The therapeutic efficacy of Drospirenone can be decreased when used in combination with Belzutifan. |
Dyclonine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Dyclonine. |
Efavirenz | The serum concentration of Belzutifan can be increased when it is combined with Efavirenz. |
Elagolix | The serum concentration of Belzutifan can be increased when it is combined with Elagolix. |
Emapalumab | The metabolism of Belzutifan can be increased when combined with Emapalumab. |
Enasidenib | The serum concentration of Enasidenib can be decreased when it is combined with Belzutifan. |
Entrectinib | The serum concentration of Entrectinib can be decreased when it is combined with Belzutifan. |
Enzalutamide | The serum concentration of Belzutifan can be decreased when it is combined with Enzalutamide. |
Erdafitinib | The serum concentration of Erdafitinib can be decreased when it is combined with Belzutifan. |
Ergotamine | The serum concentration of Ergotamine can be decreased when it is combined with Belzutifan. |
Erlotinib | The serum concentration of Erlotinib can be decreased when it is combined with Belzutifan. |
Erythropoietin | The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Belzutifan. |
Escitalopram | The metabolism of Belzutifan can be decreased when combined with Escitalopram. |
Esketamine | The metabolism of Belzutifan can be decreased when combined with Esketamine. |
Eslicarbazepine | The serum concentration of Belzutifan can be increased when it is combined with Eslicarbazepine. |
Eslicarbazepine acetate | The serum concentration of Belzutifan can be increased when it is combined with Eslicarbazepine acetate. |
Esomeprazole | The serum concentration of Belzutifan can be increased when it is combined with Esomeprazole. |
Estradiol | The therapeutic efficacy of Estradiol can be decreased when used in combination with Belzutifan. |
Estradiol benzoate | The therapeutic efficacy of Estradiol benzoate can be decreased when used in combination with Belzutifan. |
Estradiol cypionate | The therapeutic efficacy of Estradiol cypionate can be decreased when used in combination with Belzutifan. |
Estradiol valerate | The therapeutic efficacy of Estradiol valerate can be decreased when used in combination with Belzutifan. |
Estrone sulfate | The therapeutic efficacy of Estrone sulfate can be decreased when used in combination with Belzutifan. |
Etanercept | The metabolism of Belzutifan can be increased when combined with Etanercept. |
Ethambutol | The metabolism of Belzutifan can be decreased when combined with Ethambutol. |
Ethanol | The serum concentration of Belzutifan can be increased when it is combined with Ethanol. |
Ethinylestradiol | The serum concentration of Belzutifan can be increased when it is combined with Ethinylestradiol. |
Ethyl chloride | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Ethyl chloride. |
Ethynodiol diacetate | The therapeutic efficacy of Ethynodiol diacetate can be decreased when used in combination with Belzutifan. |
Etidocaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Etidocaine. |
Etonogestrel | The therapeutic efficacy of Etonogestrel can be decreased when used in combination with Belzutifan. |
Etoposide | The serum concentration of Etoposide can be decreased when it is combined with Belzutifan. |
Etoricoxib | The serum concentration of Belzutifan can be increased when it is combined with Etoricoxib. |
Etravirine | The serum concentration of Belzutifan can be increased when it is combined with Etravirine. |
Everolimus | The serum concentration of Everolimus can be decreased when it is combined with Belzutifan. |
Fedratinib | The metabolism of Belzutifan can be decreased when combined with Fedratinib. |
Felbamate | The serum concentration of Belzutifan can be increased when it is combined with Felbamate. |
Fenofibrate | The serum concentration of Belzutifan can be increased when it is combined with Fenofibrate. |
Fexinidazole | The serum concentration of Belzutifan can be increased when it is combined with Fexinidazole. |
Fluconazole | The serum concentration of Belzutifan can be increased when it is combined with Fluconazole. |
Fluoxetine | The serum concentration of Belzutifan can be increased when it is combined with Fluoxetine. |
Fluvastatin | The serum concentration of Belzutifan can be increased when it is combined with Fluvastatin. |
Fluvoxamine | The serum concentration of Belzutifan can be increased when it is combined with Fluvoxamine. |
Formoterol | The metabolism of Belzutifan can be decreased when combined with Formoterol. |
Fosphenytoin | The serum concentration of Fosphenytoin can be decreased when it is combined with Belzutifan. |
Gemfibrozil | The serum concentration of Belzutifan can be increased when it is combined with Gemfibrozil. |
Gestrinone | The therapeutic efficacy of Gestrinone can be decreased when used in combination with Belzutifan. |
Gliclazide | The metabolism of Belzutifan can be decreased when combined with Gliclazide. |
Glyburide | The metabolism of Belzutifan can be decreased when combined with Glyburide. |
Golimumab | The metabolism of Belzutifan can be increased when combined with Golimumab. |
Hydroxyprogesterone | The therapeutic efficacy of Hydroxyprogesterone caproate can be decreased when used in combination with Belzutifan. |
Idelalisib | The serum concentration of Idelalisib can be decreased when it is combined with Belzutifan. |
Ifosfamide | The serum concentration of Ifosfamide can be decreased when it is combined with Belzutifan. |
Imatinib | The metabolism of Belzutifan can be decreased when combined with Imatinib. |
Imipramine | The serum concentration of Belzutifan can be increased when it is combined with Imipramine. |
Indomethacin | The serum concentration of Belzutifan can be increased when it is combined with Indomethacin. |
Infliximab | The metabolism of Belzutifan can be increased when combined with Infliximab. |
Irinotecan | The serum concentration of Irinotecan can be decreased when it is combined with Belzutifan. |
Isavuconazole | The serum concentration of Belzutifan can be increased when it is combined with Isavuconazole. |
Isoniazid | The serum concentration of Belzutifan can be increased when it is combined with Isoniazid. |
Ivosidenib | The serum concentration of Ivosidenib can be decreased when it is combined with Belzutifan. |
Ixabepilone | The serum concentration of Ixabepilone can be decreased when it is combined with Belzutifan. |
Ixazomib | The serum concentration of Ixazomib can be decreased when it is combined with Belzutifan. |
Ketoconazole | The serum concentration of Belzutifan can be increased when it is combined with Ketoconazole. |
Labetalol | The metabolism of Belzutifan can be decreased when combined with Labetalol. |
Lacosamide | The metabolism of Belzutifan can be decreased when combined with Lacosamide. |
Lansoprazole | The serum concentration of Belzutifan can be increased when it is combined with Lansoprazole. |
Lapatinib | The metabolism of Belzutifan can be decreased when combined with Lapatinib. |
Letermovir | The metabolism of Belzutifan can be increased when combined with Letermovir. |
Letrozole | The serum concentration of Belzutifan can be increased when it is combined with Letrozole. |
Levacetylmethadol | The serum concentration of Levacetylmethadol can be decreased when it is combined with Belzutifan. |
Levobupivacaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Levobupivacaine. |
Levonorgestrel | The therapeutic efficacy of Levonorgestrel can be decreased when used in combination with Belzutifan. |
Lidocaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Lidocaine. |
Lomitapide | The serum concentration of Lomitapide can be decreased when it is combined with Belzutifan. |
Lonafarnib | The serum concentration of Belzutifan can be increased when it is combined with Lonafarnib. |
Losartan | The serum concentration of Belzutifan can be increased when it is combined with Losartan. |
Luliconazole | The serum concentration of Belzutifan can be increased when it is combined with Luliconazole. |
Lumacaftor | The serum concentration of Belzutifan can be decreased when it is combined with Lumacaftor. |
Lynestrenol | The serum concentration of Belzutifan can be increased when it is combined with Lynestrenol. |
Manidipine | The serum concentration of Belzutifan can be increased when it is combined with Manidipine. |
Mavacamten | The serum concentration of Belzutifan can be decreased when it is combined with Mavacamten. |
Medroxyprogesterone | The therapeutic efficacy of Medroxyprogesterone acetate can be decreased when used in combination with Belzutifan. |
Megestrol acetate | The therapeutic efficacy of Megestrol acetate can be decreased when used in combination with Belzutifan. |
Meloxicam | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Meloxicam. |
Memantine | The serum concentration of Belzutifan can be increased when it is combined with Memantine. |
Mephenytoin | The serum concentration of Belzutifan can be increased when it is combined with Mephenytoin. |
Mepivacaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Mepivacaine. |
Mestranol | The therapeutic efficacy of Mestranol can be decreased when used in combination with Belzutifan. |
Methadone | The metabolism of Belzutifan can be decreased when combined with Methadone. |
Methimazole | The serum concentration of Belzutifan can be increased when it is combined with Methimazole. |
Methotrexate | The serum concentration of Methotrexate can be decreased when it is combined with Belzutifan. |
Methoxy polyethylene | The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Belzutifan. |
Methsuximide | The serum concentration of Belzutifan can be increased when it is combined with Methsuximide. |
Methylene blue | The serum concentration of Belzutifan can be increased when it is combined with Methylene blue. |
Methylphenobarbital | The metabolism of Belzutifan can be decreased when combined with Methylphenobarbital. |
Miconazole | The serum concentration of Belzutifan can be increased when it is combined with Miconazole. |
Midostaurin | The serum concentration of Midostaurin can be decreased when it is combined with Belzutifan. |
Mifepristone | The therapeutic efficacy of Mifepristone can be decreased when used in combination with Belzutifan. |
Moclobemide | The serum concentration of Belzutifan can be increased when it is combined with Moclobemide. |
Modafinil | The serum concentration of Belzutifan can be increased when it is combined with Modafinil. |
Nebivolol | The metabolism of Belzutifan can be decreased when combined with Nebivolol. |
Neratinib | The serum concentration of Neratinib can be decreased when it is combined with Belzutifan. |
Nicardipine | The serum concentration of Belzutifan can be increased when it is combined with Nicardipine. |
Nilotinib | The serum concentration of Nilotinib can be decreased when it is combined with Belzutifan. |
Nilutamide | The serum concentration of Belzutifan can be increased when it is combined with Nilutamide. |
Nilvadipine | The serum concentration of Belzutifan can be increased when it is combined with Nilvadipine. |
Nomegestrol | The therapeutic efficacy of Nomegestrol can be decreased when used in combination with Belzutifan. |
Norethisterone | The therapeutic efficacy of Norethisterone can be decreased when used in combination with Belzutifan. |
Norethynodrel | The therapeutic efficacy of Norethynodrel can be decreased when used in combination with Belzutifan. |
Norgestimate | The therapeutic efficacy of Norgestimate can be decreased when used in combination with Belzutifan. |
Norgestrel | The therapeutic efficacy of Norgestrel can be decreased when used in combination with Belzutifan. |
Nortriptyline | The serum concentration of Nortriptyline can be decreased when it is combined with Belzutifan. |
Olanzapine | The serum concentration of Belzutifan can be increased when it is combined with Olanzapine. |
Olaparib | The serum concentration of Olaparib can be decreased when it is combined with Belzutifan. |
Omeprazole | The serum concentration of Belzutifan can be increased when it is combined with Omeprazole. |
Oritavancin | The serum concentration of Belzutifan can be increased when it is combined with Oritavancin. |
Osilodrostat | The serum concentration of Belzutifan can be increased when it is combined with Osilodrostat. |
Osimertinib | The serum concentration of Osimertinib can be decreased when it is combined with Belzutifan. |
Oxcarbazepine | The serum concentration of Belzutifan can be increased when it is combined with Oxcarbazepine. |
Oxetacaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Oxetacaine. |
Oxybuprocaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Oxybuprocaine. |
Paclitaxel | The serum concentration of Paclitaxel can be decreased when it is combined with Belzutifan. |
Palbociclib | The serum concentration of Palbociclib can be decreased when it is combined with Belzutifan. |
Panobinostat | The serum concentration of Panobinostat can be decreased when it is combined with Belzutifan. |
Pantoprazole | The serum concentration of Belzutifan can be increased when it is combined with Pantoprazole. |
Paroxetine | The metabolism of Belzutifan can be decreased when combined with Paroxetine. |
Pazopanib | The serum concentration of Pazopanib can be decreased when it is combined with Belzutifan. |
Peginesatide | The risk or severity of Thrombosis can be increased when Peginesatide is combined with Belzutifan. |
Pentamidine | The metabolism of Belzutifan can be decreased when combined with Pentamidine. |
Pentobarbital | The metabolism of Belzutifan can be decreased when combined with Pentobarbital. |
Pexidartinib | The serum concentration of Pexidartinib can be decreased when it is combined with Belzutifan. |
Phenelzine | The serum concentration of Belzutifan can be increased when it is combined with Phenelzine. |
Phenobarbital | The metabolism of Belzutifan can be decreased when combined with Phenobarbital. |
Phenol | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Phenol. |
Phenprocoumon | The serum concentration of Phenprocoumon can be decreased when it is combined with Belzutifan. |
Phenytoin | The metabolism of Belzutifan can be increased when combined with Phenytoin. |
Pimozide | The serum concentration of Pimozide can be decreased when it is combined with Belzutifan. |
Piperaquine | The serum concentration of Belzutifan can be increased when it is combined with Piperaquine. |
Pirfenidone | The metabolism of Belzutifan can be decreased when combined with Pirfenidone. |
Pomalidomide | The serum concentration of Pomalidomide can be decreased when it is combined with Belzutifan. |
Ponatinib | The serum concentration of Ponatinib can be decreased when it is combined with Belzutifan. |
Pramocaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Pramocaine. |
Praziquantel | The metabolism of Belzutifan can be decreased when combined with Praziquantel. |
Prilocaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Prilocaine. |
Primidone | The metabolism of Belzutifan can be decreased when combined with Primidone. |
Probenecid | The serum concentration of Belzutifan can be increased when it is combined with Probenecid. |
Procaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Procaine. |
Progesterone | The serum concentration of Belzutifan can be increased when it is combined with Progesterone. |
Proguanil | The metabolism of Belzutifan can be decreased when combined with Proguanil. |
Proparacaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Proparacaine. |
Propoxycaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Propoxycaine. |
Propranolol | The metabolism of Belzutifan can be decreased when combined with Propranolol. |
Quinidine | The serum concentration of Quinidine can be decreased when it is combined with Belzutifan. |
Quinine | The serum concentration of Belzutifan can be increased when it is combined with Quinine. |
Rabeprazole | The serum concentration of Belzutifan can be increased when it is combined with Rabeprazole. |
Ramelteon | The metabolism of Belzutifan can be decreased when combined with Ramelteon. |
Regorafenib | The serum concentration of Regorafenib can be decreased when it is combined with Belzutifan. |
Ribociclib | The serum concentration of Ribociclib can be decreased when it is combined with Belzutifan. |
Rifabutin | The metabolism of Belzutifan can be increased when combined with Rifabutin. |
Rifampicin | The metabolism of Belzutifan can be increased when combined with Rifampicin. |
Rifamycin | The serum concentration of Belzutifan can be increased when it is combined with Rifamycin. |
Rifapentine | The metabolism of Belzutifan can be increased when combined with Rifapentine. |
Rilonacept | The metabolism of Belzutifan can be increased when combined with Rilonacept. |
Rilpivirine | The metabolism of Belzutifan can be decreased when combined with Rilpivirine. |
Ritonavir | The serum concentration of Belzutifan can be increased when it is combined with Ritonavir. |
Romidepsin | The serum concentration of Romidepsin can be decreased when it is combined with Belzutifan. |
Ropivacaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Ropivacaine. |
Rucaparib | The serum concentration of Belzutifan can be increased when it is combined with Rucaparib. |
Ruxolitinib | The serum concentration of Ruxolitinib can be decreased when it is combined with Belzutifan. |
Safinamide | The serum concentration of Belzutifan can be increased when it is combined with Safinamide. |
Natalizumab | The serum concentration of Belzutifan can be decreased when it is combined with Satralizumab. |
Secukinumab | The metabolism of Belzutifan can be increased when combined with Secukinumab. |
Progesterone acetate | The therapeutic efficacy of Segesterone acetate can be decreased when used in combination with Belzutifan. |
Selumetinib | The metabolism of Belzutifan can be decreased when combined with Selumetinib. |
Sertraline | The serum concentration of Belzutifan can be increased when it is combined with Sertraline. |
Sildenafil | The serum concentration of Belzutifan can be increased when it is combined with Sildenafil. |
Siltuximab | The metabolism of Belzutifan can be increased when combined with Siltuximab. |
Siponimod | The serum concentration of Siponimod can be decreased when it is combined with Belzutifan. |
Sirolimus | The serum concentration of Sirolimus can be decreased when it is combined with Belzutifan. |
Sitaxentan | The serum concentration of Belzutifan can be increased when it is combined with Sitaxentan. |
Somapacitan | The serum concentration of Belzutifan can be increased when it is combined with Somapacitan. |
Somatotropin | The serum concentration of Belzutifan can be increased when it is combined with Somatotropin. |
Sonidegib | The serum concentration of Sonidegib can be decreased when it is combined with Belzutifan. |
Sorafenib | The serum concentration of Sorafenib can be decreased when it is combined with Belzutifan. |
St. John’s Wort | The metabolism of Belzutifan can be decreased when combined with St. John’s Wort. |
Stiripentol | The serum concentration of Belzutifan can be increased when it is combined with Stiripentol. |
Sulfanilamide | The serum concentration of Belzutifan can be increased when it is combined with Sulfanilamide. |
Sunitinib | The serum concentration of Sunitinib can be decreased when it is combined with Belzutifan. |
Tacrolimus | The serum concentration of Tacrolimus can be decreased when it is combined with Belzutifan. |
Tamoxifen | The serum concentration of Tamoxifen can be decreased when it is combined with Belzutifan. |
Tecovirimat | The metabolism of Belzutifan can be decreased when combined with Tecovirimat. |
Telmisartan | The serum concentration of Belzutifan can be increased when it is combined with Telmisartan. |
Temsirolimus | The serum concentration of Temsirolimus can be decreased when it is combined with Belzutifan. |
Teniposide | The serum concentration of Teniposide can be decreased when it is combined with Belzutifan. |
Testosterone | The metabolism of Belzutifan can be decreased when combined with Testosterone. |
Testosterone | The therapeutic efficacy of Testosterone enanthate can be decreased when used in combination with Belzutifan. |
Tetracaine | The risk or severity of methemoglobinemia can be increased when Belzutifan is combined with Tetracaine. |
Thalidomide | The serum concentration of Belzutifan can be increased when it is combined with Thalidomide. |
Theophylline | The serum concentration of Theophylline can be decreased when it is combined with Belzutifan. |
Thiopental | The metabolism of Belzutifan can be decreased when combined with Thiopental. |
Thioridazine | The metabolism of Belzutifan can be decreased when combined with Thioridazine. |
Thiotepa | The serum concentration of Thiotepa can be decreased when it is combined with Belzutifan. |
Ticlopidine | The serum concentration of Belzutifan can be increased when it is combined with Ticlopidine. |
Timolol | The metabolism of Belzutifan can be decreased when combined with Timolol. |
Tioconazole | The serum concentration of Belzutifan can be increased when it is combined with Tioconazole. |
Tipranavir | The serum concentration of Belzutifan can be increased when it is combined with Tipranavir. |
Tocilizumab | The metabolism of Belzutifan can be increased when combined with Tocilizumab. |
Tolvaptan | The serum concentration of Tolvaptan can be decreased when it is combined with Belzutifan. |
Topiramate | The serum concentration of Belzutifan can be increased when it is combined with Topiramate. |
Trabectedin | The serum concentration of Trabectedin can be decreased when it is combined with Belzutifan. |
Tranylcypromine | The serum concentration of Belzutifan can be increased when it is combined with Tranylcypromine. |
Trastuzumab | The serum concentration of Trastuzumab emtansine can be decreased when it is combined with Belzutifan. |
Triclabendazole | The metabolism of Belzutifan can be decreased when combined with Triclabendazole. |
Trimethadione | The metabolism of Belzutifan can be decreased when combined with Trimethadione. |
Ulipristal | The therapeutic efficacy of Ulipristal can be decreased when used in combination with Belzutifan. |
Valproic acid | The serum concentration of Belzutifan can be increased when it is combined with Valproic acid. |
Vandetanib | The serum concentration of Vandetanib can be decreased when it is combined with Belzutifan. |
Vemurafenib | The serum concentration of Vemurafenib can be decreased when it is combined with Belzutifan. |
Venetoclax | The serum concentration of Venetoclax can be decreased when it is combined with Belzutifan. |
Verapamil | The metabolism of Belzutifan can be decreased when combined with Verapamil. |
Vilazodone | The metabolism of Belzutifan can be decreased when combined with Vilazodone. |
Vinblastine | The serum concentration of Vinblastine can be decreased when it is combined with Belzutifan. |
Vincristine | The serum concentration of Vincristine can be decreased when it is combined with Belzutifan. |
Vindesine | The serum concentration of Vindesine can be decreased when it is combined with Belzutifan. |
Vinflunine | The serum concentration of Vinflunine can be decreased when it is combined with Belzutifan. |
Vinorelbine | The serum concentration of Vinorelbine can be decreased when it is combined with Belzutifan. |
Vismodegib | The serum concentration of Belzutifan can be increased when it is combined with Vismodegib. |
Vonoprazan | The serum concentration of Belzutifan can be increased when it is combined with Vonoprazan. |
Voriconazole | The serum concentration of Belzutifan can be increased when it is combined with Voriconazole. |
Vortioxetine | The metabolism of Belzutifan can be decreased when combined with Vortioxetine. |
Voxelotor | The metabolism of Belzutifan can be decreased when combined with Voxelotor. |
Warfarin | The serum concentration of Warfarin can be decreased when it is combined with Belzutifan. |
Zafirlukast | The serum concentration of Belzutifan can be increased when it is combined with Zafirlukast. |
Zanubrutinib | The serum concentration of Zanubrutinib can be decreased when it is combined with Belzutifan. |
Pregnancy and Lactation
US FDA pregnancy category Not Assigned
Pregnancy
Do not take belzutifan if you are pregnant, plan to become pregnant, or plan to father a child. You will have to take a pregnancy test before starting treatment. If you are female, you will need to use non-hormonal birth control during your treatment and for 1 week after your final dose.
Lactation
Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during therapy with this drug and for 1 week after.
How should this medicine be used?
Belzutifan comes as a tablet to take by mouth. It is usually taken once daily with or without food. Take belzutifan at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take belzutifan exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Swallow the tablets whole; do not split, chew, or crush them.
If you vomit after taking belzutifan, do not take another dose. Continue your regular dosing schedule on the next day.
Your doctor may temporarily or permanently stop your treatment or decrease your dose if you experience certain side effects. Be sure to tell your doctor how you are feeling during your treatment with belzutifan. Continue to take belzutifan even if you feel well. Do not stop taking belzutifan without talking to your doctor.
What special precautions should I follow?
Before taking belzutifan,
- tell your doctor and pharmacist if you are allergic to belzutifan, any other medications, or any of the ingredients in belzutifan tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section any of the following: imatinib (Gleevec), fentanyl (Duragesic), fluvoxamine (Luvox), midazolam, and ticlopidine. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with belzutifan, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
- tell your doctor if you have or have ever had anemia (a lower-than-normal number of red blood cells).
- tell your doctor if you are breastfeeding. You should not breastfeed while you are taking belzutifan and for 1 week after your final dose.
- you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking belzutifan.
References