Atrasentan
/api/v1/drug/atrasentanBoxed warning
EMBRYO-FETAL TOXICITY VANRAFIA is contraindicated for use in pregnant patients; it may cause major birth defects based on animal data [see Contraindications (4.1), Warnings and Precautions (5.1), Use in Specific Populations (8.1)] . Exclude pregnancy prior to initiation of treatment with VANRAFIA. Advise use of effective contraception before the initiation of treatment, during treatment, and for two weeks after discontinuation of treatment with VANRAFIA. Stop VANRAFIA as soon as possible if the patient becomes pregnant [see Dosage and Administration (2.1), Contraindications (4.1), Warnings and Precautions (5.1), Use in Specific Populations (8.1, 8.3)] . WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. VANRAFIA may cause major birth defects if used during pregnancy ( 4.1 , 5.1 , 8.1 ) Exclude pregnancy before start of treatment. ( 2.1 , 4.1 , 5.1 , 8.3 ) Use effective contraception before start of treatment, during treatment and two weeks after treatment. ( 4.1 , 5.1 , 8.3 ) Discontinue VANRAFIA if pregnancy occurs. ( 4.1 , 5.1 )
Mechanism of action
Sourced from openFDAAtrasentan is an ET A receptor antagonist (Ki = 0.034 nM) with >1800-fold selectivity for the ET A receptor compared to the endothelin type B receptor (Ki = 63.3 nM). Endothelin (ET)-1 is thought to contribute to the pathogenesis of IgAN via the ET A R.
Indications
Sourced from openFDA- VANRAFIA is indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥ 1.5 g/g. This indication is approved under accelerated approval based on a reduction of proteinuria [see Clinical Studies (14.1)] .
Contraindications
Sourced from openFDA- Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 ) 4.1 Pregnancy Use of VANRAFIA is contraindicated in patients who are pregnant [see Dosage and Administration (2.1), Warnings and Precautions (5.1), Use in Specific Populations (8.1)] . 4.2 Hypersensitivity VANRAFIA is contraindicated in patients with a history of a hypersensitivity reaction to atrasentan or any component of the product.contraindicated
Dosage & administration
Sourced from openFDA0.75 mg orally once daily with or without food ( 2.2 ) 2.1 Pregnancy Testing Exclude pregnancy before initiating VANRAFIA [see Warnings and Precautions (5.1), Use in Specific Populations (8.1, 8.3)] . 2.2 Recommended Dosage The recommended dose of VANRAFIA is 0.75 mg administered orally once daily with or without food [see Clinical Pharmacology (12.3)] . Swallow tablets whole. Do not cut, crush, or chew. If a dose or doses are missed, take the prescribed dose at the next scheduled time. Do not double the dose to make up for a missed dose.
Warnings & precautions
Sourced from openFDAHepatotoxicity ( 5.2 ) Fluid Retention ( 5.3 ) Decreased Sperm Counts ( 5.4 , 8.3 ) 5.1 Embryo-Fetal Toxicity Based on data from animal reproduction studies, VANRAFIA may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. The available human data for endothelin receptor antagonists do not establish the presence or absence of major birth defects related to the use of VANRAFIA. Counsel patients who can become pregnant of the potential risk to a fetus. Exclude pregnancy prior to initiation of treatment with VANRAFIA. Advise patients to use effective contraception prior to initiation of treatment, during treatment, and for two weeks after discontinuation of treatment with VANRAFIA [see Dosage and Administration (2.1) and Use in Specific Populations (8.1, 8.3)] . When pregnancy is detected, discontinue VANRAFIA as soon as possible [see Dosage and Administration (2.1), Contraindications (4.1), Use in Specific Populations (8.1, 8.3)] . 5.2 Hepatotoxicity Some endothelin receptor antagonists (ERAs) have caused elevations of aminotransferases, hepatotoxicity, and liver failure. Asymptomatic and transient transaminase elevations have been observed with VANRAFIA [see Adverse Reactions (6.1)] . Obtain liver enzyme testing before initiating VANRAFIA and repeat during treatment as clinically indicated. In patients with elevated aminotransferases at baseline (>3 × upper limit of normal [ULN]), consider periodic liver test monitoring. Do not initiate VANRAFIA in patients with severe hepatic impairment.
Adverse reactions
Sourced from openFDAThe following clinically significant adverse reactions are described elsewhere in the labeling: Embryo-fetal Toxicity [see Warnings and Precautions (5.1)] Hepatotoxicity [see Warnings and Precautions (5.2)] Fluid Retention [see Warnings and Precautions (5.3)] Decreased Sperm Counts [see Warnings and Precautions (5.4)] Most common adverse reactions (incidence ≥ 5%) were peripheral edema and anemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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 VANRAFIA was evaluated in ALIGN (NCT04573478), a randomized, double-blind, placebo controlled clinical study in 403 adults with IgAN [see Clinical Studies (14.1)] . The median duration of treatment was 47 weeks (range: 0 to 128 weeks). The most common adverse reactions (≥ 5%) with VANRAFIA were peripheral edema and anemia. Table 1 describes the adverse reactions that occurred in ≥ 2% of patients treated with VANRAFIA and higher than placebo in the ALIGN study.
Use in specific populations
Sourced from openFDALactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on data from animal reproductive toxicity studies, VANRAFIA may cause fetal harm, including birth defects and fetal death, when administered to a pregnant patient and is contraindicated during pregnancy [see Contraindications (4.1)] . There are no available data on VANRAFIA use in pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Available data from published literature and post-marketing surveillance over decades of use with products in the same pharmacologic class (ERA) have not identified an increased risk of major birth defects. However, these data are limited and do not establish the presence or absence of a drug-associated risk of major birth defects. Methodological limitations of these post marketing reports and published literature include lack of a control group; limited information regarding dose, duration, and timing of exposure; and missing data. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal endothelin receptor antagonist use.
Pharmacokinetics
Sourced from openFDA- Metabolism
- Atrasentan area under the time concentration curve (AUC) is dose proportional across the 0.35 mg to 30 mg (0.47 to 40 times the approved recommended dosage) dose range. Atrasentan steady state plasma concentrations are reached within 7 days with 2- to 3-fold accumulation.
Overdosage
Sourced from openFDAThere is no experience with overdose of VANRAFIA. Atrasentan has been given in a single dose up to 139.5 mg and multiple doses up to 40 mg/day in healthy volunteers. Overdose of VANRAFIA may result in headache or vasodilation. In the event of an overdose, standard supportive measures should be taken, as required. Dialysis is unlikely to be effective because atrasentan is highly protein-bound.
Approval history
Sourced from openFDA- Apr 2, 2025NDANDA219208Novartis
FAERS reports
- 1Drug Ineffective79.3%
- 2Fatigue56.7%
- 3Nausea56.7%
- 4Product Dose Omission Issue56.7%
- 5Swelling56.7%
- 6Anaemia45.3%
- 7Blood Creatinine Increased45.3%
- 8Fluid Retention45.3%
- 9Oedema45.3%
- 10Proteinuria45.3%
- 11Blood Potassium Increased34.0%
- 12Oedema Peripheral34.0%
- 13Peripheral Swelling34.0%
- 14Rash34.0%
- 15Vomiting34.0%
Literature
Recent PubMed references pinned to Atrasentan as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.
- Urinary clusterin as a biomarker of human kidney disease progression and response to the endothelin receptor antagonist atrasentan: An exploratory analysis from the SONAR trial.Nature communications · 2026 · Ju W, Nair V, Vart P, et al.PMID 41654492DOI 10.1038/s41467-026-68973-5
- Effects of Atrasentan on Kidney Gene Transcription, Mesangial Cell Proliferation, and Proteinuria in IgA Nephropathy.Kidney360 · 2026 · Kuo JJ, Wu J, Gunawan MG, et al.PMID 41442197DOI 10.34067/KID.0000001000
- Atrasentan: First Approval.Drugs · 2025 · Keam SJPMID 40760295DOI 10.1007/s40265-025-02208-7
- Sex differences in response to the endothelin receptor antagonist atrasentan in individuals with type 2 diabetes and chronic kidney disease: a post hoc analysis of the SONAR trial.Diabetologia · 2025 · Smeijer JD, de Vries ST, Kohan DE, et al.PMID 39661119DOI 10.1007/s00125-024-06326-x
- The effect of the endothelin receptor antagonist atrasentan on insulin resistance in phenotypic clusters of patients with type 2 diabetes and chronic kidney disease.Diabetes, obesity & metabolism · 2025 · Smeijer JD, Gomez MF, Rossing P, et al.PMID 39503150DOI 10.1111/dom.16041
- Atrasentan in Patients with IgA Nephropathy.The New England journal of medicine · 2025 · Heerspink HJL, Jardine M, Kohan DE, et al.PMID 39460694DOI 10.1056/NEJMoa2409415
- Clinical trial designs to assess treatment effects on glomerular filtration rate decline.Kidney international · 2024 · Heerspink HJL, Little DJ, Frison L, et al.PMID 38969296DOI 10.1016/j.kint.2024.06.007
- Early Response in Albuminuria and Long-Term Kidney Protection during Treatment with an Endothelin Receptor Antagonist: A Prespecified Analysis from the SONAR Trial.Journal of the American Society of Nephrology : JASN · 2021 · Heerspink HJL, Xie D, Bakris G, et al.PMID 34551995DOI 10.1681/ASN.2021030391
Clinical trials
The 10 most recently updated of 24 ClinicalTrials.gov registrations naming Atrasentan as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.
- Atrasentan in Patients With IgA NephropathyActive not recruiting · Phase 3 · Interventional · 404 enrolled · Novartis PharmaceuticalsNCT04573478updated 2026-06-04
- Atrasentan in Patients With Proteinuric Glomerular DiseasesActive not recruiting · Phase 2 · Interventional · 103 enrolled · Novartis PharmaceuticalsNCT04573920updated 2026-06-01
- Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgANNot yet recruiting · Phase 3 · Interventional · 28 enrolled · Novartis PharmaceuticalsNCT07498335updated 2026-06-01
- IgA Nephropathy Insights From Treatment Experience Among Patients Receiving Iptacopan and/or Atrasentan Using Primary Data CollectionNot yet recruiting · Observational · 80 enrolled · Novartis PharmaceuticalsNCT07481084updated 2026-03-18
- Randomized, Double-blind, Placebo-controlled, Crossover Study of Atrasentan in Subjects With IgA NephropathyCompleted · Phase 2 · Interventional · 54 enrolled · Novartis PharmaceuticalsNCT05834738updated 2026-01-30
- Managed Access Programs for EXV811, AtrasentanAvailable · Expanded access · Novartis PharmaceuticalsNCT07319585updated 2026-01-22
- A Mobile App-Based Study to Evaluate Disease Burden and Treatment Patterns in Immunoglobulin A Nephropathy (IgAN) in the USRecruiting · Observational · 300 enrolled · Novartis PharmaceuticalsNCT06952426updated 2025-06-17
- Atrasentan in Treating Patients With Locally Recurrent or Metastatic Kidney CancerCompleted · Phase 2 · Interventional · 180 enrolled · Eastern Cooperative Oncology GroupNCT00039429updated 2023-06-22
- S0421, Docetaxel and Prednisone With or Without Atrasentan in Treating Patients With Stage IV Prostate Cancer and Bone Metastases That Did Not Respond to Previous Hormone TherapyCompleted · Phase 3 · Interventional · 1,038 enrolled · SWOG Cancer Research NetworkNCT00134056updated 2021-10-27
- Atrasentan Spermatogenesis and Testicular FunctionCompleted · Phase 2 · Interventional · 20 enrolled · AbbVieNCT02118714updated 2019-05-07
Frequently asked questions
- How does Atrasentan work?
- Atrasentan is an ET A receptor antagonist (Ki = 0.034 nM) with >1800-fold selectivity for the ET A receptor compared to the endothelin type B receptor (Ki = 63.3 nM). Endothelin (ET)-1 is thought to contribute to the pathogenesis of IgAN via the ET A R.
- What is Atrasentan used for?
- According to FDA labeling, Atrasentan carries indications including: VANRAFIA is indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥ 1.5 g/g. This indication is approved under accelerated approval based on a reduction of proteinuria [see Clinical Studies (14.1)] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
- What class of drug is Atrasentan?
- Atrasentan is classified as Endothelin Receptor Antagonist, Endothelin Receptor Antagonists.
- What are the brand names for Atrasentan?
- Atrasentan is marketed under brand names including Vanrafia.
- What are the contraindications for Atrasentan?
- Atrasentan labeling lists contraindications including: Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 ) 4.1 Pregnancy Use of VANRAFIA is contraindicated in patients who are pregnant [see Dosage and Administration (2.1), Warnings and Precautions (5.1), Use in Specific Populations (8.1)] . 4.2 Hypersensitivity VANRAFIA is contraindicated in patients with a history of a hypersensitivity reaction to atrasentan or any component of the product.. Always consult the full prescribing information and a clinician.
atrasentan is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.