Vanrafia
atrasentan · Tablet, Film Coated · Oral
Uses
1 INDICATIONS AND USAGE 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)] . It has not been established whether VANRAFIA slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial. VANRAFIA is an endothelin receptor antagonist 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. ( 1 ) This indication is approved under accelerated approval based on a reduction of proteinuria. It has not been established whether VANRAFIA slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial. ( 1 )
Dosage and administration
0.75 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.
Dosage forms and strengths
0.75 mg: film-coated, round, biconvex, white to off-white tablet debossed with “7” on one side and unmarked on the other side. Tablets: 0.75 mg ( 3 )
Contraindications
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.
Warnings and precautions
Hepatotoxicity ( 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. Advise patients to report symptoms suggesting hepatic injury (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching). If clinically relevant aminotransferase elevations occur, or if elevations are accompanied by an increase in bilirubin >2 x ULN, or by clinical symptoms of hepatotoxicity, discontinue VANRAFIA. Consider re-initiation of VANRAFIA when hepatic enzyme levels normalize in patients who have not experienced clinical symptoms of hepatotoxicity or jaundice. 5.3 Fluid Retention Fluid retention may occur with ERAs and has been observed in clinical studies with VANRAFIA [see Adverse Reactions (6.1)] . VANRAFIA has not been evaluated in IgAN patients with heart failure. If clinically significant fluid retention develops, consider initiating or increasing diuretic treatment and interrupting VANRAFIA treatment. 5.4 Decreased Sperm Counts VANRAFIA, similar to other ERAs, may have an adverse effect on spermatogenesis. Counsel men about potential effects on fertility [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1)] .
Side effects
The 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. Table 1: Adverse Reactions Reported in ≥ 2% of Adult Patients with IgAN Treated with VANRAFIA and Higher than Placebo in ALIGN * Includes related terms ** Elevations in ALT or AST > 3-fold upper limit of normal (ULN) Adverse Reaction VANRAFIA (N = 201) n (%) Placebo (N = 202) n (%) Peripheral edema* 21 (10%) 14 (7%) Anemia* 12 (6%) 2 (1%) Liver transaminase elevation** 4 (2%) 2 (1%) Laboratory Tests and Vital Signs Hemoglobin Decrease At Week 36, the mean change in hemoglobin from baseline for those patients receiving VANRAFIA in the ALIGN study was -0.7 g/dL compared to -0.2 g/dL for those receiving placebo. The incidence of a hemoglobin decrease > 2 g/dL compared to baseline and below the lower limit of normal was greater for the VANRAFIA arm (12%) compared to the placebo arm (4%). These decreases are thought to be in part due to hemodilution. There were no treatment discontinuations due to anemia or hemoglobin decrease in the ALIGN study. Blood Pressure Decrease At Week 36, the mean change from baseline in systolic and diastolic blood pressure (BP) for patients receiving VANRAFIA in the ALIGN study was -4 mmHg and -4 mmHg, respectively, compared to +3 mmHg and +2 mmHg, respectively, in patients receiving placebo. Hypotension observed in VANRAFIA treated patients was mild or moderate in severity, rarely symptomatic, and did not necessitate treatment discontinuation.
Drug interactions
Strong or moderate CYP3A inducers: Avoid concomitant use. ( 7.1 ) OATP1B1/1B3 inhibitors: Avoid concomitant use. ( 7.1 ) 7.1 Effect of Other Drugs on VANRAFIA Strong or Moderate CYP3A Inducers Avoid concomitant use with a strong or moderate CYP3A inducer. Atrasentan is a CYP3A substrate [see Clinical Pharmacology (12.3)] . Concomitant use with a strong and moderate CYP3A inducer is expected to decrease atrasentan exposure [see Clinical Pharmacology (12.3)] , which may reduce VANRAFIA efficacy. OATP1B1/1B3 Inhibitors Avoid concomitant use with organic anion transporting polypeptides 1B1/1B3 (OATP1B1/1B3) inhibitors. Atrasentan is a OATP1B1/1B3 substrate [see Clinical Pharmacology (12.3)] . Concomitant use with a OATP1B1/1B3 inhibitor increases atrasentan exposure [see Clinical Pharmacology (12.3)] , which may increase the risk of VANRAFIA adverse reactions.
Use in specific populations
Lactation: 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. In animal reproduction studies, oral administration of atrasentan to pregnant rats and rabbits throughout organogenesis at doses that were below the maximum recommended human dose (MRHD) based on area under the curve (AUC) caused teratogenic effects in rats and rabbits (see Data) . Advise pregnant patients of the potential risk to the fetus [see Contraindications (4.1)] . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In embryo-fetal development studies in pregnant rats and rabbits, teratogenicity and/or embryo-fetal toxicity were observed. In pregnant rats, oral administration of atrasentan throughout organogenesis at doses of 0.1, 0.3, 1.0, and 3.0 mg/kg/day resulted in developmental abnormalities primarily including the ear, lower jaw, or skull in all treated groups with detectable plasma exposures to atrasentan. The no adverse effect level of atrasentan plasma exposure was not determined. In pregnant rabbits, oral administration of atrasentan throughout organogenesis at doses of 0.1, 0.3, 1.0 and 3.0 mg/kg/day resulted in visceral malformations including deformities in the cardiovascular system in all atrasentan-treated groups. The lowest detectable plasma exposures to atrasentan were approximately 0.2 times the AUC at the MRHD. In the pre- and postnatal development study in rats, atrasentan was orally administered to pregnant rats at doses of 1, 10, or 100 mg/kg/day during the period from gestation Day 15 through lactation Day 20. No adverse effects on pre- and postnatal development were observed at doses up to 10 mg/kg/day which resulted in maternal exposure approximately 55 times the AUC at the MRHD. Higher exposure to atrasentan (dose of 100 mg/kg/day) increased pup mortality during the pre-weaning period, and increased heart weight which correlated histologically with myocardial hypertrophy. 8.2 Lactation Risk Summary There are no data on the presence of atrasentan in human milk, the effects on the breastfed infant, or the effect on milk production. Because of the potential for adverse reactions, such as fluid retention in breastfed infants, advise patients not to breastfeed during treatment with VANRAFIA. 8.3 Females and Males of Reproductive Potential 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), Use in Specific Populations (8.1)] . Pregnancy Testing Exclude pregnancy before initiating VANRAFIA in females of reproductive potential. The patient should contact their physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected. If pregnancy is confirmed, the physician should discuss with the patient the risks to the pregnancy and the fetus. Contraception Patients who can become pregnant while using VANRAFIA should use effective contraception prior to initiation of treatment, during treatment, and for two weeks after discontinuation of treatment with VANRAFIA to prevent pregnancy [see Warnings and Precautions (5.1)] . Infertility Decreased sperm counts have been observed in some patients with diabetic kidney disease (DKD) receiving VANRAFIA 0.75 mg once daily with return to normal levels within approximately 3 months after drug discontinuation. This effect has not been studied in patients with IgAN [see Nonclinical Toxicology (13.1)] . 8.4 Pediatric Use The safety and efficacy of VANRAFIA in pediatric patients have not been established. 8.5 Geriatric Use There were 29 (7%) patients 65 years of age and older in the ALIGN study of VANRAFIA. Of the total number of VANRAFIA-treated patients, 15 (7%) were 65 years to 75 years of age, and 3 (2%) were 75 years of age and older. No overall differences in safety and effectiveness were observed between these patients and younger patients. 8.6 Hepatic Impairment No dose adjustment is required for patients with mild or moderate hepatic impairment. Do not initiate VANRAFIA in patients with severe hepatic impairment [see Warnings and Precautions (5.2)] .
Pregnancy
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. In animal reproduction studies, oral administration of atrasentan to pregnant rats and rabbits throughout organogenesis at doses that were below the maximum recommended human dose (MRHD) based on area under the curve (AUC) caused teratogenic effects in rats and rabbits (see Data) . Advise pregnant patients of the potential risk to the fetus [see Contraindications (4.1)] . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In embryo-fetal development studies in pregnant rats and rabbits, teratogenicity and/or embryo-fetal toxicity were observed. In pregnant rats, oral administration of atrasentan throughout organogenesis at doses of 0.1, 0.3, 1.0, and 3.0 mg/kg/day resulted in developmental abnormalities primarily including the ear, lower jaw, or skull in all treated groups with detectable plasma exposures to atrasentan. The no adverse effect level of atrasentan plasma exposure was not determined. In pregnant rabbits, oral administration of atrasentan throughout organogenesis at doses of 0.1, 0.3, 1.0 and 3.0 mg/kg/day resulted in visceral malformations including deformities in the cardiovascular system in all atrasentan-treated groups. The lowest detectable plasma exposures to atrasentan were approximately 0.2 times the AUC at the MRHD. In the pre- and postnatal development study in rats, atrasentan was orally administered to pregnant rats at doses of 1, 10, or 100 mg/kg/day during the period from gestation Day 15 through lactation Day 20. No adverse effects on pre- and postnatal development were observed at doses up to 10 mg/kg/day which resulted in maternal exposure approximately 55 times the AUC at the MRHD. Higher exposure to atrasentan (dose of 100 mg/kg/day) increased pup mortality during the pre-weaning period, and increased heart weight which correlated histologically with myocardial hypertrophy.
Pediatric use
8.4 Pediatric Use The safety and efficacy of VANRAFIA in pediatric patients have not been established.
Geriatric use
8.5 Geriatric Use There were 29 (7%) patients 65 years of age and older in the ALIGN study of VANRAFIA. Of the total number of VANRAFIA-treated patients, 15 (7%) were 65 years to 75 years of age, and 3 (2%) were 75 years of age and older. No overall differences in safety and effectiveness were observed between these patients and younger patients.
Overdosage
There 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.
Description
11 DESCRIPTION VANRAFIA contains atrasentan, an endothelin type A (ET A ) receptor antagonist. The chemical name of atrasentan hydrochloride is (2 R , 3 R , 4 S )-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)-3-pyrrolidinecarboxylic acid hydrochloride. Atrasentan hydrochloride has a molecular weight of 547.09 g/mol, a molecular formula of C 29 H 38 N 2 O 6 HCl and the following structural formula. Atrasentan is a slightly hygroscopic white to off-white powder that is slightly soluble in water. VANRAFIA is available as a film-coated tablet for oral administration. Each VANRAFIA tablet contains 0.75 mg atrasentan (equivalent to 0.803 mg of atrasentan hydrochloride) and contains the following excipients: crospovidone, glyceryl dibehenate, hypromellose, lactose monohydrate, L-cysteine hydrochloride monohydrate, polyethylene glycol, and silicon dioxide. Atrasentan structural formula
Mechanism of action
12.1 Mechanism of Action 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.
How supplied
16 HOW SUPPLIED/STORAGE AND HANDLING VANRAFIA is supplied as follows: 0.75 mg tablets are film-coated, round, biconvex, white to off-white tablets debossed with “7” on one side and unmarked on the other side, packaged in a high-density polyethylene (HDPE) bottle containing a desiccant, with induction seal and child-resistant cap. Each bottle contains 30 tablets (NDC 0078-1420-15). Storage Store at 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C and 30°C (59°F and 86°F). [See USP Controlled Room Temperature] . Store and dispense VANRAFIA in its original container.
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide) Embryo-Fetal Toxicity Educate and counsel female patients of reproductive potential to use effective contraception prior to starting treatment with VANRAFIA, during treatment and for two weeks after treatment discontinuation. Patients who can become pregnant should have a negative pregnancy test prior to treatment with VANRAFIA [see Dosage and Administration (2.1), Contraindications (4.1), Warnings and Precautions (5.1), Use in Specific Populations (8.1, 8.3)] . Patients should be instructed to immediately contact their physician if they suspect they may be pregnant. Patients should seek additional contraceptive advice as needed. Educate and counsel patients who can become pregnant on the use of emergency contraception in the event of unprotected sex or contraceptive failure. Advise patients to contact their healthcare provider if they want to change the form of birth control which is used to ensure that another acceptable form of birth control is selected. Hepatotoxicity Some members of this pharmacological class are hepatotoxic. Educate patients on signs of hepatotoxicity. Advise patients that they should contact their doctor if they have unexplained nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching [see Warnings and Precautions (5.2)] . Fluid Retention Educate patients on signs of fluid retention. Advise patients that they should contact their doctor if they have unusual weight increase or swelling of the ankles or legs [see Warnings and Precautions (5.3)] . Lactation Advise patients not to breastfeed during treatment with VANRAFIA [see Use in Specific Populations (8.2)] . Other Risks Associated with VANRAFIA Instruct patients that the risks associated with VANRAFIA also include the following: Decreases in sperm count [see Warnings and Precautions (5.4)] Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936 © 2025 Novartis T2025-18
Label text from the FDA structured product label by Novartis Pharmaceuticals Corporation (revised Jun 12, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Atrasentan Hydrochloride in 1 product
Vanrafia NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0078-1420 | Atrasentan Hydrochloride .75 mg/1 Tablet, Film Coated | Novartis Pharmaceuticals Corporation | NDA |
Frequently asked questions
What is Vanrafia used for?
1 INDICATIONS AND USAGE 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)] . It has not been established whether VANRAFIA…
What are the side effects of Vanrafia?
The 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… See the full label for the complete list.
Who makes Vanrafia?
Vanrafia is listed by 1 labeler in the FDA NDC directory, including Novartis Pharmaceuticals Corporation.