VANRAFIA atrasentan .75 mg Tablet, Film Coated, 30-count
🆔 Identity & classification
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🏭 Manufacturer & labeler
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🩺 Clinical
Atrasentan is used to reduce proteinuria (protein in the urine) in certain patients with immunoglobulin A (IgA) nephropathy (a kidney disease where IgA deposits build up in the kidneys causing inflammation). Atrasentan is in a class of medications called endothelin receptor antagonists. It works by blocking the substance, endothelin, to slow disease progression.
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $445.99 | $13,379.63 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $454.70 | $13,641.11 / 30 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Vanrafia .75 mgthis 00078-1420-15 | Novartis | 30 tablets | — | — | FDA listed | — |
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⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 12521369 ↗ | Method of use | U-3980 | Mar 2, 2041 |
| US 8623819 ↗ | Method of use | U-3980 | Aug 22, 2028 |
| US 12370174 ↗ | Method of use | U-3980 | Dec 16, 2040 |
| US 12121509 ↗ | Method of use | U-3980 | Dec 16, 2040 |
| US 11998526 ↗ | Method of use | U-3980 | Dec 16, 2040 |
| US 11874283 ↗ | Method of use | U-3980 | Feb 18, 2032 |
| US 11491137 ↗ | Method of use | U-3980 | Dec 16, 2040 |
| US 9364458 ↗ | Method of use | U-3980 | Jul 7, 2034 |
| US 12582631 ↗ | Method of use | U-3980 | Mar 25, 2043 |
| US 10016393 ↗ | Drug product | — | Jul 7, 2034 |
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Apr 2, 2030 |
Is there a generic version of VANRAFIA 0.75 MG TABLET?
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00078-1420-15 You're viewing this | 30 TABLET, FILM COATED in 1 BOTTLE (0078-1420-15) | 2025-04-02 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
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 )
🎯 Indications and Usage ▾
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 ▾
2 DOSAGE AND ADMINISTRATION 0.75 mg orally once daily with or without food ( 2.2 )
2.1Pregnancy Testing Exclude pregnancy before initiating VANRAFIA [see Warnings and Precautions (5.1), Use in Specific Populations (8.1, 8.3)] .
2.2Recommended 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 ▾
3 DOSAGE FORMS AND STRENGTHS VANRAFIA 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 ▾
4 CONTRAINDICATIONS Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 )
4.1Pregnancy 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)] .
4.2Hypersensitivity VANRAFIA is contraindicated in patients with a history of a hypersensitivity reaction to atrasentan or any component of the product.
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hepatotoxicity ( 5.2 ) Fluid Retention ( 5.3 ) Decreased Sperm Counts ( 5.4 , 8.3 )
5.1Embryo-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)] .
5.2Hepatotoxicity 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.
5.3Fluid 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.
5.4Decreased 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)] .
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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 .
6.1Clinical 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 ▾
7 DRUG INTERACTIONS Strong or moderate CYP3A inducers: Avoid concomitant use. ( 7.1 ) OATP1B1/1B3 inhibitors: Avoid concomitant use. ( 7.1 )
7.1Effect 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 ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 )
8.1Pregnancy 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.
8.2Lactation 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.
8.3Females 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), U…
🤰 Pregnancy ▾
8.1Pregnancy 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 ▾
8.4Pediatric Use The safety and efficacy of VANRAFIA in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric 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 ▾
10 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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.
12.2Pharmacodynamics Dose-response information is not available. At the recommended dose regimen, no statistically significant exposure-response (E-R) relationship was identified between atrasentan exposure and the percentage reduction from baseline in UPCR at Week 36 over the observed atrasentan exposure range. Increased atrasentan exposure was associated with an increased incidence of anemia, but no association was observed between atrasentan exposure and hypotension or peripheral edema.
Cardiac Electrophysiology At exposures 40% higher than the clinical exposure at the maximum recommended dose, clinically significant QTc interval prolongation was not observed.
12.3Pharmacokinetics 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. Absorption Atrasentan time to peak plasma concentration (T max ) is approximately 0.5 hour.
Effect of Food No clinically significant differences in atrasentan pharmacokinetics were observed following administration with a high-fat meal (800 to 1000 Kcal, > 50% fat) in healthy subjects. Distribution Atrasentan steady-state apparent (oral) volume of distribution (Vd/F) is 1180 L. Atrasentan is > 99% bound to human plasma proteins, in vitro.
Elimination Atrasentan effective half-life is approximately 24 to 41 hours with an apparent (oral) clearance (CL/F) of 19 L/h. Metabolism Atrasentan is extensively metabolized by CYP3A and multiple uridine 5'-diphospho-glucuronosyltransferases (UGTs) with approximately half via CYP3A and the remaining half via glucuronidation by multiple UGTs. Excretion After a single dose of radiolabeled atrasentan 10 mg to healthy subjects, approximately 86% of the dose was recovered in feces (5.5% as parent atrasentan).
Renal excretion was minimal, with < 4% recovered in urine (negligible amounts of parent atrasentan). Specific Populations No clinically significant differences in the pharmacokinetics of atrasentan were observed based on age (19 to 77 years), sex, race, mild to severe renal impairment (eGFR 15 to 90 mL/min/1.73 m 2 , estimated by CKD-EPI), or mild to moderate hepatic impairment (Child-Pugh class A or B). The effect of severe hepatic impairment (Child-Pugh class C) or end-stage renal disease (eGFR < 15 mL/min/1.73 m 2 ) on atrasentan pharmacokinetics is unknown.
Drug Interaction Studies Clinical Studies and Model-Informed Approaches Strong and moderate CYP3A inducers : Atrasentan C trough decreased by 90% following coadministration of a single dose of 10 mg VANRAFIA with rifampin (strong CYP3A inducer). OATP1B1/1B3 inhibitors : Atrasentan C max was 4.3 times as high and AUC was 3.8 times as high following coadministration of a single dose of 0.75 mg VANRAFIA with cyclosporine (OATP1B1/1B3 inhibitor). Strong CYP3A inhibitors : Atrasentan AUC increased by 90% following coadministration of a single dose of 10 mg VANRAFIA with ketoconazole (strong CYP3A inhibitor).
Other Drugs : No clinically significant differences in the pharmacokinetics of midazolam (CYP3A4 substrate), losartan (CYP2C9 and CYP3A4 substrate) or fexofenadine (P-gp substrate) were observed or expected when used concomitantly with VANRAFIA. In Vitro Studies CYP450 Enzymes : Atrasentan is a CYP3A substrate. Atrasentan inhibits in vitro CYP3A, CYP2B6, CYP2C8 and CYP2C9 and induces CYP3A and CYP2B6, but is not expected to cause clinically significant interactions with these CYP450 enzymes in the liver.
Atrasentan does not inhibit CYP1A2, CYP2C19, or CYP2D6 and is not an inducer of CYP1…
🧬 Mechanism of Action ▾
12.1Mechanism 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 / Storage and Handling ▾
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.
📋 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
💬 Information for Patients ▾
17 PATIENT COUNSELING 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
💬 Medication Guide ▾
This Medication Guide has been approved by the U.S. Food and Drug Administration. Issued: April 2025 MEDICATION GUIDE VANRAFIA ™ (van-rah-fee-ah) (atrasentan) tablets What is the most important information I should know about VANRAFIA?
VANRAFIA can cause serious birth defects if taken during pregnancy. Females should not be pregnant when they start taking VANRAFIA or become pregnant during treatment with VANRAFIA or for two weeks after stopping treatment with VANRAFIA. Females who can become pregnant should have a negative pregnancy test before starting VANRAFIA.
Females who can become pregnant are those who: have entered puberty, even if they have not started their menstrual period, and have a uterus, and have not gone through menopause. Menopause means that you have not had a menstrual period for at least 12 months for natural reasons, or that you have had your ovaries removed. Females who cannot become pregnant are those who: have not yet entered puberty, or do not have a uterus, or have gone through menopause.
Menopause means that you have not had a menstrual period for at least 12 months for natural reasons, or that you have had your ovaries removed, or are infertile for any other medical reason and this infertility is permanent and cannot be reversed. Females who can become pregnant should use effective birth control before starting treatment with VANRAFIA, during treatment with VANRAFIA and for 2 weeks after stopping VANRAFIA because the medicine may still be in your body. Talk with your healthcare provider or gynecologist (a healthcare provider who specializes in reproduction) to find out about options for effective forms of birth control that you may use to prevent pregnancy during treatment with VANRAFIA.
If you decide that you want to change the form of birth control that you use, talk with your healthcare provider or gynecologist to be sure that you choose another effective form of birth control. Do not have unprotected sex. Talk to your healthcare provider or pharmacist right away if you have unprotected sex or if you think your birth control has failed.
Your healthcare provider may talk with you about using emergency birth control. Tell your healthcare provider right away if you miss a menstrual period or think you may be pregnant. See “What are the possible side effects of VANRAFIA?” for more information about side effects.
What is VANRAFIA? VANRAFIA is a prescription medicine used to reduce levels of protein in the urine (proteinuria) in adults with a kidney disease called primary immunoglobulin A nephropathy (IgAN) who are at risk of their disease getting worse quickly. It is not known if VANRAFIA is safe and effective in children.
Who should not take VANRAFIA? Do not take VANRAFIA if you are pregnant, plan to become pregnant, or become pregnant during treatment with VANRAFIA. VANRAFIA can cause serious birth defects.
See “What is the most important information I should know about VANRAFIA?” allergic to atrasentan or any of the ingredients in VANRAFIA. See the end of this Medication Guide for a complete list of ingredients in VANRAFIA. Before taking VANRAFIA, tell your healthcare provider about all your medical conditions including if you: have liver problems are pregnant or plan to become pregnant during VANRAFIA treatment.
VANRAFIA can cause serious birth defects. See "What is the most important information I should know about VANRAFIA?” are breastfeeding or plan to breastfeed. It is not known if VANRAFIA passes into your breast milk.
Do not breastfeed during treatment with VANRAFIA. Talk with your healthcare provider about the best way to feed your baby if you take VANRAFIA. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Taking VANRAFIA with certain other medicines may affect the way VANRAFIA, and the other medicine works and may increase your risk for side effects. Do not start any new medicine until y…