Version July 2025
Atrasentan is contraindicated for use in pregnant patients; it may cause major birth defects based on animal data. Exclude pregnancy prior to initiation of treatment with atrasentan. Advise use of effective contraception before the initiation of treatment, during treatment, and for 2 weeks after discontinuation of treatment with atrasentan. Stop atrasentan as soon as possible if the patient becomes pregnant.
IgA nephropathy, primary, nonvariant (alternative agent): Oral: 0.75 mg once daily.
Note: Kidney function may be estimated using the CKD-EPI formula.
eGFR >90 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 15 to 90 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling; however, dosage adjustment unlikely necessary since no significant pharmacokinetic differences observed in patients with mild to severe kidney impairment.
eGFR <15 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Liver impairment prior to treatment initiation:
Mild or moderate impairment: No dosage adjustment necessary.
Severe impairment: Use not recommended.
Hepatotoxicity during treatment: Discontinue atrasentan in patients who develop symptoms of liver injury (eg, anorexia, dark urine, fatigue, fever, itching, jaundice, nausea, right upper quadrant pain, vomiting) or who experience clinically relevant aminotransferase elevations, or if aminotransferase elevations are accompanied by elevated bilirubin (>2 × ULN). If hepatic enzyme levels normalize may consider reinitiation of atrasentan in patients who have not experienced clinical symptoms of hepatotoxicity or jaundice.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%: Hematologic & oncologic: Decreased hemoglobin (12%)
1% to 10%:
Cardiovascular: Peripheral edema (10%)
Hematologic & oncologic: Anemia (6%)
Hepatic: Increased serum transaminases (2%)
Frequency not defined:
Cardiovascular: Hypotension
Endocrine & metabolic: Fluid retention
Hypersensitivity to atrasentan or any component of the formulation; pregnancy.
Concerns related to adverse effects:
• Fluid retention: Fluid retention has been observed; use has not been evaluated in IgA nephropathy patients with heart failure. Consider initiating or increasing diuretic treatment or interrupting atrasentan therapy if significant fluid retention occurs.
• Hepatic effects: Asymptomatic and transient transaminase elevations have been reported; some endothelin receptor antagonists have caused increases in serum liver aminotransferases, hepatotoxicity, and liver failure.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Vanrafia: 0.75 mg
No
Tablets (Vanrafia Oral)
0.75 mg (per each): $534.25
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: Administer with or without food. Swallow tablets whole; do not crush, chew, or cut.
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Atrasentan may cause teratogenicity, reproductive toxicity, and/or has a structural/toxicity profile similar to existing hazardous agents.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
IgA nephropathy, primary, nonvariant: To reduce proteinuria in adults with primary IgA nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio ≥1.5 g/g.
Substrate of CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors), OATP1B1/1B3, P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Asciminib: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Bulevirtide: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Coadministration of bulevirtide with OATP1B1/1B3 (also known as SLCO1B1/1B3) substrates should be avoided when possible. If used together, close clinical monitoring is recommended. Risk D: Consider Therapy Modification
Ceftobiprole Medocaril: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
CYP3A4 Inducers (Moderate): May decrease serum concentration of Atrasentan. Risk X: Avoid
CYP3A4 Inducers (Strong): May decrease serum concentration of Atrasentan. Risk X: Avoid
Leniolisib: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors: May increase serum concentration of Atrasentan. Risk X: Avoid
Pretomanid: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Sparsentan: May increase adverse/toxic effects of Endothelin Receptor Antagonists. Risk X: Avoid
Trofinetide: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider Therapy Modification
Voclosporin: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Exclude pregnancy prior to treatment.
Patients who could become pregnant should use effective contraception prior to, during treatment, and for 2 weeks after the last dose of atrasentan.
Reversible decreases in sperm counts may occur during treatment with atrasentan.
Based on data from animal reproductions studies, following oral administration of atrasentan at doses below the maximum recommended human dose, in utero exposure may cause fetal harm.
Atrasentan is contraindicated for use during pregnancy; discontinue as soon as possible if pregnancy occurs during treatment.
It is not known if atrasentan is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, such as fluid retention, breastfeeding is not recommended by the manufacturer.
Pregnancy status prior to therapy and when menses is delayed or pregnancy is suspected; transaminases prior to initiation of therapy and repeat as clinically appropriate; periodic serum transaminases in patients with elevated aminotransferases at baseline (>3 × ULN); clinical signs/symptoms of liver injury (eg, anorexia, dark urine, fatigue, fever, itching, jaundice, nausea, right upper quadrant pain, vomiting); fluid retention.
Atrasentan blocks the activation of endothelin-A receptors (ETAR) by endothelin (ET)-1, which is thought to contribute to the pathogenesis of IgA nephropathy. Atrasentan inhibits ET-1 receptors with >1,800-fold selectivity for the ETAR (Ki = 0.034 nM) compared to the endothelin type B receptor (Ki = 63.3 nM).
Distribution: Vd/F: 1,180 L.
Protein binding: >99%.
Metabolism: Metabolized by CYP3A (~50%) and glucuronidated via multiple uridine 5'-diphospho-glucuronosyltransferases (UGTs) (~50%).
Half-life elimination: 24 to 41 hours.
Time to peak: ~0.5 hour.
Excretion: Feces: ~86% (5.5% as unchanged drug); Urine: <4%.
Clearance/F: 19 L/hour.
