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 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3)]</span> . Concomitant use with a strong and moderate CYP3A inducer is expected to decrease atrasentan exposure <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3)]</span> , 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 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3)]</span> . Concomitant use with a OATP1B1/1B3 inhibitor increases atrasentan exposure <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3)]</span> , which may increase the risk of VANRAFIA adverse reactions.
Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 )
4.1 Pregnancy Use of VANRAFIA is contraindicated in patients who are pregnant <span class="opacity-50 text-xs">[see Dosage and Administration (2.1), Warnings and Precautions (5.1), Use in Specific Populations (8.1)]</span> .
4.2 Hypersensitivity VANRAFIA is contraindicated in patients with a history of a hypersensitivity reaction to atrasentan or any component of the product.
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 <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) and Use in Specific Populations (8.1, 8.3)]</span> . When pregnancy is detected, discontinue VANRAFIA as soon as possible <span class="opacity-50 text-xs">[see Dosage and Administration (2.1), Contraindications (4.1), Use in Specific Populations (8.1, 8.3)]</span> .
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 <span class="opacity-50 text-xs">[see Adverse Reactions (6.1)]</span> . 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 <span class="opacity-50 text-xs">[see Adverse Reactions (6.1)]</span> . 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 <span class="opacity-50 text-xs">[see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1)]</span> .