Atrasentan

Atrasentan is a prescription medication 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) of 1.5 g/g and more.

• Atrasentan is available under the following different brand names: Vanrafia.

Common side effects of Atrasentan include:

• peripheral edema
• anemia

Serious side effects of Atrasentan include:

• serious birth defects
• symptoms of liver problems include nausea or vomiting, pain in the upper right stomach, tiredness, loss of appetite, yellowing of the skin or whites of the eyes, dark urine, fever, and itching 
• fluid retention symptoms include unusual weight gain, trouble breathing, or swelling in the ankles or legs
• decreased sperm count

Rare side effects of Atrasentan include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 0.75 mg

IgA nephropathy

• Adult dosage
  • 0.75 mg orally daily

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

Drug interaction overview

• Substrate of CYP3A and OATP1B1/1B3
• Strong or moderate CYP3A inducers
  • Avoid
  • Coadministration is expected to decrease atrasentan systemic exposure, which may reduce efficacy
• OATP1B1/1B3 inhibitors
  • Avoid
  • Coadministration may increase atrasentan systemic exposure, which may increase the risk of adverse effects

Contraindications

• Pregnancy
• History of hypersensitivity to atrasentan or any product components

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Atrasentan?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Atrasentan?”

Cautions

Embryo-fetal toxicity

• Contraindicated during pregnancy
• May cause fetal harm when administered during pregnancy
• Counsel patients who can become pregnant with potential fetal risks
• Excluding pregnancy before initiating treatment
• Advise patients to use effective contraception before starting treatment, during treatment, and for 2 weeks after discontinuing
• If pregnancy is detected, discontinue as soon as possible

Hepatotoxicity

• May cause elevations of aminotransferases, hepatotoxicity, and liver failure
• Asymptomatic and transient transaminase elevations observed
• Obtain liver enzyme testing before initiating and repeat during treatment as clinically indicated
• In patients with baseline elevated aminotransferases at baseline, consider periodic liver test monitoring
• Do not initiate with severe hepatic impairment
• Advise patients to report symptoms suggesting hepatic injury (.eg, nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching)
• Discontinue if clinically relevant aminotransferase elevations occur, or if elevations are accompanied by an increase in bilirubin more than 2x ULN, or by clinical symptoms of hepatotoxicity
• Consider reinitiation when hepatic enzyme levels normalize in patients who have not experienced clinical symptoms of hepatotoxicity or jaundice

Fluid retention

• Fluid retention observed
• Has not been evaluated in IgAN patients with heart failure
• If clinically significant fluid retention develops, consider initiating or increasing diuretic treatment and interrupting Atrasentan treatment

Decreased sperm counts

• Like other endothelin receptor antagonists (ERAs), it may have an adverse effect on spermatogenesis
• Counsel men about potential effects on fertility

Pregnancy and Lactation

• Contraindicated during pregnancy

Females and males of reproductive potential

• Pregnancy testing
  • Exclude pregnancy before initiating in females of reproductive potential
  • Instruct the patient to contact their physician immediately for pregnancy testing if the onset of menses is delayed or pregnancy is suspected
  • If pregnancy is confirmed, discuss fetal and pregnancy risks with the patient
• Contraception in females of reproductive potential
  • Use effective contraception before initiating, during treatment, and for 2 weeks after discontinuing
• Infertility
  • Decreased sperm counts observed in some patients with diabetic kidney disease (DKD) receiving atrasentan
  • Counts returned to normal levels within approximately 3 months after discontinuing the drug
  • This effect has not been studied in patients with IgAN

Lactation

• There is no data on the presence of atrasentan in human milk, effects on breastfed infants, or effects on milk production
• Owing to the potential for adverse reactions (.eg, fluid retention in breastfed infants), advise patients not to breastfeed during treatment