Instructions for Atrasentan and related precautions for use

1. Common name: Atrasentan, Atrasentan

Product name:Vanrafia, Noruida

Other names: Atrasentan hydrochloride tablets

2. Indications:

Atrasentan reduces proteinuria in adults with primary immunoglobulin Anephropathy (IgAN) who are at risk for rapid disease progression, typically with a urine protein/creatinine ratio (UPCR) ≥1.5 g/g. This indication received accelerated approval based on reduction in proteinuria. It has not been determined whether atrasentan can slow the decline in renal function in patients with IgAN.

3. Usage and dosage:

1. Pregnancy test: rule out pregnancy before starting atrasentan.

2. Recommended dosage: The recommended dosage of atrasentan is 0.75 mg, once a day, which can be taken orally with or without food. Swallow slices whole. Do not cut, crush or chew.

If you miss one or more doses, take the prescribed dose at the next scheduled time. Do not double your dose to make up for a missed dose.

4. Adverse reactions:

In clinical studies of atrasentan, common adverse reactions may include peripheral edema and anemia.

5. Supply and storage:

Atrasentan is supplied as0.75 mg tablets, stored at 20°C to 25°C (68°F to 77°F). Excursions allowed between 15°C and 30°C (59°F and 86°F). Store atrasentan tablets in the original container and dispense.

6. Taboo:

Atrasentan is contraindicated in the following patients:

1. Pregnancy: Atrasentan is contraindicated in pregnant women.

2. Allergy: This product is prohibited for patients with a history of allergic reaction to atrasentan or any component of this product.

7. Mechanism of action:

Atrasentan is an ETA receptor antagonist (Ki = 0.034 nM). Its selectivity for ETA receptors is more than 1800 times that of endothelin type B receptors (Ki = 63.3 nM). Endothelin (ET)-1 is believed to be involved in the pathogenesis of IgAN through ETAR.

8. Notes:

1. Embryo-fetal toxicity: According to data from animal reproduction studies, atrasentan may cause harm to the fetus when used in pregnant women and is contraindicated during pregnancy. Available human data on endothelin receptor antagonists do not demonstrate the presence or absence of major birth defects associated with atrasentan use.

Inform potentially pregnant patients of the potential risk to the fetus. Rule out pregnancy before initiating treatment with atrasentan. Advise patients to use effective contraception before starting treatment, during treatment, and for two weeks after discontinuing Vigenta. Atrasentan should be discontinued as soon as possible when pregnancy is detected.

2. Hepatotoxicity: Some endothelin receptor antagonists (ERAs) cause elevated transaminases, hepatotoxicity and liver failure. Asymptomatic and transient aminotransferase elevations have been observed in patients treated with atrasentan. Perform liver enzyme tests before initiating atrasentan and repeat during treatment as clinically indicated. Consider periodic monitoring with liver examinations in patients with elevated baseline transaminases (>3 times the upper limit of normal [ULN]). Do not use atrasentan in patients with severe hepatic impairment.

Advise patients to report symptoms suggestive of liver injury (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching). Discontinue use if clinically relevant transaminase elevations occur, or if the elevation is accompanied by an increase in bilirubin >2 times the ULN, or if there are clinical signs of hepatotoxicity. Consider reinitiating atrasentan when liver enzyme levels are normal in patients without clinical signs of hepatotoxicity or jaundice.

3. Fluid retention:Fluid retention may occur with ERAs and has been observed in clinical studies with atrasentan. Atrasentan has not been evaluated in patients with IgAN heart failure. If clinically significant fluid retention occurs, consider initiating or increasing diuretic therapy and interrupting atrasentan therapy.

4. Decreased sperm count: Atrasentan is similar to other inhibitors and may have an adverse effect on spermatogenesis. Men are advised to be aware of the potential effects on fertility.

Reference materials:https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9a7e7f85-bfd0-44a0-beda-3bcfa8215c64