Daprodustat drug instructions and detailed usage introduction

1. Name:

Daprodustat（Daprodustat)

Product name:JESDUVROQ, Duvroq

2. Indications:

Daprostat is approved to treat an anemic condition caused by chronic kidney disease (CKD) in adults who have been receiving dialysis for at least four months.

Limitations on use include: Daprostat has not been shown to significantly improve a patient's quality of life, reduce fatigue, or improve fitness. Therefore, dapoxostat is not indicated for the treatment of anemia in patients with chronic kidney disease who are not receiving dialysis and should not be used as an alternative to red blood cell transfusion in patients who require prompt correction of anemia.

3. Usage and dosage:

1. Preparation before medication:

1)Assessment of anemia and iron stores: Before starting treatment with daprostat, the cause of anemia must be confirmed and other possible factors, such as vitamin deficiency, metabolic or chronic inflammation, bleeding, etc., must be ruled out. At the beginning and during the treatment, the patient's iron status needs to be assessed regularly to ensure that the serum ferritin level is not less than 100ng/ml, or the serum transferrin saturation is not less than 20%. If insufficient is found, iron supplementation is required.

2) Liver function test: Before treatment with daprostat, the patient's liver function should be evaluated, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin and other indicators should be detected. If symptoms related to liver disease occur during treatment, liver function tests need to be re-tested.

2. Medication management:

Daprostat can be taken with food or alone and does not affect the use of iron or phosphate binders. Medication should be tailored to the patient's specific condition, using the lowest effective dose to reduce the need for red blood cell transfusions. During treatment, the target hemoglobin level should not exceed11g/dL.

3. Recommended dosage:

For adult patients not receiving erythropoietic agent therapy, if the hemoglobin level before treatment is less than 9g/dL, the recommended starting dose is 4 mg once a day; if it is between 9g/dL and 10g/dL, the starting dose is 2mg once a day; and if the hemoglobin level has exceeded 10g/dL, the starting dose is 1mg once a day. The maximum recommended dose is 24 mg once daily.

4. Dosage adjustment:

After treatment begins, hemoglobin levels need to be monitored every two weeks for the first month and every four weeks thereafter. When adjusting the dose, the rate of increase or decrease in hemoglobin and its variability need to be considered, and the frequency of dose adjustments should not exceed once every four weeks. If the hemoglobin rises rapidly or exceeds 11g/dL, the dose of daprostat needs to be appropriately reduced; if it exceeds 12g/dL, treatment should be interrupted.

If hemoglobin levels remain within the target range, treatment can be restarted at a lower dose level. If there is no significant increase in hemoglobin after 24 weeks of treatment, other factors that may affect the efficacy should be considered.

1) Special adjustments for hepatic impairment: For patients with moderate hepatic impairment, the starting dose should be halved, while daprostat is not recommended for patients with severe hepatic impairment.

2) Use of moderateCYP2C8 inhibitors: In patients using clopidogrel or other moderateCYP2C8 inhibitors, the starting dose should be reduced by half, and hemoglobin levels need to be monitored regularly during treatment to make appropriate dose adjustments.

4. Adverse reactions:

According to clinical studies, the most common adverse reactions of daplestat include hypertension, thrombotic vascular events and abdominal pain, with incidence rates greater than 10%.

5. Storage:

Daprostat should be stored20°C to 25°C (68°F to 77°F), with temperature fluctuations between 15°C and 30°C (59°F to 86°F) allowed.

6. Taboo:

Daprostat is contraindicated in the following patients:

Patients receiving strongCYP2C8 inhibitor treatment, such as gemfibrozil (gemfibrozil);

Patients with uncontrolled hypertension.

7. Mechanism of action:

Daprostat's mechanism of action is to reversibly inhibitHIF-PH1, PH2 and PH3, with IC50 values in the low nanomolar range. This activity promotes an increase in the stability of HIF-1α and HIF-2α transcription factors, leading to their accumulation in the nucleus, thereby enhancing the transcriptional activity of HIF-responsive genes including erythropoietin. This mechanism provides a theoretical basis for alleviating anemia caused by chronic kidney disease.

Reference materials:https://en.wikipedia.org/wiki/Daprodustat