Daprodustat is used to treat anemia caused by chronic kidney disease (CKD) in adult patients who have been on dialysis for a minimum of four months.

This medicine is not intended to be used:

• As a replacement for red blood cell transfusions when rapid correction of anemia is needed.
• For treating anemia related to chronic kidney disease in patients who are not undergoing dialysis.

Daprodustat is a hypoxia-inducible factor–prolyl hydroxylase inhibitor (HIF-PHI). It works by blocking HIF-PH enzymes, which normally regulate the breakdown of hypoxia-inducible factor (HIF), a key transcription factor that controls genes responsible for red blood cell production (erythropoiesis). Activation of the HIF pathway is essential for the body’s adaptation to low oxygen levels (hypoxia), as it helps increase red blood cell formation. By reversibly inhibiting HIF-PH, Daprodustat triggers a coordinated increase in red blood cell production. This includes raising endogenous erythropoietin (EPO) levels, regulating iron transport proteins, and reducing hepcidin (an iron-regulating hormone that is often elevated during inflammation in chronic kidney disease). As a result, iron availability improves, hemoglobin (Hb) production increases, and the total red blood cell mass is enhanced.

Pre-Treatment and On-Treatment Evaluations of Anemia, Iron Stores, and Liver Tests

Evaluation of Anemia and Iron Stores: Correct and exclude other causes of anemia (e.g„vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding) before initialing Daprodustat, Evaluate the iron status in all patients before and during treatment with Daprodustat. Administer supplemental iron therapy when serum ferritin is less than 100 mcg/mL or when serum transferrin saturation is less than 20%. The majority of patients with CKD will require supplemental iron during the course of therapy.

Liver Testing: Assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin prior to initiation of Daprodustat. Repeat the liver tests if the patient develops signs or symptoms that could be consistent with liver disease during treatment with Daprodustat.

Important Dosing Information: Individualize dosing and use the lowest dose of Daprodustat sufficient to reduce the need for red blood cell transfusions. Do not target a hemoglobin higher than 11 g/dL. Daprodustat can be taken with or without food, and without regard to concomitant administration of iron or phosphate binders. Daprodustat should be swallowed whole. Tablets should not be cut, crushed, or chewed. Daprodustat can be administered without regard to the timing or type of dialysis, if a dose of Daprodustat is missed, it should be taken as soon as possible, unless it is the same day as the next dose. In this case, the missed dose should be skipped, and the next  বাংলায় দেখুন dose taken at the usual time. Double-doses should not be taken to make-up for a missed dose.

Recommended Starting Dose of Daprodustat: Adults with Anemia Due to Chronic Kidney Disease Receiving Dialysis for at least 4 Months

Adults Not Being Treated with an ESA: For adults not being treated with an ESA, the starting dose of Daprodustat is based on the hemoglobin level. Dose modifications are needed for patients receiving concomitant treatment with a moderate CYP2C8 inhibitor or moderate hepatic impairment.

Monitoring Response to Therapy and Dose Adjustment: Following initiation of therapy and after each dose adjustment, monitor hemoglobin every 2 weeks for the first month and then every 4 weeks thereafter. When adjusting doses of Daprodustat, consider hemoglobin rate of rise, rate of decline and hemoglobin variability. Do not increase the dose of Daprodustat more frequently than once every 4 weeks 

• If the dose of Daprodustat needs to be adjusted, increase or decrease by one dose level at a time
• Decrease the dose of Daprodustat if hemoglobin increases rapidly (e.g., greater than 1 g/dL over 2 weeks or greater than 2 g/dL over 4 weeks) or if the hemoglobin exceeds 11 g/dL
• If hemoglobin exceeds 12 g/dL, interrupt treatment with Daprodustat, When the hemoglobin is within the target range, treatment may be restarted at one dose level lower
• Treatment with Daprodustat should not be continued beyond 24 weeks of therapy if a clinically meaningful increase in hemoglobin level is not achieved. Alternative explanations for an inadequate response should be sought and treated before re-starting therapy.

Dosage Modification for Hepatic Impairment: Reduce the starting dose of Daprodustat by half in patients with moderate hepatic impairment (Child-Pugh Class B) except in patients whose starting dose is already 1 mg. Use of Daprodustat in patients with severe hepatic impairment (Child-Pugh Class C) is not recommended.

Dosage Modification for Concomitant Treatment with Moderate CYP2C8 Inhibitors: Reduce the starting dose of Daprodustat by half in patients who are on clopidogrel or a moderate CYP2C8 inhibitor except in patients whose starting dose is already 1 mg. Monitor hemoglobin and adjust the dose of Daprodustat when initiating or stopping therapy with clopidogrel or a moderate CYP2C8 inhibitor during treatment with Daprodustat.

CYP2C8 Inhibitors:
The use of strong CYP2C8 inhibitors (such as gemfibrozil) together with Daprodustat is contraindicated, as it can significantly increase Daprodustat exposure in the body.

CYP2C8 Inducers:
CYP2C8 enzyme inducers (such as rifampin) may reduce Daprodustat exposure in the body, which can lead to decreased effectiveness of the treatment.

• Patients who are taking a strong CYP2C8 inhibitor (e.g., gemfibrozil).
• Patients with poorly controlled (uncontrolled) hypertension.

• Increased risk of hospitalization due to heart failure
• Elevated blood pressure (hypertension)
• Damage or erosion of the lining of the gastrointestinal tract, including the stomach, esophagus (food pipe), and intestines

May cause harm to the fetus. Breastfeeding is not recommended until at least one week after the last dose.

• Increased risk of death, heart attack (myocardial infarction), stroke, venous thromboembolism, and thrombosis of vascular access
• Higher risk of hospitalization due to heart failure
• Elevated blood pressure (hypertension)
• Gastrointestinal tract erosion
• Serious adverse events in patients with anemia due to chronic kidney disease who are not on dialysis
• Risk of malignancy (cancer)

Use in children: The safety and effectiveness of Daprostat in pediatric patients have not been established.

Headache and gastrointestinal side effects (such as nausea) may occur in cases of acute Daprodustat overdose. There is no specific antidote available. Hemodialysis is not effective in significantly removing Daprodustat due to its high protein binding

Store at a temperature below 30°C in a cool, dry place. Protect from light exposure. Keep all medicines out of the reach of children.