Daprodustat

Daprodustat is a HIF-PHI that reversibly inhibits HIF-PH enzymes, which control intracellular levels of HIF, a transcription factor that regulates the expression of genes involved in erythropoiesis. Through reversible inhibition of HIF-PH, Daprodustat stimulates a coordinated erythropoietic response that includes increase of plasma endogenous EPO levels, regulation of iron transporter proteins, and reduction of hepcidin. This results in improved iron bioavailability, increased Hb production, and increased red cell mass.

• Anemia due to chronic kidney disease (CKD) in adults on dialysis for at least 4 months

Daprodustat is a HIF-PHI. The activity of HIF-PH enzymes controls intracellular levels of HIF, a transcription factor that regulates the expression of genes involved in erythropoiesis. Through the reversible inhibition of HIF-PH, Daprodustat stimulates a coordinated erythropoietic response that includes the increase of plasma endogenous EPO levels, regulation of iron transporter proteins and reduction of hepcidin. This results in improved iron bioavailability, increased Hb production and increased red cell mass.

Daprodustat reversibly inhibits HIF-PH enzymes, stabilizing HIF, which increases EPO production and improves iron metabolism, leading to increased red blood cell production.

Not on ESA: Hb <9 g/dL: 4 mg once daily; Hb 9-10 g/dL: 2 mg once daily; Hb >10 g/dL: 1 mg once daily.

Switching from ESA: Based on prior ESA dose, dose ranges from 4-12 mg once daily. Maximum dose: 24 mg once daily.

Moderate hepatic impairment: Reduce starting dose by half. Not recommended in severe hepatic impairment.

Take with or without food. Swallow tablet whole, do not cut, crush, or chew. Can be administered without regard to dialysis timing or type.

If you miss a dose, take it as soon as possible, unless it is the same day as the next dose. In that case, skip the missed dose. Do not double the dose.

Serious: Risk of hospitalization due to heart failure, high blood pressure, gastrointestinal erosion (damage to the lining of the stomach, esophagus, and intestines).

Increased risk of death, MI, stroke, VTE, & vascular access thrombosis; hospitalization for heart failure; hypertension; gastrointestinal erosion; serious adverse events in non-dialysis CKD patients; malignancy. May affect driving ability.

Receiving a strong CYP2C8 inhibitor (e.g., gemfibrozil); with uncontrolled hypertension.

Strong CYP2C8 inhibitors (gemfibrozil): Contraindicated (marked increase in daprodustat exposure).

CYP2C8 inducers (rifampin): May decrease daprodustat exposure, resulting in loss of efficacy.

Moderate CYP2C8 inhibitors (clopidogrel): Reduce starting dose by half.

Caution is advised when consuming alcohol with Daprodustat. Please consult your doctor.

May cause fetal harm. No adequate data in pregnant women. Use during pregnancy only if potential benefit justifies potential risk to the fetus.

Breastfeeding is not recommended until one week after the final dose.

Safety and efficacy in children have not been established.

No specific dosage adjustment is necessary for elderly patients.

Renal impairment: Safe in any degree of renal impairment. No dose adjustment recommended. Dialysis does not significantly impact daprodustat exposure.

Hepatic impairment: Moderate (Child-Pugh B): Reduce starting dose by half. Severe (Child-Pugh C): Not recommended.

Acute overdose may cause headache and gastrointestinal adverse reactions (e.g., nausea). No specific antidote. Hemodialysis will not substantially remove daprodustat (highly protein bound).

Store below 30°C, in a cool and dry place. Keep away from light. Keep out of reach of children.

Daprodustat