Daprosis

Daprodustat is a hypoxia-inducible factor, prolyl hydroxylase inhibitor (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. Activation of the HIF pathway is important in the adaptive response to hypoxia to increase red blood cell production. Through the reversible inhibition of HIF-PH, Daprodustat stimulates a coordinated erythropoietic response that includes the increase of plasma endogenous erythropoietin (EPO) levels, regulation of iron transporter proteins and reduction of hepcidin (an iron regulator protein that is increased during inflammation in CKD). This results in improved iron bioavailability, increased Hb production and increased red cell mass.

CYP2C8 Inhibitors: Concomitant administration of strong CYP2C8 inhibitors (e.g., gemfibrozil) with Daprodustat is contraindicated due to a marked increase in daprodustat exposure.

CYP2C8 Inducers: CYP2C8 inducers (e.g., rifampin) may decrease Daprodustat exposure, which may result in loss of efficacy.

• Risk of hospitalization due to heart failure
• High blood pressure
• Damage to the lining of the stomach, the tube that connects the mouth and stomach (esophagus), and intestines (gastrointestinal erosion).

• Increased Risk of Death, Myocardial Infarction, Stroke, Venous Thromboembolism, & Thrombosis of Vascular Access
• Risk of Hospitalization for Heart Failure
• Hypertension
• Gastrointestinal Erosion
• Serious Adverse Events in Patients with Anemia Due to Chronic Kidney Disease and Not on Dialysis
• Malignancy

Headache and gastrointestinal adverse reactions (e.g., nausea) may be seen with acute overdose with Daprodustat. There is no specific antidote. Hemodialysis will not substantially remove Daprodustat because it is highly protein bound.

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