Daprodustat (1 brand name, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- JESDUVROQ
Boxed Warning
JESDUVROQ increases the risk of thrombotic vascular events, including major adverse cardiovascular events (MACE) [see Warnings and Precautions (5.1)]. Targeting a hemoglobin level greater than 11 g/dL is expected to further increase the risk of death and arterial venous thrombotic events, as occurs with erythropoietin stimulating agents (ESAs), which also increase erythropoietin levels [see Warnings and Precautions (5.1)]. No trial has identified a hemoglobin target level, dose of JESDUVROQ, or dosing strategy that does not increase these risks [see Dosage and Administration (2.4)]. Use the lowest dose of JESDUVROQ sufficient to reduce the need for red blood cell transfusions [see Dosage and Administration (2.4)].
Indications and Usage
JESDUVROQ is indicated for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least four months. Limitations of Use JESDUVROQ has not been shown to improve quality of life, fatigue, or patient well-being. JESDUVROQ is not indicated for use: •As a substitute for red blood cell transfusions in patients who require immediate correction of anemia. •For treatment of anemia of chronic kidney disease in patients who are not on dialysis.
Contraindications
JESDUVROQ is contraindicated in patients: •Receiving a strong CYP2C8 inhibitor such as gemfibrozil [see Drug Interactions (7.1), Clinical Pharmacology (12.3)]. •With uncontrolled hypertension [see Warnings and Precautions (5.3)].
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: •Increased Risk of Death, Myocardial Infarction, Stroke, Venous Thromboembolism, and Thrombosis of Vascular Access [see Boxed Warning, Warnings and Precautions (5.1)]. •Risk of Hospitalization for Heart Failure [see Warnings and Precautions (5.2)]. •Hypertension [see Warnings and Precautions (5.3)]. •Gastrointestinal Erosion [see Warnings and Precautions (5.4)].
Mechanism of Action
Daprodustat is a reversible inhibitor of HIF-PH1, PH2 and PH3 (IC50 in the low nM range). This activity results in the stabilization and nuclear accumulation of HIF-1α and HIF-2α transcription factors, leading to increased transcription of the HIF-responsive genes, including erythropoietin.
Overdosage
Headache and gastrointestinal adverse reactions (e.g., nausea) may be seen with acute overdose with JESDUVROQ. There is no specific antidote. Hemodialysis will not substantially remove daprodustat because it is highly protein bound.