Daprodustat

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. JESDUVROQ is a hypoxia-inducible factor prolyl hydroxylase (HIF PH) inhibitor indicated for the treatment of anemia due to chronic kidney disease in adults who have been receiving dialysis for at least four months. Limitations of Use Not shown to improve quality of life, fatigue, or patient well-being.

Daprodustat is a reversible inhibitor of HIF-PH1, PH2 and PH3 (IC 50 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.

• Administer orally once daily, with or without food. • See Full Prescribing Information for starting dosage based on hemoglobin level, liver function and concomitant medications, and for dose titration and monitoring recommendations.

JESDUVROQ is contraindicated in patients: • Receiving a strong CYP2C8 inhibitor such as gemfibrozil. • With uncontrolled hypertension. • Strong cytochrome P450 2C8 (CYP2C8) inhibitors such as gemfibrozil. • Uncontrolled hypertension.

Boxed warning: increases the risk of thrombotic vascular events, including major adverse cardiovascular events (MACE). 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. • Risk of Hospitalization for Heart Failure: Increased in patients with a history of heart failure. • Hypertension: Worsening hypertension, including hypertensive crisis may occur. Monitor blood pressure. Adjust anti-hypertensive therapy as needed. • Gastrointestinal Erosion: Gastric or esophageal erosions and gastrointestinal bleeding have been reported. • Not indicated for treatment of anemia of CKD in patients who are not dialysis-dependent. • Malignancy: May have unfavorable effects on cancer growth.

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. • Risk of Hospitalization for Heart Failure. • Hypertension. • Gastrointestinal Erosion. Most common adverse reactions (incidence ≥10%) are hypertension, thrombotic vascular events, and abdominal pain.

• Moderate CYP2C8 Inhibitors: Reduce starting dose. • CYP2C8 Inducers: Monitor hemoglobin and adjust the dose of JESDUVROQ as appropriate.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F to 86°F).