Lippincott ^® NursingCenter ^®

daprodustat

Jesduvroq

Pharmaceutical company: GlaxoSmithKline

Pharmacologic classification:Hypoxia-inducible factor prolyl hydroxylase inhibitor

Therapeutic classification:Hematopoietic

AVAILABLE FORMS

Tablets: 1 mg; 2 mg; 4 mg; 6 mg; 8 mg

INDICATIONS AND DOSAGES

Anemia due to chronic kidney disease in patients who have been receiving dialysis for at least 4 months

Adults not being treated with an erythropoiesis stimulating agent (ESA): If the pretreatment hemoglobin is less than 9 g/dL, give 4 mg PO once daily; if the pretreatment hemoglobin is 9 to 10 g/dL, give 2 mg PO once daily; if the pretreatment hemoglobin is greater than 10 to 11 g/dL, give 1 mg PO once daily.
Adults being switched from an ESA: For patients switching from epoetin alfa, darbepoetin alfa, or ethoxy PEG-epoetin beta, refer to the manufacturer's instructions for daprodustat dosing instructions based on current ESA drug and dosage.

Adjust-a-dose: Increase or decrease dose by one dose level at a time. Dose levels are 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 12 mg, 16 mg, and 24 mg. Decrease dose if hemoglobin increases rapidly by more than 1 g/dL over 2 weeks or 2 g/dL over 4 weeks, or if hemoglobin exceeds 11 g/dL. Don't increase the dose more frequently than every 4 weeks. If hemoglobin exceeds 12 g/dL, interrupt treatment. Restart at one dose level lower when hemoglobin drops to within the target range. Maximum dose is 24 mg once daily.
Reduce daprodustat starting dose by half in patients on clopidogrel or a moderate CYP2C8 inhibitor, or with moderate hepatic impairment (Child-Pugh class B), except in patients whose starting dose is already 1 mg.
Discontinue therapy if a clinically meaningful hemoglobin increase isn't achieved by 24 weeks.
 

CONTRAINDICATIONS AND CAUTIONS

• Black Box Warning: Daprodustat increases the risk of thrombotic vascular events (MI, stroke, venous thromboembolism, and vascular access thrombosis), that may be fatal.
• Alert: Patients with CV or cerebrovascular disease are at increased risk. Avoid use in patients with a history of MI, cerebrovascular event, or acute coronary syndrome within 3 months prior to starting. A hemoglobin rise of greater than 1 g/dL over 2 weeks may contribute to these risks.
• Black Box Warning: Targeting hemoglobin greater than 11 g/dL is expected to further increase the risk of death and arterial and venous thrombotic events, as occurs with ESAs, which also increase erythropoietin levels. No trial has identified a hemoglobin target, daprodustat dose or dosing strategy that does not increase these risks. Use the lowest dose sufficient to reduce the need for RBC transfusion.
• Alert: Contraindicated in patients with uncontrolled hypertension. Hypertensive crises, including hypertensive encephalopathy and seizures, have been reported.
• This drug isn't indicated for use in patients not on dialysis as they may be at greater risk for CV mortality, stroke, thromboembolism, serious acute kidney injury, hospitalization for heart failure, and serious GI erosions.
• Use in severe hepatic impairment (Child-Pugh class C) isn't recommended.
• Patients with a preexisting history of heart failure are at increased risk of hospitalization for heart failure.
• Gastric or esophageal erosions, including GI bleeding and need for RBC transfusion, may occur. Use cautiously in patients at increased risk, including patients with a history of GI erosion or peptic ulcer disease, concomitant medications that increase the risk of GI erosion, current tobacco smoking, and current alcohol use.
• Use isn't recommended in patients with active malignancies. Increased hypoxia inducible factor-1 levels may be associated with unfavorable effects on cancer growth.
• This drug has not been shown to improve quality of life, fatigue, or patient well-being.
• Daprodustat is not a substitute for transfusion in patients requiring immediate correction of anemia.
• Safety and effectiveness in children haven't been established.
• Intentional drug abuse for its rewarding psychological or physiologic effects may be seen in athletes for the effects on erythropoiesis.
• Dialyzable drug: No.

PREGNANCY-LACTATION-REPRODUCTION

• This drug is associated with adverse fetal outcomes in animal studies. Advise patients who are pregnant of the fetal risk.
• There are no data on the presence of daprodustat in human milk, the effects on the breastfed child, or effects on milk production. Due to serious adverse reactions of the drug, patients should not breastfeed during treatment and for 1 week after the final dose.

INTERACTIONS

Drug-drug. CYP2C8 inducers (rifampin): May decrease daprodustat level and decrease its efficacy. Monitor hemoglobin and adjust daprodustat dose when initiating or discontinuing CYP2C8 inducers.

Moderate CYP2C8 inhibitors (clopidogrel): May increase daprodustat level. Reduce daprodustat starting dose when initiating treatment unless starting dose is already 1 mg. Monitor hemoglobin and adjust daprodustat dose when initiating or stopping CYP2C8 inhibitors.

Strong CYP2C8 inhibitors (gemfibrozil): May increase level of daprodustat. Concomitant use in contraindicated.

Drug-lifestyle. Tobacco smoking, alcohol use: May increase risk of gastric or esophageal erosions. Discourage use together.

ADVERSE REACTIONS

CNS: stroke, dizziness.

CV: thrombotic vascular events (MI, deep vein thrombosis, pulmonary embolism, vascular access thrombosis), heart failure, hypertension..

GI: GI erosion, abdominal pain.

Other: hypersensitivity.

Reactions in bold italics are life-threatening.

Released: May 2023

Nursing Drug Handbook

© 2023 Wolters Kluwer

---

lecanemab-irmb

Download these updates as a PDF