Materia Medica

Dosing

Daprodustat dosing should be individualized so patients are on the lowest dose to reduce the need for red blood cell transfusions. As with ESAs, doses should not be used to target a Hb concentration greater than 11 g/dL. Starting doses of daprodustat are found in the tables below, differing between patients not on ESA therapy and those who are.6

Starting Dose for Adults not Receiving an ESA

Contraindications, Warnings, and Adverse Reactions

Starting Dose for Adults Switching from an ESA

The use of daprodustat is contraindicated in those taking strong CYP2C8 inhibitors or who have uncontrolled hypertension. Providers should avoid using daprodustat in those who have had a myocardial infarction, cerebrovascular event, or acute coronary syndrome within the three months before consideration of therapy.6 Most common adverse reactions reported in the ASCEND-D trial were hypertension (16%), diarrhea (11%), and headache (8%). Some patients experienced other serious effects such as hospitalization due to heart failure (28.6%), gastrointestinal erosions (4.0%), and malignancy (3.2%). Although there are serious risks associated with daprodustat, they are similar to the risks of using ESAs. Additionally, as previously mentioned, the ASCEND-D trial showed no significant difference between daprodustat and ESAs in terms of safety data.7

Drug Interactions

of 24 mg once daily. Doses should be adjusted for patients with moderate hepatic impairment (Child-Pugh Class B) and those taking moderate CYP2C8 inhibitors. For moderate hepatic impairment, starting doses should be reduced by half unless the starting dose is 1 mg. Use is not recommended in patients with severe hepatic impairment (Child-Pugh Class C). For patients taking clopidogrel or moderate CYP2C8 inhibitors, starting doses should also be reduced by half, except in those whose starting dose is 1 mg.6

Monitoring

After initiation and each dose adjustment, monitor Hb every two weeks for the first month and every four weeks after. If adjusting a dose, increase or decrease by one dose level at a time. If a clinically meaningful increase in Hb is not achieved by week 24 of therapy, daprodustat should be discontinued. Recommendations for dose adjustments based on Hb levels are below.6

Daprodustat is metabolized through the CYP2C8 pathway and should not be used with strong CYP2C8 inhibitors due to a significant increase in daprodustat exposure. For moderate CYP2C8 inhibitors, daprodustat doses should be reduced as specified in the dosing instructions. Patients receiving CYP2C8 inducers along with daprodustat should have their Hb levels monitored, and the daprodustat dose should be adjusted when the CYP2C8 inducer is initiated or discontinued.6

Special Populations

There is a lack of data surrounding the use of daprodustat in pregnancy, lactation, and pediatrics. However, due to the presence of daprodustat in the milk of lactating rats, patients should not breastfeed during therapy and one week after discontinuation. As for geriatrics, 43% of participants treated in the ASCEND-D trial were aged 65 years and older. Evaluation • Restart at one dose level lower when Hb falls within target range