Daprodustat Dosage

Medically reviewed by Drugs.com. Last updated on Sep 28, 2023.

Usual Adult Dose for Anemia Associated with Chronic Renal Failure

Adults Not Being Treated with an Erythropoiesis-Stimulating Agent (ESA):

• Pre-Treatment Hemoglobin Level less than 9 g/dL: 4 mg orally once daily
• Pre-Treatment Hemoglobin Level 9 to 10 g/dL: 2 mg orally once daily
• Pre-Treatment Hemoglobin Level greater than 10 g/dL: 1 mg orally once daily

Dosing based on adults being switched from an ESA:

• Dose of daprodustat: 4 mg orally once daily
• Epoetin alfa intravenous less than or equal to 2,000 units/week
• Darbepoetin alfa subcutaneous/intravenous 20 to 30 mcg/4 weeks
• Methoxy PEG-epoetin beta subcutaneous/intravenous 30 to 40 mcg/month

• Dose of daprodustat: 6 mg orally once daily
• Epoetin alfa intravenous greater than 2,000 to less than 10,000 units/week
• Darbepoetin alfa subcutaneous/intravenous greater than 30 to 150 mcg/4 weeks
• Methoxy PEG-epoetin beta subcutaneous/intravenous greater than 40 to 180 mcg/month

• Dose of daprodustat: 8 mg orally once daily
• Epoetin alfa intravenous greater than 2,000 to less than 10,000 units/week
• Darbepoetin alfa subcutaneous/intravenous greater than 150 to 300 mcg/4 weeks
• Methoxy PEG-epoetin beta subcutaneous/intravenous greater than 180 to 360 mcg/month

• Dose of daprodustat: 12 mg orally once daily
• Epoetin alfa intravenous greater than or equal to 20,000 units/week
• Darbepoetin alfa subcutaneous/intravenous greater than 300 mcg/4 weeks
• Methoxy PEG-epoetin beta subcutaneous/intravenous greater than 360 mcg/month

Maximum dose: 24 mg orally once daily

Comments:

• Correct and exclude anemia from other causes before starting this treatment (e.g. bleeding, metabolic, vitamin deficiency or chronic inflammatory conditions).
• Check iron levels in all patients before and during treatment and provide supplemental iron therapy if serum ferritin is less than 100 mcg/mL or serum transferrin saturation is less than 20%. Most patients with chronic kidney disease (CKD) will need supplemental iron during therapy.
• Evaluate serum levels of ALT, AST, alkaline phosphatase, and total bilirubin before starting this drug. If the patient exhibits symptoms that may indicate liver disease during the treatment, conduct liver tests again.
• After starting the treatment and with every modification in dosage, it is recommended to monitor hemoglobin levels every two weeks for the first month, and then every four weeks subsequently.
• For patients switching from subcutaneous epoetin alfa it is first necessary to determine the equivalent weekly intravenous dose by multiplying the weekly subcutaneous dose by 1.42. The weekly intravenous epoetin alfa dose can then be used to determine the appropriate daprodustat starting dose.

Use: Treatment of anemia caused by CKD in adults on dialysis for at least 4 months.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Moderate hepatic impairment (Child-Pugh Class B): The initial dose should be decreased by 50%, except for patients who are already taking 1 mg as their starting dose.
Severe hepatic impairment (Child-Pugh Class C): Use is not recommended.

Dose Adjustments

When modifying dosage, take into account the hemoglobin rise rate, decline rate, and variability. Avoid increasing the dose more than once every 4 weeks.

Adjustment recommendations:

• When modifying the dosage, change the dose by one daily dose level at a time, whether increasing or decreasing.
• Daily dose levels: 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 12 mg, 16 mg, 24 mg
• Lower the dosage if hemoglobin rises too quickly (for example, by more than 1 g/dL in 2 weeks or more than 2 g/dL in 4 weeks) or if it goes beyond 11 g/dL.
• If the hemoglobin level is above 12 g/dL, discontinue treatment. Once the hemoglobin is back within the target range, resume treatment at a lower dose level.
• If treatment fails to cause a clinically significant increase in hemoglobin levels, it should not be continued beyond 24 weeks. Before resuming treatment, explore alternative reasons for an unsatisfactory response and treat accordingly.

Dosage Modification for Concomitant Treatment with Moderate CYP2C8 Inhibitors:

• In patients who are taking clopidogrel or a moderate CYP2C8 inhibitor, the starting dose of this drug should be reduced by half, unless the starting dose is already 1 mg.
• Monitor the hemoglobin levels and modify the dose of this drug when starting or stopping therapy with clopidogrel or a moderate CYP2C8 inhibitor while undergoing treatment with this drug.

Precautions

US BOXED WARNING: Increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access

• The use of this drug elevates the risk of thrombotic vascular events, which may include major adverse cardiovascular events (MACE).
• Targeting a hemoglobin level above 11 g/dL is likely to increase the risk of death and arterial venous thrombotic events, similar to the effects of erythropoietin stimulating agents (ESAs), which boost erythropoietin levels.
• There has been no study that has determined a hemoglobin target level, drug dosage, or dosing plan that doesn't raise these hazards.
• Administer the minimum effective dose of this drug that will decrease the requirement for red blood cell transfusions.

CONTRAINDICATIONS:

• Strong CYP2C8 inhibitor such as gemfibrozil
• Uncontrolled hypertension

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Individualize the dosage of this drug and administer the minimum effective dose that will decrease the requirement for red blood cell transfusions. Avoid targeting a hemoglobin level above 11 g/dL.
• This drug can be taken with or without food and regardless of the simultaneous intake of iron or phosphate binders.
• Tablets must be ingested whole and should not be crushed or chewed.
• This drug can be given regardless of the timing or modality of dialysis.
• If a dose is skipped, the patient should take it as soon as possible, unless it is close to the time for the next dose, in which case the missed dose should be skipped and the patient should resume their usual dosing schedule. Patients should not take double doses to make up for missed doses.

Storage requirements:

• Store at a temperature of 20C to 25C (68F to 77F); temporary temperature fluctuations between 15C and 30C (59F to 86F) are acceptable.

General:
This drug is not indicated:

• As a substitute for red blood cell transfusions for patients who need immediate correction of anemia.
• To treat anemia caused by chronic kidney disease in patients who are not currently undergoing dialysis.

Patient advice:

• Instruct patients to read the patient labeling approved by the FDA.
• Inform the patient about the higher risks of mortality, heart attack, stroke, blood clots in veins, and blockages in vascular access.
• Inform the patient about the risk of hospitalization due to heart failure, the symptoms and signs associated with heart failure, and the importance of promptly reporting these symptoms to their healthcare provider.
• Inform the patient about the risk of hypertension and the importance of regular blood pressure monitoring. Encourage the patient to follow the prescribed anti-hypertensive regimen.
• Patients should be informed of the risk of gastric erosions and gastrointestinal bleeding associated with this drug and advised to report any associated symptoms or signs to their healthcare provider.
• Patients should be informed of the necessity for regular hemoglobin laboratory tests.
• Patients should be informed to notify their healthcare provider if they are using potent CYP2C8 inhibitors, such as gemfibrozil, or moderate CYP2C8 inhibitors.
• Inform female patients that this drug may cause harm to a developing fetus and advise them to notify their healthcare provider immediately if they suspect or become aware of a pregnancy.
• Females should be advised not to breastfeed while receiving this drug and for a week after the last dose.

Frequently asked questions

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Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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