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Daprodustat (Jesduvroq-GSK) Oral Tablets for Anemia of CKD


Drug Name: Daprodustat

Brand Name: Jesduvroq

FDA Approval Date: 1st Feb 2023 [Ref]

Primary Indication: Anemia of CKD

Manufacturer’s Name: GlaxoSmithKline (GSK)

Jesduvroq tablets (Daprodustat) are the first FDA-approved oral treatment indicated for the treatment of anemia in CKD patients who are on dialysis for at least four months.

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Daprodustat (Jesduvroq) Indications:

JESDUVROQ is a medication that is used to treat anemia in adults who have chronic kidney disease and who are on maintenance dialysis for at least four months.

It is not indicated for the rapid correction of hemoglobin or as a substitute for blood transfusion.

It has also not been approved for CKD patients who are not on dialysis.

Daprodustat (Jesduvroq) Dosage:

General instructions before treatment initiation:

  • Use the smallest effective dose.
  • The target hemoglobin should not exceed 11 gm/dl
  • The drug can be taken regardless of the timings of the meals and type or timing of dialysis or with iron or phosphate binders.
  • The tablets should be swallowed whole without chewing, crushing, or opening them.
  • Double dosing to make up for the missed dose should be avoided.

Check LFTs and Blood CBC before starting the treatment:

  • Check LFTs before starting the treatment. If the tests are abnormal, recheck them. Although dose adjustment is not recommended in deranged LFTs, monitoring is recommended.
  • Exclude other causes of anemia such as iron deficiency, vitamin B12 deficiency, and blood loss. In case of iron deficiency (Ferritin of less than 100 mc/ml or TSats of less than 20%), iron supplementation is recommended.

Recommended Starting Dose of Daprodustat (Jesduvroq):

The starting dose will depend on the hemoglobin level and the current dose of an erythropoiesis-stimulating agent (ESA).

  • Starting Dose for Adults Not Being Treated with an ESA:

The recommended dose is based on baseline Hb:

  • Hemoglobin level <9 g/dL:
    • 4 mg per day
  • Hemoglobin level ≥9 to ≤10 g/dL:
    • 2 mg per day
  • Hemoglobin level >10 g/dL:
    • 1 mg per day
  • Starting Dose for Adults Being Switched from an ESA:

Starting Dose of Daprodustat (Jesduvroq) for Adults on Dialysis Switching from an Erythropoiesis-Stimulating Agent is given in the table below:

Current Dose of ESA

Dose of Jesduvroq

Epoetin Alfa IV (units/week)
  • >/= 2,000 units/week:
    • 4 mg
  • >2,000 to < 10,000:
    • 6 mg
  • >10,000 to < 20,000:
    • 8 mg
  • > 20,000:
    • 12 mg
Darbepoetin Alfa S/C or IV (mcg/month)
  • >/= 30:
    • 4 mg
  • > 30 to 150:
    • 6 mg
  • >150 to 300:
    • 8 mg
  • > 300:
    • 12 mg
Methoxy PEG-Epoetin Beta S/C or IV (mcg/month)
  • >/= 40:
    • 4 mg
  • > 40 to 180:
    • 6 mg
  • >180 to 360:
    • 8 mg
  • > 360:
    • 12 mg

If the patient is using subcutaneous epoetin alfa, their dose needs to be converted to an intravenous dose by multiplying the weekly subcutaneous dose by 1.42.

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Monitoring Response to Therapy

To ensure optimal treatment with JESDUVROQ, it is important to monitor the hemoglobin levels of patients regularly.

This should be done every 2 weeks during the first month of therapy and monthly thereafter. Consider the rate of rise, decline, and variability of hemoglobin levels when adjusting the dose.

Dose Adjustment

  • Adjust the dose not more than once a month and by one level at a time

The dose should be decreased if:

  • The rise in Hb is greater than 1 g/dL over 2 weeks or more than 2 g/dL over 4 weeks, or
  • The Hb level exceeds 11 g/dL.

Stop Treatment

  • If the Hb level exceeds 12 g/dL. May restart at a lower dose once the Hb drops.

Discontinuation of Treatment

If there is no significant improvement in the hemoglobin level after 24 weeks of treatment with JESDUVROQ, the medication should be stopped.

Before restarting treatment, it is important to identify and treat any underlying issues that may have caused the inadequate response.

Dosage Modification for Hepatic Impairment

Child-Pugh ClassStarting Dose
A2 mg/day
B1 mg/day (or half of the usual starting dose)
CNot recommended

Dosage Modification with Moderate CYP2C8 Inhibitors

CYP2C8 InhibitorStarting Dose
None2 mg/day
Moderate1 mg/day (or half of the usual starting dose)
Clopidogrel1 mg/day (or half of the usual starting dose)
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Contraindications to Daprodustat (Jesduvroq):

The use of JESDUVROQ is prohibited in patients who:

  • Are currently receiving a potent CYP2C8 inhibitor such as gemfibrozil
  • Have uncontrolled high blood pressure

Warning and Precautions:

JESDUVROQ is a drug prescribed to treat anemia in adults with chronic kidney disease who are on dialysis.

However, there are some important warnings and precautions that should be taken into account before starting treatment.

  • Increased Risk of Thrombotic Events:

Daprodustat (Jesduvroq) increases the risk of thrombosis and cardiovascular events. CKD patients who are on dialysis and receiving Daprodustat (Jesduvroq) may develop:

  • Myocardial infarction
  • Ischemic stroke
  • Deep vein thrombosis, and
  • Pulmonary embolism.

Because of the above-mentioned thrombotic episodes, the risk of death increases.

It should be used with caution in patients with underlying cardiovascular diseases or those with a prior history of thrombosis.

If there has been a recent cardiovascular event like stroke or MI within the past three months, the drug should not be used.

It is best to target a Hemoglobin not exceeding 11 g/dl as overcorrection, as well as rapid correction of hemoglobin (1 gm over 2 weeks), increase the risk of thrombotic events and death.

To avoid serious complications such as stroke or MI, it is best to use the lowest effective dose.

  • Risk of Hospitalization for Heart Failure:

Daprodustat (Jesduvroq) increases the risk of symptomatic heart failure and the need to hospitalize the patient.

The rates of hospitalizations due to heart failure in patients receiving Daprodustat were higher compared to those receiving recombinant human erythropoietin (rhEPO).

The manufacturer recommends avoiding it in patients with a history of heart failure or those with symptomatic heart failure especially who have been recently hospitalized.

  • Hypertension:

Daprodustat (Jesduvroq) has been associated with worsening hypertension including severe cases of hypertension such as hypertensive encephalopathy and seizures.

In clinical trials, 24% of the patients were observed to experience a worsening of their hypertension with 3.1%  of the patients developing severe hypertension and hypertensive crisis.

When Daprodustat treatment is started, patients should monitor their blood pressure frequently. The blood pressure medicines may need to be adjusted too.

  • Gastrointestinal Erosion:

Gastritis and gastric erosions are common with the treatment. In studies, 5.7% of the patients in the treatment group develop gastric erosions while 3.6% had severe erosions resulting in GI bleeding and the need to transfuse blood.

Patients should be informed about the symptoms of gastritis and GI bleeding. Prophylactic antacids or PPIs may be added to the treatment regimen to reduce the risk of gastric erosions.

However, if the patient’s symptoms worsen or there is bleeding, early intervention is necessary.

  • CKD patients not on dialysis:

The drug is not approved for treating anemia in CKD patients who are not on dialysis. Non-dialysis CKD patients had an increased risk of:

  • Cardiovascular mortality
  • Stroke
  • Myocardial infarction
  • Thrombosis
  • Embolism
  • Acute on chronic kidney disease
  • Symptomatic heart failure requiring hospitalization, and
  • Gastrointestinal erosions.
  • Malignancy:

Daprodustat (Jesduvroq) may increase the risk of cancers. The risk was estimated to be 4.4% (1.9 cases per 100 patient years).

It should be avoided in patients with anemia of chronic disease secondary to cancers and in patients with active ongoing cancer.

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Side Effects of Daprodustat (Jesduvroq):

The common and serious side effects of Daprodustat (Jesduvroq):

Common side effects

Severe side effects

Nausea and eructationsBlood clots
DiarrheaHeart attack
Stomach painHigh blood pressure
HeadacheSevere allergic reactions
FatigueLiver problems
DizzinessWorsening of kidney function
Joint painCancers

In clinical trials, the most common side effects noted were abdominal pain, hypertension, and thrombotic events.

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Daprodustat (Jesduvroq) Drug interactions:



CYP2C8 InhibitorsAvoid taking strong CYP2C8 inhibitors (such as gemfibrozil) with JESDUVROQ, as it can lead to a significant increase in the plasma levels of Daprodustat.

Concomitant use of moderate CYP2C8 inhibitors (such as clopidogrel) can increase Daprodustat levels. Lower the starting dose of Daprodustat by half (except for patients already on 1 mg).

Hemoglobin levels should be monitored, and the dose of Daprodustat (Jesduvroq) should be adjusted with clopidogrel or other moderate CYP2C8 inhibitor during the treatment.

CYP2C8 InducersCYP2C8 inducers (such as Rifampin) can decrease the levels of Daprodustat in the plasma reducing its efficacy.

Monitor hemoglobin levels with CYP2C8 inducers during the treatment.

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Use Of Daprodustat (Jesduvroq) in Specific Populations


  • The drug has not been studied in pregnant women. Avoid using it during pregnancy because of potential serious birth defects.


  • Avoid the drug during breastfeeding and at least for a week after the last dose.
  • The drug can enter breast milk and may increase the risk of thrombotic events in the child.

Pediatric Use:

  • Not studied in children.

Geriatric Use:

  • No difference in safety and efficacy was observed in older people.

Hepatic Impairment:

  • No dose adjustment is recommended.

Drug abuse and dependence:

JESDUVROQ is a drug that can be misused by athletes to enhance erythropoiesis. This can be dangerous for healthy individuals as it can lead to life-threatening complications such as stroke, myocardial infarction, and thromboembolism.

Controlled substance:

  • JESDUVROQ is not a controlled substance.

Daprodustat (Jesduvroq) Overdosage:

  • Acute overdose may cause headaches and gastrointestinal adverse reactions such as nausea.
  • No specific antidote is available.
  • Daprodustat is highly protein-bound, therefore hemodialysis is not expected to substantially remove it.
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Mechanism of Action (MOA) of Daprodustat (Jesduvroq):

Daprodustat inhibits HIF-PH1, PH2, and PH3, leading to the accumulation of HIF-1α and HIF-2α transcription factors.

This increases the transcription of erythropoietin-producing genes, promoting the production of red blood cells.

The effect of Daprodustat is dose-dependent and its effects can be seen within 6 to 8 hours of administration.

It increases reticulocyte counts after 7 to 15 days, followed by an increase in red blood cell production, reaching steady-state levels after several weeks.

Daprodustat also affects iron metabolism and utilization, increasing serum transferrin and TIBC while decreasing serum ferritin, transferrin saturation, and hepcidin.

The drug has no effect on QT interval even at doses 10 times higher than the recommended dose.



AbsorptionIt is easily absorbed Peak plasma concentration: 1 to 4 hours.
DistributionIn healthy individuals, it is distributed evenly between blood and plasma, and its volume at steady-state is 14.3 liters.
Plasma Protein BindingPlasma protein binding exceeds 99%.
EliminationApproximately 1 to 4 hours.
Metabolism95% is metabolized by the enzyme CYP2C8, and 5% by CYP3A4.
ExcretionOn average, 18.9 liters of JESDUVROQ are cleared from the plasma per hour, which is equivalent to 15 liters cleared from the blood.

About 99.5% of the dose is eliminated from the body as metabolites resulting from oxidation, and the remaining portion is Daprodustat.

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Patient Counselling Information for Daprodustat (Jesduvroq):



FDA guideAdvise patients to read the FDA guide
RisksExplain the risks of death, heart attack, stroke, blood clots, thrombosis, hospitalization due to heart failure, hypertension, and GI bleeding
Regular check-upsMonitor blood pressure and check hemoglobin.
Strong inhibitorsInform the healthcare provider if using a strong or moderate CYP2C8 inhibitor
PregnancyAvoid getting pregnant.
LactationAvoid breastfeeding during the treatment and at least for one week after the last dose.
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Written by Dr. Ahmed

I am Dr. Ahmed (MBBS; FCPS Medicine), an Internist and a practicing physician. I am in the medical field for over fifteen years working in one of the busiest hospitals and writing medical posts for over 5 years.

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