What is the recommended dosing regimen of desidustat for an adult patient with end‑stage renal disease on dialysis?

Desidustat Dosing in End-Stage Renal Disease on Dialysis

For adult patients with ESRD on dialysis, desidustat should be initiated at 100 mg orally three times per week on non-dialysis days, with dose titration to 150 mg or 200 mg three times weekly based on hemoglobin response. 1

Starting Dose and Administration Schedule

• Begin with desidustat 100 mg orally three times per week (every other day dosing pattern) in dialysis-dependent patients 1
• Administer on non-dialysis days to prevent premature drug removal, following the standard principle for medications in ESRD patients 2
• The medication should be taken in fasting conditions (empty stomach) 3

Dose Titration Algorithm

• Assess hemoglobin response at 6 weeks: if hemoglobin increase is <1 g/dL, escalate to 150 mg three times weekly 3
• Further escalation to 200 mg three times weekly may be considered if response remains inadequate at 150 mg dose 3
• The 200 mg dose achieved a mean hemoglobin increase of 2.92 g/dL with an 83% responder rate (≥1 g/dL increase) in clinical trials 3

Target Hemoglobin Range

• Aim for hemoglobin levels of 10-12 g/dL, consistent with standard anemia management in dialysis patients 4
• Evaluate hemoglobin response during weeks 16-24 as the primary efficacy endpoint 1

Pharmacokinetic Considerations in ESRD

• No dose adjustment is required based on renal function alone—steady-state pharmacokinetic properties (Cmax, AUC, tmax) of desidustat are comparable between patients with normal renal function and those with advanced CKD or on dialysis 5
• Metabolite exposure (AUC and Cmax) is higher in dialysis patients compared to those with normal renal function, but this does not necessitate dose reduction 5
• Hemodialysis does not significantly alter desidustat pharmacokinetics—there is no clinically relevant difference in drug exposure between dialysis and non-dialysis days 5

Efficacy Evidence in Dialysis Populations

• In the DREAM-D trial of dialysis-dependent patients, desidustat demonstrated non-inferiority to darbepoetin for treating anemia 4
• The hemoglobin responder rate (≥1 g/dL increase) was 77.78% with desidustat versus 68.48% with darbepoetin (p=0.0181), showing statistical superiority in response rate 1
• Desidustat significantly reduced hepcidin levels compared to ESA therapy, potentially improving iron utilization 1

Safety Monitoring

• Monitor hemoglobin levels every 2-4 weeks during dose titration, then monthly once stable 1
• Assess iron parameters (ferritin, transferrin saturation) as desidustat increases iron utilization and may unmask functional iron deficiency 1
• Monitor for cardiovascular events, as HIF-PHI agents have theoretical thrombotic risk (though desidustat was well-tolerated in phase 3 trials) 1
• VEGF levels should be monitored if clinically indicated, though changes were not statistically significant in trials 1

Common Pitfalls to Avoid

• Do not administer desidustat on dialysis days—this wastes the dose through dialytic removal 2
• Do not use desidustat as monotherapy if iron deficiency is present—ensure adequate iron stores (ferritin >100 ng/mL, TSAT >20%) before initiating therapy 1
• Do not continue ineffective dosing beyond 6-8 weeks—if hemoglobin fails to increase by ≥1 g/dL, escalate the dose rather than prolonging inadequate therapy 3
• Do not combine desidustat with ESAs initially—desidustat is designed as ESA replacement therapy, though low-dose roxadustat (a related HIF-PHI) combined with ESA has shown efficacy in ESA-resistant cases 6

Alternative Dosing Strategy for ESA-Resistant Anemia

• If patients have documented ESA resistance (requiring high ESA doses with poor response), consider low-dose roxadustat 50-60% of standard dose combined with continued ESA therapy as an alternative approach, though this is off-label for desidustat 6
• This combination strategy achieved a 72% hemoglobin response rate in ESA-resistant hemodialysis patients 6