What is the recommended dosage of Desidustat (Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor) for patients with Chronic Kidney Disease (CKD)?

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Desidustat Dosing in CKD Patients

Desidustat should be initiated at 100 mg orally three times per week in non-dialysis-dependent CKD patients with anemia, with dose adjustments available up to 200 mg three times per week based on hemoglobin response. 1, 2

Starting Dose and Administration

  • Initiate desidustat at 100 mg orally three times per week in non-dialysis-dependent CKD patients with baseline hemoglobin between 7.0-10.0 g/dL 1
  • Administer doses on alternate days (e.g., Monday, Wednesday, Friday) in fasting conditions 2
  • This starting dose demonstrated a mean hemoglobin increase of 1.57 g/dL over 6 weeks, with 66% of patients achieving ≥1 g/dL hemoglobin increase 2

Dose Titration Strategy

Available dose escalation options include 150 mg and 200 mg three times per week, depending on hemoglobin response:

  • 150 mg three times per week produces a mean hemoglobin increase of 2.22 g/dL with 75% responder rate 2
  • 200 mg three times per week achieves a mean hemoglobin increase of 2.92 g/dL with 83% responder rate 2
  • Dose adjustments should be made based on hemoglobin response during the evaluation period of weeks 16-24 1

Target Hemoglobin Range

  • Aim for hemoglobin levels between 10.0-12.0 g/dL (100-120 g/L) 1
  • Approximately 77.78% of patients achieved hemoglobin response with desidustat treatment over 24 weeks 1

Monitoring Parameters

Check the following at baseline and during treatment:

  • Hemoglobin levels should be monitored at weeks 6,12,16, and 24 to assess response 1, 2
  • Hepcidin levels decrease significantly with desidustat treatment (statistically significant at weeks 12 and 24) 1
  • Low-density lipoprotein cholesterol decreases significantly by week 24 1
  • VEGF levels should be monitored, though changes are not statistically significant compared to erythropoiesis-stimulating agents 1
  • Vital signs, electrocardiographic parameters, and safety laboratory values require routine monitoring 2

Special Considerations for CKD Stages

  • Desidustat is specifically indicated for non-dialysis-dependent CKD patients 1, 2
  • The drug has been studied in CKD patients across various stages without dialysis need 1
  • No specific dose adjustments are provided based on CKD stage in the available evidence, though all patients must have non-dialysis-dependent disease 1

Pharmacokinetic Properties

  • Desidustat demonstrates dose-related increases in both Cmax and AUC 2
  • The drug exhibits predictable pharmacokinetics with dose-proportional exposure across the 100-200 mg range 2

Safety Profile

Desidustat is well-tolerated with minimal adverse events:

  • Only 18 patients (15.4%) experienced treatment-emergent adverse events in phase 2 trials 2
  • Five patients (4.3%) reported drug-related mild adverse events 2
  • No deaths or serious adverse events were reported during clinical trials 2
  • The drug demonstrates comparable safety to biosimilar darbepoetin over 24 weeks 1

Comparative Efficacy

  • Desidustat is non-inferior to darbepoetin 0.75 μg/kg subcutaneously once every 2 weeks for treating anemia in non-dialysis-dependent CKD 1
  • The hemoglobin change from baseline to weeks 16-24 was 1.95 g/dL with desidustat versus 1.83 g/dL with darbepoetin (difference: 0.11 g/dL; 95% CI: -0.12,0.34) 1

Mechanism-Based Benefits

  • Desidustat improves iron utilization by decreasing hepcidin levels 1, 3
  • The drug reduces inflammation markers (IL-6, IL-1β) and increases liver ferroportin 3
  • It can overcome erythropoietin hyporesponsive states by reducing EPO requirements and anti-EPO antibodies 3

Common Pitfalls to Avoid

  • Do not use desidustat in dialysis-dependent CKD patients - the evidence base is specifically for non-dialysis-dependent patients 1, 2
  • Avoid administering with food - doses should be given in fasting conditions 2
  • Do not skip the alternate-day dosing schedule (three times per week) - this is the validated regimen 1, 2
  • Do not exceed 200 mg three times per week without additional safety data 2

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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