What are the dosing regimen, contraindications, monitoring parameters, and alternative treatments for desidustat in adult chronic kidney disease (CKD)‑associated anemia?

Desidustat for CKD-Associated Anemia

Dosing Regimen

Desidustat is administered orally at 100 mg three times per week, with dose adjustments based on hemoglobin response to maintain target levels of 10-12 g/dL. 1, 2, 3

Starting Dose

• 100 mg orally three times per week is the standard starting dose for both dialysis-dependent and non-dialysis-dependent CKD patients 2, 3
• Lower starting doses should be considered for ESA-naïve patients compared to those transitioning from other ESAs 1

Dose Adjustments

• Titrate dose based on hemoglobin response, with the goal of maintaining hemoglobin between 10-12 g/dL 1, 2
• Temporarily discontinue treatment if hemoglobin exceeds 12-13 g/dL, following protocols similar to other HIF-PHIs 1
• Consider discontinuation if hemoglobin targets are not achieved despite dose escalation 1

Administration

• Administer in fasting conditions for optimal absorption 4
• Oral route provides significant practical advantages over injectable ESAs, particularly for non-dialysis and peritoneal dialysis patients 1

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Contraindications

Desidustat should not be used in patients with polycystic kidney disease, active malignancy where cure is anticipated, or pediatric patients under 18 years. 1

Absolute Contraindications

• Polycystic kidney disease - HIF activation may potentially enhance cyst expansion based on preclinical models 1
• Active malignancy when cure is the anticipated outcome, including primary and adjuvant chemotherapy for potentially curable malignancies 1
• Pediatric patients under 18 years - excluded from clinical trials 1

Relative Contraindications/Cautions

• Kidney transplant recipients - limited data and potential concerns about HIF-PHIs affecting immune cell function 1
• History of stroke - ESAs carry increased risk, and caution should be exercised with HIF-PHIs 5
• History of malignancy - use with great caution 5

Critical Safety Warning

• Never combine desidustat with erythropoietin or other ESAs - creates additive stimulation of red blood cell production, substantially increasing risk of exceeding safe hemoglobin targets and associated cardiovascular events, stroke, and mortality 6

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Monitoring Parameters

Monitor hemoglobin at least every 3 months during maintenance therapy, with more frequent monitoring during initiation or dose adjustments. 5, 1, 6

Hemoglobin Monitoring

• At least every 3 months during maintenance phase for non-dialysis patients 5
• Monthly for dialysis-dependent patients 5
• More frequently when initiating therapy, increasing dose, or when blood loss occurs 5
• Target hemoglobin range: 10-12 g/dL 1, 6, 2

Iron Status Monitoring

• Check TSAT and ferritin at least every 3 months during desidustat therapy 5, 6, 7
• Monitor more frequently when initiating or increasing dose, after blood loss, or when monitoring response to iron therapy 5
• Stop iron supplementation when ferritin >500 ng/mL or TSAT >50% 7

Safety Monitoring

• Evaluate for potential drug-drug interactions with other oral medications 1
• Monitor for thromboembolic events given the pleiotropic effects of HIF activation beyond erythropoiesis 1
• Assess cardiovascular status regularly, though specific cardiovascular safety data for desidustat in large outcomes trials is limited compared to other HIF-PHIs 1

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Alternative Treatments

ESAs (erythropoietin, darbepoetin alfa) remain the primary alternative, with iron supplementation as first-line therapy before initiating any erythropoietic agent. 5, 1

First-Line: Iron Supplementation

• Trial of IV iron (or 1-3 month trial of oral iron for non-dialysis patients) should be attempted first if TSAT ≤30% and ferritin ≤500 ng/mL 5, 7
• Oral iron: 200 mg elemental iron daily, divided into 2-3 doses, taken on empty stomach 7
• IV iron preferred when feasible for CKD stage 4-5 patients 7

Second-Line: ESAs

• Darbepoetin alfa - demonstrated non-inferiority to desidustat in the DREAM-ND trial, with mean hemoglobin change of 1.83 g/dL vs 1.95 g/dL for desidustat 2
• Epoetin alfa - shown comparable efficacy to desidustat in dialysis-dependent patients (DREAM-D trial) 3
• ESAs should only be initiated after iron stores corrected and hemoglobin remains <10 g/dL 6

Other HIF-PHIs (Alternative to Desidustat)

• Roxadustat, vadadustat, and daprodustat - have more extensive cardiovascular safety data from large phase 3 programs compared to desidustat 5, 1
• All HIF-PHIs are superior to placebo and non-inferior to ESAs in increasing and maintaining hemoglobin 1
• Target hemoglobin 10-12 g/dL applies to all HIF-PHIs, same as ESAs 1

When ESAs/HIF-PHIs Are Ineffective or Contraindicated

• Red blood cell transfusions may be necessary in patients with hemoglobinopathies, bone marrow failure, or ESA resistance 5
• Transfusions should be avoided when possible to minimize allosensitization risk in transplant-eligible patients 5

Critical Hemoglobin Targets Across All Therapies

• Never intentionally increase hemoglobin above 13 g/dL - multiple large trials demonstrate increased cardiovascular events, stroke, and mortality 5, 6
• In general, do not maintain hemoglobin above 11.5 g/dL in adult CKD patients, though individualization may be necessary for quality of life 5

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Clinical Efficacy Data

Desidustat demonstrated non-inferiority to darbepoetin in non-dialysis CKD patients (mean Hb increase 1.95 g/dL vs 1.83 g/dL) with 77.78% responders vs 68.48% 2. In dialysis-dependent patients, desidustat was non-inferior to epoetin alfa with significantly higher responder rates (59.22% vs 48.37%, p=0.0382) 3. The safety profile was comparable to ESAs with predominantly mild adverse events 2, 3, 8.