Is Farxiga (dapagliflozin) indicated for patients with Chronic Kidney Disease (CKD) without heart failure?

Farxiga (Dapagliflozin) is Indicated for CKD in Patients Without Heart Failure

Dapagliflozin is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression, regardless of heart failure status. 1

Indications for Dapagliflozin in CKD Without Heart Failure

• Dapagliflozin 10 mg once daily is FDA-approved for patients with chronic kidney disease at risk of progression, with or without heart failure 1
• The DAPA-CKD trial demonstrated that dapagliflozin reduces the primary composite outcome (sustained decline in eGFR of ≥50%, end-stage kidney disease, or death from renal or cardiovascular causes) by 39% (HR 0.61 [95% CI 0.51-0.72]) 2, 3
• The kidney-specific composite outcome (excluding cardiovascular death) was reduced by 44% (HR 0.56 [95% CI 0.45-0.68]) in CKD patients, regardless of heart failure status 2, 3
• The benefits of dapagliflozin in CKD patients are consistent regardless of whether they have heart failure at baseline (HR: 0.58 [95% CI: 0.37-0.91] with HF vs HR: 0.62 [95% CI: 0.51-0.75] without HF; P interaction = 0.59) 4

Patient Selection Criteria

• Dapagliflozin is indicated for CKD patients with eGFR 25-75 mL/min/1.73 m² and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g 2, 3
• Benefits are seen in both diabetic and non-diabetic CKD patients (HR 0.64 [95% CI 0.52-0.79] with diabetes vs HR 0.50 [95% CI 0.35-0.72] without diabetes; p interaction=0.24) 3
• Dapagliflozin is effective across various etiologies of CKD, including diabetic nephropathy (HR 0.63 [95% CI 0.51-0.78]), glomerulonephritides (HR 0.43 [95% CI 0.26-0.71]), and ischemic/hypertensive CKD (HR 0.75 [95% CI 0.44-1.26]) 3

Dosing Considerations

• For CKD indication, the recommended dose is 10 mg orally once daily 1
• Dapagliflozin can be initiated in patients with eGFR as low as 25 mL/min/1.73 m² for kidney protection 2, 1
• Dapagliflozin should not be initiated when eGFR is below 25 mL/min/1.73 m² 5, 1
• If eGFR falls below 25 mL/min/1.73 m² during treatment, the 10 mg daily dose may be continued 5

Important Limitations and Contraindications

• Dapagliflozin is not recommended for CKD treatment in patients with polycystic kidney disease 1
• It is not recommended for patients with recent history of immunosuppressive therapy for kidney disease 1
• While dapagliflozin is not recommended for glycemic control when eGFR <45 mL/min/1.73 m² (likely ineffective for this purpose), it still provides cardiovascular and renal benefits at lower eGFR levels 5, 1

Monitoring and Safety Considerations

• Assess renal function prior to initiation and periodically thereafter 5, 1
• Evaluate volume status before starting; correct volume depletion if present 5, 1
• Common side effects include increased urination, genital mycotic infections (1.5-1.7%), and urinary tract infections (2.3-2.7%) 2, 6
• Consider withholding dapagliflozin for at least 3 days prior to major surgery or procedures requiring prolonged fasting 5
• The safety profile is consistent among patients with and without heart failure 4, 7

Clinical Implementation

• Dapagliflozin can be used safely in combination with other cardiovascular medications without increased adverse events 7
• The benefits of dapagliflozin on kidney outcomes are consistent regardless of concomitant cardiovascular medication use 7
• All-cause mortality is significantly decreased in CKD patients taking dapagliflozin compared to placebo (P < 0.004) 2