What are the considerations for using Farxiga (dapagliflozin) in patients with impaired renal function?

Dapagliflozin (Farxiga) Use in Renal Dysfunction

Dapagliflozin should not be used for glycemic control when eGFR is less than 45 mL/min/1.73 m² as it is ineffective for this purpose, but can be initiated and continued for heart failure or chronic kidney disease benefits with eGFR as low as 25 mL/min/1.73 m². 1, 2

Renal Function Thresholds for Different Indications

For Glycemic Control in Type 2 Diabetes

• Not recommended when eGFR < 45 mL/min/1.73 m² 1
• Avoid initiating if eGFR < 60 mL/min/1.73 m² 3
• Not recommended with eGFR 30-60 mL/min/1.73 m² 3
• Contraindicated with eGFR < 30 mL/min/1.73 m² 3

For Heart Failure or Chronic Kidney Disease

• Can be initiated with eGFR ≥ 25 mL/min/1.73 m² 2
• Standard dosing: 10 mg once daily 2
• Can be continued even if eGFR falls below initiation threshold 2, 4

Monitoring Requirements

1. Before Initiation:

   • Assess renal function (eGFR)
   • Evaluate volume status
   • Correct volume depletion if present 1

2. During Treatment:

   • Monitor renal function regularly
   • Assess for signs of volume depletion, especially in:
     • Elderly patients
     • Patients with renal impairment
     • Patients on diuretics
     • Patients with low systolic blood pressure 1

Benefits in Renal Dysfunction

Despite limited glycemic efficacy in advanced renal dysfunction, dapagliflozin provides significant benefits:

• Reduces risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death in CKD patients 5
• Provides cardiovascular and renal benefits even when eGFR falls below 25 mL/min/1.73 m² 4
• Reduces primary composite outcome (cardiovascular death, hospitalization for heart failure) with HR 0.53 (95% CI: 0.33-0.83) in patients with deteriorating renal function 4
• Benefits observed regardless of diabetes status 5

Safety Considerations

• Higher incidence of adverse reactions related to volume depletion in renal impairment 1
• Withhold dapagliflozin for at least 3 days prior to major surgery or procedures with prolonged fasting 2
• Resume when patient is clinically stable and has resumed oral intake 2
• May require reduction in loop diuretic dosing due to intravascular volume contraction 2

Clinical Approach Algorithm

1. Determine indication for dapagliflozin:

   • If for glycemic control only → Do not use if eGFR < 45 mL/min/1.73 m²
   • If for heart failure or CKD → Can initiate if eGFR ≥ 25 mL/min/1.73 m²

2. For patients already on dapagliflozin who experience renal decline:

   • If using for glycemic control and eGFR falls below 45 mL/min/1.73 m² → Consider discontinuation and alternative agents
   • If using for heart failure or CKD → Continue therapy even if eGFR falls below 25 mL/min/1.73 m² as benefits persist 4

3. Dosing adjustment:

   • For all indications except glycemic control: 10 mg once daily
   • For glycemic control: Start with 5 mg daily, can increase to 10 mg daily if needed and tolerated 1

Common Pitfalls to Avoid

• Discontinuing dapagliflozin prematurely when eGFR declines in heart failure or CKD patients
• Failing to assess volume status before initiation
• Not reducing concomitant diuretic doses when needed
• Using dapagliflozin solely for glycemic control in patients with eGFR < 45 mL/min/1.73 m²
• Not monitoring for signs of volume depletion in high-risk patients

The most recent evidence strongly supports continuing dapagliflozin in heart failure patients even when renal function deteriorates, as the cardiovascular benefits persist without increased safety concerns 4.