Is Farxiga (dapagliflozin) suitable for a patient with impaired renal function?

Farxiga (Dapagliflozin) Can Be Used in Impaired Renal Function

Yes, Farxiga can and should be used in patients with impaired renal function down to an eGFR of 25 mL/min/1.73 m², and may be continued even if eGFR falls below 25 mL/min/1.73 m² during treatment. 1

Understanding the Renal Function Thresholds

The key is distinguishing between glycemic control versus cardiovascular and renal protection:

For Glycemic Control (Diabetes Management)

• Do not initiate dapagliflozin if eGFR <45 mL/min/1.73 m² when the goal is glucose lowering 2, 1
• The glucose-lowering effect diminishes significantly as kidney function declines because the drug works by blocking glucose reabsorption in the kidneys 1, 3
• Metformin should not be initiated if eGFR <45 mL/min/1.73 m² but can be continued if eGFR ≥30 mL/min/1.73 m² 2

For Cardiovascular and Renal Protection (The Primary Indication)

• Initiate dapagliflozin 10 mg daily if eGFR ≥25 mL/min/1.73 m² for heart failure or chronic kidney disease indications 2, 1
• The landmark DAPA-CKD trial enrolled patients with eGFR 25-75 mL/min/1.73 m² and demonstrated a 39% reduction in the composite endpoint of sustained eGFR decline, end-stage kidney disease, or renal/cardiovascular death 4, 1
• Continue dapagliflozin even if eGFR falls below 25 mL/min/1.73 m² during treatment, up until dialysis initiation 1

The Evidence Supporting Use in Impaired Renal Function

The DAPA-CKD trial provides the strongest evidence:

• Reduced risk of kidney disease progression by 44% (HR 0.56,95% CI 0.45-0.68) 1
• Reduced cardiovascular death or heart failure hospitalization by 29% (HR 0.71,95% CI 0.55-0.92) 2, 1
• Slowed the rate of eGFR decline over time 2, 1
• Benefits were consistent regardless of diabetes status 4

The EMPEROR-Reduced trial included patients down to eGFR 20 mL/min/1.73 m² and showed similar cardiovascular and renal benefits 2

Critical Monitoring After Initiation

Expect and accept an initial eGFR dip:

• A transient decrease of 3-5 mL/min/1.73 m² typically occurs within 1-4 weeks of starting dapagliflozin 1, 5
• This initial dip is not harmful and actually predicts better long-term renal outcomes 1
• Patients with an acute eGFR reduction >10% at 2 weeks had slower long-term eGFR decline (-1.58 vs -2.44 mL/min/1.73 m²/year) 1

Monitoring schedule:

• Check eGFR and creatinine within 1-2 weeks after initiation 2, 1
• Assess volume status before starting and monitor for intravascular volume contraction 2, 1
• If eGFR decreases >30% from baseline AND there are signs of hypovolemia, reduce diuretic doses first before considering dapagliflozin adjustment 1

Important Safety Considerations in Renal Impairment

Volume depletion risk:

• Use caution in patients already on diuretics, elderly patients, or those with low systolic blood pressure 1
• The mild diuretic effect of dapagliflozin may necessitate reduction in loop diuretic dosing 2, 6
• Assess and correct volume depletion before initiating therapy 1

Sick day management is critical:

• Withhold dapagliflozin during any acute illness, particularly with fever, vomiting, diarrhea, or reduced oral intake 1
• Hold for at least 3 days before major surgery or procedures requiring prolonged fasting 1
• Monitor for diabetic ketoacidosis even with normal blood glucose levels during illness 1
• Resume only after recovery and normal oral intake is re-established 1

Common Pitfalls to Avoid

1. Don't confuse glycemic thresholds with cardio-renal protection thresholds - The eGFR <45 mL/min/1.73 m² contraindication applies only to glucose lowering, not to heart failure or CKD indications 2, 1

2. Don't stop dapagliflozin due to the initial eGFR dip - This transient decline is expected and beneficial long-term 1, 5

3. Don't overlook hyperkalemia management - Dapagliflozin actually reduces hyperkalemia risk and can facilitate use of mineralocorticoid receptor antagonists 1

4. Don't forget patient education on sick day rules - Failure to hold the medication during acute illness significantly increases risk of ketoacidosis and volume depletion 1

The Bottom Line Algorithm

For patients with impaired renal function:

• eGFR ≥45 mL/min/1.73 m²: Use dapagliflozin 10 mg daily for any indication 1
• eGFR 25-44 mL/min/1.73 m²: Use dapagliflozin 10 mg daily for heart failure or CKD protection (not for glycemic control alone) 2, 1
• eGFR <25 mL/min/1.73 m²: Do not initiate, but continue if already established 1
• On dialysis: Contraindicated 2

The cardiovascular and renal protective benefits of dapagliflozin are preserved even when glucose-lowering effects are minimal, making it an essential therapy for patients with impaired renal function 2, 1, 4