Dosing Recommendations for Farxiga (Dapagliflozin) in Patients with Renal Impairment
For patients with renal impairment, Farxiga (dapagliflozin) dosing should be adjusted based on estimated glomerular filtration rate (eGFR) and treatment indication, with initiation not recommended below eGFR 25 mL/min/1.73 m² for heart failure or chronic kidney disease indications, and not recommended below eGFR 45 mL/min/1.73 m² for glycemic control in type 2 diabetes.
Dosing Based on Indication and Renal Function
For Glycemic Control in Type 2 Diabetes:
- eGFR ≥45 mL/min/1.73 m²: Standard dosing (5-10 mg once daily)
- eGFR <45 mL/min/1.73 m²: Not recommended for glycemic control 1
For Heart Failure and Chronic Kidney Disease:
- eGFR ≥25 mL/min/1.73 m²: Standard dosing (10 mg once daily)
- eGFR <25 mL/min/1.73 m²:
Clinical Evidence Supporting Recommendations
The FDA label for dapagliflozin clearly states that for glycemic control, the drug is not recommended for patients with eGFR less than 45 mL/min/1.73 m² as it is likely to be ineffective in this setting due to its mechanism of action 1. This is because dapagliflozin's glucose-lowering effect depends on renal filtration and tubular function.
For heart failure and chronic kidney disease indications, recent evidence from the DAPA-HF and DELIVER trials supports continued use of dapagliflozin even when eGFR falls below the threshold for initiation. A 2023 study showed that patients who experienced deterioration of eGFR to <25 mL/min/1.73 m² while on dapagliflozin still benefited from the medication with a hazard ratio of 0.53 (95% CI: 0.33-0.83) for the primary outcome compared to placebo, with no excess in safety outcomes 2.
Monitoring Recommendations
When initiating dapagliflozin:
- Assess renal function prior to initiation
- Evaluate volume status and correct volume depletion before starting treatment
- Monitor renal function periodically after initiation, particularly in patients with borderline renal function
For patients with heart failure, the American College of Cardiology (2021) recommends:
- Close monitoring of volume status as intravascular volume contraction may necessitate reduction in loop diuretic dosing
- Regular assessment of renal function based on clinical stability 3
Special Considerations
Volume Status
Volume depletion should be corrected before initiating dapagliflozin, as SGLT2 inhibitors can cause intravascular volume contraction 1.
Temporary Interruption
Withhold dapagliflozin for at least 3 days prior to major surgery or procedures associated with prolonged fasting. Resume when the patient is clinically stable and has resumed oral intake 1.
Continuation Despite Renal Decline
For patients already on dapagliflozin for heart failure or CKD who experience a decline in renal function, recent evidence suggests continuing the medication may still provide cardiovascular and renal benefits without increased safety concerns 2.
Common Pitfalls to Avoid
Inappropriate initiation: Do not start dapagliflozin in patients with eGFR below the recommended thresholds for each indication.
Failure to distinguish between indications: Remember that the eGFR threshold differs depending on whether dapagliflozin is being used for glycemic control (≥45 mL/min/1.73 m²) or heart failure/CKD (≥25 mL/min/1.73 m²).
Premature discontinuation: Recent evidence suggests patients may continue to benefit from dapagliflozin even when eGFR falls below initiation thresholds while on treatment 2.
Inadequate monitoring: Regular assessment of renal function is essential, especially in patients with borderline renal function or those at risk for acute kidney injury.
By following these evidence-based recommendations, clinicians can optimize the use of dapagliflozin in patients with renal impairment while maximizing benefits and minimizing risks.