Is Farxiga (dapagliflozin) safe to use in patients with End-Stage Renal Disease (ESRD) on Hemodialysis (HD)?

Farxiga (Dapagliflozin) in ESRD on Hemodialysis

Farxiga (dapagliflozin) is not recommended for use in patients with end-stage renal disease (ESRD) on hemodialysis due to lack of established efficacy and safety data in this population.

Rationale for Recommendation

Pharmacokinetic Considerations

Recent pharmacokinetic data from 2023 provides some insights about dapagliflozin in dialysis patients:

• A small study found that dapagliflozin was only slightly dialyzable (0.10% of administered dose recovered from dialysate) 1
• The drug showed a slightly higher peak concentration (Cmax) in kidney failure patients (117 ng/ml) compared to controls (97.6 ng/ml) 1
• The accumulation ratio was higher in kidney failure patients (26.7%) compared to controls (9.5%) 1

However, this small pharmacokinetic study alone is insufficient to establish safety and efficacy for routine clinical use.

Efficacy Considerations

The primary mechanism of action of dapagliflozin is inhibition of SGLT2 in the renal proximal tubule, which reduces renal glucose reabsorption 2. In patients with ESRD:

• The functional nephron mass is severely reduced
• The primary site of action for the medication is largely non-functional
• The glycosuric effect that drives the medication's antihyperglycemic properties cannot be achieved

Safety Considerations

While the DAPA-CKD trial showed significant benefits of dapagliflozin in patients with chronic kidney disease, it's important to note:

• The trial included patients with eGFR 25-75 mL/min/1.73m² 3
• Patients with ESRD on dialysis were not included in this landmark trial
• The benefits observed (39% reduction in primary composite outcome) cannot be extrapolated to the ESRD population 4

Clinical Decision Algorithm

1. For patients with ESRD on hemodialysis:

   • Discontinue dapagliflozin if previously prescribed
   • Consider alternative agents appropriate for ESRD patients

2. For patients with advanced CKD approaching dialysis (eGFR 25-30 mL/min/1.73m²):

   • Dapagliflozin may still provide cardiorenal benefits
   • Plan to discontinue when dialysis is initiated

3. For patients with moderate CKD (eGFR >30 mL/min/1.73m²):

   • Dapagliflozin has demonstrated benefits in reducing CKD progression 3
   • Continue therapy with appropriate monitoring

Common Pitfalls to Avoid

1. Continuing SGLT2 inhibitors after dialysis initiation:

   • The mechanism of action becomes largely ineffective
   • Risk of adverse effects may continue or increase

2. Assuming cardiorenal benefits extend to ESRD population:

   • Clinical trial data does not support this extrapolation
   • Benefits seen in CKD patients (eGFR 25-75 mL/min/1.73m²) cannot be assumed in ESRD

3. Overlooking alternative management strategies for ESRD patients:

   • Focus on appropriate vascular access management
   • Proper mineral metabolism management
   • Symptomatic management of dialysis-related issues

Conclusion

While dapagliflozin has shown impressive cardiorenal benefits in patients with CKD, including those with severely reduced kidney function, the evidence does not support its use in patients who have progressed to ESRD requiring hemodialysis. The small pharmacokinetic study showing non-accumulating properties and minimal dialyzability is promising but insufficient to recommend clinical use in this population without efficacy data.