Is Empagliflozin (Empagliflozin) contraindicated in End-Stage Renal Disease (ESRD)?

Empagliflozin is Contraindicated in ESRD and Dialysis

Empagliflozin (Jardiance) is contraindicated in patients with end-stage renal disease (ESRD) and in patients on dialysis according to FDA labeling. 1

Contraindications and Renal Function Thresholds

Empagliflozin has specific contraindications related to renal function:

• Severe renal impairment: Contraindicated in severe renal impairment 1
• End-stage renal disease: Explicitly contraindicated 1
• Dialysis: Explicitly contraindicated 1

The FDA-approved labeling clearly states these contraindications in the "CONTRAINDICATIONS" section of the drug label 1.

Dosing Recommendations Based on eGFR

Renal function significantly impacts empagliflozin dosing and usage:

• eGFR ≥45 mL/min/1.73 m²: Safe to initiate empagliflozin 1
• eGFR <45 mL/min/1.73 m²: Do not initiate empagliflozin 1
• eGFR persistently <45 mL/min/1.73 m²: Discontinue empagliflozin 1

According to the American Diabetes Association and KDIGO consensus report, empagliflozin use is not recommended with eGFR <45 mL/min/1.73 m² 2.

Pharmacokinetic and Pharmacodynamic Considerations

The contraindication in ESRD is supported by pharmacokinetic and pharmacodynamic data:

• Systemic exposure (AUC) of empagliflozin increases by approximately 48% in patients with renal failure/ESRD compared to healthy subjects 3
• Urinary glucose excretion (UGE) decreases significantly with increasing renal impairment 3
• The mechanism of action (inhibition of SGLT2 in renal tubules) becomes ineffective in ESRD due to minimal functioning nephrons

Rationale for Contraindication

The contraindication in ESRD is based on several factors:

1. Lack of efficacy: The glucose-lowering effect of empagliflozin is dependent on renal function and is minimal in ESRD 2

2. Safety concerns: Patients with ESRD may be at increased risk for adverse effects including:

   • Volume depletion
   • Hypotension
   • Electrolyte imbalances
   • Acute kidney injury

3. Regulatory guidance: The FDA label explicitly lists ESRD as a contraindication 1

Clinical Trials and Evidence

Clinical trials with empagliflozin have generally excluded patients with ESRD:

• The EMPA-REG OUTCOME trial included patients with eGFR ≥30 mL/min/1.73 m² but not those with ESRD 2
• The EMPA-KIDNEY trial included patients with eGFR ≥20 mL/min/1.73 m² but not those on dialysis 4

Important Considerations for Practitioners

When managing patients with diabetes and kidney disease:

• Regular monitoring: Assess renal function before initiating empagliflozin and periodically during treatment 1
• Discontinuation protocol: Stop empagliflozin if eGFR falls persistently below 45 mL/min/1.73 m² 1
• Alternative medications: For patients with ESRD, consider other antidiabetic medications without renal contraindications

Conclusion

Based on FDA labeling and clinical guidelines, empagliflozin is contraindicated in patients with ESRD and in those on dialysis. The medication should not be initiated in patients with eGFR <45 mL/min/1.73 m², and should be discontinued if eGFR falls persistently below this threshold.