What is the recommended dose of Empagliflozin (Synjardy) for patients with Impaired renal function?

Empagliflozin (Synjardy) Dosing in Impaired Renal Function

For patients with impaired renal function, empagliflozin (Synjardy) should not be initiated if eGFR is less than 45 mL/min/1.73 m², and should be discontinued if eGFR falls persistently below this threshold. 1

Dosing Recommendations Based on Renal Function

• Normal to mild renal impairment (eGFR ≥45 mL/min/1.73 m²):

  • Recommended dose: 10 mg once daily in the morning, with or without food 1
  • May increase to 25 mg once daily if needed and tolerated 1
  • No dose adjustment required in this range 1, 2

• Moderate to severe renal impairment (eGFR <45 mL/min/1.73 m²):

  • Initiation is not recommended 2, 1
  • If already on empagliflozin when eGFR declines below 45 mL/min/1.73 m², the medication should be discontinued 1

Clinical Considerations in Renal Impairment

• Efficacy considerations:

  • Glucose-lowering efficacy of empagliflozin decreases with declining renal function due to reduced urinary glucose excretion 2, 3
  • In patients with severe renal impairment (eGFR 15-<30 mL/min/1.73 m²), urinary glucose excretion is significantly reduced compared to patients with normal renal function 3, 4

• Pharmacokinetic changes:

  • Empagliflozin exposure increases with worsening renal function, but the increase is generally less than 2-fold 3, 4
  • Renal clearance of empagliflozin correlates with eGFR 3

• Cardiovascular and renal benefits:

  • Despite reduced glucose-lowering efficacy, cardiovascular and renal benefits of empagliflozin appear to be preserved in patients with eGFR as low as 30 mL/min/1.73 m² 5
  • The EMPA-KIDNEY trial demonstrated that empagliflozin reduced the risk of kidney disease progression in patients with eGFR as low as 20 mL/min/1.73 m² 6

Monitoring Recommendations

• Before initiation:

  • Assess renal function prior to starting empagliflozin 1
  • Evaluate volume status, especially in patients with renal impairment 1

• During treatment:

  • Monitor renal function periodically during therapy 1
  • More frequent monitoring may be needed in patients with eGFR close to 45 mL/min/1.73 m² 2
  • Assess for signs of volume depletion, particularly in elderly patients or those on diuretics 1

Safety Considerations

• Volume depletion:

  • Patients with renal impairment are at increased risk for volume depletion 1
  • Consider correcting volume status before initiating therapy 1
  • May need to adjust doses of concomitant diuretics 2

• Acute kidney injury:

  • Consider temporarily discontinuing empagliflozin in settings of reduced oral intake or fluid losses 1
  • If acute kidney injury occurs, discontinue empagliflozin and treat promptly 1

• Other adverse effects:

  • Risk of genital mycotic infections (6% vs 1% with placebo) 2
  • Potential for euglycemic ketoacidosis, especially during acute illness 2
  • The adverse event profile in patients with impaired renal function is generally similar to that in the overall population 5

Special Considerations for Synjardy (Empagliflozin/Metformin)

• Since Synjardy contains metformin, additional renal restrictions apply:
  • For eGFR 30-44 mL/min/1.73 m²: Metformin dose should be reduced to 1000 mg/day 2
  • For eGFR <30 mL/min/1.73 m²: Metformin is contraindicated 2
  • Therefore, Synjardy (combination product) should not be used in patients with eGFR <45 mL/min/1.73 m² due to restrictions on both components 2

By following these dosing recommendations and monitoring protocols, the risk of adverse events can be minimized while maximizing potential cardiovascular and renal benefits in appropriate patients with type 2 diabetes and impaired renal function.