Should Jardiance (Empagliflozin) be held in patients with severe impaired renal function, specifically a creatinine clearance of 25?

Empagliflozin (Jardiance) Use in Patients with Creatinine Clearance of 25 mL/min

Jardiance (empagliflozin) should be discontinued in patients with a creatinine clearance of 25 mL/min as this falls below the recommended threshold for use. 1

Renal Function Considerations for Empagliflozin

• The FDA drug label for Jardiance indicates that the medication causes acute impairment in renal function, with increases in serum creatinine and decreases in eGFR, particularly in patients with moderate renal impairment at baseline 1

• Empagliflozin's glucose-lowering efficacy is significantly reduced in patients with severe renal impairment, as urinary glucose excretion decreases substantially with declining renal function 2

• In patients with severe renal impairment (eGFR 15-<30 mL/min/1.73m²), urinary glucose excretion is reduced to approximately one-third of that seen in patients with normal renal function 2

Pharmacokinetic Considerations

• Empagliflozin exposure increases with worsening renal function - patients with severe renal impairment have approximately 1.5 times higher drug exposure compared to those with normal renal function 2

• While pharmacokinetic data alone might not necessitate dose adjustment (as increases in exposure are <2-fold), the significantly reduced efficacy and potential safety concerns in severe renal impairment outweigh any benefits 2

Safety Concerns

• Patients with renal impairment are at higher risk for adverse events related to volume depletion (hypotension, dehydration, hypovolemia) due to empagliflozin's osmotic diuretic effect 1

• The risk of acute kidney injury may be increased in patients with severe renal impairment, especially when combined with other medications that affect renal function 1, 3

• Creatinine clearance of 25 mL/min represents severe renal dysfunction, which is associated with significantly higher mortality and adverse outcomes in patients with cardiovascular conditions 4

Specific Guidance from Drug Label

• The FDA drug label for Jardiance does not provide specific dosing recommendations for patients with creatinine clearance below 30 mL/min, indicating that the medication is not recommended in this population 1

• This contrasts with some other medications like metformin, which has specific dose reduction recommendations for various levels of renal impairment 5

Alternative Considerations

• For patients with type 2 diabetes and severe renal impairment (CrCl 25 mL/min), consider alternative glucose-lowering medications with established safety profiles in renal dysfunction 6

• Gliclazide may be a suitable alternative for patients with advanced CKD as it undergoes hepatic metabolism with minimal renal excretion 6

Clinical Decision Algorithm

1. Discontinue Jardiance in patients with creatinine clearance of 25 mL/min 1
2. Monitor renal function after discontinuation, as the acute impairment in renal function observed with empagliflozin may reverse after treatment discontinuation 1
3. Consider alternative diabetes medications appropriate for severe renal impairment 6
4. Ensure adequate management of cardiovascular risk factors, as patients with renal dysfunction are at higher risk for adverse cardiovascular outcomes 4, 3

Conclusion from Evidence

The evidence clearly indicates that empagliflozin should not be used in patients with creatinine clearance of 25 mL/min due to reduced efficacy, altered pharmacokinetics, and potential safety concerns. The FDA drug label does not support its use in this level of renal impairment 1, 2.