In an elderly patient with heart failure (or chronic kidney disease) on furosemide, can I increase empagliflozin (Jardiance) from 10 mg to 25 mg daily?

Increasing Empagliflozin (Jardiance) from 10 mg to 25 mg in Elderly Patients with Heart Failure or CKD on Furosemide

Yes, you can increase empagliflozin from 10 mg to 25 mg daily in elderly patients with heart failure or chronic kidney disease on furosemide, provided the eGFR remains ≥45 mL/min/1.73 m² and volume status is carefully assessed before and after the dose increase. 1

FDA-Approved Dosing Guidelines

• The FDA label for Jardiance specifies that the recommended starting dose is 10 mg once daily, which may be increased to 25 mg once daily in patients who tolerate the medication 1
• Both the 10 mg and 25 mg doses are approved for cardiovascular death reduction in patients with type 2 diabetes and established cardiovascular disease 2
• No dose adjustment is required for either dose when eGFR is ≥45 mL/min/1.73 m² 1

Critical Renal Function Threshold

• Empagliflozin should not be initiated if eGFR is <45 mL/min/1.73 m² 1
• If eGFR falls persistently below 45 mL/min/1.73 m² during treatment, the medication should be discontinued per FDA labeling 1
• However, more recent guidelines suggest that empagliflozin can be continued for cardiovascular and renal protection down to eGFR ≥20 mL/min/1.73 m², even though glucose-lowering efficacy is reduced 2, 3

Volume Status Assessment Before Dose Escalation

• Before increasing the dose, you must assess for volume depletion and correct it if present, as empagliflozin causes intravascular volume contraction 1
• This is particularly critical in elderly patients, those with low systolic blood pressure, and those on concurrent diuretics like furosemide 1
• The FDA label explicitly warns about symptomatic hypotension after initiating empagliflozin, especially in patients with renal impairment and the elderly 1

Managing Concurrent Furosemide Therapy

• Consider temporarily reducing the furosemide dose when increasing empagliflozin to 25 mg to prevent excessive volume depletion 4, 5
• Monitor for signs and symptoms of hypotension after the dose increase, with increased vigilance in clinical situations where volume contraction is expected 1
• Elderly patients (≥75 years) face heightened risk of hypotension but this does not contraindicate SGLT2 inhibitor use; it simply requires more careful monitoring 4

Evidence for 25 mg Dose in Heart Failure

• The EMPEROR-Reduced trial used empagliflozin 10 mg daily (not 25 mg) and demonstrated consistent cardiovascular and renal benefits across all age groups, including patients ≥75 years 6
• The 25 mg dose does not provide substantially greater cardiovascular or renal protection compared to 10 mg; the primary benefit of the higher dose is additional glucose lowering in patients with diabetes 3
• In heart failure trials, the standard dose was 10 mg daily, and this is the dose with the strongest evidence for mortality and hospitalization reduction 2

Clinical Decision Algorithm

1. Check current eGFR: Must be ≥45 mL/min/1.73 m² to increase the dose per FDA labeling 1
2. Assess volume status: Look for orthostatic hypotension, dry mucous membranes, reduced skin turgor, or recent weight loss 1
3. Review blood pressure: If systolic BP is consistently <100 mmHg, consider reducing furosemide before increasing empagliflozin 2
4. Evaluate the indication:
   • If the goal is additional glucose lowering in a patient with diabetes and eGFR ≥45 mL/min/1.73 m², increasing to 25 mg is appropriate 2, 3
   • If the goal is cardiovascular or renal protection alone, the 10 mg dose is sufficient and increasing to 25 mg offers minimal additional benefit 3, 6
5. Reduce furosemide dose by 25-50% at the time of empagliflozin dose increase if the patient is at high risk for volume depletion 4, 5
6. Recheck eGFR, electrolytes, and blood pressure within 1-2 weeks after the dose increase 4

Safety Monitoring After Dose Increase

• Monitor for symptomatic hypotension, dizziness, or falls in the first 2-4 weeks 1
• An acute, reversible eGFR decline of 2-5 mL/min/1.73 m² may occur; this is hemodynamic and should not prompt discontinuation unless accompanied by volume depletion 4
• Watch for increased frequency of genital mycotic infections (occurs in ~6% of patients on SGLT2 inhibitors) 4, 5
• Educate the patient to withhold empagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea 4, 3

Common Pitfalls to Avoid

• Do not increase to 25 mg if the primary goal is heart failure management; the 10 mg dose has the strongest evidence base for cardiovascular outcomes 2, 6
• Do not increase the dose without first assessing volume status, especially in elderly patients on loop diuretics 1
• Do not discontinue empagliflozin if eGFR falls below 45 mL/min/1.73 m² after the dose increase; instead, continue at 10 mg for cardiovascular and renal protection 2, 4
• Do not combine the dose increase with simultaneous up-titration of other diuretics or ACE inhibitors/ARBs, as this compounds the risk of hypotension and acute kidney injury 4

When 25 mg Is Most Appropriate

• The 25 mg dose is most justified when the patient has type 2 diabetes, eGFR ≥45 mL/min/1.73 m², and requires additional glucose lowering beyond what 10 mg provides 2, 3, 1
• In patients without diabetes or with eGFR 20-44 mL/min/1.73 m², the 10 mg dose should be maintained for cardiovascular and renal protection 2, 3