Is it okay to continue empagliflozin (Empagliflozin) in patients with urinary tract infection (UTI) and urosepsis?

Should Empagliflozin Be Discontinued in Patients with UTI and Urosepsis?

Empagliflozin should be temporarily discontinued in patients with urosepsis and promptly treated urinary tract infections until the infection is adequately controlled with appropriate antibiotics.

Rationale Based on FDA Labeling and Guidelines

The FDA-approved prescribing information for empagliflozin explicitly warns about urosepsis and pyelonephritis, stating: "Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated" and recommends considering "temporary discontinuation of therapy in clinical situations known to predispose to ketoacidosis" 1. The 2021 ACC Expert Consensus specifically lists urosepsis and pyelonephritis as cautions requiring evaluation and prompt treatment 2.

Clinical Evidence Supporting Temporary Discontinuation

• Serious infections documented: A case report described septic shock due to Serratia marcescens pyelonephritis and bacteremia in a patient taking empagliflozin, which resolved after discontinuation and antibiotic therapy with no recurrent UTIs in the following 4 months 3.

• FDA postmarketing surveillance: The FDA label includes postmarketing reports of urosepsis and pyelonephritis requiring hospitalization in patients receiving SGLT2 inhibitors 1.

• Increased UTI risk confirmed: A real-world observational study found patients treated with SGLT2 inhibitors had 3.70 times higher risk of UTI compared with non-SGLT2 inhibitors (95% CI 2.60-5.29), with an overall incidence of 33.49% 4.

When to Consider Temporary Discontinuation

Discontinue empagliflozin immediately if:

• Patient presents with signs of urosepsis (fever, rigors, altered mental status, hypotension with qSOFA ≥2) 2
• Pyelonephritis is diagnosed (flank pain, costovertebral angle tenderness, fever) 2
• Patient has reduced oral intake or fluid losses that could predispose to acute kidney injury 2, 1

Management Algorithm

1. Assess severity: Determine if patient has simple UTI versus complicated UTI/pyelonephritis/urosepsis 2

2. For urosepsis or pyelonephritis:

   • Discontinue empagliflozin immediately 1, 3
   • Obtain urine and blood cultures before antibiotics 2
   • Initiate empirical broad-spectrum antibiotics (amoxicillin plus aminoglycoside, second-generation cephalosporin plus aminoglycoside, or IV third-generation cephalosporin) 2
   • Ensure adequate hydration and monitor renal function 2, 1

3. For uncomplicated UTI:

   • Consider temporary discontinuation during acute infection, particularly in high-risk patients (elderly, reduced eGFR, volume depletion) 2, 1
   • Treat with appropriate antibiotics for 3-5 days 2, 5
   • Monitor closely for progression 5

4. Resumption criteria:

   • Complete resolution of infection symptoms 6
   • Completion of antibiotic course 2, 5
   • Documented negative urine culture if obtained 6
   • Adequate oral intake and hydration status restored 2, 1

Special Populations at Higher Risk

• Women: Higher incidence of both UTIs (18.4% vs 3.6% in men) and serious UTIs with empagliflozin 1, 7, 4
• Elderly patients: Increased risk of volume depletion and UTI complications 2, 1
• Patients with bladder outlet obstruction: Urinary stasis increases infection risk; caution advised 8
• History of recurrent UTIs: More likely to experience UTI on empagliflozin 1

Long-Term Safety Considerations

A large meta-analysis of 10,472 patients found that serious urinary tract infections and serious pyelonephritis/urosepsis occurred at similar rates overall with empagliflozin versus placebo, but were higher in women taking empagliflozin 7. Most UTIs in clinical trials were mild to moderate and responded to standard antimicrobial treatment, with discontinuation rates due to UTI being rare (0.2-0.3%) 1, 9.

Common Pitfalls to Avoid

• Do not continue empagliflozin during active urosepsis or severe pyelonephritis, as this represents a serious infection requiring aggressive treatment 1, 3
• Do not treat asymptomatic bacteriuria in catheterized patients unless they develop systemic symptoms 2, 10
• Do not restart empagliflozin until infection is fully resolved and patient is adequately hydrated 2, 1
• Do not ignore volume status: Assess and correct volume depletion before restarting, especially in elderly or those on diuretics 2, 1