Can empagliflozin (Jardiance) cause urethral redness?

Empagliflozin and Urethral Redness

Empagliflozin does not directly cause urethral redness, but the glucosuria it induces creates a glucose-rich genitourinary environment that significantly increases the risk of genital mycotic infections and urinary tract infections, which can present with urethral inflammation and redness. 1, 2

Mechanism of Genitourinary Complications

Empagliflozin inhibits glucose reabsorption in the renal proximal tubules, leading to persistent glucosuria that creates an ideal environment for microbial growth in the genitourinary tract. 3 This osmotic diuresis increases urine volume and frequency, which may contribute to local irritation. 2

Genital Mycotic Infections

The most common cause of urethral redness with empagliflozin is genital mycotic infection, occurring in approximately 6% of patients versus 1% on placebo. 3

• Male genital mycotic infections (including balanitis, balanoposthitis, and genital candidiasis) occurred in 3.1% of patients on empagliflozin 10 mg and 1.6% on 25 mg, compared to 0.4% on placebo. 2
• Female genital mycotic infections occurred in 5.4% on empagliflozin 10 mg and 6.4% on 25 mg, compared to 1.5% on placebo. 2
• These infections can present with urethral redness, irritation, discharge, and discomfort. 1, 4

Urinary Tract Infections

Serious urinary tract infections, including those that may cause urethral inflammation, have been reported with empagliflozin, though clinical trials show no significant overall difference compared to placebo. 1

• Urinary tract infections occurred in 9.3% of patients on empagliflozin 10 mg and 7.6% on 25 mg, compared to 7.6% on placebo. 2
• Women taking empagliflozin had higher rates of serious pyelonephritis or urosepsis compared to placebo. 5
• UTIs can present with dysuria, urethral burning, and visible urethral redness. 6

Clinical Management Approach

For uncomplicated urethral redness without systemic symptoms, maintain empagliflozin and treat the underlying infection with appropriate antimicrobials or antifungals. 6

When to Continue Empagliflozin:

• Mild genital mycotic infections can be managed with topical antifungals and proper genital hygiene while continuing empagliflozin. 1
• Uncomplicated UTIs can be treated with 3-5 day antibiotic courses without discontinuing empagliflozin in most patients. 6

When to Discontinue Empagliflozin:

Immediately discontinue empagliflozin if the patient develops signs of urosepsis (fever, rigors, altered mental status, hypotension with qSOFA ≥2) or pyelonephritis. 6

• Consider temporary discontinuation in high-risk patients (elderly, reduced eGFR, volume depletion) with acute UTI. 6
• Discontinue if reduced oral intake or fluid losses could predispose to acute kidney injury. 6

Resumption Criteria:

• Resume empagliflozin after complete resolution of infection symptoms, completion of antibiotic course, and documented negative urine culture if obtained. 6
• Ensure adequate oral intake and hydration status are restored before resuming. 6

Important Caveats

The cardiovascular and renal protective benefits of empagliflozin (38% reduction in cardiovascular death, 35% reduction in heart failure hospitalization) often outweigh the risk of genitourinary infections in appropriate patients. 1, 7

• Real-world data from the FDA Adverse Event Reporting System confirms strong associations between SGLT-2 inhibitors and both UTIs and genital mycotic infections. 8
• The risk appears consistent across empagliflozin, canagliflozin, and dapagliflozin. 4, 8
• Patient education about proper genital hygiene and early recognition of infection symptoms is essential to minimize complications. 1