How should dapagliflozin (Forxiga) be used in patients with infections, particularly urinary tract infections (UTIs)?

Dapagliflozin Use in Patients with Infections

Dapagliflozin increases the risk of urinary tract infections (UTIs) and should be used with caution in patients with active infections, particularly those involving the urinary tract. 1

Key Safety Considerations

Urinary Tract Infections and Urosepsis

• Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been reported in patients receiving SGLT2 inhibitors, including dapagliflozin. 1

• The FDA label explicitly warns that dapagliflozin treatment increases the risk for urinary tract infections and recommends evaluating patients for signs and symptoms of UTIs and treating promptly if indicated. 1

• If a patient develops signs or symptoms of a UTI while on dapagliflozin, evaluate and treat the infection promptly with appropriate antimicrobial therapy. 1

Infection Risk Profile

• Clinical trial data demonstrates that UTI incidence ranges from 4.3% to 5.7% with dapagliflozin (5-10 mg) compared to 3.7% with placebo. 2

• Most UTIs associated with dapagliflozin are mild to moderate in severity and respond to standard antimicrobial treatment. 2, 3

• Discontinuation due to UTI is rare, occurring in only 0.3% of dapagliflozin-treated patients. 2

• Women are disproportionately affected, with 76.2% of UTIs occurring in female patients. 3

Clinical Management Algorithm

Before Initiating Dapagliflozin

• Screen for active urinary tract infections and treat any existing infections before starting dapagliflozin. 1

• Assess for urinary tract outlet obstruction, particularly in male patients, as this significantly increases UTI risk when combined with dapagliflozin-induced glucosuria. 4

• Evaluate volume status and renal function, as volume depletion may predispose to both renal complications and infections. 1

During Active Infection

• Continue dapagliflozin during mild to moderate UTIs while treating with appropriate antibiotics, as most infections respond well to standard antimicrobial therapy. 2, 3

• For complicated UTIs with flank pain indicating pyelonephritis, initiate empirical treatment with intravenous third-generation cephalosporin (e.g., ceftriaxone) or amoxicillin plus aminoglycoside according to European Urology guidelines. 5

• Consider temporarily discontinuing dapagliflozin in cases of severe infection, urosepsis, or when the patient requires hospitalization for infection management. 1

Special Infection Considerations

Necrotizing Fasciitis (Fournier's Gangrene)

• Immediately discontinue dapagliflozin if necrotizing fasciitis of the perineum is suspected. 1

• Patients presenting with pain, tenderness, erythema, or swelling in the genital or perineal area along with fever or malaise require urgent assessment. 1

• Start broad-spectrum antibiotics immediately and arrange surgical debridement if necessary. 1

Genital Mycotic Infections

• Dapagliflozin increases the risk of genital mycotic infections, which should be monitored and treated appropriately without necessarily discontinuing the medication. 1

• Patients with a history of genital mycotic infections are at higher risk for recurrence. 1

High-Risk Populations Requiring Extra Caution

Patients with Urinary Outlet Obstruction

• Exercise extreme caution when prescribing dapagliflozin to male patients with evidence of bladder outlet obstruction or incomplete bladder emptying. 4

• A case report documented recurrent E. coli septicemia in a patient with 180 mL post-void residual volume on dapagliflozin, with complete resolution after drug cessation. 4

• The combination of urinary stasis and dapagliflozin-induced glucosuria creates an ideal environment for bacterial growth. 4

Elderly and Volume-Depleted Patients

• Elderly patients and those on loop diuretics are at increased risk for both volume depletion and UTI complications. 1

• Monitor volume status and renal function closely in these populations. 1

Dose Considerations

• Recent evidence suggests a dose-dependent increase in UTI symptoms, with the 10 mg dose showing higher rates of urinary frequency (55% vs ~25%) and urgency (48% vs ~20%) compared to the 5 mg dose. 6

• However, the original pooled trial data did not demonstrate a definitive dose-relationship between glucosuria and UTI incidence. 2

• Consider starting with 5 mg in patients at higher baseline risk for UTIs. 6

Common Pitfalls to Avoid

• Do not screen for or treat asymptomatic bacteriuria in patients on dapagliflozin unless they are pregnant or undergoing urological procedures breaching the mucosa. 7

• Do not automatically discontinue dapagliflozin for mild UTIs, as most respond well to standard treatment while continuing the medication. 2, 3

• Do not overlook the possibility of serious infections like urosepsis or Fournier's gangrene, which require immediate intervention and drug discontinuation. 1

• Avoid prescribing dapagliflozin to patients with unrecognized urinary retention or outlet obstruction, as this substantially increases infection risk. 4