What is the next step in managing an elderly patient with hyperglycosuria, bilirubinuria, proteinuria, and hematuria, on Farxiga (dapagliflozin) 5mg, after a resolved urinary tract infection?

Management of Urinalysis Abnormalities in an Elderly Patient on Farxiga After Resolved UTI

The most critical next step is to immediately discontinue Farxiga (dapagliflozin) and obtain urgent evaluation for serious complications including urosepsis, pyelonephritis, Fournier's gangrene, and hepatobiliary pathology, given the concerning combination of bilirubinuria, hematuria, and proteinuria in this high-risk elderly patient. 1

Immediate Actions Required

Discontinue Dapagliflozin

• Stop Farxiga immediately due to multiple FDA warnings about serious urinary tract complications in the setting of recent UTI 1
• The FDA label explicitly warns that SGLT2 inhibitors like dapagliflozin increase risk for serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization 1
• Elderly patients on diuretics (which includes the osmotic diuresis from SGLT2 inhibitors) are at increased risk for volume depletion and acute kidney injury 1

Urgent Diagnostic Evaluation

• Obtain urine culture with antimicrobial susceptibility testing immediately to rule out persistent or recurrent UTI, as the European Urology guidelines recommend this before any treatment decisions 2, 3, 4
• Assess for necrotizing fasciitis of the perineum (Fournier's gangrene) - examine for pain, tenderness, erythema, or swelling in the genital or perineal area, as this is a rare but life-threatening complication of SGLT2 inhibitors requiring urgent surgical intervention 1
• Evaluate for urosepsis or pyelonephritis - check vital signs, assess for fever, altered mental status (common atypical presentation in elderly), flank pain, or systemic symptoms 2, 3, 4, 1

Investigate Bilirubinuria

• Order comprehensive hepatobiliary workup including liver function tests, complete metabolic panel, and consider hepatobiliary imaging 2
• Bilirubinuria suggests conjugated hyperbilirubinemia from hepatic or biliary pathology, which is unrelated to diabetes or SGLT2 inhibitors and requires separate investigation 2
• This finding may indicate concurrent hepatobiliary disease, drug-induced liver injury, or biliary obstruction requiring urgent evaluation 2

Assess Hematuria and Proteinuria

• Obtain renal function tests (serum creatinine, eGFR, BUN) to assess for acute kidney injury, as elderly patients on SGLT2 inhibitors are at increased risk for volume depletion-related AKI 1
• Quantify proteinuria with urine protein-to-creatinine ratio to determine severity 2
• Consider renal ultrasound if symptoms are severe or not improving, to rule out obstructive uropathy or other structural abnormalities 2

Understanding the Clinical Context

Why Farxiga Must Be Stopped

The FDA drug label provides clear warnings that are directly applicable to this clinical scenario:

• Volume depletion risk: "Before initiating DAPAGLIFLOZIN TABLETS in patients with one or more of these characteristics [elderly, renal impairment, on diuretics], assess volume status and renal function" 1
• Serious UTI complications: "Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been reported in patients receiving SGLT2 inhibitors, including dapagliflozin" 1
• Post-marketing AKI reports: "There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including dapagliflozin" 1

The Glucosuria-Infection Relationship

• Dapagliflozin causes marked glucosuria (>1000 mg/dL in this case) by design, which creates a glucose-rich environment in the urinary tract 5, 6
• While research shows UTI incidence with dapagliflozin is only modestly increased (5.3-5.7%), these infections can be more severe in elderly patients 7, 8, 9
• The 10 mg dose shows higher urinary frequency (55%) and urgency (48%) compared to 5 mg dose (~25% and ~20% respectively), suggesting dose-dependent effects 7

Special Considerations in Elderly Patients

• Elderly patients with UTI frequently present with atypical symptoms including altered mental status, functional decline, falls, or fatigue rather than classic urinary symptoms 2, 3, 4
• The specificity of urine dipstick tests is only 20-70% in elderly patients, making clinical correlation essential 3, 4
• Elderly patients have higher rates of adverse reactions related to hypotension and volume depletion with SGLT2 inhibitors 1

Treatment Algorithm After Farxiga Discontinuation

If Urine Culture is Positive

• Initiate targeted antibiotic therapy based on culture and susceptibility results 2, 3
• For complicated UTI in elderly patients, treatment duration is typically 7-14 days 3
• Fosfomycin 3g single dose can be used even in renal impairment 3
• Avoid fluoroquinolones if local resistance >10%, recent use within 6 months, or increased risk of adverse effects (tendon rupture, CNS effects) in elderly 3
• Avoid nitrofurantoin if creatinine clearance <30 mL/min 3

If Urine Culture is Negative

• Do not treat asymptomatic bacteriuria, which affects up to 40% of institutionalized elderly patients and should not be treated 4
• Focus investigation on the bilirubinuria, hematuria, and proteinuria as separate pathologies 2
• Consider non-infectious causes of urinary abnormalities including glomerulonephritis, interstitial nephritis, or drug-induced nephrotoxicity 10

Glycemic Management After Stopping Farxiga

• Transition to alternative diabetes therapy that does not increase UTI risk 10
• In elderly patients, glucose targets should prevent both hypoglycemia and severe hyperglycemia, keeping levels below the renal threshold (~180 mg/dL) 10
• Consider basal insulin or other oral agents, avoiding those causing gastrointestinal symptoms or excess weight loss in frail elderly 10

Critical Pitfalls to Avoid

Do Not Continue SGLT2 Inhibitor

• Never continue dapagliflozin in the setting of active urinary tract pathology - the FDA label explicitly warns to evaluate and treat UTI signs promptly 1
• The combination of recent UTI, persistent urinary abnormalities, and elderly age creates unacceptable risk for serious complications 1

Do Not Ignore Bilirubinuria

• Bilirubinuria is never normal and always requires hepatobiliary investigation - this is not explained by diabetes or SGLT2 inhibitors 2
• Failure to investigate could miss serious hepatobiliary pathology including cholangitis, hepatitis, or biliary obstruction 2

Do Not Delay Evaluation for Fournier's Gangrene

• Any genital or perineal pain, tenderness, erythema, or swelling with fever requires immediate assessment for this life-threatening complication 1
• If suspected, start broad-spectrum antibiotics immediately and obtain urgent surgical consultation 1

Do Not Restart Farxiga Without Resolution

• Only consider restarting SGLT2 inhibitor after complete resolution of urinary abnormalities, confirmation of no ongoing infection, and careful risk-benefit assessment 1
• In this elderly patient with multiple urinary abnormalities, alternative diabetes therapy is strongly preferred 10, 1

Monitoring and Follow-up

Short-term (48-72 hours)

• Daily assessment of vital signs, mental status, urinary symptoms, and signs of systemic infection 2, 4
• Monitor renal function and electrolytes closely given risk of AKI in elderly patients 1
• Reassess clinical status and adjust antibiotics based on culture results if applicable 2, 3

Medium-term (1-2 weeks)

• Follow-up urine culture 1-2 weeks after completing antibiotics to confirm eradication if UTI was treated 2
• Repeat urinalysis to ensure resolution of hematuria and proteinuria 2
• Complete hepatobiliary workup and address any identified pathology 2

Long-term

• Avoid reintroduction of SGLT2 inhibitors in this patient given the complicated course 1
• Optimize alternative diabetes therapy with careful attention to avoiding hypoglycemia in elderly patients 10
• Consider nephrology referral if proteinuria or hematuria persists after infection resolution 10