What is the recommended dosing for Sulfatrim (sulfamethoxazole/trimethoprim) in a patient with impaired renal function, specifically an estimated glomerular filtration rate (eGFR) of 49, and a solitary kidney?

Renal Dosing for Sulfamethoxazole/Trimethoprim with eGFR 49 and Solitary Kidney

For a patient with eGFR 49 mL/min/1.73 m² and a solitary kidney, reduce the standard sulfamethoxazole/trimethoprim dose by half for prophylactic indications, or use standard dosing with close monitoring for treatment of active infections like Pneumocystis jiroveci pneumonia. 1

Dosing Based on Indication

For Prophylaxis (e.g., PCP prophylaxis, UTI prevention)

• eGFR 30-49 mL/min: Use half the standard dose 1
  • Standard prophylaxis: 1 double-strength tablet daily or 3 times weekly
  • Adjusted dose: 1 single-strength tablet daily, or 1 double-strength tablet 3 times weekly 1

For Treatment of Active Infections (e.g., PCP pneumonia)

• eGFR 30-50 mL/min: Reduce dosing frequency to every 12 hours instead of every 6-8 hours 1
  • Standard treatment dose: 3-5 mg/kg (as trimethoprim) IV every 6-8 hours
  • Adjusted dose: 3-5 mg/kg (as trimethoprim) IV every 12 hours 1

For eGFR 15-30 mL/min

• Use half the standard dose or consider alternative agents 1
• For treatment: 3-5 mg/kg (as trimethoprim) every 24 hours 1

Critical Monitoring Requirements

The solitary kidney status increases vulnerability to nephrotoxicity and requires heightened vigilance. 2

• Baseline assessment: Measure serum creatinine, BUN, and electrolytes before initiating therapy 2
• During therapy monitoring:
  • Check creatinine and BUN after 2-3 days, then at 7 days 1
  • Monitor at least every 1-2 weeks during maintenance therapy 1
  • Increase monitoring frequency if eGFR declines or patient has diabetes/hypertension 2

Key Pharmacokinetic Considerations

Trimethoprim and sulfamethoxazole disposition are not significantly altered until creatinine clearance falls below 30 mL/min, but metabolites accumulate and half-lives increase with renal impairment. 3, 4

• Mean half-life of sulfamethoxazole: 10 hours (normal), increases with renal impairment 3
• Mean half-life of trimethoprim: 8-10 hours (normal), increases to 23.7 hours in end-stage renal disease 5
• Both drugs are primarily excreted renally through glomerular filtration and tubular secretion 3
• Approximately 70% of sulfamethoxazole and 44% of trimethoprim are protein-bound 3

Risk Factors for Acute Kidney Injury

Acute kidney injury occurs in approximately 11% of patients treated with sulfamethoxazole/trimethoprim for ≥6 days, with higher risk in those with pre-existing renal disease, diabetes, and hypertension. 2

• Patients with poorly controlled hypertension and diabetes have significantly increased AKI risk 2
• A solitary kidney represents a vulnerable state with reduced renal reserve
• Most AKI cases resolve promptly after discontinuation, but dialysis may rarely be required 2
• Intrinsic renal impairment rather than interstitial nephritis causes the majority of cases 2

When to Discontinue or Adjust

• Stop immediately if serum creatinine rises ≥0.5 mg/dL above baseline 2
• Stop immediately if BUN increases disproportionately to creatinine 2
• Consider alternative agents if eGFR drops below 15 mL/min 1

Alternative Considerations

For patients at high risk of nephrotoxicity or with eGFR <30 mL/min, consider alternative antimicrobials based on the specific infection being treated. 1, 6

• The presence of a solitary kidney does not absolutely contraindicate sulfamethoxazole/trimethoprim use, but demands careful dose adjustment and monitoring 4, 7
• Dosing adjustments should be calculated using eGFR from the CKD-EPI equation rather than Cockcroft-Gault in older patients 1