Ceftriaxone Dosing in Renal Impairment (GFR 29)
No dose adjustment is required for ceftriaxone in a patient with a GFR of 29 mL/min/1.73 m²—the standard dose of 1-2 grams once daily can be safely administered. 1
Key Dosing Principles
The FDA label explicitly states that "patients with renal failure normally require no adjustment in dosage when usual doses of ceftriaxone are administered" and that "dosage adjustments should not be necessary in patients with hepatic dysfunction." 1 This is because ceftriaxone has dual elimination pathways—both renal and biliary excretion—which provides a safety margin in renal impairment. 1
Standard Adult Dosing Applies
- Usual adult dose: 1-2 grams once daily (or divided twice daily), with a maximum of 4 grams per day 1
- No modification needed in elderly patients up to 2 grams per day, provided there is no severe combined renal and hepatic impairment 1
Important Caveats and Monitoring
Combined Renal and Hepatic Dysfunction
Exercise caution if both severe renal disease AND hepatic dysfunction are present—in this specific scenario, do not exceed 2 grams daily and provide close clinical monitoring. 1 This is the only situation where dose limitation is recommended.
Dialysis Considerations
- Ceftriaxone is not removed by hemodialysis or peritoneal dialysis 1
- No supplementary dosing is required after dialysis 1
- However, a small percentage of end-stage renal disease patients on hemodialysis may show substantially prolonged elimination half-lives, warranting plasma concentration monitoring if available 2
Pharmacokinetic Rationale
Research supports the FDA guidance:
- In patients with severe renal impairment (CrCl <15 mL/min), the elimination half-life increases modestly from 8 hours to approximately 12-17 hours 2, 3
- Plasma clearance decreases by less than 50% compared to normal renal function 2
- The substantial nonrenal (biliary) elimination pathway (30-60% of drug) compensates for reduced renal clearance 3
- Studies in patients with creatinine clearance 31-60 mL/min showed mean half-life of 11.9 hours with adequate plasma concentrations at standard dosing 4
Target Attainment
Recent pharmacodynamic data demonstrate that 2 grams every 24 hours achieves adequate target attainment (>90% probability) for pathogens with MIC ≤2 mg/L in non-ICU patients, even with reduced renal function (eGFR as low as 36 mL/min). 5
Clinical Pitfalls to Avoid
Do not confuse ceftriaxone with other cephalosporins that require dose adjustment—ceftriaxone's unique dual elimination makes it an exception 1, 3
Ensure adequate hydration to prevent ceftriaxone-calcium precipitates in the urinary tract, which can cause urolithiasis 1
Monitor for gallbladder pseudolithiasis on imaging, which appears reversible upon discontinuation 1
Check prothrombin time in patients with impaired vitamin K synthesis, chronic liver disease, or malnutrition, as ceftriaxone can prolong PT 1