Cephalexin Dosing at eGFR 50 mL/min/1.73 m²
At an eGFR of 50 mL/min/1.73 m², cephalexin requires dose adjustment with extended dosing intervals, typically administering standard doses (250-500 mg) every 8-12 hours rather than every 6 hours, as renal impairment significantly reduces drug clearance through both glomerular filtration and tubular secretion.
Standard Dosing vs. Renal Adjustment
- The FDA label specifies that adult dosing ranges from 1-4 grams daily in divided doses, with typical dosing of 250 mg every 6 hours or 500 mg every 12 hours for uncomplicated infections 1
- However, patients with creatinine clearances less than 30 mL/min require dose reduction proportional to their reduced renal function 2
- At eGFR 50 mL/min/1.73 m², which represents moderate renal impairment (CKD Stage 3a), dose adjustment is warranted though less dramatic than in severe renal failure 2
Pharmacokinetic Rationale for Adjustment
- Cephalexin depends heavily on active renal tubular secretion for urinary excretion, and renal failure substantially diminishes maximum transport capacity in renal tubules 3
- The serum half-life of cephalexin is highly correlated with creatinine clearance (r = 0.94), increasing from 58 minutes at CrCl 100 mL/min to 15.4 hours in anephric patients 4
- At eGFR 50 mL/min, the half-life is approximately doubled compared to normal renal function, necessitating interval extension 4
Specific Dosing Recommendations
For eGFR 50 mL/min/1.73 m²:
- Administer 250-500 mg every 8-12 hours (rather than every 6 hours) for most infections 2, 4
- For severe infections requiring higher doses, use 500 mg-1 gram every 12 hours rather than more frequent dosing 1, 4
- The total daily dose should generally not exceed 2-3 grams at this level of renal function 4
Critical Safety Considerations
- Avoid supratherapeutic dosing, as beta-lactam antibiotics including cephalosporins can cause neurotoxicity and seizures through drug accumulation, particularly in patients with renal dysfunction, older age, or pre-existing CNS conditions 5
- Dosage adjustment based solely on creatinine clearance underestimates the need for interval prolongation because it doesn't account for reduced tubular secretion—research suggests intervals may need to be extended up to 20 times normal in severe renal failure, though at eGFR 50 the adjustment is more modest 3
- Monitor for signs of drug accumulation including altered mental status, myoclonus, or seizures, especially if dosing intervals are not appropriately extended 5
Monitoring Parameters
- Assess renal function before initiating therapy and monitor periodically during treatment, particularly if renal function is declining 2
- For urinary tract infections, cephalexin achieves urinary concentrations of 500-1000 mcg/mL following 250-500 mg doses, well above MIC for typical uropathogens even with dose adjustment 2
- Therapeutic drug monitoring is not routinely available for cephalexin but should be considered in patients with fluctuating renal function or signs of toxicity 5