Renal Dosing of Cephalexin (Keflex) for UTI
For patients with creatinine clearance <30 mL/min, reduce cephalexin dosing to 250-500 mg every 12 hours rather than the standard every 6-hour regimen, as the drug is primarily renally cleared and accumulation can occur with impaired kidney function. 1, 2
Standard Dosing in Normal Renal Function
- The typical dose for UTI is cephalexin 500 mg four times daily (every 6 hours) for 7 days in patients with normal renal function 3, 4
- Recent evidence supports that 500 mg twice daily may be equally effective for uncomplicated UTIs, with no difference in treatment failure rates (12.7% vs 17%, P=0.343) compared to four-times-daily dosing 4
- Cephalexin achieves urinary concentrations of 500-1000 mcg/mL following 250-500 mg oral doses, far exceeding the minimum inhibitory concentration for common uropathogens 2
Renal Dosing Adjustments
The critical threshold for dose adjustment is creatinine clearance <30 mL/min 2:
- CrCl ≥30 mL/min: Use standard dosing (500 mg every 6-12 hours) 2
- CrCl <30 mL/min: Reduce dosage proportionally to the degree of renal impairment; typical adjustment is 250-500 mg every 12 hours 2
- Anephric patients: Single doses of 250-500 mg result in high, prolonged serum concentrations with peak levels within 1 hour (though delayed absorption up to 12 hours can occur in some patients) 5
Pharmacokinetic Considerations in Renal Impairment
- Cephalexin is 70-100% excreted unchanged in urine within 6-8 hours after each dose 2
- The drug is cleared primarily by glomerular filtration and tubular secretion 6
- Even in patients with impaired renal function, urinary concentrations remain adequate for treating most UTIs caused by E. coli, Klebsiella, and Proteus mirabilis 5
- Hemodialysis removes approximately 58% of cephalexin over 6 hours, so dosing should occur after dialysis 5
Practical Dosing Algorithm
Step 1: Calculate creatinine clearance 1, 2:
- Use Cockcroft-Gault equation or measured creatinine clearance
- Serum creatinine alone may underestimate degree of impairment
Step 2: Adjust dose based on renal function 2:
- CrCl >50 mL/min: 500 mg every 6 hours OR 500 mg every 12 hours
- CrCl 30-50 mL/min: 500 mg every 8-12 hours
- CrCl 10-30 mL/min: 250-500 mg every 12 hours
- CrCl <10 mL/min: 250 mg every 12-24 hours
Step 3: For hemodialysis patients 5:
- Administer dose after dialysis session
- Use 250-500 mg every 12-24 hours on non-dialysis days
Important Caveats and Monitoring
- Careful clinical observation and laboratory monitoring are essential in patients with markedly impaired renal function, as safe dosage may be lower than usually recommended 1
- Monitor for signs of drug accumulation, particularly in elderly patients who may have reduced renal function despite normal serum creatinine 2
- Cephalexin does not require dose adjustment for hepatic impairment as it undergoes no measurable metabolism 2
- The drug interacts with metformin by inhibiting tubular secretion; careful monitoring and metformin dose adjustment may be needed in patients taking both medications 1
Treatment Duration
- Minimum 7 days for uncomplicated UTI in both males and females 7, 3, 4
- Consider 10-14 days for complicated UTIs or when prostatitis cannot be excluded in males 7
- Obtain urine culture before starting therapy to guide definitive treatment 7
When Cephalexin May Not Be Appropriate
- Avoid in patients with CrCl <10 mL/min if alternative agents are available, as urinary concentrations may be suboptimal 6
- Not recommended for pyelonephritis as first-line therapy; fluoroquinolones or parenteral agents are preferred 8
- Consider alternatives if local E. coli resistance to first-generation cephalosporins exceeds 20% 7