What is the appropriate cephalexin dosing regimen for an adult with end‑stage renal disease, including hemodialysis considerations?

Cephalexin Dosing in ESRD Requires Dose Reduction and Extended Intervals

Cephalexin 250 mg four times daily is inappropriate for ESRD patients; the dose must be reduced proportionally to renal function (creatinine clearance <30 mL/min requires dosage reduction), and the dosing interval should be extended rather than maintaining frequent administration.

Critical Dosing Principles for ESRD

The fundamental approach to antibiotic dosing in severe renal impairment differs from normal renal function:

• Extend the interval, not reduce individual doses for most antibiotics to maintain adequate peak concentrations while preventing accumulation 1, 2
• However, cephalexin specifically requires dose reduction proportional to reduced renal function when creatinine clearance falls below 30 mL/min 3
• Cephalexin achieves 70-100% urinary excretion within 6-8 hours in normal renal function, but this is dramatically impaired in ESRD 3

Specific Cephalexin Adjustments for ESRD

For patients with creatinine clearance <30 mL/min or on hemodialysis:

• Reduce the total daily dose proportionally to the degree of renal impairment 3
• A typical adjustment would be 250 mg every 12-24 hours rather than 250 mg four times daily
• Cephalexin is significantly removed by hemodialysis (58% reduction over 6 hours), requiring post-dialysis supplementation 4
• Administer doses after hemodialysis sessions to prevent premature drug removal 1, 2

Important Clinical Caveats

Cephalexin is not a first-line agent for UTI in hemodialysis patients despite adequate urinary concentrations:

• β-lactams like cephalexin are classified as alternative rather than first-line agents due to inferior clinical efficacy compared to fluoroquinolones in ESRD patients with UTI 1
• Even with impaired renal function, urinary concentrations remain adequate for common uropathogens (E. coli, Klebsiella, Proteus mirabilis) 4
• However, fluoroquinolones (levofloxacin 750 mg three times weekly post-dialysis, or ciprofloxacin 500 mg three times weekly post-dialysis) demonstrate superior outcomes 1

Practical Dosing Algorithm

For an ESRD patient requiring cephalexin:

1. Determine dialysis status: If on hemodialysis, plan all doses post-dialysis 1, 2
2. Calculate appropriate dose reduction: Reduce from standard 250-500 mg QID to approximately 250 mg every 12-24 hours based on residual renal function 3
3. Monitor for delayed absorption: Peak levels may be delayed up to 6-12 hours in some anephric patients rather than the typical 1 hour 4
4. Supplement post-dialysis: Give an additional dose after each dialysis session due to significant drug removal 4

Monitoring Considerations

• Serum drug concentration monitoring should be considered to ensure adequate absorption without excessive accumulation 5
• Watch for prolonged half-life: In anephric patients, single doses result in high, prolonged serum concentrations with unpredictable absorption patterns 4