What is the recommended dose of Keflex (Cephalexin) for a patient with severe impaired renal function (eGFR 25)?

Keflex Dosing in Severe Renal Impairment (eGFR 25)

For a patient with eGFR 25 mL/min, reduce the Keflex (cephalexin) dosing interval to every 8-12 hours with standard individual doses (250-500 mg), or alternatively use 500 mg every 12 hours as a practical starting regimen, with further adjustment based on infection severity and clinical response. 1, 2

Pharmacokinetic Rationale

Cephalexin is eliminated almost exclusively by the kidneys through both glomerular filtration and active tubular secretion, with 70-100% of the dose appearing unchanged in urine within 6-8 hours in patients with normal renal function 1. In severe renal impairment:

• The elimination half-life is significantly prolonged when creatinine clearance falls below 30 mL/min, necessitating dosage adjustment 1
• Active tubular secretion is substantially diminished in renal failure patients with glomerulonephritis, affecting cephalexin excretion more than predicted by creatinine clearance alone 2
• Standard creatinine clearance-based adjustments may underestimate the required interval prolongation because they don't account for reduced tubular secretory capacity 2

Specific Dosing Recommendations

Standard Approach

• Patients with creatinine clearance less than 30 mL/min require proportional dose reduction based on their reduced renal function 1
• The dosing interval should be extended rather than reducing individual doses, to maintain adequate peak concentrations at the infection site 1, 2

Practical Regimen for eGFR 25

• Start with 500 mg every 12 hours for moderate infections (skin, soft tissue, uncomplicated UTI) 1
• For severe infections, consider 500 mg every 8 hours initially, then extend to every 12 hours once clinical improvement occurs 1
• Avoid doses exceeding 1-1.5 g per day total in this degree of renal impairment to prevent accumulation 1, 2

Critical Monitoring Considerations

Monitor for drug accumulation signs including CNS effects (confusion, seizures in severe cases), as cephalosporins can accumulate in renal failure 2. Unlike drugs that undergo hepatic metabolism, cephalexin has no alternative elimination pathway 1.

Common Pitfalls to Avoid

• Do not rely solely on creatinine clearance calculations for dosing adjustments, as research demonstrates that tubular secretory function declines disproportionately in glomerulonephritis-related renal failure, requiring up to 20-fold interval prolongation versus the 5-fold suggested by creatinine clearance alone 2
• Do not reduce individual doses below therapeutic levels (less than 250 mg); instead, extend the dosing interval to maintain adequate peak concentrations while preventing accumulation 1, 2
• Avoid assuming normal dosing is safe even with "mild" symptoms, as cephalexin does not distribute into cells and accumulates in extracellular fluid when renal clearance is impaired 1

Comparison with Other Cephalosporins

Unlike cefotaxime (which has active metabolites that accumulate but maintains relatively stable parent drug half-life in renal failure) 3, or ceftazidime (which requires 36-48 hour intervals in severe renal failure) 4, cephalexin's simpler pharmacokinetics make every 8-12 hour dosing appropriate at eGFR 25 1, 2.

Dialysis Considerations

If the patient progresses to requiring hemodialysis, administer a supplementary dose after each dialysis session, as cephalexin is removed by dialysis 4, 1. The standard approach is to give the regular dose post-dialysis to facilitate directly observed therapy 4.