How should Keflex (cephalexin) be used in patients with impaired renal function?

Cephalexin Dosing in Renal Failure

Cephalexin requires dose reduction in patients with severe renal impairment (creatinine clearance <30 mL/min), with the dosing interval extended proportionally to the degree of renal dysfunction while maintaining therapeutic efficacy. 1

Key Dosing Principles

Monitoring and Baseline Assessment

• Administer cephalexin with caution in markedly impaired renal function, with careful clinical observation and laboratory monitoring required, as safe dosage may be lower than usually recommended. 1
• Patients with creatinine clearance less than 30 mL/min require dose reduction proportional to their reduced renal function. 2

Pharmacokinetic Changes in Renal Failure

• In anephric patients, single doses of 250-500 mg result in high, prolonged serum concentrations with peak levels typically within 1 hour, though delayed absorption up to 6-12 hours can occur. 3
• Serum half-life increases dramatically from approximately 1 hour in normal subjects to 8.47 hours in patients with creatinine clearance of 0 mL/min. 4
• The total elimination rate constant (Ke) correlates directly with creatinine clearance: Ke = 0.0766 + 0.0060 × CrCl. 4

Specific Dosing Adjustments

For patients with severe renal impairment:

• The dosing interval should be prolonged up to 20 times that used in normal subjects, far exceeding the 5-fold extension suggested by creatinine clearance alone. 5
• This substantial adjustment is necessary because cephalexin depends heavily on active renal tubular secretion for elimination, and tubular function diminishes substantially in renal failure. 5

Critical consideration: Standard creatinine clearance-based dosing is inadequate for cephalexin because it fails to account for the disproportionate reduction in tubular secretory capacity that occurs in renal failure. 6, 5

Hemodialysis Considerations

• Hemodialysis for 6 hours reduces serum cephalexin concentration by approximately 58%. 3
• Despite significant removal during dialysis, urinary concentrations remain adequate for treating most urinary tract infections caused by E. coli, Klebsiella, and Proteus mirabilis even in patients with impaired renal function. 3

Practical Dosing Algorithm

Step 1: Determine creatinine clearance accurately using measured values rather than estimates. 6

Step 2: For CrCl <30 mL/min, extend the dosing interval proportionally:

• Calculate the elimination rate constant: Ke = 0.0766 + 0.0060 × CrCl 4
• Adjust interval based on the ratio of normal to impaired elimination 4

Step 3: Consider both glomerular filtration and tubular secretion function, as non-parallel decreases in these functions limit conventional dosing methods. 6

Step 4: Monitor serum creatinine and clinical response closely, as safe dosage may be lower than typically recommended. 1

Important Caveats

• Do not rely solely on creatinine clearance for dose adjustment - cephalexin's dependence on tubular secretion requires consideration of both glomerular and tubular function. 6, 5
• Delayed absorption can occur unpredictably in anephric patients, with peak levels sometimes not reached until 6-12 hours post-dose. 3
• Prothrombin time should be monitored in patients with renal impairment receiving cephalexin, as cephalosporins may be associated with decreased prothrombin activity. 1
• Concomitant metformin use requires careful monitoring and potential dose adjustment, as cephalexin increases metformin exposure by inhibiting tubular secretion. 1