Keflex (Cephalexin) Safety in Severe Renal Impairment (eGFR 17)
Keflex can be used in patients with an eGFR of 17, but requires significant dose reduction and extended dosing intervals to prevent drug accumulation and toxicity. 1
Dose Adjustment Requirements
The FDA label explicitly states that cephalexin should be administered with caution in markedly impaired renal function, with careful clinical observation and laboratory monitoring, as safe dosage may be lower than usually recommended. 1
Specific Dosing Modifications for eGFR 17
Reduce the standard dose by 50-75% and extend the dosing interval to every 12-24 hours based on pharmacokinetic data showing that elimination half-life increases from approximately 1 hour in normal renal function to 8.5 hours in anephric patients 2, 3
A loading dose of 500 mg can be given initially, followed by maintenance doses of 250 mg every 12-24 hours to achieve therapeutic levels while preventing accumulation 3
The dosing interval should be prolonged up to 20 times that of normal subjects when creatinine clearance approaches zero, as both glomerular filtration and tubular secretion are substantially diminished 4
Pharmacokinetic Considerations
Cephalexin depends heavily on both glomerular filtration and active tubular secretion for elimination, and both mechanisms are severely impaired at eGFR 17 4
In anephric patients, peak serum levels remain elevated and prolonged, with some patients showing delayed absorption peaks at 6-12 hours rather than the typical 1-2 hours 2
Urinary concentrations remain adequate for treating most urinary tract infections even in severe renal impairment, as the drug concentrates in urine 2
Monitoring Requirements
Close clinical observation and laboratory monitoring are mandatory when using cephalexin in severe renal impairment: 1
Monitor for signs of drug accumulation including CNS effects (confusion, seizures), gastrointestinal symptoms, and allergic reactions 1, 5
Check renal function (serum creatinine, eGFR) regularly during therapy to detect any further deterioration 1
Monitor for superinfection and Clostridioides difficile-associated diarrhea, which can occur even 2 months after the last dose 1
Important Drug Interactions at eGFR 17
If the patient is taking metformin, dose adjustment of metformin is essential as cephalexin increases metformin exposure by 34% (Cmax) and 24% (AUC) through inhibition of tubular secretion 1
Probenecid inhibits renal excretion of cephalexin and should be avoided or used with extreme caution in this setting 1
Risk Mitigation Strategies
To minimize toxicity risk in severe renal impairment: 5
Ensure adequate hydration (saline loading) prior to and during therapy, as volume depletion is a major risk factor for nephrotoxicity 5
Avoid concurrent nephrotoxins including NSAIDs, aminoglycosides, and contrast media 5
Consider alternative non-renally cleared antibiotics if clinically appropriate for the infection being treated 5
Special Populations
Elderly patients with eGFR 17 require particular caution as they are more likely to have decreased renal function and greater sensitivity to adverse effects 1
The risk of toxic reactions is substantially greater in patients with impaired renal function, as cephalexin is primarily excreted by the kidney 1
Clinical Pitfalls to Avoid
Do not use standard dosing regimens (typically 500 mg every 6-8 hours) as this will lead to dangerous drug accumulation 3, 4
Do not rely solely on creatinine clearance calculations for dose adjustment, as tubular secretion is disproportionately affected compared to glomerular filtration in chronic kidney disease 4
Do not assume consistent absorption patterns, as delayed peak levels can occur in patients with severe renal impairment 2