Risk of Overdose with Keflex (Cephalexin)
Cephalexin overdose risk is significantly elevated in elderly patients and those with renal impairment because the drug is substantially excreted by the kidney, and accumulation occurs when renal clearance is reduced. 1
Primary Risk Factors
Elderly patients are at inherently higher risk because:
- Age-related renal decline reduces function by approximately 1% per year after age 30-40, meaning a 70-year-old may have lost 40% of baseline renal function 2
- Serum creatinine alone is unreliable in elderly patients due to age-related muscle mass loss, potentially masking significant renal impairment 3
- The FDA label explicitly states that elderly patients are more likely to have decreased renal function, and the risk of toxic reactions is greater in patients with impaired renal function 1
Renal impairment dramatically alters cephalexin pharmacokinetics:
- In anephric patients, single doses of 250-500 mg result in high, prolonged serum concentrations with peak levels sometimes delayed up to 6-12 hours due to altered absorption 4
- Serum half-life increases from 1.03 hours in normal subjects to theoretically 8.47 hours in patients with creatinine clearance of 0 mL/min 5
- Patients with creatinine clearance less than 30 mL/min require proportional dose reduction based on reduced renal function 6
Clinical Manifestations of Overdose
While the FDA label does not specify exact overdose symptoms for cephalexin 1, cephalosporin-class neurotoxicity can occur:
- Life-threatening neurologic symptoms have been documented with cephalosporin overdose in elderly patients with impaired renal function 7
- Symptoms may include confusion, seizures, and altered mental status, particularly when drug accumulation occurs 7
Mandatory Precautions
Before prescribing cephalexin, you must:
- Calculate estimated GFR using the Cockcroft-Gault equation rather than relying on serum creatinine alone 2, 3
- Document baseline renal function with a monitoring plan 3
- Ensure adequate hydration status before initiating therapy 3
Dose adjustment is essential when creatinine clearance is <30 mL/min:
- Reduce dosage proportionally to the degree of renal impairment 6
- The FDA label mandates careful clinical observation and laboratory monitoring under conditions of markedly impaired renal function, as safe dosage may be lower than usually recommended 1
- Monitor renal function throughout therapy, particularly in elderly patients 1
Drug Interactions That Increase Risk
Probenecid significantly increases overdose risk by inhibiting renal excretion of cephalexin, leading to drug accumulation 1
Metformin coadministration requires heightened vigilance:
- Cephalexin increases metformin plasma concentrations by 34% (Cmax) and 24% (AUC) while decreasing metformin renal clearance by 14% 1
- Careful patient monitoring and metformin dose adjustment are recommended when coadministered 1
Management of Suspected Overdose
If overdose or toxicity is suspected:
- Hemodialysis reduces serum cephalexin concentration by 58% over 6 hours 4
- At least one session of intermittent hemodialysis may shorten time to nontoxic range by approximately 15 hours and should be considered early in severe clinically patent intoxication, even in frail elderly patients 7
- Pharmacokinetic modeling demonstrates that high-flux, high-efficiency hemodialysis effectively removes cephalexin 7
Critical Pitfalls to Avoid
- Never assume normal renal function in elderly patients based solely on serum creatinine - always calculate creatinine clearance 2, 3
- Do not use standard dosing in patients with creatinine clearance <30 mL/min without dose reduction 6
- Do not overlook delayed absorption patterns - peak levels in anephric patients may occur 6-12 hours post-dose rather than the typical 1-2 hours 4
- Monitor for neurologic symptoms in elderly patients with renal impairment receiving cephalexin, as cephalosporin neurotoxicity can be life-threatening 7