Keflex (Cephalexin) Dosing
For adults, Keflex is dosed at 250 mg every 6 hours (1 g daily) for mild infections, with 500 mg every 12 hours as an alternative for specific infections like uncomplicated cystitis, streptococcal pharyngitis, and skin infections; for children, the standard dose is 25-50 mg/kg/day divided into 3-4 doses, though twice-daily dosing is equally effective and improves adherence. 1
Adult Dosing
Standard Regimens
- Mild infections: 250 mg every 6 hours (QID)
- Moderate infections: 500 mg every 6 hours OR 500 mg every 12 hours (BID) for:
- Uncomplicated cystitis (7-14 days)
- Streptococcal pharyngitis
- Skin and soft tissue infections
- Severe infections: Up to 4 g daily in divided doses 1
Important caveat: If doses exceeding 4 g daily are required, switch to parenteral cephalosporins 1. For skin and soft tissue infections specifically, the IDSA guidelines recommend 500 mg QID for MSSA infections 2.
Simplified Dosing for Better Adherence
Recent evidence supports twice-daily dosing as equally effective as four-times-daily dosing. A 2023 study demonstrated that 500 mg BID achieved the same treatment success as 500 mg QID for uncomplicated UTIs (treatment failure: 12.7% vs 17%, p=0.343) 3. This approach significantly improves patient adherence without compromising efficacy 4.
Pediatric Dosing
Standard Regimens
- Routine infections: 25-50 mg/kg/day divided into 3-4 doses
- Streptococcal pharyngitis and skin infections: May divide total daily dose into twice-daily dosing (every 12 hours) 1
- Otitis media: 75-100 mg/kg/day in 4 divided doses 1
- Severe infections: Double the standard dose 1
Evidence-Based Simplified Dosing
For MSSA bone and joint infections, 45 mg/kg (maximum 1.5 g) three times daily has proven highly effective with 99% cure rate and good tolerability 5. For twice-daily dosing in MSSA infections, doses of 22-45 mg/kg BID are required depending on organism susceptibility 6.
Critical point: For β-hemolytic streptococcal infections, treat for at least 10 days regardless of dosing frequency 1.
Renal Impairment Adjustments
Assessment Method
Use estimated GFR (eGFR) rather than Cockcroft-Gault equation to assess renal function, as this aligns with current FDA and clinical practice guidelines 7, 8.
Dosing Adjustments
The pharmacokinetic relationship between renal function and cephalexin elimination is well-established: Ke = 0.0766 + 0.0060 × CrCl 9.
Practical adjustments:
- Normal renal function (CrCl >50 mL/min): Standard dosing
- Moderate impairment (CrCl 30-50 mL/min): Reduce dose by 40% or extend dosing interval
- Severe impairment (CrCl 10-30 mL/min): Reduce dose by 50-60% or significantly extend interval
- Anephric patients (CrCl 0): Half-life increases to 15.4 hours (vs 58 minutes in normal function); use loading dose based on weight, then maintenance doses adjusted to 10-25% of standard 10
The drug is substantially excreted renally, making dose adjustment essential in elderly patients who commonly have decreased renal function 1.
Key Drug Interactions
Metformin: Cephalexin increases metformin AUC by 24% and Cmax by 34% through inhibition of renal tubular secretion. Monitor patients closely and adjust metformin dose as needed 1.
Probenecid: Inhibits renal excretion of cephalexin, increasing drug levels 1.
Common Pitfalls
- Avoid using cephalexin for MRSA infections—it is inactive against methicillin-resistant strains 2
- Monitor for C. difficile infection up to 2 months after treatment completion 1
- False-positive urine glucose tests may occur with Benedict's, Fehling's solutions, and Clinitest tablets 1
- In pregnancy (Category B), use only if clearly needed despite favorable animal studies 1
- Cephalexin reaches 4 μg/mL in breast milk at 4 hours post-dose; exercise caution in nursing mothers 1