Keflex (Cephalexin) Indications and Dosing for Adults
For adults without drug allergies, renal or hepatic impairment, Keflex is indicated for skin and soft tissue infections, respiratory tract infections (including streptococcal pharyngitis), and uncomplicated urinary tract infections, with standard dosing of 250 mg every 6 hours or 500 mg every 12 hours depending on infection severity 1.
FDA-Approved Indications
Keflex treats infections caused by susceptible organisms including:
- Skin and soft tissue infections (SSTI)
- Respiratory tract infections including streptococcal pharyngitis
- Uncomplicated urinary tract infections (UTIs)
- Bone infections
- Otitis media (in pediatric patients)
Standard Adult Dosing Regimens
General Dosing Framework
The FDA label specifies adult dosing ranges from 1 to 4 grams daily in divided doses 1.
Specific Infection-Based Dosing
Mild to Moderate Infections:
- 250 mg every 6 hours (standard dose) 1
Streptococcal Pharyngitis, Uncomplicated SSTIs, and Uncomplicated Cystitis:
- 500 mg every 12 hours 1
- For cystitis, continue therapy for 7-14 days 1
- Recent evidence supports twice-daily dosing is equally effective as four-times-daily dosing for both UTIs and SSTIs 2, 3, 4
Severe Infections or Less Susceptible Organisms:
- Higher doses may be needed within the 1-4 gram daily range 1
- If >4 grams daily required, switch to parenteral cephalosporins 1
IDSA Guideline Context for SSTIs
For surgical site infections away from axilla/perineum, the IDSA guidelines list cephalexin 500 mg every 6 hours orally as an appropriate option 5. This represents the higher end of dosing for more significant infections.
Key Clinical Considerations
Dosing Frequency Simplification: Multiple studies demonstrate that twice-daily dosing (500 mg BID) is as effective as four-times-daily dosing for both UTIs and SSTIs 2, 3, 4. This improves adherence without compromising efficacy. The 2023 multicenter study showed no difference in treatment failure between BID (12.7%) versus QID (17%) dosing for UTIs (P=0.343) 2.
Duration of Therapy:
- Beta-hemolytic streptococcal infections: minimum 10 days 1
- Uncomplicated cystitis: 7-14 days 1
- Other infections: typically 7-10 days based on clinical response
Common Pitfalls to Avoid:
- Do not use cephalexin for infections requiring broader gram-negative coverage or anaerobic coverage
- Avoid in patients with immediate hypersensitivity reactions to penicillins (cross-reactivity risk) 1
- Monitor for Clostridioides difficile infection with prolonged use 1
- Be aware of false-positive urine glucose tests with Benedict's/Fehling's solutions 1
Drug Interactions:
- Metformin: Cephalexin increases metformin levels by 34% (Cmax) and 24% (AUC); monitor glucose and adjust metformin dose 1
- Probenecid: Inhibits renal excretion of cephalexin, increasing levels 1
When Cephalexin is Suboptimal: The 2025 study comparing cefdinir to cephalexin for UTIs reinforces cephalexin's superiority, with cefdinir showing nearly twice the failure rate 6. This supports cephalexin as the preferred first-generation cephalosporin for UTIs when beta-lactams are chosen.