What is the recommended dosing of Keflex (cephalexin) for an otherwise healthy adult with a mild‑to‑moderate infection, including pediatric weight‑based dosing, adjustments for impaired renal function, contraindications, and monitoring?

Keflex (Cephalexin) Dosing Recommendations

For otherwise healthy adults with mild-to-moderate infections, cephalexin should be dosed at 500 mg every 6 hours (four times daily) for most infections, with treatment duration typically 7-10 days. 1

Adult Dosing for Common Infections

Standard Dosing Regimens

• Skin and soft tissue infections (MSSA): 500 mg four times daily for 7-10 days 2, 1
• Streptococcal pharyngitis: 500 mg every 12 hours (twice daily) for at least 10 days 1
• Uncomplicated cystitis (>15 years): 500 mg every 12 hours for 7-14 days 1
• Respiratory tract infections: 500 mg four times daily 2

Dosing Flexibility

• The FDA label specifies that adult dosage ranges from 1-4 grams daily in divided doses 1
• For mild infections, 250 mg every 6 hours may be adequate 1
• If daily doses exceeding 4 grams are required, switch to parenteral cephalosporins 1

Alternative Twice-Daily Dosing

• Recent evidence supports 500 mg twice daily for uncomplicated UTIs with similar efficacy to four-times-daily dosing 3, 4
• Twice-daily dosing (500 mg BID) may improve adherence without compromising outcomes for urinary tract infections 3

Pediatric Weight-Based Dosing

Standard Pediatric Dosing

• Mild-to-moderate infections: 25-50 mg/kg/day divided into 4 doses 1
• MSSA skin/soft tissue infections: 75-100 mg/kg/day divided into 3-4 doses 2
• Otitis media: 75-100 mg/kg/day in 4 divided doses 1
• Streptococcal pharyngitis: Total daily dose may be divided every 12 hours in patients >1 year 1

Severe Infections

• Dosage may be doubled for severe infections 1
• β-hemolytic streptococcal infections require at least 10 days of therapy to prevent rheumatic fever 1

Renal Function Adjustments

Monitoring Requirements

• Patients with creatinine clearance <30 mL/min require dosage reduction proportional to reduced renal function 5
• Cephalexin is 70-100% renally excreted within 6-8 hours 5
• Clinical and laboratory monitoring should occur in patients with markedly impaired renal function 1

Practical Approach

• Determine creatinine clearance or serum creatinine before dosing 5
• Reduce dose proportionally based on degree of renal impairment 5
• Monitor for drug accumulation in severe renal dysfunction 1

Contraindications and Precautions

Absolute Contraindications

• History of anaphylaxis, angioedema, or urticaria to penicillins or cephalosporins 6, 7
• Documented severe IgE-mediated reactions to β-lactams 7

Relative Contraindications and Cautions

• Cross-reactivity risk: Cephalosporins should not be used in patients with immediate hypersensitivity to penicillins 6, 1
• History of gastrointestinal disease, particularly colitis (risk of C. difficile) 1
• Patients on anticoagulant therapy (monitor prothrombin time) 1
• Renal or hepatic impairment 1

Drug Interactions

• Metformin: Cephalexin increases metformin Cmax by 34% and AUC by 24%; careful monitoring and dose adjustment of metformin recommended 1
• Probenecid: Inhibits renal excretion of cephalexin, increasing drug levels 1

Monitoring Parameters

Clinical Monitoring

• Efficacy: Resolution of infection symptoms within 48-72 hours 2
• If no improvement by day 5, extend treatment duration 7
• Monitor for superinfection with prolonged use 1

Laboratory Monitoring

• Renal function: Baseline and periodic monitoring in patients with impaired renal function 1, 5
• Prothrombin time: In patients on anticoagulants or at risk for coagulopathy 1
• False-positive urine glucose: May occur with Benedict's, Fehling's solutions, or Clinitest tablets 1
• Positive direct Coombs' test: May occur during treatment 1

Safety Monitoring

• Gastrointestinal adverse events: Occur in approximately 4-5% of patients 2, 7
• Diarrhea: Common; if watery/bloody stools develop, evaluate for C. difficile colitis 1
• Allergic reactions (discontinue immediately if occurs) 1

Critical Clinical Considerations

Spectrum Limitations

• No activity against MRSA – use alternative agents if MRSA suspected 2, 7
• Poor coverage for Haemophilus influenzae and Moraxella catarrhalis (avoid for sinusitis/respiratory infections with these pathogens) 2
• Completely ineffective against Pseudomonas aeruginosa 2
• Limited anaerobic coverage (unsuitable for deep abscesses) 7

Treatment Duration Pitfalls

• Streptococcal infections require minimum 10 days to prevent rheumatic fever 6, 1
• Completing full course is essential even if symptoms improve early 1
• Skipping doses increases resistance risk 1

Dosing Schedule Optimization

• Four-times-daily dosing (every 6 hours) maintains optimal time above MIC for β-lactam antibiotics 2
• Possible administration times: 6 AM, 12 PM, 6 PM, 12 AM 2
• For severe infections requiring higher sustained levels, maintain QID dosing 2