What is the recommended dose of levofloxacin (Levaquin) in pediatrics?

Levofloxacin Dosing in Pediatric Patients

For pediatric patients ≥6 months of age, levofloxacin should be dosed at 8-10 mg/kg once daily (maximum 750 mg/day) for children 5-16 years old, or 16-20 mg/kg/day divided every 12 hours for children 6 months to 5 years old, based on FDA approval and IDSA/PIDS guidelines. 1, 2

Age-Based Dosing Algorithm

Children 6 months to <5 years:

• Dose: 10 mg/kg every 12 hours (total 20 mg/kg/day) 1, 3
• Maximum single dose: 250 mg 1
• Rationale: Younger children clear levofloxacin nearly twice as fast as adults, requiring divided dosing to maintain therapeutic exposures 3

Children 5 to 16 years:

• Dose: 8-10 mg/kg once daily 1, 2
• Maximum daily dose: 750 mg 1, 2
• Rationale: Clearance approaches adult levels by age 5 years, permitting once-daily dosing 3

Adolescents with skeletal maturity:

• Dose: 500 mg once daily for most infections 1
• Alternative: 750 mg once daily for severe infections 1

FDA-Approved Indications in Pediatrics

Levofloxacin is FDA-approved in children ≥6 months only for specific indications where benefits outweigh musculoskeletal risks 2:

• Inhalational anthrax (post-exposure): 8 mg/kg twice daily (maximum 250 mg per dose) for children 6 months to <5 years; 8 mg/kg once daily (maximum 500 mg) for children ≥5 years 2, 4
• Plague (treatment and prophylaxis): Same dosing as anthrax 2

Off-Label Use for Respiratory Infections

The IDSA/PIDS guidelines list levofloxacin as an alternative agent (not first-line) for specific pediatric respiratory infections 1:

Community-Acquired Pneumonia:

• For β-lactamase-producing Haemophilus influenzae: 16-20 mg/kg/day every 12 hours (ages 6 months-5 years) or 8-10 mg/kg/day once daily (ages 5-16 years), maximum 750 mg/day 1
• For atypical pathogens (Mycoplasma, Chlamydophila): Same dosing as above, but only for children >7 years when macrolides fail 1
• Preferred alternatives: Azithromycin remains first-line for atypical pneumonia; amoxicillin or amoxicillin-clavulanate for H. influenzae 1

Critical Safety Considerations

Musculoskeletal Toxicity (Black Box Warning):

• Levofloxacin causes arthralgia, arthritis, and tendinopathy in 3-4% of pediatric patients versus 1-2% with non-fluoroquinolones 2
• Most events are mild-to-moderate, involving weight-bearing joints, and resolve within 7-9 days without sequelae 2
• Risk increases with: Age >65 years (if treating adolescents approaching adulthood), concomitant corticosteroid use, and prolonged therapy >14 days 2
• Action required: Discontinue immediately if tendon pain, swelling, or inflammation occurs 2

Hepatotoxicity:

• Severe, sometimes fatal hepatotoxicity reported postmarketing, particularly in patients ≥65 years 2
• Monitor liver function if therapy extends beyond 14 days 2

Renal Dosing:

• No adjustment needed for creatinine clearance ≥50 mL/min 5
• For CrCl <50 mL/min, reduce dose or extend interval (specific adjustments not detailed in pediatric guidelines) 5

Pharmacokinetic Considerations

Age-Dependent Clearance:

• Clearance reaches 50% of adult maturity by 2 months of age and 100% by 2 years 6
• Children <5 years have clearance rates of 0.28-0.32 L/h/kg, approximately double that of adults, necessitating twice-daily dosing 3
• HIV infection reduces clearance by 16%, potentially requiring dose adjustment 6

Formulation Differences:

• Dispersible 100 mg tablets have 21.5% higher bioavailability than crushed 250 mg non-dispersible tablets 7
• If using crushed tablets, consider increasing dose by 20-25% to achieve equivalent exposures 7

Multidrug-Resistant Tuberculosis (Specialized Dosing)

For MDR-TB in children, emerging evidence suggests higher doses may be required 6, 7, 8:

• Current WHO recommendation: 15-20 mg/kg/day once daily 8
• Optimized dosing based on recent PK studies: 20-30 mg/kg/day may be needed to achieve target fAUC/MIC ratio of 100 8
• Weight-based dosing for dispersible tablets: 16-30 mg/kg/day; for crushed non-dispersible tablets: 20-38 mg/kg/day 7
• Important caveat: These higher doses require further prospective validation and should only be used in consultation with pediatric infectious disease specialists 6, 7, 8

Common Pitfalls to Avoid

• Do not use levofloxacin as first-line therapy for common pediatric infections where safer alternatives exist (e.g., amoxicillin for pneumococcal pneumonia, azithromycin for atypical pneumonia) 1
• Do not prescribe for >14 days without documented safety monitoring, as long-term use is not approved due to bone/cartilage concerns 2
• Do not co-administer within 2 hours of antacids or divalent cations (calcium, magnesium, iron), which reduce absorption by up to 50% 5
• Do not exceed maximum daily dose of 750 mg regardless of weight 1, 2