What is the recommended dose of Levofloxacin (fluoroquinolone antibiotic) in an Anti-Tuberculosis Treatment (ATT) regimen?

Levofloxacin Dosing in Anti-Tuberculosis Treatment Regimens

Recommended Dose

For adults with multidrug-resistant tuberculosis (MDR-TB), levofloxacin should be dosed at 750-1,000 mg once daily, with 1,000 mg/day representing the optimal balance between efficacy and tolerability. 1, 2

Standard Adult Dosing Algorithm

For Drug-Susceptible TB

• Levofloxacin is not a first-line agent and should only be used when patients are intolerant of first-line drugs 1

For MDR-TB (Resistant to Isoniazid and Rifampin)

• Standard dose: 750-1,000 mg once daily 1, 2
• Optimal dose: 1,000 mg/day achieves target drug exposure (AUC/MIC) in nearly all adults while maintaining acceptable tolerability 3
• Higher doses (1,250-1,500 mg/day) increase adverse events without improving time to sputum culture conversion 3

The evidence strongly supports 1,000 mg/day as the ceiling dose: a 2025 randomized controlled trial demonstrated that doses exceeding 1,000 mg/day resulted in 37% of patients experiencing grade 3-5 adverse events compared to only 16% at lower doses, yet provided no additional efficacy benefit 3. This represents the highest quality evidence available, directly comparing four different dose levels in MDR-TB patients.

Pediatric Dosing

Children ≥5 Years

• 10 mg/kg once daily (maximum 750 mg) 2

Children 6 Months to <5 Years

• 10 mg/kg divided every 12 hours (maximum 750 mg/day) due to faster drug clearance in younger children 2, 4

Important Pediatric Caveat

• Long-term fluoroquinolone use is not FDA-approved in children due to concerns about bone and cartilage growth effects 1
• However, most experts agree levofloxacin should be considered for children with MDR-TB when benefits outweigh risks 1, 2
• The optimal pediatric dose is not definitively established 1

Renal Dose Adjustments

For creatinine clearance <50 mL/min: reduce to 750-1,000 mg three times weekly 1, 5

• Levofloxacin is 80% renally cleared, necessitating dose modification in renal insufficiency 1, 5
• No supplemental doses are needed after hemodialysis as the drug is not cleared by dialysis 1
• Adjust frequency rather than switching to twice-daily dosing 4

Hepatic Considerations

• No dose adjustment required for hepatic disease 1
• Drug levels are unaffected by liver dysfunction 1
• Use with caution in severe liver disease as with all medications 1

Critical Administration Requirements

Timing with Other Medications

• Do not administer within 2 hours of antacids or medications containing divalent cations (calcium, magnesium, aluminum, iron) 1, 5
• These agents markedly decrease fluoroquinolone absorption 1, 5

Available Formulations

• Tablets: 250 mg, 500 mg, 750 mg 1, 5
• Intravenous solution: 500 mg aqueous solution for patients unable to take oral medications 1, 5

Contraindications and Warnings

Pregnancy

• Avoid in pregnancy due to teratogenic effects 1, 2, 4
• This is a class effect of fluoroquinolones 1

Common Adverse Effects (at standard doses)

• Gastrointestinal: nausea, bloating (0.5-1.8% of patients) 1
• Neurologic: dizziness, insomnia, tremulousness, headache (0.5%) 1
• Cutaneous: rash, pruritus, photosensitivity (0.2-0.4%) 1

Treatment Duration

• Minimum 24 weeks (168 doses) as part of multidrug MDR-TB regimen 3
• Total treatment duration for MDR-TB typically extends 18-24 months depending on response 3

Pharmacokinetic Targets

• Target AUC/MIC ratio for maximal bacterial kill: 146 6
• Target AUC/MIC ratio for suppression of acquired drug resistance: 360 6
• The 1,000 mg/day dose achieves these targets in most adults with typical MIC values ≤0.5 mg/L 3, 7