Levofloxacin

Levofloxacin is a fluoroquinolone with better Gram-positive and atypical activity than ciprofloxacin, used for community-acquired pneumonia, urinary infection, sinusitis and multidrug-resistant tuberculosis. It shares the class warnings.

Classification. Fluoroquinolone, third generation.

Mechanism. Inhibits DNA gyrase and topoisomerase IV; bactericidal, concentration-dependent.

Spectrum. Pneumococci, Haemophilus, Moraxella, Legionella, Mycoplasma, Chlamydia, Enterobacterales, Pseudomonas aeruginosa (less than ciprofloxacin), Mycobacterium tuberculosis and some staphylococci. Anaerobic activity is weak. Resistance is rising in Escherichia coli.

Pharmacokinetics. Oral bioavailability about 99%, so oral and IV doses are equal. Half-life 6 to 8 hours. Mainly renal excretion unchanged; much less CYP interaction than ciprofloxacin.

Maximum 750 mg daily in most indications (1 g daily in specialist tuberculosis use).

Adults, oral or IV, once daily.

• Community-acquired pneumonia: 750 mg once daily for 5 days, or 500 mg once daily for 7 to 14 days.
• Hospital-acquired pneumonia: 750 mg once daily for 7 to 14 days, with a second active agent for Pseudomonas.
• Pyelonephritis and complicated urinary tract infection: 750 mg once daily for 5 days, or 250 mg once daily for 10 days.
• Acute bacterial sinusitis: 750 mg once daily for 5 days.
• Chronic bacterial prostatitis: 500 mg once daily for 28 days.
• Skin and soft tissue infection: 500 to 750 mg once daily for 7 to 14 days.
• Drug-resistant tuberculosis: 750 to 1000 mg once daily (or 10 to 15 mg/kg in under 50 kg) as part of a multidrug regimen under specialist direction.
• Inhalational anthrax post-exposure, plague: 500 mg once daily for 60 days (anthrax).

Children. Use only when alternatives are unsuitable. 6 months to under 5 years 10 mg/kg every 12 hours; 5 years and over 10 mg/kg once daily (maximum 750 mg). Tuberculosis in children under 5 years 15 to 20 mg/kg once daily; 5 years and over 10 to 15 mg/kg once daily.

Alternatives. Amoxicillin, doxycycline, azithromycin, moxifloxacin, ceftriaxone, nitrofurantoin.

Boxed-warning level risks. Tendinitis and tendon rupture, peripheral neuropathy, central nervous system effects, aggravation of myasthenia gravis, aortic aneurysm or dissection risk. Use for uncomplicated infection is discouraged.

Contraindications. Fluoroquinolone hypersensitivity; previous tendon disorder with a fluoroquinolone; uncorrected QT prolongation or hypokalaemia.

Adverse effects. Nausea, diarrhoea, headache, insomnia, dizziness. Serious: tendon rupture, QT prolongation, dysglycaemia (including hypoglycaemia in older adults with diabetes), neuropathy, seizures, psychiatric reactions, hepatotoxicity, aortic aneurysm or dissection, Clostridioides difficile infection, severe skin reactions.

Interactions. Cations (separate by 2 hours before or 2 hours after), QT-prolonging drugs, warfarin (INR rise), corticosteroids (tendon risk), sulphonylureas and insulin (dysglycaemia), NSAIDs (seizure risk), theophylline (small effect), and antidiabetic drugs.

Common prescribing errors. Using it for simple cystitis or minor respiratory infection, forgetting to reduce the dose in kidney impairment, and giving it with antacids or iron.

Special groups.

• Pregnancy: avoid unless essential
• Breastfeeding: avoid; short use is acceptable if essential
• Older adults: higher risk of tendon rupture, delirium and dysglycaemia
• Kidney impairment (750 mg regimen): creatinine clearance 20 to 49 mL/min 750 mg every 48 hours; 10 to 19 mL/min and dialysis 750 mg then 500 mg every 48 hours
• Kidney impairment (500 mg regimen): creatinine clearance 20 to 49 mL/min 500 mg then 250 mg every 24 hours; 10 to 19 mL/min 500 mg then 250 mg every 48 hours
• Liver impairment: no adjustment
• Region: valuable in drug-resistant tuberculosis programmes in East Africa; community use for minor infection speeds resistance

Preparation. Oral with or without food, separated from cations. IV: infuse over 60 minutes (250 to 500 mg) or 90 minutes (750 mg) at 5 mg/mL in 0.9% sodium chloride or 5% glucose; never as a rapid bolus.

Baseline and monitoring. - Baseline: medication review, ECG and potassium in cardiac risk, glucose in diabetes, creatinine, pregnancy status. - During treatment: tendon pain, paraesthesia, mood and sleep; liver tests, ECG and potassium in prolonged tuberculosis regimens.

Stop rules. Stop for tendon pain, neuropathic symptoms, psychiatric disturbance, seizure, severe hypoglycaemia, jaundice or severe rash.

Referral and escalation. Refer for tendon rupture, QT prolongation, drug-resistant tuberculosis and aortic symptoms.