What is Levaquin (levofloxacin)?

What is Levaquin (Levofloxacin)?

Levaquin (levofloxacin) is a fluoroquinolone antibiotic that is the pure L-isomer of ofloxacin, used to treat a broad range of bacterial infections including respiratory tract infections, urinary tract infections, skin infections, and certain bioterrorism-related infections like anthrax and plague. 1

Drug Classification and Mechanism

• Levofloxacin is a synthetic broad-spectrum fluoroquinolone antibacterial agent that works by inhibiting bacterial topoisomerase, preventing bacterial DNA replication 1
• It is the optically pure levorotatory (S-) isomer of the racemic drug ofloxacin, and is significantly more active against bacterial pathogens than the R-(+)-ofloxacin isomer 2, 3

Antimicrobial Spectrum

Levofloxacin demonstrates broad-spectrum activity superior to older fluoroquinolones like ciprofloxacin for respiratory pathogens:

• Gram-positive organisms: Enhanced activity against Streptococcus pneumoniae (including penicillin-resistant strains) compared to ciprofloxacin or ofloxacin 4, 5, 3
• Gram-negative organisms: Active against Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa 6, 7
• Atypical pathogens: Effective against Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, and Mycobacterium tuberculosis 7, 2

FDA-Approved Indications

Levofloxacin is approved for adults (18 years and older) to treat 1:

• Community-acquired pneumonia
• Nosocomial pneumonia
• Acute bacterial sinusitis
• Acute exacerbations of chronic bronchitis
• Complicated and uncomplicated skin infections
• Complicated and uncomplicated urinary tract infections
• Acute pyelonephritis (kidney infection)
• Chronic bacterial prostatitis
• Inhalational anthrax (post-exposure)
• Plague

For children 6 months and older, levofloxacin is approved only for inhalational anthrax exposure and plague treatment or prevention 1

Available Formulations and Dosing

Levofloxacin is available in multiple formulations with 99% oral bioavailability, allowing seamless transition between intravenous and oral therapy: 1, 2

• Oral tablets: 250 mg, 500 mg, 750 mg 4
• Intravenous solution: 500 mg for infusion 4
• Oral solution (bioequivalent to tablets) 1

Standard adult dosing regimens: 4, 6

• Respiratory infections: 500-750 mg once daily for 5-14 days
• Severe pneumonia/ICU care: 750 mg once daily 6
• Drug-resistant tuberculosis: 500-1,000 mg once daily 4
• Urinary tract infections: 250-750 mg once daily for 5-14 days 8

Pharmacokinetic Advantages

Levofloxacin has pharmacokinetic properties that make it particularly useful for serious infections:

• Rapid and complete oral absorption with peak concentrations in 1-2 hours 1, 2
• Excellent tissue penetration with concentrations exceeding plasma levels in lung, skin, and prostate 1, 3
• CSF penetration of 16-20% of serum levels (adequate for some CNS infections) 4
• Linear, predictable pharmacokinetics allowing once-daily dosing 1
• Steady-state achieved within 48 hours 1

Critical Safety Warnings

The FDA requires a boxed warning for serious adverse effects that can result in death or permanent disability: 1

Tendon Rupture and Tendinitis

• Risk is highest in patients over 60 years, those taking corticosteroids, or transplant recipients 1
• Most commonly affects the Achilles tendon but can occur at any tendon site 1
• Stop levofloxacin immediately at first sign of tendon pain, swelling, or inflammation 1
• Rupture can occur during treatment or up to several months after completion 1

Worsening of Myasthenia Gravis

• Fluoroquinolones can cause life-threatening worsening of muscle weakness and breathing problems in patients with myasthenia gravis 1
• Call healthcare provider immediately if muscle weakness or breathing problems worsen 1

Other Serious Adverse Effects

• Neurologic effects: Dizziness, insomnia, tremulousness, headache (0.5% incidence) 4
• Gastrointestinal: Nausea and bloating (0.5-1.8% incidence) 4
• Cutaneous reactions: Rash, pruritus, photosensitivity (0.2-0.4% incidence) - notably lower than some other fluoroquinolones 4, 5
• QT prolongation: Risk in patients with pre-existing arrhythmias or electrolyte abnormalities 1

Important Drug Interactions

Levofloxacin absorption is significantly reduced by divalent and trivalent cations - these must be separated by at least 2 hours: 4, 1

• Antacids containing aluminum or magnesium
• Multivitamins with iron or zinc
• Sucralfate
• Didanosine

Other clinically significant interactions: 1

• NSAIDs may increase risk of CNS effects and seizures
• Warfarin requires close monitoring
• Corticosteroids increase tendon rupture risk

Special Populations

Pregnancy and Breastfeeding

• Avoid in pregnancy due to teratogenic effects on bone and cartilage 4
• Unknown if excreted in breast milk; should not breastfeed while taking levofloxacin 1

Renal Impairment

• 80% cleared by kidneys; requires dosage adjustment when creatinine clearance <50 mL/minute 4
• Recommended dose: 750-1,000 mg three times weekly in severe renal insufficiency 4
• Not removed by hemodialysis; no supplemental doses needed after dialysis 4

Hepatic Impairment

• Drug levels not significantly affected by liver disease 4
• Can be used in severe liver disease with caution and monitoring 4

Pediatric Use

• Long-term use (>14 days) not approved in children due to concerns about bone and cartilage growth 4
• Exception: Children with multidrug-resistant tuberculosis where benefits outweigh risks 4
• Safety and effectiveness in children under 6 months not established 1

Clinical Role and Positioning

Levofloxacin is NOT a first-line agent for drug-susceptible infections but serves specific clinical roles: 4

Preferred Uses According to CDC Guidelines:

• Drug-resistant tuberculosis as the preferred oral fluoroquinolone based on long-term safety data 4
• Community-acquired pneumonia in patients with penicillin allergy or recent beta-lactam exposure (within 3 months) 6
• Severe pneumonia requiring ICU care as part of combination therapy with a beta-lactam 6
• Suspected Pseudomonas aeruginosa infections in combination with an antipseudomonal beta-lactam 6

Important Limitations:

• Should NOT be used as first-line for drug-susceptible tuberculosis except when first-line agents cannot be used 4
• Avoid in HIV-infected patients with pneumonia unless bacterial pneumonia is strongly suspected over tuberculosis, to prevent delayed TB diagnosis 6
• Cross-resistance exists among ciprofloxacin, ofloxacin, and levofloxacin 4

Resistance Considerations

• Prevalence of S. pneumoniae resistance to levofloxacin is <1% overall in the US 9
• Rising resistance rates should be considered before prescribing, particularly for H. pylori treatment 6
• High-dose (750 mg), short-course (5-day) regimens may reduce resistance development by maximizing concentration-dependent bactericidal activity 8

Comparative Advantages

Levofloxacin offers a unique combination of efficacy and safety compared to other fluoroquinolones: 5, 9

• More active against S. pneumoniae than ciprofloxacin but less active than newer agents like gatifloxacin or moxifloxacin 4, 5
• Superior respiratory tract penetration compared to ciprofloxacin, making it inappropriate to use ciprofloxacin for community-acquired pneumonia 4, 7
• Better established long-term safety profile than moxifloxacin or gatifloxacin 4
• Lower phototoxicity than some other fluoroquinolones 5, 9
• Rare cardiac and hepatic adverse events compared to other quinolones 5, 9