Levaquin - Drug Monograph

Introduction

Levaquin (levofloxacin) is a synthetic broad-spectrum fluoroquinolone antibiotic approved by the FDA in 1996. It is the L-isomer of ofloxacin and demonstrates enhanced activity against both Gram-positive and Gram-negative pathogens compared to earlier quinolones. Levaquin is commonly prescribed for various bacterial infections due to its excellent tissue penetration and bioavailability.

Mechanism of Action

Levaquin exerts its bactericidal effects by inhibiting bacterial DNA gyrase (topoisomerase II) and topoisomerase IV. DNA gyrase is essential for DNA replication, transcription, and repair in Gram-negative bacteria, while topoisomerase IV primarily functions in Gram-positive bacteria. By binding to these enzymes, levofloxacin causes double-stranded DNA breaks, leading to rapid bacterial cell death.

Indications

FDA-approved indications include:

• Community-acquired pneumonia (due to S. pneumoniae, S. aureus, H. influenzae, H. parainfluenzae, K. pneumoniae, M. catarrhalis, M. pneumoniae, C. pneumoniae, or L. pneumophila)
• Hospital-acquired pneumonia
• Acute bacterial sinusitis
• Acute bacterial exacerbation of chronic bronchitis
• Complicated and uncomplicated urinary tract infections
• Acute pyelonephritis
• Complicated skin and skin structure infections
• Chronic bacterial prostatitis
• Inhalational anthrax (post-exposure)
• Plague

Dosage and Administration

• 250-750 mg orally or IV once daily
• Duration: 7-14 days depending on infection type

• Renal impairment: Adjust based on CrCl

- CrCl 20-49 mL/min: 250-500 mg q48h - CrCl 10-19 mL/min: 250-500 mg q48h - HD or CAPD: 250-500 mg q48h

• Hepatic impairment: No adjustment needed
• Elderly: Adjust based on renal function
• Pediatrics: Generally contraindicated except for inhalational anthrax

Pharmacokinetics

• Absorption: Rapid and complete (99% oral bioavailability)
• Distribution: Extensive tissue penetration (Vd: 1.1 L/kg)
• Metabolism: Minimal hepatic metabolism (<5%)
• Elimination: Primarily renal excretion (87% unchanged)
• Half-life: 6-8 hours
• Protein binding: 24-38%

Contraindications

• History of hypersensitivity to levofloxacin or other quinolones
• Concomitant administration with tizanidine
• Known history of myasthenia gravis

Warnings and Precautions

• Tendinitis and tendon rupture (especially Achilles tendon)
• Peripheral neuropathy
• Central nervous system effects (seizures, psychosis)
• Exacerbation of myasthenia gravis

• QT prolongation and arrhythmias
• Hypersensitivity reactions
• Clostridium difficile-associated diarrhea
• Photosensitivity reactions
• Hepatic dysfunction
• Blood glucose disturbances
• Aortic aneurysm and dissection

Drug Interactions

• Antacids containing aluminum, magnesium, calcium, or iron: ↓ absorption
• Sucralfate: ↓ absorption
• QT-prolonging drugs (antiarrhythmics, antipsychotics, antidepressants): ↑ QT prolongation risk
• NSAIDs: ↑ CNS stimulation/seizure risk
• Warfarin: ↑ anticoagulant effect
• Corticosteroids: ↑ tendon rupture risk
• Theophylline: ↑ theophylline levels

Adverse Effects

• Nausea (7%)
• Diarrhea (5%)
• Headache (6%)
• Constipation (3%)
• Dizziness (3%)
• Insomnia (4%)

• Tendon rupture
• Peripheral neuropathy
• QT prolongation/torsades de pointes
• Seizures
• Hepatotoxicity
• Blood dyscrasias
• Severe hypersensitivity reactions
• C. difficile colitis

Monitoring Parameters

• Clinical response to therapy
• Renal function (baseline and during therapy)
• Liver function tests (baseline)
• Signs of tendon inflammation/rupture
• Neurological symptoms
• Blood glucose in diabetic patients
• ECG in patients at risk for QT prolongation
• Signs of hypersensitivity
• Stool frequency/consistency for diarrhea

Patient Education

• Complete entire course even if feeling better
• Take with water, 2 hours before or after antacids
• Report immediately: tendon pain/weakness, numbness/tingling, unusual pain
• Avoid excessive sun exposure (use sunscreen)
• Maintain adequate hydration
• Report diarrhea, especially if bloody
• Inform all providers of levaquin use
• Do not crush or chew tablets
• Separate dosing from dairy products/calcium-fortified juices by 2 hours

References

1. FDA Prescribing Information: Levaquin (levofloxacin). 2023 2. Mandell LA, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 3. Owens RC Jr, Ambrose PG. Antimicrobial safety: focus on fluoroquinolones. Clin Infect Dis. 2005 4. Rubinstein E, et al. Levofloxacin for the treatment of skin and skin structure infections. Int J Antimicrob Agents. 1999 5. Stahlmann R, Lode H. Safety considerations of fluoroquinolones in the elderly. Drugs Aging. 2010 6. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 2023 7. FDA Drug Safety Communication. 2016 8. Micromedex Solutions. Levofloxacin Drug Monograph. 2023 9. Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy. 2023 10. UpToDate. Levofloxacin: Drug Information. 2023