Ofloxacin - Drug Monograph

Introduction

Ofloxacin is a synthetic broad-spectrum fluoroquinolone antibiotic approved by the FDA in 1990. It exhibits bactericidal activity against a wide range of gram-positive and gram-negative pathogens, atypical organisms, and some anaerobic bacteria. Ofloxacin is commonly prescribed for various bacterial infections including respiratory, urinary tract, skin, and soft tissue infections.

Mechanism of Action

Ofloxacin exerts its bactericidal effect by inhibiting bacterial DNA gyrase (topoisomerase II) and topoisomerase IV enzymes. These enzymes are essential for DNA replication, transcription, repair, and recombination. By binding to the DNA-DNA gyrase complex, ofloxacin stabilizes the cleavage complex and prevents religation of DNA strands, leading to double-stranded DNA breaks and ultimately bacterial cell death.

Indications

FDA-approved indications include:

• Community-acquired pneumonia
• Acute exacerbations of chronic bronchitis
• Uncomplicated skin and skin structure infections
• Complicated urinary tract infections
• Prostatitis
• Acute pelvic inflammatory disease
• Uncomplicated urethral and cervical gonorrhea
• Mixed infections of the urethra and cervix
• Traveler's diarrhea caused by E. coli

Dosage and Administration

• Respiratory, skin, and UTI infections: 200-400 mg orally every 12 hours
• Prostatitis: 300 mg orally every 12 hours for 6 weeks
• Gonorrhea: 400 mg single dose
• Traveler's diarrhea: 300 mg every 12 hours for 3 days

• CrCl 20-50 mL/min: 50% of usual dose
• CrCl <20 mL/min: 25% of usual dose

• Oral tablets may be taken with or without food
• Maintain adequate hydration during therapy
• Complete full course of therapy even if symptoms improve

Pharmacokinetics

• Absorption: Well absorbed orally with bioavailability of 98%
• Distribution: Widely distributed to tissues and body fluids; CSF penetration approximately 50-70% of serum levels
• Protein binding: Approximately 25%
• Metabolism: Minimally metabolized in the liver (<10%)
• Elimination: Primarily renal excretion (70-80% unchanged); half-life 4-8 hours
• Time to peak concentration: 1-2 hours post-dose

Contraindications

• History of hypersensitivity to ofloxacin or other quinolones
• Concurrent administration with tizanidine
• Patients with known QT prolongation or uncorrected hypokalemia
• History of tendon disorders related to fluoroquinolone use

Warnings and Precautions

• Tendinitis and tendon rupture (risk increases with age >60, corticosteroid use, renal impairment)
• Exacerbation of myasthenia gravis
• Peripheral neuropathy

• QT interval prolongation and risk of torsades de pointes
• Central nervous system effects (seizures, dizziness, confusion)
• Photosensitivity reactions
• Clostridium difficile-associated diarrhea
• Hepatic dysfunction monitoring
• Crystalluria and nephrotoxicity

Drug Interactions

• Antacids containing aluminum, magnesium, calcium, or iron: Decreased absorption (separate by 2-4 hours)
• Sucralfate: Decreased absorption (separate by 2 hours)
• Warfarin: Increased anticoagulant effect (monitor INR)
• NSAIDs: Increased risk of CNS stimulation and seizures
• Corticosteroids: Increased risk of tendon rupture
• Antiarrhythmics (Class IA, III): Increased risk of QT prolongation
• Theophylline: Increased theophylline levels (monitor concentrations)

Adverse Effects

• Nausea (3-7%)
• Headache (3-9%)
• Dizziness (3-8%)
• Insomnia (3-7%)
• Diarrhea (1-4%)

• Tendinitis/tendon rupture
• Peripheral neuropathy
• QT prolongation and arrhythmias
• Seizures
• Hepatotoxicity
• Blood dyscrasias
• Severe skin reactions (Stevens-Johnson syndrome)
• Clostridium difficile-associated diarrhea

Monitoring Parameters

• Clinical response to therapy
• Renal function (BUN, creatinine) at baseline and during prolonged therapy
• Liver function tests with prolonged use
• Signs of tendon inflammation or rupture
• Neurological symptoms (peripheral neuropathy, CNS effects)
• ECG monitoring in patients with cardiac risk factors
• International Normalized Ratio (INR) in patients on warfarin
• Blood glucose in diabetic patients (may cause dysglycemia)

Patient Education

• Complete the entire course of medication as prescribed
• Report any tendon pain, swelling, or inflammation immediately
• Avoid excessive sunlight exposure and use sunscreen (photosensitivity risk)
• Maintain adequate hydration (2-3 L/day unless contraindicated)
• Do not take with antacids, iron, or calcium supplements (separate by 2-4 hours)
• Report any numbness, tingling, or unusual sensations
• Be aware of potential dizziness and avoid driving if affected
• Inform all healthcare providers of ofloxacin use
• Report severe diarrhea, even weeks after treatment completion
• Do not share medication with others

References

1. FDA Prescribing Information: Ofloxacin (2023) 2. Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy. 52nd ed. 3. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th ed. 4. Micromedex® DrugDex® Evaluations: Ofloxacin 5. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Ofloxacin monograph. 6. American Society of Health-System Pharmacists. AHFS Drug Information®. 7. UpToDate: Ofloxacin drug information 8. Lancet Infectious Diseases. Fluoroquinolone safety updates. 2018;18(11):e368-e378.