Ofloxacin

Ofloxacin is an older fluoroquinolone, the racemic parent of levofloxacin, used for urinary, genital and skin infections, leprosy and drug-resistant tuberculosis. It is used less often now because levofloxacin has twice its activity for each milligram.

Classification. Fluoroquinolone, second generation.

Mechanism. Inhibits DNA gyrase and topoisomerase IV; bactericidal.

Spectrum. Enterobacterales, Haemophilus, Neisseria, Chlamydia, Mycoplasma, Mycobacterium leprae and Mycobacterium tuberculosis, and some staphylococci. Weaker than levofloxacin against pneumococci. Limited Pseudomonas activity.

Pharmacokinetics. Oral bioavailability about 95%. Half-life 5 to 8 hours. Mainly renal excretion unchanged (about 80%). Low protein binding.

Maximum 800 mg daily.

Adults, oral. 200 to 400 mg every 12 hours.

• Uncomplicated urinary tract infection: 200 mg every 12 hours for 3 days.
• Complicated urinary infection and pyelonephritis: 200 to 400 mg every 12 hours for 7 to 10 days.
• Pelvic inflammatory disease: 400 mg every 12 hours for 14 days with metronidazole 400 to 500 mg every 12 hours.
• Epididymo-orchitis, prostatitis: 200 to 400 mg every 12 hours for 14 to 28 days.
• Leprosy (alternative in multidrug regimens): 400 mg once daily.
• Drug-resistant tuberculosis (specialist): 400 mg every 12 hours as part of a multidrug regimen.
• Skin and soft tissue infection: 400 mg every 12 hours for 7 to 14 days.

Children. Not advised except in specialist tuberculosis or leprosy programmes.

Alternatives. Levofloxacin, ciprofloxacin, nitrofurantoin, ceftriaxone, doxycycline.

Boxed-warning level risks. The same class risks as ciprofloxacin: tendon rupture, neuropathy, central nervous system effects, aortic aneurysm risk and myasthenia aggravation.

Contraindications. Fluoroquinolone hypersensitivity; previous tendon disorder with a fluoroquinolone; epilepsy (relative); uncorrected QT prolongation.

Adverse effects. Nausea, diarrhoea, insomnia, headache, dizziness. Serious: tendon rupture, QT prolongation, dysglycaemia, neuropathy, seizures, psychosis, hepatotoxicity, photosensitivity, Clostridioides difficile infection, severe skin reactions.

Interactions. Cations (separate by 2 hours before or 2 hours after), warfarin, theophylline, sulphonylureas and insulin, QT-prolonging drugs, corticosteroids and NSAIDs.

Common prescribing errors. Giving it with antacids or iron, no dose reduction in renal failure, and using it for minor infection.

Special groups.

• Pregnancy: avoid unless essential.
• Breastfeeding: avoid; short use is acceptable if essential.
• Older adults: higher tendon and central nervous system risk; use the lower dose.
• Kidney impairment: creatinine clearance 20 to 50 mL/min usual dose every 24 hours; under 20 mL/min half the dose every 24 hours; haemodialysis 100 to 200 mg every 24 hours.
• Liver impairment: severe disease, maximum 400 mg daily.
• Region: limited availability in East Africa; levofloxacin is usually preferred.

Preparation. Oral tablets with or without food, with plenty of fluid, separated from cations.

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

Stop rules. Stop for tendon pain, neuropathy, psychiatric disturbance, seizure or severe rash.

Referral and escalation. Refer for treatment failure, tendon rupture and drug-resistant tuberculosis or leprosy.