Levofloxacin for Tuberculosis

Levofloxacin is a respiratory fluoroquinolone and a core drug in regimens for rifampicin-resistant and multidrug-resistant tuberculosis. It is also used for isoniazid-resistant disease and for preventive treatment of contacts of patients with multidrug-resistant tuberculosis. It has a better cardiac safety profile than moxifloxacin but slightly lower bactericidal activity.

Class. Fluoroquinolone; second-generation respiratory quinolone.

Mechanism. Inhibits DNA gyrase and topoisomerase IV. gyrA and gyrB mutations cause resistance; resistance extends across the class.

Pharmacokinetics. Near-complete absorption, peak at 1 to 2 hours, half life 6 to 8 hours, excellent tissue and sputum penetration. Excreted mostly unchanged by the kidney.

Rifampicin-resistant and multidrug-resistant tuberculosis (adults). - 750 mg orally once daily (range 750 to 1000 mg, or 10 to 15 mg/kg); maximum 1000 mg daily. - Duration: set by the regimen, from 6 to 20 months. - Loading dose: none. Titration: none.

Isoniazid-resistant, rifampicin-susceptible tuberculosis. Levofloxacin added to rifampicin, ethambutol and pyrazinamide for 6 months.

Contacts of multidrug-resistant tuberculosis. Preventive therapy for 6 months, weight-based, 10 to 15 mg/kg once daily in adults and older children; specialist-directed.

Children. 15 to 20 mg/kg daily (once daily from 5 years, twice daily under 5), maximum 1000 mg daily.

Intravenous. Same dose as oral, infused over 60 minutes for 500 mg to 750 mg.

Contraindications. Prior fluoroquinolone tendon disorder, QT prolongation, hypersensitivity, myasthenia gravis (relative) and uncorrected hypokalaemia.

Serious adverse effects (boxed-warning-level). Tendinopathy and rupture, peripheral neuropathy, central nervous system effects (seizures, psychosis), worsening myasthenia gravis, aortic aneurysm and dissection, dysglycaemia, QT prolongation, hepatotoxicity and Clostridioides difficile colitis.

Common adverse effects. Nausea, diarrhoea, headache, insomnia and photosensitivity.

Interactions. Divalent and trivalent cations (antacids, iron, zinc, calcium, didanosine) reduce absorption; take levofloxacin 2 hours before or 2 hours after. Additive QT prolongation with bedaquiline, delamanid, clofazimine and macrolides. Corticosteroids increase tendon risk; NSAIDs increase seizure risk; antidiabetic drugs risk hypoglycaemia; warfarin effect increases.

Common prescribing errors. Using it empirically for pneumonia before tuberculosis is excluded, not adjusting for kidney function, and administering with antacids.

Special groups. - Pregnancy: avoid unless essential; used when no alternative in resistant disease. - Breastfeeding: low milk levels; short use acceptable. - Children: used in resistant tuberculosis despite cartilage concerns; arthralgia monitored. - Older adults: higher tendon, central nervous system and QT risk. - Kidney impairment: with CrCl under 30 mL/min, give 750 to 1000 mg three times weekly. - Liver impairment: no adjustment.

Formulations. Tablets 250 mg, 500 mg and 750 mg, dispersible tablets and intravenous solution 5 mg/mL.

Administration. Once daily with water, with or without food, separated from cations.

Baseline. ECG with QTcF where QT drugs are used, potassium, creatinine, glucose and liver tests.

Monitoring. ECG with the other QT-prolonging drugs; electrolytes monthly; glucose in diabetes; ask about tendon pain and neuropathy at each visit.

Stopping thresholds. Stop at the first tendon pain, QTcF over 500 ms (confirmed), seizures, psychosis or severe hypersensitivity.

Referral and escalation. Manage within a drug-resistant tuberculosis programme; urgent review for tendon rupture, aortic symptoms or severe colitis.