Moxifloxacin for Tuberculosis

Moxifloxacin is a fourth-generation fluoroquinolone and the most active fluoroquinolone against Mycobacterium tuberculosis. It is a core drug in short and long regimens for rifampicin-resistant tuberculosis and in some shortened regimens for drug-susceptible disease. It prolongs the QT interval more than levofloxacin.

Class. Fluoroquinolone; fourth-generation.

Mechanism. Inhibits DNA gyrase and topoisomerase IV. gyrA mutations cause class-wide cross-resistance.

Pharmacokinetics. About 90% bioavailability, peak at 1 to 3 hours, half life about 12 hours. Hepatic glucuronide and sulphate conjugation, with excretion in faeces and urine. Rifampicin lowers levels by about 30%.

Rifampicin-resistant and multidrug-resistant tuberculosis (adults). - 400 mg orally once daily. - Duration: set by the regimen, from 6 months in short regimens to 18 to 20 months. - Loading dose: none. Titration: none. Maximum: 400 mg daily in routine use.

Drug-susceptible tuberculosis (shortened regimen). 400 mg daily with rifapentine, isoniazid and pyrazinamide for 8 weeks, then with rifapentine and isoniazid for 9 weeks, in patients aged 12 years and over and 40 kg or more.

Specialist use. Higher doses of 600 to 800 mg are used in some centres for low-level resistance but are not advised in routine practice because of QT and tolerability concerns.

Children. Weight-based, about 10 mg/kg daily, under specialist care.

Contraindications. QT prolongation, uncorrected hypokalaemia, severe liver impairment, prior fluoroquinolone tendon disorder and hypersensitivity.

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

Common adverse effects. Nausea, diarrhoea, headache and dizziness.

Interactions. Additive QT prolongation with bedaquiline, delamanid, clofazimine, macrolides and antipsychotics. Cations (antacids, iron, zinc) reduce absorption; take 4 hours before or 8 hours after. Rifampicin lowers levels. Corticosteroids increase tendon risk.

Common prescribing errors. Using it with many QT-prolonging drugs without ECG, giving it with antacids, and using high doses outside specialist care.

Special groups. - Pregnancy: avoid unless essential. - Breastfeeding: limited data; present in milk. - Children: weight-based use in resistant disease only. - Older adults: higher QT, tendon and central nervous system risk. - Kidney impairment: no adjustment. - Liver impairment: avoid in severe impairment; caution in mild to moderate.

Formulations. Tablets 400 mg and intravenous solution 1.6 mg/mL.

Administration. Once daily, with or without food; separate from cations. Intravenous dose infused over 60 minutes.

Baseline. ECG with QTcF, potassium, magnesium, calcium, liver tests and glucose.

Monitoring. ECG at baseline, 2, 4, 8, 12 and 24 weeks with other QT-prolonging drugs; electrolytes monthly; liver tests monthly; tendon pain at each visit.

Stopping thresholds. Stop for QTcF over 500 ms (confirmed), tendon pain, ALT over three times the upper limit of normal with symptoms, or seizures.

Referral and escalation. Manage within a drug-resistant tuberculosis programme; cardiology for syncope or ventricular arrhythmia.