Moxifloxacin

Moxifloxacin is a respiratory fluoroquinolone with strong activity against pneumococci, atypical bacteria and anaerobes, used for pneumonia, complicated intra-abdominal infection, skin infection, drug-resistant tuberculosis and Mycoplasma genitalium. It has the greatest QT effect of the group and weak urinary excretion.

Classification. Fluoroquinolone, fourth generation.

Mechanism. Inhibits DNA gyrase and topoisomerase IV; bactericidal.

Spectrum. Pneumococci (including penicillin-resistant), Haemophilus, Moraxella, Legionella, Mycoplasma, Chlamydia, Mycobacterium tuberculosis, many anaerobes, and Enterobacterales in part. Not reliable against Pseudomonas.

Pharmacokinetics. Oral bioavailability about 90%. Half-life 12 hours. Hepatic metabolism (glucuronide and sulphate conjugates); only about 20% excreted unchanged in urine.

Maximum 400 mg daily in usual indications, so no dose adjustment is made for renal or mild to moderate hepatic impairment.

Adults, oral or IV, once daily.

• Community-acquired pneumonia: 400 mg once daily for 7 to 14 days.
• Acute exacerbation of chronic bronchitis, acute sinusitis: 400 mg once daily for 5 to 10 days.
• Complicated intra-abdominal infection: 400 mg once daily for 5 to 14 days.
• Complicated skin and soft tissue infection: 400 mg once daily for 7 to 21 days.
• Pelvic inflammatory disease: 400 mg once daily for 14 days with ceftriaxone where gonococcal risk exists.
• Mycoplasma genitalium after doxycycline failure: 400 mg once daily for 7 to 10 days.
• Drug-resistant tuberculosis: 400 mg once daily as part of a multidrug regimen under specialist direction.
• Not suitable for urinary tract infection.

Children. Not advised outside specialist drug-resistant tuberculosis programmes, where 7.5 to 10 mg/kg once daily is used.

Alternatives. Amoxicillin, doxycycline, azithromycin, levofloxacin, co-amoxiclav, ceftriaxone.

Boxed-warning level risks. Tendinitis and tendon rupture, peripheral neuropathy, central nervous system effects, aggravation of myasthenia gravis, aortic aneurysm risk.

Contraindications. Fluoroquinolone hypersensitivity; QT prolongation, uncorrected hypokalaemia or hypomagnesaemia; clinically relevant bradycardia; heart failure with reduced ejection fraction; previous arrhythmia; severe hepatic impairment (Child-Pugh C); concurrent QT-prolonging drugs such as amiodarone, sotalol, quinine and antipsychotics.

Adverse effects. Nausea, diarrhoea, dizziness, headache, raised liver enzymes. Serious: QT prolongation and torsades de pointes, fulminant hepatitis and liver failure, tendon rupture, dysglycaemia, neuropathy, seizures, psychosis, aortic aneurysm or dissection, Clostridioides difficile infection, severe skin reactions.

Interactions. Cations (take moxifloxacin 2 hours before or 6 hours after), all QT-prolonging drugs, warfarin (INR rise), corticosteroids, diuretics causing hypokalaemia, insulin and sulphonylureas, rifampicin (lower levels).

Common prescribing errors. Giving it with other QT-prolonging drugs without an ECG, using it in urinary infection, and giving it with antacids.

Special groups. - Pregnancy: avoid unless essential. Breastfeeding: avoid. - Older adults: monitor QT and glucose closely. - Kidney impairment: no adjustment. - Liver impairment: mild to moderate disease no adjustment but monitor; avoid in Child-Pugh C. - Region: used in multidrug-resistant tuberculosis programmes in East Africa; ECG access is a practical limit.

Preparation. Oral tablets with or without food, separated from cations. IV: infuse 400 mg (250 mL premixed solution) over 60 minutes; do not give as a rapid bolus.

Baseline and monitoring. - Baseline: ECG with QTc, potassium, magnesium, medication review, liver tests, pregnancy status. - During treatment: repeat ECG if other QT drugs are used, electrolytes change or the course is long; liver tests in prolonged use.

Stop rules. Stop for QTc over 500 ms, palpitations or syncope, jaundice, tendon pain, neuropathy or psychiatric disturbance.

Referral and escalation. Cardiology review for QT prolongation or arrhythmia; hepatology review for jaundice; tuberculosis specialist for drug-resistant disease.