Azithromycin

Azithromycin is an azalide macrolide with long tissue half-life, allowing short courses and single doses. It is used for atypical pneumonia, chlamydial infection, typhoid, cholera, trachoma, yaws and pertussis, with fewer drug interactions than erythromycin or clarithromycin.

Classification. Macrolide (azalide).

Mechanism. Binds the 50S ribosomal subunit and blocks protein synthesis; bacteriostatic, with high intracellular and tissue concentrations.

Spectrum. Streptococci and pneumococci (resistance common), MSSA, Haemophilus, Moraxella, Neisseria, Legionella, Mycoplasma, Chlamydia, Bordetella pertussis, Campylobacter, Salmonella Typhi (susceptible strains), Vibrio cholerae, Treponema pallidum (resistance common), Treponema pallidum subspecies pertenue (yaws), Mycobacterium avium complex and Chlamydia trachomatis. Not active against Enterobacterales or Pseudomonas.

Pharmacokinetics. Oral bioavailability about 37%. Terminal half-life about 68 hours. Large volume of distribution with intracellular accumulation. Mainly biliary excretion. Weak CYP3A4 inhibitor.

Maximum 500 mg a day in most regimens (1 g single doses and 2 g single dose for yaws).

Adults.

• Community-acquired pneumonia (with a beta-lactam): 500 mg once daily for 3 days, or 500 mg then 250 mg daily for 4 days; IV 500 mg once daily for at least 2 days, then oral.
• Uncomplicated chlamydial infection (when doxycycline cannot be used): 1 g single oral dose.
• Enteric fever, uncomplicated (alternative where susceptible): 1 g on day 1 then 500 mg once daily for 6 days, or 10 to 20 mg/kg once daily (maximum 1 g) for 7 days.
• Cholera: 1 g single dose; children 20 mg/kg (maximum 1 g).
• Traveller’s diarrhoea: 500 mg once daily for 3 days, or 1 g single dose.
• Pertussis: 500 mg on day 1, then 250 mg once daily for 4 days.
• Trachoma and yaws: trachoma 20 mg/kg single dose (maximum 1 g); yaws 30 mg/kg single dose (maximum 2 g).
• Chancroid: 1 g single dose.

Gonorrhoea: not used alone because of resistance. - COPD exacerbation prevention or bronchiectasis (specialist): 250 mg once daily or 500 mg three times weekly after exclusion of nontuberculous mycobacteria and baseline ECG and hearing review. - Mycobacterium avium complex disease: 500 to 600 mg once daily with ethambutol and a rifamycin.

Children. Otitis media: 30 mg/kg single dose or 10 mg/kg once daily for 3 days. Pharyngitis: 12 mg/kg once daily for 5 days (maximum 500 mg). Pneumonia, pertussis: 10 mg/kg on day 1 then 5 mg/kg once daily for 4 days.

Alternatives. Doxycycline, clarithromycin, amoxicillin, ceftriaxone.

Contraindications. Hypersensitivity to macrolides; history of cholestatic jaundice or hepatic dysfunction with azithromycin.

Adverse effects. Nausea, vomiting, diarrhoea, abdominal pain. Serious: QT prolongation and torsades, hepatotoxicity, hearing loss with prolonged or high-dose use, severe skin reactions, Clostridioides difficile infection, exacerbation of myasthenia gravis, infantile hypertrophic pyloric stenosis in infants under 6 weeks.

Interactions. QT-prolonging drugs; warfarin (INR rise); ciclosporin; digoxin (raised levels); colchicine; aluminium and magnesium antacids (take azithromycin 1 hour before or 2 hours after); nelfinavir.

Common prescribing errors. Using azithromycin alone for gonorrhoea or syphilis, long courses without screening for nontuberculous mycobacteria, and combining it with QT-prolonging drugs.

Special groups. - Pregnancy: acceptable and often the preferred macrolide for chlamydia and pertussis. Breastfeeding: acceptable. - Older adults: increased QT risk. - Kidney impairment: no adjustment when creatinine clearance is over 10 mL/min; use caution at lower values. - Liver impairment: caution; avoid in severe disease.

Preparation. Tablets with or without food; suspension 200 mg in 5 mL, shaken and measured accurately. IV: reconstitute 500 mg with 4.8 mL water, dilute to 1 mg/mL and infuse over 3 hours, or to 2 mg/mL over 1 hour; never as a bolus.

Baseline and monitoring. - Baseline: medication review, ECG in cardiac disease or other QT drugs, liver tests in prolonged use. - During treatment: hearing and ECG in long-term prophylaxis; liver tests periodically.

Stop rules. Stop for syncope or palpitations, jaundice, severe skin reaction, or hearing change.

Referral and escalation. Refer for treatment failure and for long-term therapy decisions.