azithromycin
Brand: Zithromax, Z-Pak, Zmax
Prototype: erythromycin
Drug Class: antibiotic
Drug Family: antibiotic
Subclass: macrolide
Organ Systems: infectious-disease
Mechanism of Action
Binds the 50S ribosomal subunit, inhibiting translocation and elongation of the growing peptide chain; bacteriostatic (sometimes bactericidal at high concentrations); has anti-inflammatory properties beyond antibiotic activity.
50S ribosomal subunit (23S rRNA)
Indications
- community-acquired pneumonia (outpatient)
- atypical pneumonia (Mycoplasma, Chlamydophila)
- sinusitis
- acute exacerbation of chronic bronchitis
- chlamydia (1 g single dose)
- gonorrhea (with ceftriaxone — no longer routinely added)
- MAC prophylaxis/treatment (HIV)
- pediatric otitis media (5-day pack)
Contraindications
- history of cholestatic jaundice/hepatic impairment with prior azithromycin
- known QTc prolongation
Adverse Effects
Common
- nausea
- diarrhea
- abdominal pain
- vomiting
Serious
- QTc prolongation and torsades de pointes (dose-dependent)
- hepatotoxicity (rare)
- drug-induced liver injury
- sensorineural hearing loss (high doses/prolonged use)
- C. difficile colitis
Pharmacokinetics (ADME)
| Absorption | ~37% oral bioavailability; largely independent of food for tablets (dairy may reduce absorption of oral suspension) |
| Distribution | Highly protein-bound to tissues (not plasma) — Vd ~31 L/kg; concentrates intracellularly (leukocytes carry drug to sites of infection); very low serum concentrations |
| Metabolism | Hepatic (not CYP) via demethylation |
| Excretion | Biliary/fecal primarily |
| Half-life | 68 hours (tissue); 40–68 hours |
| Onset | 2–4 hours |
| Peak | 2–3 hours |
| Duration | 24 hours; tissue levels maintained for days after oral course completion |
| Protein Binding | Extensively tissue-bound; serum ~51% |
| Vd | ~31 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| QTc-prolonging drugs (hydroxychloroquine, antipsychotics, fluoroquinolones) | additive QTc prolongation | major |
| warfarin | can increase INR; mechanism incompletely understood | moderate |
| colchicine | azithromycin inhibits P-glycoprotein; colchicine toxicity in renal impairment | major |
Nursing Considerations
- Obtain baseline ECG and electrolytes in patients with risk factors for QTc prolongation (electrolyte abnormalities, cardiac disease, concurrent QTc-prolonging drugs) before initiating azithromycin
- The 'Z-Pak' (5-day course with loading dose) achieves high tissue concentrations that persist for 7–10 days after completion due to the long tissue half-life — this is the rationale for short courses
- IV azithromycin: infuse over 1 hour minimum (500 mg dose); venous irritation is common; dilute in 250 mL NS or D5W
- Azithromycin is a first-line treatment for chlamydia — 1 g PO single observed dose is equally effective to 7-day doxycycline and preferred for compliance
Clinical Pearls
- Azithromycin's extraordinarily high tissue-to-plasma ratio (tissue Vd ~31 L/kg vs. serum ~0.15 L/kg) means serum levels are poor indicators of efficacy — the drug concentrates in macrophages and is delivered to infection sites
- A 2012 NEJM study found a small but statistically significant increase in cardiovascular death with a 5-day azithromycin course — this led to FDA safety communication; the absolute risk remains very low in healthy patients but deserves consideration in high-risk cardiac patients
Safety Profile
Pregnancy generally-safe
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.
Acute Exacerbation Of Chronic Bronchitis Antibiotic Atypical Pneumonia (Mycoplasma, Chlamydophila) Chlamydia (1 G Single Dose) Community-acquired Pneumonia (outpatient) Gonorrhea (with Ceftriaxone — No Longer Routinely Added) MAC Prophylaxis/treatment (HIV) Pediatric Otitis Media (5-day Pack) Sinusitis