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Azithromycin

Azithromycin

Zithromax Z-Pak AzaSite Azasite Azithrocin

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Updated: December 06, 2025

Overview

Azithromycin is a broad-spectrum macrolide antibiotic with enhanced activity against certain gram-negative organisms compared to other macrolides. It belongs to the azalide subclass, characterized by a 15-membered ring structure that provides improved acid stability and tissue penetration. Azithromycin is particularly valued for its convenient dosing regimen and prolonged tissue half-life, allowing shorter treatment courses than many other antibiotics. It demonstrates activity against respiratory pathogens, atypical organisms, and some sexually transmitted infections while generally having better gastrointestinal tolerability than erythromycin.

Drug Class

Antibacterial • Macrolide antibiotic • Azalide subclass

Mechanism of Action

Azithromycin binds to the 50S ribosomal subunit of susceptible microorganisms, inhibiting RNA-dependent protein synthesis. Key features: • Bacteriostatic at typical concentrations • May become bactericidal at higher concentrations • Demonstrates post-antibiotic effect • More stable in acidic environments than erythromycin

Pharmacokinetics

Absorption: Rapid but variable (37% bioavailability); food reduces absorption of capsules but not tablets Distribution: Extensive tissue distribution with tissue concentrations often exceeding serum levels by 10-100x Metabolism: Minimal hepatic metabolism (only 10% metabolized) Excretion: Primarily biliary excretion (50-60%) with some renal excretion (6-12% unchanged drug) Half-life: Terminal half-life of 68 hours (allows once-daily dosing)

Pharmacodynamics

• Concentration-dependent killing • Prolonged tissue persistence • Immunomodulatory effects at sub-antimicrobial doses • Potential QT interval prolongation at high doses

Indications

• Community-acquired pneumonia (typical and atypical) • Acute bacterial exacerbations of chronic bronchitis • Acute bacterial sinusitis • Pharyngitis/tonsillitis caused by Streptococcus pyogenes • Uncomplicated skin/skin structure infections • Urethritis/cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae • Genital ulcer disease (chancroid) • Mycobacterial infections (MAC prophylaxis) • Otitis media in children

Contraindications

Absolute: • Hypersensitivity to azithromycin, erythromycin, or other macrolides • History of cholestatic jaundice/hepatic dysfunction with prior azithromycin use Relative: • Severe hepatic impairment • Known QT prolongation or arrhythmias • Myasthenia gravis • Concurrent use of other QT-prolonging agents

Dosage & Administration

Community-acquired pneumonia: 500 mg PO/IV once daily for at least 2 days, followed by 500 mg PO daily to complete 7-10 day course Acute bacterial sinusitis: 500 mg PO daily for 3 days Uncomplicated skin infections: 500 mg PO on day 1, then 250 mg PO daily on days 2-5 Chlamydia infections: 1 g PO single dose MAC prophylaxis: 1200 mg PO once weekly Pediatric otitis media: 10 mg/kg PO on day 1 (max 500 mg), then 5 mg/kg/day on days 2-5 (max 250 mg/day)

Special Populations

Pediatric: Safety established for children ≥6 months; dosage based on weight Geriatric: No dosage adjustment required but increased monitoring for QT effects Renal impairment: No dosage adjustment for GFR >10 mL/min Hepatic impairment: Use with caution in severe impairment (Child-Pugh C)

Adverse Effects

Common (>10%): • Diarrhea (5-14%) • Nausea (3-12%) • Abdominal pain (3-7%) Serious (<1%): • Hepatotoxicity • QT prolongation/torsades de pointes • Clostridioides difficile-associated diarrhea • Severe skin reactions (SJS, TEN) • Hearing loss (reversible)

Drug Interactions

• Antacids: Separate administration by 2 hours • Warfarin: May potentiate anticoagulant effect • Nelfinavir: Increases azithromycin levels • QT-prolonging agents: Additive risk of arrhythmias • Cyclosporine: May increase cyclosporine levels

Warnings & Precautions

• Risk of QT prolongation and cardiac arrhythmias • Potential for worsening myasthenia gravis • May cause exacerbation of porphyria • Superinfections including C. difficile-associated diarrhea • Hepatotoxicity reported (monitor LFTs) • Not effective for viral infections

Pregnancy & Lactation

Pregnancy: FDA Category B • Generally considered safe but use only if clearly needed • Crosses placenta but no established teratogenicity Lactation: Excreted in breast milk • Considered compatible with breastfeeding • AAP considers acceptable with monitoring

Monitoring Parameters

• Clinical response to therapy • Liver function tests with prolonged use • ECG monitoring in high-risk patients • Renal function in severe impairment • Signs of superinfection/C. difficile • Hearing assessment with long-term use

Patient Counseling

• Complete full course even if symptoms improve • May take with food if stomach upset occurs • Report severe diarrhea, abdominal pain, or yellowing of skin • Avoid antacids within 2 hours of dose • Inform provider of any heart conditions or medications • Do not use for viral infections like colds or flu

Storage & Stability

• Store tablets/capsules at 15-30°C (59-86°F) • Protect from moisture • Oral suspension stable for 10 days at room temperature • IV solution stable for 24 hours at room temperature or 7 days refrigerated

Clinical Pearls

• Consider 3-day regimen for improved adherence • Tissue concentrations remain therapeutic for 5-7 days after last dose • Not first-line for strep throat due to increasing resistance • Useful for travelers' diarrhea prophylaxis • May have anti-inflammatory effects at sub-antimicrobial doses

References

• Zithromax® (azithromycin) package insert. Pfizer Labs. • Bradley JS, et al. The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age. Clin Infect Dis. 2011. • FDA Drug Safety Communication: Azithromycin and risk of potentially fatal heart rhythms. 2013. • Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy. 52nd edition.