Azithromycin

1. Generic & Brand Names

• Generic: Azithromycin

• Brands: Zithromax® (global), Azithrocin®, Aziwok®

• Key Formulations: Tablets (250mg, 500mg), Powder for oral suspension (100mg/5mL, 200mg/5mL), IV injection

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2. Drug Class & Mechanism

• Class: Macrolide antibiotic (subclass: azalide)

• Mechanism: Binds 50S ribosomal subunit → inhibits bacterial protein synthesis

• Spectrum:

  • Gram-positive: S. pneumoniae, S. pyogenes

  • Atypical: Mycoplasma, Chlamydia, Legionella

  • Limited Gram-negative: H. influenzae

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3. FDA-Approved Respiratory Uses

Infection	Key Pathogens	Treatment Duration
Strep Pharyngitis	S. pyogenes (Group A Strep)	5 days
Community-Acquired Pneumonia (CAP)	S. pneumoniae, M. pneumoniae, H. influenzae	5 days (PO/IV)
Acute Bacterial Sinusitis	S. pneumoniae, H. influenzae	3-5 days
COPD Exacerbations	H. influenzae, M. catarrhalis	3-5 days

⚠️ Not for viral infections or routine colds

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4. Dosing Regimens

Infection Type	Adult Dose	Pediatric Dose (≥6 months)
Strep Pharyngitis	500 mg Day 1 → 250 mg Days 2-5	12 mg/kg/day x 5 days (max 500mg)
CAP/Sinusitis	500 mg daily x 3 days	10 mg/kg Day 1 → 5 mg/kg Days 2-5
COPD Exacerbation	500 mg daily x 3 days	Not recommended
IV Pneumonia	500 mg IV daily → switch to PO	10 mg/kg IV daily

Key Administration Notes:

• Take 1 hour before or 2 hours after food (↑ absorption)

• Suspension: Shake well; room temp stable for 10 days

• Complete full course even if symptoms improve

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5. Side Effects

Common (≥5%)	Serious (Discontinue Immediately)
Diarrhea/Nausea	Hepatotoxicity (jaundice, ALT↑)
Abdominal pain	QT Prolongation → Torsades de Pointes
Headache	Clostridioides difficile colitis
Cardiac Risk: Higher in elderly, existing QT prolongation, or with interacting drugs

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6. Black Box Warnings & Contraindications

• 🚫 Absolute Contraindications:

  • Known QT prolongation or history of TdP

  • Concomitant QT-prolonging drugs (see table below)

  • Severe liver impairment (Child-Pugh C)

• High-Risk Groups:

  • Cardiac patients: CHF, bradycardia, hypokalemia

  • Myasthenia gravis: Risk of fatal respiratory failure

  • Pregnancy (Category B): Use only if benefit > risk

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7. Critical Drug Interactions

Medication Class	Examples	Risk
QT-Prolonging Agents	Amiodarone, Ciprofloxacin	↑ Torsades de Pointes risk
Antacids/Al³⁺/Mg²⁺	Maalox®, Mylanta®	↓ Azithromycin absorption (separate by 2h)
Warfarin	-	↑ INR (monitor bleeding)
Nelfinavir	-	↑ Azithromycin levels (CYP3A4 inhibition)

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8. Resistance Concerns

• Not first-line for Strep throat: Penicillin preferred (azithromycin resistance ~5-8% US)

• Avoid in suspected MRSA pneumonia (no coverage)

• Atypical coverage advantage: First-line for Mycoplasma/Legionella

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9. Storage & Handling

• Tablets: 15-30°C (59-86°F) in tight container

• Oral Suspension:

  • Dry powder: Room temperature

  • Reconstituted: Refrigerate or keep at ≤30°C

  • Discard after 10 days

• IV Formulation: Requires dilution; administer over ≥60 minutes

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Clinical Practice Insights

⚠️ Cardiac Safety Alert:

• Avoid in patients with QTC >450 ms or on antiarrhythmics - ECG monitoring recommended

• Higher mortality risk vs. amoxicillin in CVD patients (NEJM 2012)

✅ Stewardship Tips:

• Use 3-day regimens for outpatient CAP/COPD (tissue half-life = 68h)

• Reserve for penicillin-allergic patients or atypical pneumonia

• Avoid for URIs without confirmed bacterial cause

💡 Pneumonia Coverage:

Combine with ceftriaxone for severe CAP to cover resistant S. pneumoniae

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Azithromycin vs. Other Macrolides

Parameter	Azithromycin	Clarithromycin	Erythromycin
Dosing Frequency	Once daily	Twice daily	4x daily
GI Tolerance	Moderate	Poor	Very poor
QT Risk	High	Moderate	Low
Atypical Coverage	Excellent	Excellent	Good

📊 Efficacy Data:

• COPD exacerbations: 3-day course reduces relapse by 27% vs. placebo (JAMA)

• CAP: 5-day oral = 7-10 days of other antibiotics (CID 2019)

Prescribing Note: Always assess cardiac risk profile before use. Report adverse events to FDA MedWatch.