Azithromycin

# Azithromycin ## Overview - **Classification**: Macrolide antibiotic (azalide subclass) - **Mechanism**: Inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit, preventing peptide translocation. ## Primary Indications 1. **Community-Acquired Pneumonia (CAP)** - Caused by susceptible organisms. 2. **Acute Bacterial Exacerbation of COPD (ABECB)** - Caused by susceptible organisms. 3. **Pharyngitis/Tonsillitis** - Due to *Streptococcus pyogenes* (penicillin-allergic patients). 4. **Uncomplicated Skin/Skin Structure Infections** - Caused by *Staphylococcus aureus*, *Streptococcus pyogenes*, *S. agalactiae*. 5. **Urethritis/Cervicitis** - Caused by *Chlamydia trachomatis* or *Neisseria gonorrhoeae*. 6. **Genital Ulcer Disease** - Due to *Haemophilus ducreyi* (chancroid). 7. **Mycobacterium Avium Complex (MAC)** - Prevention or treatment in advanced HIV. ## Adult Dosing ### Standard Dosing **Community-Acquired Pneumonia (CAP), Pharyngitis/Tonsillitis, Skin/Skin Structure, ABECB** - **Dose**: Day 1: **500 mg**; Days 2-5: **250 mg** - **Frequency**: Once daily - **Route**: Oral - **Duration**: 5 days total **Urethritis/Cervicitis (Chlamydia trachomatis)** - **Dose**: **1 gram** (1000 mg) - **Frequency**: Single dose - **Route**: Oral - **Duration**: Single dose **Urethritis/Cervicitis (Neisseria gonorrhoeae)** - *Often with Ceftriaxone* - **Dose**: **1 gram** (1000 mg) OR **2 grams** (2000 mg) - **Frequency**: Single dose - **Route**: Oral - **Duration**: Single dose (2g for suspected reduced susceptibility) **Genital Ulcer Disease (Chancroid)** - **Dose**: **1 gram** (1000 mg) - **Frequency**: Single dose - **Route**: Oral - **Duration**: Single dose **Mycobacterium Avium Complex (MAC) Prophylaxis** - **Dose**: **1200 mg** - **Frequency**: Once weekly - **Route**: Oral - **Duration**: Long-term ### Dose Adjustments - **Renal Impairment**: No adjustment for mild-moderate; caution in severe (CrCl < 10 mL/min). - **Hepatic Impairment**: No adjustment for mild-moderate; use with caution in severe hepatic impairment. - **Elderly Patients**: No specific adjustment; monitor QTc if cardiac risk factors. ## Pediatric Dosing *Note: Oral suspension typically **100 mg/5 mL** or **200 mg/5 mL*** ### Neonates (0-28 days) *Use generally limited due to risk of Infantile Hypertrophic Pyloric Stenosis (IHPS).* - **Chlamydia trachomatis conjunctivitis/pneumonia**: - **Dose**: **20 mg/kg** - **Frequency**: Once daily - **Duration**: 3 days - **Special Notes**: Monitor closely for feeding intolerance, vomiting (IHPS risk). ### Infants (1-12 months) **Acute Otitis Media (AOM)** - **Single Dose**: **30 mg/kg** as single dose. - **3-Day Course**: **10 mg/kg** once daily for 3 days. - **5-Day Course**: Day 1: **10 mg/kg**; Days 2-5: **5 mg/kg** once daily. - **Maximum**: **1500 mg** total for 5-day course. - **Special Notes**: IHPS risk highest in first 42 days of life. ### Children (1-12 years) **Pharyngitis/Tonsillitis (Streptococcus pyogenes)** - **Dose**: **12 mg/kg** - **Frequency**: Once daily - **Duration**: 5 days - **Maximum**: **500 mg/day**; total max **2500 mg** (5 days). **Community-Acquired Pneumonia (CAP)** - **Dose**: Day 1: **10 mg/kg**; Days 2-5: **5 mg/kg** - **Frequency**: Once daily - **Duration**: 5 days - **Maximum**: **500 mg/day**; total max **2500 mg** (5 days). **Acute Otitis Media (AOM)** - **Single Dose**: **30 mg/kg** as single dose. - **3-Day Course**: **10 mg/kg** once daily for 3 days. - **5-Day Course**: Day 1: **10 mg/kg**; Days 2-5: **5 mg/kg** once daily. - **Maximum**: **1500 mg** total for 5-day course. ### Adolescents (13-18 years) - **Dose**: Adult dosing typically applies. - **Maximum**: Follow adult maximum doses for respective indications. ## Safety Information ### Contraindications - **Absolute**: History of cholestatic jaundice/hepatic dysfunction due to prior azithromycin. - **Absolute**: Hypersensitivity to azithromycin, erythromycin, or any macrolide/ketolide. - **Relative**: Congenital or documented acquired QTc prolongation. - **Relative**: History of Torsades de Pointes. - **Relative**: Uncorrected hypokalemia or hypomagnesemia. - **Relative**: Concomitant use with other QTc-prolonging drugs. ### Common Adverse Effects - **Very Common (>10%)**: Diarrhea. - **Common (1-10%)**: Nausea, abdominal pain, vomiting, headache, dizziness, flatulence. - **Serious but Rare**: **QT prolongation** (risk of Torsades de Pointes), **Clostridioides difficile-associated diarrhea (CDAD)**, **hepatotoxicity** (including cholestatic jaundice), **allergic reactions** (e.g., SJS, TEN, DRESS), **infantile hypertrophic pyloric stenosis (IHPS)** in young infants. ### Key Drug Interactions - **Antacids (Al/Mg)**: Reduce azithromycin peak levels. Administer azithromycin **1 hour before or 2 hours after** antacids. - **QTc-prolonging drugs**: Increased Torsades de Pointes risk (e.g., Class IA/III antiarrhythmics, antipsychotics). Avoid coadministration if possible. - **Warfarin**: Potential for increased INR. Monitor INR closely, especially upon initiation/discontinuation. - **Nelfinavir**: Significantly increases azithromycin concentrations. Monitor for increased adverse effects. - **Digoxin**: May increase digoxin concentrations. Monitor digoxin levels. ## Monitoring & Follow-up - **Before Treatment**: Assess baseline QTc if cardiac risk factors. Review concomitant QTc-prolonging drugs. - **During Treatment**: Monitor for signs of C. diff diarrhea, allergic reactions, or hepatotoxicity. - **Clinical Signs**: Watch for persistent vomiting, abdominal pain, or projectile vomiting in infants (IHPS). Monitor for new-onset arrhythmia symptoms, jaundice, or severe rash. ## Clinical Pearls - 💡 **Administration**: Can be taken with or without food. Oral suspension absorption is best on an empty stomach. - 💡 **Single Dose/Short Course**: Long half-life allows for shorter treatment durations for some infections. - 💡 **Post-antibiotic Effect**: Prolonged antibacterial activity due to high tissue concentrations and slow elimination. - 💡 **Patient Counseling**: Emphasize completing the entire course, even if symptoms improve. - 💡 **Taste**: Oral suspension can be bitter; advise mixing with small amount of applesauce (avoid dairy). > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.