Indications

FDA-Approved Indications

Acute Bacterial Chronic Obstructive Pulmonary Disease (COPD) Exacerbation (see Chronic Obstructive Pulmonary Disease, [[Chronic Obstructive Pulmonary Disease]])

• xxx

Acute Bacterial Rhinosinusitis (see Acute Rhinosinusitis, [[Acute Rhinosinusitis]])

• xxx

Community-Acquired Pneumonia (CAP) (see Pneumonia, [[Pneumonia]])

• VA Retrospective Cohort Study of Azthromycin in Patients >65 y/o with CAP (2014) [MEDLINE]
  • Study: n = 73,690 patients from 118 hospitals
  • Main Findings
    • Azithromycin decreased 90-day mortality, as compared to use of other antibiotics
    • Azithromycin significantly increased risk of myocardial infarction: with no difference in risk of arrhythmias or congestive heart failure

Pharyngitis/Tonsillitis (see Pharyngitis, [[Pharyngitis]])

• xxx

Uncomplicated Skin and Skin Structure Infections

• xxx

Urethritis/Cervicitis (see Urethritis, [[Urethritis]])

• xxx

Prophylaxis Against Chronic Obstructive Pulmonary Disease (COPD) Exacerbation (see Chronic Obstructive Pulmonary Disease, [[Chronic Obstructive Pulmonary Disease]])

• General Comments: off-label use
• COPD Clinical Research Network Daily Azithromycin Trial (NEJM, 2011) [MEDLINE]
  • Study: randomized, placebo-controlled trial (n = 1577) with daily azithromycin (250 mg PO) x 1 year
  • Exclusion Criteria: asthma, a resting HR >100 beats, prolonged QTc >450 msec, use of medications that prolong the QTc or are associated with torsades (with the exception of amiodarone), and hearing impairment
  • Main Findings
    • Azithromycin decreased COPD exacerbations (1.48 vs 1.83 per year)
    • Azithromycin improved QOL
    • Azithromycin decreased colonization with selected respiratory pathogens (but increased colonization with macrolide-resistant organisms)
    • Azithromycin resulted in a small increase in hearing decrements (25% vs 20% of subjects)
    • No clear impact on microbial resistance patterns

Other Indications

• Acute Salmonellosis (see Salmonellosis, [[Salmonellosis]])
• Endocarditis Prophylaxis (see Endocarditis, [[Endocarditis]])
• Mycobacterium Avium Complex (MAC) (see Mycobacterium Avium Complex, [[Mycobacterium Avium Complex]])
• Pelvic Inflammatory Disease (PID) (see Pelvic Inflammatory Disease, [[Pelvic Inflammatory Disease]])
• Typhoid Fever (see Typhoid Fever, [[Typhoid Fever]])

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Pharmacology

• Macrolide Antibiotic (see Macrolides, [[Macrolides]])

Metabolism

• xxx

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Administration

• PO (COPD Exacerbation/Acute Bacterial Sinusitis/Pharyngitis/Tonsillitis): 500 mg on day 1, then 250 mg qday x4 days (Z-Pak)
  • Alternate: 500 mg qday x 3 days
• PO (Acute Salmonellosis): 1 g qday x1 day, then 500 mg qday x 2-6 days (or 7 days, if immunocompromised)
• PO (Chlamydial Infection, Non-Gonococcal Urethritis/Cervicitis, Chancroid): 1 g x1
• PO (Endocarditis Prophylaxis): 500 mg x1
• PO (MAI Primary Prophylaxis): 1200 mg qweek or 600 mg 2x/week
• PO (MAI Secondary Prophylaxis): 500-600 mg qday
• PO (MAI Treatment): 500-600 mg qday
• IV (CAP): 500 mg qday x7-10 day course
• IV (PID): 500 mg qday x7-10 day course

Dose Adjustment

• Hepatic
• Renal

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Adverse Effects

Cardiovascular Adverse Effects

Acute Myocardial Infarction (MI) (see Coronary Artery Disease, [[Coronary Artery Disease]])

• Epidemiology: azithromycin increases the risk of acute MI in patients >65 y/o with community-acquired pneumonia (see above), although its use is associated with an overall decreased mortality rate, as compared to other antibiotics

General Cardiovascular Risk

• Risk of Cardiovascular and All-Cause Mortality: increased with a 5-day oral course of azithromycin, as compared to no drug [MEDLINE]
  • Hazard ratio 2.88 (for cardiovascular mortality)
  • Hazard ratio 1.85 (for all-cause mortality)
• Risk of Cardiovascular and All-Cause Mortality: increased with a 5-day oral course of azithromycin, as compared to amoxacillin [MEDLINE]
  • Hazard ratio 2.49 (for cardiovascular mortality)
  • Hazard ratio 2.02 (for all-cause mortality)
• Risk of Cardiovascular Death: significantly greater with azithromycin than with ciprofloxacin, but did not differ significantly from that with levofloxacin [MEDLINE]

Q-T Prolongation with Definite Association with Torsade (see Torsade, [[Torsade]])

• FDA Warning Issued in 2013
• Risk Factors
  • Clinically-Significant Bradycardia (see Sinus Bradycardia, [[Sinus Bradycardia]])
  • Hypokalemia (see Hypokalemia, [[Hypokalemia]])
  • Hypomagnesemia (see Hypomagnesemia, [[Hypomagnesemia]])
  • Pre-Existing QT Prolongation
  • *Uncompensated Congestive Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]])
  • Use of Class IA Agents
    • Procainamide (see Procainamide, [[Procainamide]])
    • Quinidine (see Quinidine, [[Quinidine]])
  • Use of Class II Agents
    • Amiodarone (see Amiodarone, [[Amiodarone]])
    • Dofetilide (see Dofetilide, [[Dofetilide]])
    • Sotalol (see Sotalol, [[Sotalol]])
• Physiology: class effect

Otolaryngologic Adverse Effects

Hearing Loss (see Hearing Loss, [[Hearing Loss]])

• COPD Clinical Research Network Daily Azithromycin Trial (NEJM, 2011) [MEDLINE]: with use of azithromycin x 1 year, hearing decrements were more common in the azithromycin group than in the placebo group (25% vs 20%, P=0.04)

Pulmonary Adverse Effects

Drug-Induced Pulmonary Eosinophilia (see Drug-Induced Pulmonary Eosinophilia, [[Drug-Induced Pulmonary Eosinophilia]])

• Associated Agents
  • Azithromycin (Zithromax)
  • Clarithromycin (Biaxin) (see Clarithromycin, [[Clarithromycin]])
  • Erythromycin (see Erythromycin, [[Erythromycin]])
  • Roxithromycin (Biaxsig, Coroxin, Romac, Roxar, Roximycin, Roxl-150, Roxo, Roxomycin, Rulid, Rulide, Surlid, Tirabicin, Xthrocin) (see Roxithromycin, [[Roxithromycin]])
• Physiology: class effect

Other Adverse Effects

• xxxx
• xxxx
• xxxx
• xxxx

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References

• Azithromycin for Prevention of Exacerbations of COPD. NEJM 2011; 365(8): 689-698 [MEDLINE]
• Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012 May 17;366(20):1881-90 [MEDLINE]
• Cardiovascular risks with azithromycin and other antibacterial drugs. N Engl J Med 2013;368:1665-1668 [MEDLINE]
• Use of azithromycin and death from cardiovascular causes. N Engl J Med 2013;368:1704-1712 [MEDLINE]
• Association of azithromycin with mortality and cardiovascular events among older patients hospitalized with pneumonia. JAMA. 2014 Jun 4;311(21):2199-208. doi: 10.1001/jama.2014.4304 [MEDLINE]