When should a Z-Pak (azithromycin) be prescribed?

When to Prescribe Azithromycin (Z-Pak)

Azithromycin should be prescribed for confirmed or highly suspected bacterial infections where it is first-line therapy (chlamydial infections, atypical pneumonia, certain STIs) or when first-line agents are contraindicated, with the critical caveat that it should never be used for empiric pneumonia without risk stratification due to potential masking of tuberculosis and cardiac risks. 1

FDA-Approved Indications

Respiratory Tract Infections

• Community-acquired pneumonia in patients appropriate for oral therapy caused by Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, or Streptococcus pneumoniae 2
• Acute bacterial exacerbations of COPD due to H. influenzae, Moraxella catarrhalis, or S. pneumoniae 2
• Acute bacterial sinusitis due to H. influenzae, M. catarrhalis, or S. pneumoniae 2
• Pharyngitis/tonsillitis caused by Streptococcus pyogenes only as an alternative when first-line therapy (penicillin) cannot be used 2

Sexually Transmitted Infections (First-Line)

• Non-gonococcal urethritis and cervicitis due to Chlamydia trachomatis: 1 gram single dose 3, 4
• Urethritis/cervicitis due to Neisseria gonorrhoeae: 1 gram single dose 2
• Genital ulcer disease (chancroid) in men due to Haemophilus ducreyi 2

Skin and Soft Tissue Infections

• Uncomplicated skin infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae (abscesses require surgical drainage) 2

Gastrointestinal Infections

• Severe bacterial gastroenteritis with dysentery or incapacitating watery diarrhea, particularly when fluoroquinolone-resistant Campylobacter is suspected: 1 gram single dose or 500 mg daily for 3 days 5

Critical Contraindications and When NOT to Use

Pneumonia Risk Stratification (Mandatory)

Do NOT use azithromycin for pneumonia in patients with: 2

• Moderate to severe illness requiring hospitalization
• Cystic fibrosis
• Nosocomial infections
• Known or suspected bacteremia
• Elderly or debilitated patients
• Immunodeficiency or functional asplenia
• Significant underlying health problems

Safety Warnings

• Avoid in patients with QT prolongation or history of torsades de pointes due to risk of fatal cardiac arrhythmias 1
• Screen for tuberculosis in high-risk populations before initiating therapy, as azithromycin may delay TB diagnosis 1
• Use with extreme caution in myasthenia gravis due to risk of exacerbation 2

Dosing Regimens by Indication

Standard Z-Pak (5-Day Course)

• 500 mg on day 1, then 250 mg once daily on days 2-5 4
• Used for respiratory tract infections in appropriate patients 2

Single-Dose Regimens

• Chlamydial infections: 1 gram orally once 3, 4
• Bacterial gastroenteritis: 1 gram orally once 5

Alternative 3-Day Regimen

• 500 mg once daily for 3 days 5
• Equally effective for atypical pneumonia and gastroenteritis 6

Pediatric Dosing

• Otitis media, pneumonia, pharyngitis: 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg (max 250 mg) daily for days 2-5 2, 7

When to Choose Alternatives Over Azithromycin

Prefer Doxycycline for:

• Non-gonococcal urethritis as first-line (100 mg twice daily for 7 days) 3
• Azithromycin reserved for compliance concerns or doxycycline contraindications 1

Prefer Beta-Lactams for:

• Streptococcal pharyngitis: Penicillin remains first-line; azithromycin has higher recurrence rates 2, 7
• Hospitalized pneumonia patients: Beta-lactams are first-line 1
• Acute bacterial sinusitis: Amoxicillin-clavulanate shows superior efficacy 1

Consider Local Resistance Patterns

• High macrolide resistance (>25%) favors alternative agents 1
• Azithromycin's long half-life creates 14-20 day window of subinhibitory concentrations that promotes resistance 1

Administration Pearls

• Directly observe first dose to maximize compliance, especially in STI treatment 4
• Can be taken with or without food 2
• Do NOT take with aluminum/magnesium antacids (reduces absorption) 4, 2
• Abstain from sexual intercourse for 7 days after STI treatment 3, 4
• Dispense medication on-site when possible to improve adherence 3

Common Pitfalls to Avoid

• Never use empirically for pneumonia without proper risk assessment 2
• Do not rely on azithromycin to treat syphilis at recommended doses 2
• Perform syphilis serology in all patients with STI-related urethritis/cervicitis 3, 2
• Monitor prothrombin time if co-administered with warfarin 2
• Avoid in patients with creatinine clearance <10 mL/min without caution 2