Z-Pak Duration
A standard Z-Pak (azithromycin) is a 5-day treatment course consisting of 500 mg on day 1, followed by 250 mg once daily on days 2 through 5. 1
Standard Dosing Regimen
The FDA-approved Z-Pak regimen provides:
- Day 1: 500 mg as a single dose
- Days 2-5: 250 mg once daily
- Total duration: 5 days
- Total cumulative dose: 1,500 mg 1, 2
This dosing schedule achieves therapeutic tissue concentrations that persist for approximately 10 days after the final dose due to azithromycin's prolonged tissue half-life and extensive tissue distribution 1, 3.
Alternative Regimens by Indication
While the standard Z-Pak is 5 days, azithromycin duration varies significantly by clinical indication:
Shorter Courses
- Single-dose therapy (1 gram): Used for chlamydial infections (non-gonococcal urethritis/cervicitis), providing therapeutic concentrations for ~10 days 4, 1
- 3-day course (500 mg daily): FDA-approved for acute bacterial exacerbations of COPD and acute bacterial sinusitis 2
- 3-day course for atypical pneumonia: Equally effective as the 5-day regimen at the same total dose 5
Longer Courses
- Long-term prophylaxis: 250-500 mg three times weekly or 250 mg daily for 6-12 months in chronic respiratory conditions (asthma, COPD, bronchiectasis) 4
- Bronchiolitis obliterans syndrome: 250 mg daily for 5 days, then 250 mg three times weekly for at least 3 months 4, 1
Key Clinical Considerations
Administration pearls:
- Dispense medication on-site when possible and directly observe the first dose to maximize compliance 1
- Absorption may be reduced by 50% if taken with a large meal or aluminum/magnesium-containing antacids 1, 6
Common pitfalls:
- The primary advantage over alternatives like doxycycline is the short duration and once-daily dosing, which significantly improves adherence in populations with erratic healthcare-seeking behavior 1
- For sexually transmitted infections, patients must abstain from sexual intercourse for 7 days after completing therapy (or after single-dose treatment) to prevent transmission 4, 1
- Gastrointestinal side effects (diarrhea, nausea, abdominal pain) occur in approximately 12-18% of patients but are generally milder than with erythromycin 2, 7
Pharmacokinetic rationale:
- Terminal half-life exceeds 60 hours with a volume of distribution of 23 L/kg, resulting in extensive tissue accumulation despite low serum concentrations 6, 8
- Tissue concentrations remain above MIC for key respiratory pathogens (S. pyogenes, H. influenzae, S. aureus) for up to 10 days after a 5-day course 3