Z-Pak (Azithromycin) Dosing and Duration
The standard Z-Pak regimen for adults is 500 mg on day 1, followed by 250 mg once daily on days 2-5, for a total 5-day course. 1
Standard Adult Dosing by Indication
Community-Acquired Pneumonia
- 500 mg on day 1, then 250 mg daily for days 2-5 (5-day course) 1
- Alternative: 500 mg daily for 3 consecutive days 1
- The extended tissue half-life of 68 hours means therapeutic concentrations persist for 7-10 days after the 3-5 day administration period ends 1, 2
Pertussis (Whooping Cough)
- 500 mg on day 1, then 250 mg daily for days 2-5 3, 1
- This is the CDC-recommended regimen for adults 3
Chlamydial Infections
- Single 1-gram dose for uncomplicated urethritis/cervicitis 3, 4
- For lymphogranuloma venereum: 1 gram orally once weekly for 3 weeks 1
Skin and Soft Tissue Infections
- 500 mg daily for 3 days 5
- Clinical resolution rates of 83% have been demonstrated with this shorter regimen 5
Pediatric Dosing
Children ≥6 Months
- 10 mg/kg (maximum 500 mg) on day 1, then 5 mg/kg (maximum 250 mg) daily for days 2-5 3, 1
- Alternative for otitis media: 10 mg/kg daily for 3 days 6
- For pharyngitis/tonsillitis: 12 mg/kg daily for 5 days (higher dose needed due to recurrence risk) 6
Infants <6 Months
- 10 mg/kg daily for 5 days 3
- Azithromycin is preferred over erythromycin in infants <1 month due to lower risk of infantile hypertrophic pyloric stenosis 3
Critical Pharmacokinetic Considerations
The 68-hour elimination half-life is the key feature that enables shorter treatment courses. 1, 2 Tissue concentrations remain therapeutic for 7-10 days after completing a 3-5 day administration course, effectively providing 7-10 days of total antibiotic therapy 1. This extended half-life allows once-daily dosing and improves compliance 7.
Important Safety Warnings
Cardiac Risks
- Azithromycin can cause fatal cardiac arrhythmias including torsades de pointes 8
- Avoid in patients with known QT prolongation or history of torsades de pointes 8
Drug Interactions
- Do not take with aluminum- or magnesium-containing antacids simultaneously, as they reduce absorption 3, 1
- Monitor patients on digoxin, triazolam, and ergot alkaloids 3
Resistance Development
- The prolonged subinhibitory drug concentrations lasting 14-20 days after treatment create a "selective window" for resistance development 8, 2
- High macrolide resistance rates in your community may favor alternative agents 8
Common Pitfalls to Avoid
- Do not extend therapy beyond standard durations simply because chest X-ray abnormalities persist - radiographic resolution lags behind clinical improvement by weeks in pneumonia 1
- Do not use azithromycin as first-line for chlamydial urethritis - doxycycline is preferred; azithromycin should only be used if doxycycline fails, is contraindicated, or adherence is a concern 8
- Consider tuberculosis screening in high-risk populations before initiating therapy - empiric azithromycin for pneumonia may delay TB diagnosis 8
Special Populations
Pregnancy
Immunocompromised Patients
- May require extended durations of 10-14 days minimum 1
- Continue throughout neutropenia if applicable 1
Hepatic Impairment
- Prescribe with caution in patients with impaired hepatic function 3