Standard Z-Pack Dosing Regimen
The standard Z-pack (azithromycin) dosing is 500 mg on day 1, followed by 250 mg once daily on days 2 through 5, for a total 5-day course. 1
Adult Dosing
Standard Respiratory and Soft Tissue Infections
- 500 mg on day 1, then 250 mg once daily on days 2-5 (total dose: 1.5 grams over 5 days) 1, 2
- This regimen maintains steady-state concentrations with Cmax and Cmin remaining essentially unchanged from day 2 through day 5 2
- The prolonged tissue half-life (approximately 68-72 hours) allows therapeutic tissue concentrations to persist for approximately 10 days after the 5-day course 1, 2
Alternative Single-Dose Regimen
- 1 gram as a single dose for chlamydial infections (non-gonococcal urethritis/cervicitis) 1
- This single-dose approach provides therapeutic tissue concentrations for approximately 10 days due to azithromycin's extensive tissue distribution 1
- The single-dose regimen offers improved compliance and allows for directly observed therapy 1
Alternative 3-Day Regimen
- 500 mg once daily for 3 days (total dose: 1.5 grams) 2
- Pharmacokinetic studies demonstrate comparable total AUC between the 3-day and 5-day regimens when the same total dose is administered 2
- The 5-day regimen has greater evidence for pharyngitis/tonsillitis compared to the 3-day regimen 3
Pediatric Dosing
Standard Pediatric Regimen (>6 months)
- 10 mg/kg (maximum 500 mg) on day 1, followed by 5 mg/kg once daily (maximum 250 mg) on days 2-5 1
- This provides the same total dose of 30 mg/kg over 5 days 4
Streptococcal Pharyngitis in Children
- 12 mg/kg once daily for 5 days (maximum 500 mg/day) 3
- This higher dose is necessary because azithromycin shows more recurrence of streptococcal pharyngitis compared to penicillin V 3
- Azithromycin is reserved for penicillin-allergic patients, not first-line therapy 3
Infants <6 Months (Pertussis)
- 10 mg/kg once daily for 5 days 1
- Azithromycin is preferred over erythromycin in infants <1 month due to lower risk of infantile hypertrophic pyloric stenosis 1
Administration Considerations
Timing and Food
- Can be administered with or without food 3
- Food increases Cmax by 23-56% but does not affect overall AUC 2
Antacid Interactions
- Separate azithromycin from aluminum or magnesium-containing antacids by at least 2 hours 1, 3
- Concurrent administration reduces absorption by up to 50% 3
- Cimetidine does not affect azithromycin absorption 2
Compliance Strategies
- Dispense medication on-site when possible to improve adherence 1
- Consider directly observed first dose, particularly in populations with erratic healthcare-seeking behavior 1
Pharmacokinetic Rationale
Tissue Distribution
- Azithromycin achieves tissue-to-plasma concentration ratios exceeding 100:1 in lungs and tonsils, 70:1 in cervix, and 35:1 in skin 5
- Leukocyte concentrations are more than 1000-fold greater than serum concentrations 2
- Apparent steady-state volume of distribution is 31 L/kg, reflecting extensive tissue penetration 2
Elimination
- Serum half-life is approximately 68-72 hours 2
- Tissue half-life is approximately 3 days, allowing therapeutic concentrations to persist well beyond the dosing period 6
- Only 4.5-6.5% is excreted unchanged in urine 2
Common Pitfalls
Gastrointestinal Side Effects
- Most common adverse effects are diarrhea, nausea, vomiting, and abdominal pain 1, 3
- These are generally mild to moderate and less frequent than with erythromycin 1, 4
- In pediatric studies, only 2% reported adverse effects with azithromycin versus 13% with penicillin V 3