How to Order a Z-Pak (Azithromycin)
For adults, order azithromycin 500 mg on day 1, followed by 250 mg once daily on days 2-5 (total 1.5 g over 5 days). This is the standard Z-Pak regimen endorsed by CDC guidelines 1.
Age-Based Dosing Algorithm
Adults (≥18 years)
- Day 1: 500 mg orally once
- Days 2-5: 250 mg orally once daily
- Total course: 5 days (1.5 g cumulative dose)
Children and Infants (>6 months)
- Day 1: 10 mg/kg orally once (maximum 500 mg)
- Days 2-5: 5 mg/kg orally once daily (maximum 250 mg per day)
- Total course: 5 days 1
Infants (<6 months)
- All 5 days: 10 mg/kg orally once daily
- Total course: 5 days
- Critical note: Azithromycin is preferred over erythromycin in this age group due to lower risk of infantile hypertrophic pyloric stenosis (IHPS) 1
Pre-Treatment Safety Screening
Before prescribing azithromycin, you must assess for contraindications:
Absolute Contraindications
- History of hypersensitivity to any macrolide antibiotic 1
- QTc prolongation: >450 ms (men) or >470 ms (women) on baseline ECG 2
- Concurrent use of medications that prolong QT interval 2
Obtain Baseline Tests
- ECG to measure QTc interval (mandatory for cardiac risk assessment) 2
- Liver function tests if hepatic impairment suspected 1
Drug Interaction Check
Azithromycin has fewer cytochrome P450 interactions than erythromycin or clarithromycin, but monitor patients taking 1:
- Digoxin
- Triazolam
- Ergot alkaloids
- Warfarin (theoretical interaction)
Patient Counseling Points
Instruct patients to:
- Avoid aluminum/magnesium-containing antacids simultaneously with azithromycin (reduces absorption) 1
- Take with or without food (azithromycin absorption not significantly affected)
- Complete the full 5-day course even if symptoms improve
- Report immediately: severe diarrhea, irregular heartbeat, dizziness, fainting
Common Side Effects to Expect
- Gastrointestinal: nausea, vomiting, abdominal pain, diarrhea (most common) 1
- Headache and dizziness 1
- These are generally mild and self-limiting
Clinical Context Considerations
When Azithromycin is Appropriate
The evidence supports azithromycin for:
- Atypical pneumonia (Mycoplasma, Chlamydia, Legionella) 3, 4
- Pertussis treatment and prophylaxis 1
- Chlamydial infections (single 1 g dose alternative) 5, 6
- Cat scratch disease (Bartonella henselae) 7
- Streptococcal pharyngitis (alternative to penicillin) 8
When to Avoid Azithromycin
- Community-acquired pneumonia without atypical features: Beta-lactams are first-line 9, 10
- Severe CAP requiring ICU: Combine with beta-lactam, not monotherapy 9
- Gonococcal infections: Resistance concerns; use ceftriaxone + azithromycin combination 5
Alternative Dosing Regimens
3-Day Regimen (Same Total Dose)
- 500 mg once daily for 3 days (total 1.5 g)
- Evidence shows equivalent efficacy to 5-day regimen for atypical pneumonia 3, 4
- May improve compliance but less commonly prescribed
Single-Dose Regimen
- 1 g (1000 mg) single dose for uncomplicated chlamydial urethritis 5, 6
- Not appropriate for respiratory infections
Critical Safety Warnings
Cardiac Risk
Azithromycin can prolong QTc interval and cause potentially fatal arrhythmias. The 2020 British Thoracic Society guidelines emphasize that patients with baseline QTc >450 ms (men) or >470 ms (women) should not receive azithromycin 2. This is particularly important in elderly patients and those with cardiac disease.
Antimicrobial Resistance
Inappropriate azithromycin use drives macrolide resistance. The WHO and multiple guidelines stress using azithromycin only when clinically indicated, not as empiric therapy for viral infections 11, 10. Document clear clinical rationale in the medical record.
Hepatic Impairment
Use with caution in patients with impaired liver function; dose adjustment may be necessary 1.
Pregnancy
Azithromycin is FDA Pregnancy Category B—generally considered safe but use only when clearly needed 1.
Prescription Writing Template
Azithromycin 250 mg tablets
- Dispense: #6 tablets (one Z-Pak)
- Directions: Take 2 tablets (500 mg) by mouth once on Day 1, then take 1 tablet (250 mg) by mouth once daily on Days 2 through 5
- No refills
Or use the pre-packaged Z-Pak formulation which contains the exact 6-tablet course with clear day-by-day labeling.