What is the typical dosing regimen for a Z pack (azithromycin)?

Z-Pack (Azithromycin) Dosing

The standard Z-pack regimen is 500 mg on day 1, followed by 250 mg once daily on days 2 through 5, for a total 5-day course. 1, 2

Standard Adult Dosing Regimens

Classic "Z-Pack" (5-Day Regimen)

• 500 mg orally on day 1, then 250 mg once daily on days 2-5 is the most commonly prescribed regimen for respiratory tract infections including community-acquired pneumonia, acute bacterial sinusitis, and bronchitis 3, 1, 2
• This provides a total dose of 1.5 grams over 5 days 4, 5
• Can be taken with or without food, though food increases Cmax by 56% with suspension formulations 2

Alternative 3-Day Regimen

• 500 mg once daily for 3 consecutive days is equally effective for respiratory tract infections and provides the same total 1.5 gram dose 3, 4, 6
• This shorter regimen has been shown to be as effective as the 5-day course for atypical pneumonia caused by Mycoplasma pneumoniae, Chlamydia psittaci, and Coxiella burnetii 4, 5

Single-Dose Regimens

• 1 gram as a single dose is recommended specifically for non-gonococcal urethritis, cervicitis, and Chlamydia trachomatis infections 3, 1
• The single-dose regimen provides therapeutic tissue concentrations for approximately 10 days due to azithromycin's prolonged tissue half-life 1
• A 2-gram extended-release formulation (Zmax) is available for acute bacterial sinusitis and community-acquired pneumonia, though this is a specialized formulation 7

Pediatric Dosing

• 10 mg/kg (maximum 500 mg) on day 1, followed by 5 mg/kg once daily (maximum 250 mg/day) on days 2-5 is the standard pediatric regimen for respiratory tract infections 3, 1, 8
• For pertussis in infants <6 months: 10 mg/kg per day for 5 days 1
• For pertussis in children ≥6 months: 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg (max 250 mg) on days 2-5 1

Important Administration Considerations

Drug Interactions

• Separate azithromycin from aluminum- or magnesium-containing antacids by at least 2 hours, as antacids reduce absorption by up to 50% 3, 2
• Cimetidine does not affect azithromycin absorption 2

Cardiac Precautions

• Obtain baseline ECG in patients with cardiac risk factors before initiating therapy 9
• Avoid azithromycin if QTc >450 ms (men) or >470 ms (women) 10, 9
• Azithromycin can prolong QT interval and increase risk of arrhythmias 10

Common Pitfalls and Clinical Pearls

Compliance Optimization

• Dispense medication on-site and directly observe the first dose when possible to maximize adherence, particularly in sexually transmitted infection treatment 1
• The once-daily dosing and short duration significantly improve compliance compared to alternatives like doxycycline 1

Resistance Considerations

• Azithromycin is NOT first-line for streptococcal pharyngitis due to increasing macrolide resistance in group A Streptococcus 9
• Should only be used as an alternative in penicillin-allergic patients for strep throat 9
• Do not use as monotherapy for gonococcal infections due to resistance; must combine with ceftriaxone 3

Adverse Effects

• Gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea) are the most common side effects but occur less frequently than with erythromycin 1, 8, 6
• Most adverse effects are mild to moderate in severity 3

Special Populations

• Pregnancy Category B - considered safe in pregnancy and preferred over erythromycin in infants <1 month due to lower risk of infantile hypertrophic pyloric stenosis 1
• In severe renal impairment (GFR <10 mL/min), Cmax and AUC increase by 61% and 35% respectively, though no specific dose adjustment is routinely recommended 2

Pharmacokinetic Advantages

• Azithromycin achieves tissue concentrations >100-fold higher than serum levels in lung, tonsil, and other tissues 2
• Terminal elimination half-life of 68 hours allows for short-course therapy 2, 6
• Only 6% of the administered dose appears as unchanged drug in urine over one week 2