What is the typical dosing regimen for Azithromycin (macrolide antibiotic)?

Azithromycin Dosing Regimens

Azithromycin dosing varies significantly by indication, with the most common regimens being a single 1 gram dose for sexually transmitted infections, 500 mg on day 1 followed by 250 mg daily for 4 days (Z-pack) for respiratory infections, or 500 mg daily for 3 days as an alternative respiratory regimen. 1

Standard Adult Dosing by Indication

Sexually Transmitted Infections

• Single 1 gram oral dose is the recommended regimen for non-gonococcal urethritis and cervicitis caused by Chlamydia trachomatis. 2, 1 This provides therapeutic tissue concentrations in urogenital tissues for approximately 10 days due to azithromycin's prolonged tissue half-life. 3
• The single-dose regimen has the critical advantage of improved compliance and allows for directly observed therapy, which is particularly important in populations unlikely to return for follow-up. 2
• Patients should abstain from sexual intercourse for 7 days after completing therapy to prevent transmission. 1

Respiratory Tract Infections

Two primary regimens are equally effective for community-acquired pneumonia and other respiratory infections:

• 5-day regimen (Z-pack): 500 mg on day 1, followed by 250 mg once daily on days 2-5 (total dose 1.5 grams). 1, 4
• 3-day regimen: 500 mg once daily for 3 days (total dose 1.5 grams). 1, 4

Both regimens provide comparable serum and tissue concentrations, with tissue levels exceeding MICs for key respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes) for up to 10 days after completion. 3, 5 The 3-day regimen offers superior compliance while maintaining equivalent efficacy. 6, 5

Long-Term Macrolide Therapy for Chronic Respiratory Disease

For bronchiectasis with ≥3 exacerbations per year:

• Azithromycin 500 mg three times weekly is the regimen with strongest evidence for reducing exacerbations. 2
• Alternative: 250 mg daily (equivalent weekly dose). 2
• Lower starting dose of 250 mg three times weekly can be used in patients with history of drug intolerances. 2
• Treatment duration should be 6-12 months minimum to assess efficacy. 2

For asthma with frequent exacerbations:

• Same dosing as bronchiectasis (500 mg three times weekly or 250 mg daily). 2
• Requires 6-12 months of therapy to demonstrate benefit in exacerbation reduction. 2

Pediatric Dosing

Respiratory Tract Infections

• 10 mg/kg (maximum 500 mg) on day 1, followed by 5 mg/kg (maximum 250 mg) daily on days 2-5. 1, 7
• Alternative 3-day regimen: 10 mg/kg daily for 3 days. 7

Pertussis (Treatment and Prophylaxis)

• Infants <6 months: 10 mg/kg daily for 5 days. 1
• Infants and children ≥6 months: 10 mg/kg (maximum 500 mg) on day 1, then 5 mg/kg (maximum 250 mg) daily on days 2-5. 1

Cat Scratch Disease

• Patients >45 kg: 500 mg on day 1, then 250 mg daily for 4 days. 1
• Patients <45 kg: 10 mg/kg on day 1, then 5 mg/kg daily for 4 days. 1

Special Clinical Situations

Lyme Disease (Alternative Agent)

• 500 mg daily for 7-10 days for early localized disease in patients intolerant of first-line agents (doxycycline, amoxicillin, cefuroxime). 2
• Macrolides are less effective than first-line agents and patients require close observation to ensure resolution. 2

Babesiosis

• 500-1000 mg on day 1, then 250 mg daily (in combination with atovaquone). 1

Disseminated MAC Disease in AIDS

• 250 mg daily with ethambutol ± rifabutin for treatment. 1
• 1200 mg once weekly for prophylaxis in patients with CD4 <50 cells/μL. 1

Administration Considerations

Food Effects

• Tablets: Food increases Cmax by 23% but does not affect AUC; can be taken with or without food. 4
• Suspension: Food increases Cmax by 56% with unchanged AUC; preferably take on empty stomach for more predictable absorption. 4

Drug Interactions

• Do not administer simultaneously with aluminum or magnesium-containing antacids as they reduce Cmax by 24%, though AUC remains unchanged. 4 Separate administration by at least 2 hours.
• Cimetidine does not affect azithromycin absorption. 4

Pharmacokinetic Rationale

Azithromycin's unique pharmacokinetics justify short-course therapy:

• Terminal elimination half-life of 68 hours allows once-daily dosing. 4
• Tissue concentrations are >1000-fold higher than serum in leukocytes and remain elevated for days after completion. 4, 3
• Apparent volume of distribution is 31.1 L/kg, reflecting extensive tissue penetration. 4
• Only 6% excreted unchanged in urine over one week; biliary excretion is the major elimination route. 4

Safety Monitoring and Precautions

Pre-Treatment Assessment

• Obtain ECG to assess QTc interval before initiating long-term therapy; contraindicated if QTc >450 ms (men) or >470 ms (women). 2
• Measure baseline liver function tests for long-term therapy. 2

Common Adverse Effects

• Gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea) occur in 3-4% of patients and are generally mild to moderate. 2, 1
• Azithromycin is better tolerated than erythromycin with fewer GI side effects. 8
• Withdrawals due to adverse effects in clinical trials are rare. 2

Special Populations

• Pregnancy: FDA Category B; considered safe and effective. 1
• Renal impairment (GFR <10 mL/min): Cmax and AUC increase by 61% and 35% respectively; use with caution but no specific dose adjustment established. 4
• Hepatic impairment: Pharmacokinetics not established; use with caution. 4
• Elderly: Women may have 30-50% higher peak concentrations, but no dose adjustment needed. 4

Critical Pitfalls to Avoid

• Do not use azithromycin as monotherapy for gonorrhea—resistance is widespread; always combine with ceftriaxone for suspected gonococcal infection. 2
• Do not use for streptococcal pharyngitis as first-line—higher recurrence rates than penicillin; requires higher dose (12 mg/kg/day for 5 days in children) if used. 7
• Do not prescribe for dysentery without considering azithromycin first-line—superior to fluoroquinolones for Campylobacter and Shigella due to widespread fluoroquinolone resistance. 9
• Avoid in patients with prolonged QTc or those taking other QT-prolonging medications without careful risk assessment. 2