What are the recommended azithromycin dosing regimens for adults and children, including adjustments for renal or hepatic impairment?

Azithromycin Dosing Guidelines

Standard Adult Dosing by Indication

For non-gonococcal urethritis and cervicitis caused by Chlamydia trachomatis, administer a single 1 gram oral dose. This single-dose regimen is the CDC's definitive recommendation because it enables directly observed therapy and achieves superior compliance compared to multi-day regimens, while providing therapeutic tissue concentrations for approximately 10 days due to azithromycin's prolonged tissue half-life. 1, 2

Respiratory Tract Infections

• Community-acquired pneumonia (mild severity): 500 mg on day 1, followed by 250 mg once daily on days 2–5 (total 5 days). 2
• Acute bacterial exacerbations of COPD: Either 500 mg once daily for 3 days OR 500 mg on day 1 followed by 250 mg daily on days 2–5. 2
• Acute bacterial sinusitis: 500 mg once daily for 3 days. 2
• Severe community-acquired pneumonia (hospitalized, non-ICU): 500 mg IV daily for 2–5 days, then transition to oral 500 mg daily to complete 7–10 days total. 1

Other Indications

• Genital ulcer disease (chancroid): Single 1 gram oral dose. 2
• Cat scratch disease (patients >45 kg): 500 mg on day 1, then 250 mg daily for 4 additional days. 1
• Disseminated MAC disease in AIDS patients: 250 mg daily with ethambutol, with or without rifabutin. 1
• MAC prophylaxis in AIDS (CD4 <50 cells/μL): 1,200 mg once weekly. 1

Long-Term Prophylactic Regimens

• Bronchiectasis with ≥3 exacerbations per year: 500 mg three times weekly (strongest evidence) OR 250 mg daily. Minimum 6 months duration required to demonstrate benefit. 1
• Bronchiolitis obliterans syndrome in lung transplant recipients: 250 mg daily for 5 days, then 250 mg three times weekly for at least 3 months. 1

Pediatric Dosing Regimens

Standard Pediatric Dosing (Age ≥6 months)

For most pediatric respiratory infections, use either the 5-day regimen (10 mg/kg on day 1, then 5 mg/kg daily on days 2–5) or the 3-day regimen (10 mg/kg once daily for 3 days). 2, 3

Indication-Specific Pediatric Dosing

• Acute otitis media: Three options available:

  • 30 mg/kg as a single dose (1-day regimen) 2
  • 10 mg/kg once daily for 3 days (3-day regimen) 2
  • 10 mg/kg on day 1, then 5 mg/kg daily on days 2–5 (5-day regimen) 2

• Acute bacterial sinusitis: 10 mg/kg once daily for 3 days. 2

• Community-acquired pneumonia: 10 mg/kg on day 1, then 5 mg/kg daily on days 2–5. 2

• Pertussis (infants <6 months): 10 mg/kg daily for 5 days. 1

• Pertussis (infants and children ≥6 months): 10 mg/kg (maximum 500 mg) on day 1, then 5 mg/kg daily (maximum 250 mg) on days 2–5. 1

• Cat scratch disease (patients <45 kg): 10 mg/kg on day 1, then 5 mg/kg daily for 4 additional days. 1

• Streptococcal pharyngitis/tonsillitis: 12 mg/kg once daily for 5 days (total dose 60 mg/kg) provides optimal GABHS eradication. This higher dose is necessary because standard dosing results in higher recurrence rates compared to penicillin. 4

• Chlamydial conjunctivitis in neonates: 20 mg/kg once daily for 3 days. 1

Renal Impairment Dosing

No dose adjustment is required for patients with mild to moderate renal impairment (GFR 10–80 mL/min). The AUC remains similar across this range compared to normal renal function. 2, 5

• Severe renal impairment (GFR <10 mL/min): Exercise caution as AUC increases by 35% and Cmax increases by 61%. While no specific dose reduction is mandated by the FDA label, close monitoring is warranted. 2, 6

• Hemodialysis patients: No supplemental dose or timing adjustment needed, as azithromycin is not significantly removed by dialysis. 6

Hepatic Impairment Dosing

No dose adjustment recommendations can be made for patients with hepatic impairment, as pharmacokinetic data in this population are lacking. Use with caution and increase monitoring if underlying liver disease is present. 2, 1

Administration Considerations

• Food interaction: Azithromycin tablets and oral suspension can be taken with or without food. 2

• Antacid interaction: If aluminum- or magnesium-containing antacids are necessary, separate administration from azithromycin as absorption may be reduced. 1

• Directly observed therapy: Administer the first dose under direct observation when possible, particularly in populations with erratic healthcare-seeking behavior or for single-dose regimens. 1

Safety Monitoring for Long-Term Therapy

• Baseline ECG: Obtain before initiating long-term therapy; contraindicated if QTc >450 ms (men) or >470 ms (women). 1

• Baseline liver function tests: Measure before starting long-term therapy. 1

• Cardiovascular risk assessment: Avoid in patients with prolonged QTc or those taking other QT-prolonging medications without careful risk assessment. A Tennessee Medicaid cohort demonstrated increased cardiovascular deaths (HR 2.88; 95% CI 1.79–4.63) with 5-day azithromycin therapy, most pronounced in high-risk patients. 1

• NTM screening: Ensure at least one negative respiratory nontuberculous mycobacteria culture before starting long-term macrolides in bronchiectasis patients. 1

• 6-monthly monitoring: For patients on long-term therapy, review efficacy, toxicity, and continuing need every 6 months. 1

Common Side Effects

• Gastrointestinal: Abdominal discomfort/pain, diarrhea, nausea, vomiting (generally mild to moderate severity). 1, 3

• Other: Headache and dizziness. 1

• Tolerability advantage: Gastrointestinal symptoms occur less frequently than with erythromycin. 1, 3

Critical Pitfalls to Avoid

• Gonorrhea monotherapy: Never use azithromycin alone for gonorrhea due to widespread resistance; always combine with ceftriaxone if gonococcal infection is suspected. 1

• Underdosing streptococcal pharyngitis: Standard doses result in higher recurrence rates; use 12 mg/kg daily for 5 days (total 60 mg/kg) in children. 4

• Ignoring cardiovascular risk: Screen for QT prolongation risk factors before prescribing, especially in elderly patients or those with cardiovascular disease. 1

• Resistance concerns: Long-term macrolide use increases antimicrobial resistance, though clinical impact remains uncertain. 1

Special Populations

• Pregnancy: FDA Pregnancy Category B. 1

• Infants <1 month: Azithromycin is preferred over erythromycin due to lower risk of infantile hypertrophic pyloric stenosis. 1

• Elderly patients: Body weight significantly influences clearance and distribution volume; dose based on weight. 7

• Children: Age and liver function influence clearance; body weight is the primary dosing determinant. 7