What are the recommended oral azithromycin dosing regimens for adults and children, including standard, single‑dose, extended‑course, and adjustments for pregnancy, renal or hepatic impairment?

Oral Azithromycin Dosing Recommendations

For most adult bacterial infections, administer azithromycin 500 mg on day 1, followed by 250 mg once daily on days 2 through 5; for uncomplicated chlamydial infections, give a single 1 gram dose. 1

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Standard Adult Dosing by Indication

Respiratory Tract Infections

• Community-acquired pneumonia (mild severity): 500 mg on day 1, then 250 mg once daily on days 2–5 (total 5-day course). 1
• Acute bacterial exacerbations of COPD: Either 500 mg once daily for 3 days OR 500 mg on day 1, then 250 mg once daily on days 2–5. 1
• Acute bacterial sinusitis: 500 mg once daily for 3 days. 1
• Pharyngitis/tonsillitis (second-line therapy): 500 mg on day 1, then 250 mg once daily on days 2–5. 1

The 3-day regimen (500 mg daily × 3 days) provides equivalent efficacy to the 5-day regimen while improving compliance, due to azithromycin's prolonged tissue half-life of 68 hours. 2

Sexually Transmitted Infections

• Non-gonococcal urethritis and cervicitis (Chlamydia trachomatis): Single 1 gram oral dose. 1, 2
• Gonococcal urethritis and cervicitis: Single 2 gram dose (per FDA label), but azithromycin must never be used as monotherapy for gonorrhea due to widespread resistance—always combine with ceftriaxone 250–500 mg IM. 1, 2
• Genital ulcer disease (chancroid): Single 1 gram dose. 1
• Persistent non-gonococcal urethritis (after doxycycline failure): 500 mg on day 1, then 250 mg once daily for 4 days (extended 5-day regimen). 2

The single-dose regimen enables directly observed therapy and yields superior compliance, particularly in populations unlikely to return for follow-up. 2

Travelers' Diarrhea and Enteric Fever

• Travelers' diarrhea/dysentery: Either single 1 gram dose OR 500 mg once daily for 3 days. 2
• Enteric fever (typhoid): 500 mg on day 1, then 250 mg once daily on days 2–5 (adults); 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg (max 250 mg) once daily on days 2–5 (children >6 months). 3
  • Extend to 7 days (not 5) in delayed presentation, extensively drug-resistant strains, or incomplete clinical response to reduce relapse risk below 3%. 3

Specialized Indications

• Legionnaires' disease (hospitalized): 500 mg IV daily for 2–7 days, then oral to complete 7–10 days total. 2
• Legionnaires' disease (outpatient): 500 mg on day 1, then 250 mg once daily for 4 days. 2
• Cat scratch disease (>45 kg): 500 mg on day 1, then 250 mg once daily for 4 days. 4
• Babesiosis (with atovaquone): 500–1000 mg on day 1, then 250 mg once daily for 7–10 days. 2, 4
• Disseminated MAC disease (AIDS): 250 mg once daily with ethambutol ± rifabutin. 4
• MAC prophylaxis (AIDS, CD4 <50): 1200 mg once weekly. 4

Long-Term Prophylactic Regimens

• Bronchiectasis (≥3 exacerbations/year): 500 mg three times weekly OR 250 mg daily for ≥6 months. 2, 4
• Bronchiolitis obliterans syndrome (lung transplant): 250 mg daily for 5 days, then 250 mg three times weekly for ≥3 months. 4

Before initiating long-term therapy: Obtain baseline ECG (contraindicated if QTc >450 ms in men or >470 ms in women), liver function tests, and at least one negative respiratory NTM culture. 2, 4 Review every 6 months for efficacy, toxicity, and continuing need. 2

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Pediatric Dosing Regimens

Standard Respiratory and Skin Infections

• Community-acquired pneumonia: 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg (max 250 mg) once daily on days 2–5. 1, 2
• Acute otitis media: Three options:
  • Single-dose: 30 mg/kg as a single dose (max 1500 mg). 1
  • 3-day regimen: 10 mg/kg once daily for 3 days. 1
  • 5-day regimen: 10 mg/kg on day 1, then 5 mg/kg once daily on days 2–5. 1
• Acute bacterial sinusitis: 10 mg/kg once daily for 3 days. 1

Specialized Pediatric Indications

• Pertussis (treatment/prophylaxis, <6 months): 10 mg/kg once daily for 5 days. 4
• Pertussis (≥6 months): 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg (max 250 mg) once daily on days 2–5. 4
• Cat scratch disease (<45 kg): 10 mg/kg on day 1, then 5 mg/kg once daily for 4 days. 4
• Chlamydial conjunctivitis (neonates): 20 mg/kg once daily for 3 days. 4

If a child vomits within 30 minutes of the 30 mg/kg single dose for otitis media, the safety of re-dosing has not been established. 1

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Special Populations

Pregnancy

• Azithromycin is FDA Pregnancy Category B and is considered safe in pregnancy. 4
• Chlamydial infection in pregnancy: Single 1 gram dose is an acceptable alternative regimen. 4
• Azithromycin is preferred over erythromycin in infants <1 month due to lower risk of infantile hypertrophic pyloric stenosis. 2, 4

Renal Impairment

• GFR 10–80 mL/min: No dosage adjustment required. 1
• GFR <10 mL/min: AUC increases 35% and Cmax increases 61%; use with caution and increase monitoring. 1, 2
• In elderly patients, calculate eGFR rather than relying on serum creatinine alone, as age-related muscle loss can mask impairment. 2

Hepatic Impairment

• Pharmacokinetics have not been established in hepatic impairment; no dose adjustment recommendations can be made, but use with caution and increase monitoring. 1, 2

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Administration Considerations

• Food: Azithromycin can be taken with or without food. 1, 2
• Antacids: Do not administer simultaneously with aluminum- or magnesium-containing antacids; separate by at least 2 hours, as they reduce absorption by up to 50%. 2, 4
• Liquid formulations: Verify the mg/mL strength on the bottle label before calculating the mL dose—concentrations vary (100 mg/5 mL vs. 200 mg/5 mL). 2

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Critical Safety Considerations

QT Prolongation and Cardiac Risk

• The FDA warns that azithromycin prolongs QT interval and increases risk of cardiac arrhythmias, particularly in patients with prolonged baseline QTc, concurrent QT-prolonging medications, or high cardiovascular disease risk. 2
• A Tennessee Medicaid cohort showed increased cardiovascular deaths (HR 2.88; 95% CI 1.79–4.63) with 5-day azithromycin therapy, most pronounced in high-risk patients. 2
• In elderly patients (especially ≥75 years, women, or those with cardiovascular disease): Obtain baseline ECG; repeat 2–4 hours after first dose in high-risk patients; discontinue if QTc exceeds 500 ms or rises >60 ms from baseline. 2
• Avoid concurrent use with amiodarone, Class IA/III antiarrhythmics, certain antipsychotics, or fluoroquinolones unless cardiology consultation is obtained. 2
• Correct baseline potassium and magnesium levels before initiating therapy. 2

Common Adverse Effects

• Gastrointestinal symptoms (abdominal pain, diarrhea, nausea, vomiting) are the most common adverse effects, occurring less frequently than with erythromycin. 2, 4
• Headache and dizziness are generally mild to moderate in severity. 2

Resistance Concerns

• Never use azithromycin as monotherapy for gonorrhea—always combine with ceftriaxone due to widespread resistance. 2
• For macrolide-resistant Mycoplasma genitalium, switch to moxifloxacin 400 mg daily for 7–14 days. 2
• Long-term macrolide use increases antimicrobial resistance, though clinical impact remains uncertain. 2

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Common Pitfalls to Avoid

• Do not use the 1 gram single dose for streptococcal pharyngitis—this indication requires the standard 5-day regimen or higher-dose regimens (12 mg/kg/day for 5 days in children). 2
• Do not assume all liquid formulations have the same concentration—verify mg/mL strength before calculating dose. 2
• Do not prescribe azithromycin for gonorrhea without ceftriaxone—monotherapy is contraindicated. 2
• Do not initiate long-term therapy without baseline ECG, liver function tests, and negative NTM culture. 2, 4
• For sexually transmitted infections, patients should abstain from sexual intercourse for 7 days after completing therapy. 4