What is the recommended dose of azithromycin for a typical adult patient with normal renal function?

Azithromycin Dosing for Adults with Normal Renal Function

For most common infections in adults with normal renal function, azithromycin is dosed as 500 mg on day 1, followed by 250 mg once daily on days 2-5 (the standard "Z-pack" regimen), or as a single 1 gram dose for specific indications like chlamydial infections. 1, 2

Standard Dosing Regimens by Indication

Respiratory Tract Infections

• Community-acquired pneumonia (non-severe): 500 mg once daily for 3 days total, or the traditional 5-day regimen (500 mg day 1, then 250 mg daily days 2-5) 1, 2
• Acute bacterial sinusitis: Single 2 gram dose of extended-release formulation, or standard 5-day regimen 3
• Severe community-acquired pneumonia (hospitalized): 500 mg IV daily for 2-5 days, followed by oral 500 mg daily to complete 7-10 days total 1

Sexually Transmitted Infections

• Non-gonococcal urethritis/cervicitis (chlamydia): Single 1 gram oral dose, which provides therapeutic tissue concentrations for approximately 10 days due to azithromycin's prolonged tissue half-life 1, 2
• Critical advantage: Single-dose regimen allows for directly observed therapy and eliminates compliance concerns in populations unlikely to return for follow-up 1

Skin and Soft Tissue Infections

• Uncomplicated skin infections: 500 mg once daily for 3 days 4

Chronic Respiratory Conditions (Long-term Prophylaxis)

• Bronchiectasis with ≥3 exacerbations per year: 500 mg three times weekly (strongest evidence) or 250 mg daily, requiring minimum 6-12 months to demonstrate benefit 1
• Asthma with frequent exacerbations: Same dosing as bronchiectasis 1

Mycobacterial Infections

• Disseminated MAC disease in AIDS: 250 mg daily with ethambutol, with or without rifabutin 1
• MAC prophylaxis in AIDS (CD4 <50): 1,200 mg once weekly 1

Other Indications

• Cat scratch disease (>45 kg): 500 mg day 1, then 250 mg daily for 4 additional days 1
• Babesiosis (with atovaquone): 500-1000 mg day 1, then 250 mg once daily thereafter 1
• Early localized Lyme disease (intolerant of first-line): 500 mg daily for 7-10 days 1

Administration Considerations

Food Effects

• Tablets: Food increases Cmax by 23% but does not affect AUC; can be taken with or without food 2
• Suspension: Food increases Cmax by 56% with unchanged AUC 2
• Practical recommendation: Administer without regard to meals for tablets, though taking with food may reduce gastrointestinal side effects 5

Drug Interactions

• Antacids (aluminum/magnesium): Reduce Cmax by 24% and absorption by up to 50%; avoid concurrent administration or separate by >2 hours 2, 5, 1
• Cimetidine: No effect on absorption 2

Renal Function Considerations

No dose adjustment is required for renal impairment, including severe renal dysfunction. The pharmacokinetics of azithromycin (AUC, volume of distribution, Cmax) are not significantly affected by renal insufficiency, as nonrenal clearance remains the primary elimination pathway. 6 Standard dosing should be maintained in patients with any degree of renal impairment. 7

Safety Monitoring and Precautions

Cardiac Considerations

• QTc prolongation risk: Obtain baseline ECG before initiating long-term therapy; contraindicated if QTc >450 ms (men) or >470 ms (women) 1
• Avoid in patients: Taking other QT-prolonging medications without careful risk assessment, particularly elderly patients with cardiac risk factors 1, 7

Laboratory Monitoring

• Long-term therapy: Measure baseline liver function tests 1
• Routine monitoring: Uric acid measurements are not needed 1

Common Adverse Effects

• Gastrointestinal: Diarrhea, abdominal pain, nausea, vomiting (generally mild to moderate and better tolerated than erythromycin) 1, 5
• Other: Dizziness, headache 7

Critical Clinical Pitfalls

Resistance Concerns

• Never use as monotherapy for gonorrhea: Widespread resistance exists; must combine with ceftriaxone if gonococcal infection suspected 1
• Long-term use: Increases antimicrobial resistance, though clinical impact remains uncertain 1

Special Populations

• Pregnancy: FDA Category B; single 1 gram dose is an alternative for chlamydial infections in pregnancy 1
• Hepatic impairment: Use with caution and increase monitoring 1

Compliance Optimization

• Dispense on-site when possible to maximize adherence 1
• For STIs: Patients should abstain from sexual intercourse for 7 days after completing therapy 1

Pharmacokinetic Rationale

The low plasma concentrations (Cmax ~0.4-0.5 mcg/mL after 500 mg dose) reflect extensive tissue distribution with an apparent volume of distribution of 31.1 L/kg. 2 Tissue concentrations exceed plasma levels by >100-fold in some tissues, with a terminal elimination half-life of 2-5 days, supporting once-daily dosing and short-course regimens. 2, 5, 8 The bioavailability is 37-38%, with primarily biliary excretion and only 6% urinary excretion. 2, 8