What is the recommended dose of azithromycin (Zithromax) for an adult patient with normal renal function and no history of QT prolongation?

Azithromycin Dosing for Adults with Normal Renal Function

For an adult patient with normal renal function and no QT prolongation history, the standard azithromycin dose is 500 mg on day 1, followed by 250 mg once daily on days 2-5 (the "Z-pack" regimen), or a single 1 gram dose for specific indications like chlamydial infections. 1, 2

Standard Dosing Regimens by Indication

Respiratory Tract Infections

• Standard 5-day course: 500 mg orally on day 1, then 250 mg once daily on days 2-5 1, 2
• Community-acquired pneumonia (hospitalized, non-ICU): 500 mg IV daily for 2-5 days, followed by oral 500 mg daily to complete 7-10 days total 1
• This regimen maintains therapeutic tissue concentrations at infection sites for several days after the last dose due to azithromycin's prolonged tissue half-life of 68 hours 2

Sexually Transmitted Infections

• Non-gonococcal urethritis/cervicitis (chlamydia): Single 1 gram oral dose 1
• This single-dose regimen provides therapeutic tissue concentrations in urogenital tissues for approximately 10 days and has the critical advantage of directly observed therapy, ensuring compliance 1
• Never use azithromycin as monotherapy for gonorrhea due to widespread resistance; always combine with ceftriaxone if gonococcal infection is suspected 1

Chronic Prophylactic Therapy

• Bronchiectasis with ≥3 exacerbations/year: 500 mg three times weekly (strongest evidence) or 250 mg daily 1
• Requires minimum 6-month duration to demonstrate benefit in exacerbation reduction 1
• Asthma with frequent exacerbations: Same dosing as bronchiectasis (500 mg three times weekly or 250 mg daily) for 6-12 months 1

Other Specific Indications

• Cat scratch disease: 500 mg on day 1, then 250 mg daily for 4 additional days 1
• Disseminated MAC disease in AIDS: 250 mg daily with ethambutol, with or without rifabutin 1
• MAC prophylaxis in AIDS (CD4 <50 cells/μL): 1,200 mg once weekly 1
• Early localized Lyme disease (if intolerant to first-line agents): 500 mg daily for 7-10 days with close observation 1

Critical Safety Considerations

QT Prolongation Risk

• Obtain baseline ECG before long-term therapy, with contraindication if QTc >450 ms (men) or >470 ms (women) 1
• Azithromycin is listed among drugs that can cause QT prolongation and should be avoided in patients with existing QT prolongation or those taking other QT-prolonging medications 3
• Exercise particular caution in elderly patients with cardiac risk factors 4

Renal Function Considerations

• No dose adjustment needed for normal renal function (GFR >80 mL/min) 2
• In mild to moderate renal impairment (GFR 10-80 mL/min), mean Cmax and AUC increase by only 5.1% and 4.2%, respectively—clinically insignificant 2
• Severe renal impairment (GFR <10 mL/min): Cmax increases 61% and AUC increases 35%, but no formal dose adjustment is typically recommended 2, 5
• Standard doses are generally used in clinical practice for patients with normal to moderate renal dysfunction 1

Hepatic Function

• Use with caution and increase monitoring if underlying liver disease is present 1
• Measure baseline liver function tests before long-term therapy 1

Administration and Drug Interactions

Timing and Food Effects

• Food decreases bioavailability by approximately 50% when azithromycin capsules are taken with meals 2, 6
• For optimal absorption, administer on an empty stomach when possible
• Aluminum or magnesium-containing antacids reduce Cmax by 24% but do not affect overall AUC; separate administration if possible 1, 4, 2

Common Adverse Effects

• Gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea) are the most common, but less frequent than with erythromycin 1, 4, 6
• Dizziness and headache may occur 4
• Patients should be counseled about these expected side effects 4

Monitoring for Long-Term Therapy

Baseline Assessment

• ECG to assess QTc interval 1
• Liver function tests 1
• Ensure at least one negative respiratory nontuberculous mycobacteria (NTM) culture before starting long-term macrolides to minimize NTM infection risk 1

Ongoing Monitoring

• Review patients 6-monthly with assessment of efficacy, toxicity, and continuing need 1
• Regular monitoring of sputum culture and sensitivity, though in vitro resistance may not affect clinical efficacy 1

Clinical Pearls

• Extensive tissue distribution: Tissue concentrations exceed serum concentrations by up to 100-fold, with particularly high concentrations in lung, tonsil, prostate, and lymph nodes 2, 7
• Prolonged tissue half-life: The terminal elimination half-life of 68 hours allows for once-daily dosing and continued antimicrobial activity for several days after the last dose 2, 7
• Single-dose regimens maximize compliance: For sexually transmitted infections, the 1 gram single dose ensures adherence and allows for directly observed therapy 1
• Long-term use increases antimicrobial resistance, though the clinical impact remains uncertain 1
• Patients treated for STIs should abstain from sexual intercourse for 7 days after completing therapy to prevent transmission 1