Dosing Regimen for Amoxicillin-Clavulanate and Azithromycin
For adults requiring combination therapy with amoxicillin-clavulanate plus azithromycin, the recommended dosing is amoxicillin-clavulanate 875/125 mg orally twice daily and azithromycin 500 mg orally on day 1 followed by 250 mg daily for days 2-5.
Amoxicillin-Clavulanate Dosing
Adult Dosing:
- Standard dosing: 875/125 mg orally twice daily (every 12 hours)
- Duration typically 7-10 days depending on infection type
- Total daily dose: 1750 mg amoxicillin component
The twice-daily (every 12 hours) dosing of amoxicillin-clavulanate 875/125 mg has been shown to be as effective as the traditional three-times-daily (every 8 hours) regimen of 500/125 mg 1. This improved dosing schedule offers better patient compliance while maintaining equivalent clinical efficacy.
Administration Guidelines:
- Take with food to reduce gastrointestinal side effects
- Complete the entire course as prescribed
- Space doses evenly (approximately 12 hours apart)
Azithromycin Dosing
Adult Dosing:
- Day 1: 500 mg orally as a single dose
- Days 2-5: 250 mg orally once daily
- Total course: 5 days (1.5 g total)
Azithromycin's pharmacokinetic profile allows for once-daily dosing with extended tissue persistence, making it effective even with a short 5-day course 2.
Administration Guidelines:
- Can be taken with or without food
- Take at least 1 hour before or 2 hours after antacids containing aluminum or magnesium
- Take the full course even if symptoms improve before completion
Clinical Evidence Supporting This Regimen
Research has demonstrated that azithromycin 1g once daily for 3 days is at least as effective as amoxicillin-clavulanate 875/125 mg twice daily for 7 days in treating community-acquired pneumonia, with clinical success rates of 92.6% and 93.1% respectively 2.
Similarly, studies have shown that amoxicillin-clavulanate 875/125 mg given every 12 hours is as effective as the every-8-hours regimen (500/125 mg) for treating lower respiratory tract infections, with comparable clinical success rates of 93% and 94% respectively 1.
Important Considerations
Potential Side Effects:
- Amoxicillin-clavulanate: Diarrhea (most common), nausea, vomiting, rash
- Azithromycin: Gastrointestinal symptoms, potential for QT interval prolongation
Drug Interactions:
- Azithromycin may interact with medications that prolong QT interval
- Both antibiotics may reduce effectiveness of oral contraceptives
Special Populations:
- Renal impairment: Dose adjustment may be required for amoxicillin-clavulanate
- Hepatic impairment: Use azithromycin with caution
Clinical Pearls
The twice-daily dosing of amoxicillin-clavulanate has shown fewer reports of moderate to severe diarrhea compared to three-times-daily dosing 1.
Azithromycin's shorter 5-day course may improve patient adherence compared to longer antibiotic regimens.
When using this combination therapy, monitor for overlapping side effects, particularly gastrointestinal symptoms.
Taking amoxicillin-clavulanate with food significantly reduces gastrointestinal side effects without compromising efficacy.
The combination of these antibiotics provides coverage against both typical bacterial pathogens (with amoxicillin-clavulanate) and atypical pathogens (with azithromycin), making it appropriate for empiric treatment of respiratory infections where the causative organism is unknown 3.