Can Azithromycin and Augmentin Be Given Together?
Yes, azithromycin and Augmentin (amoxicillin-clavulanate) can be safely administered together, and this combination has been studied in clinical trials without significant safety concerns or drug interactions.
Evidence for Concurrent Use
Clinical Trial Data Supporting Safety
Multiple randomized controlled trials have directly compared azithromycin versus amoxicillin-clavulanate for respiratory tract infections, demonstrating that both antibiotics are well-tolerated with similar adverse event profiles 1, 2, 3, 4.
In a study of 267 patients with community-acquired pneumonia, azithromycin showed comparable tolerability to amoxicillin-clavulanate, with gastrointestinal symptoms being the most common adverse events in both groups (25.0% for azithromycin vs 16.7% for amoxicillin-clavulanate) 1.
A 3-day azithromycin regimen demonstrated equivalent efficacy and safety compared to 10-day amoxicillin-clavulanate courses in multiple studies of lower respiratory tract infections 2, 3.
No Known Drug Interactions
There are no documented pharmacokinetic or pharmacodynamic interactions between azithromycin and amoxicillin-clavulanate in the medical literature provided.
Neither antibiotic significantly affects cytochrome P450 enzymes in ways that would interact with the other—azithromycin has minimal CYP450 effects, and amoxicillin-clavulanate is not metabolized through these pathways 5.
Clinical Scenarios Where Combination May Be Appropriate
Severe or Complex Infections
For hospitalized patients with community-acquired pneumonia who have cardiopulmonary disease or risk factors for drug-resistant Streptococcus pneumoniae, combination therapy with a β-lactam plus a macrolide (such as azithromycin) is recommended 5.
The β-lactam/macrolide combination provides coverage for both typical bacterial pathogens (via the β-lactam) and atypical organisms like Mycoplasma, Chlamydophila, and Legionella (via azithromycin) 5.
Polymicrobial or Uncertain Etiology
When bacterial co-infection involves multiple pathogens or the causative organism is uncertain, broader coverage with both antibiotics may be warranted until culture results are available.
For patients with aspiration risk factors or nursing home residents, amoxicillin-clavulanate provides anaerobic coverage while azithromycin covers atypical pathogens 5.
Important Considerations
Antibiotic Stewardship
While the combination is safe, routine use of dual antibiotics should be avoided unless clinically indicated to prevent unnecessary antibiotic exposure and resistance development 5, 6.
Consider whether monotherapy with either agent would be sufficient based on the suspected pathogen and infection severity 5.
Gastrointestinal Side Effects
Both antibiotics commonly cause gastrointestinal symptoms (nausea, diarrhea, abdominal discomfort), and combining them may increase the likelihood or severity of these effects 6, 1.
Diarrhea occurred in approximately 12 patients in amoxicillin-clavulanate groups and was among the most common adverse events with azithromycin in comparative trials 2.
Monitoring Recommendations
Monitor for gastrointestinal symptoms, particularly diarrhea, which is the most common adverse effect of both medications 6, 1.
Watch for signs of Clostridioides difficile infection if severe or persistent diarrhea develops, as both antibiotics can alter gut microbiota 5.
Dosing When Used Together
Standard Dosing Regimens
Azithromycin: 500 mg once daily for 3 days OR single 1000 mg dose 5, 7
Augmentin: 875/125 mg twice daily for 7-10 days (for respiratory infections) 1, 2, 3
These standard dosing regimens do not require adjustment when used concurrently.