Can I give azithromycin (AZI) with amoxicillin?

From the Guidelines

It is recommended to use azithromycin and amoxicillin together only in specific cases, such as for outpatient adults with comorbidities, where combination therapy with a macrolide and a beta-lactam antibiotic is recommended 1. When considering the use of azithromycin and amoxicillin together, it's essential to weigh the potential benefits and risks. Both medications are antibiotics, but they work in different ways and have different spectrums of activity. Amoxicillin is a penicillin-type antibiotic effective against many gram-positive and some gram-negative bacteria, while azithromycin is a macrolide antibiotic with a somewhat different spectrum of activity 1.

Key Considerations

• The use of azithromycin and amoxicillin together may increase the risk of side effects, such as digestive issues and allergic reactions 1.
• Combination therapy with a macrolide and a beta-lactam antibiotic is recommended for outpatient adults with comorbidities, such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia 1.
• The American Thoracic Society and Infectious Diseases Society of America recommend combination therapy with amoxicillin/clavulanate and a macrolide, such as azithromycin, for certain cases of community-acquired pneumonia 1.

Specific Recommendations

• For healthy outpatient adults without comorbidities, monotherapy with amoxicillin or doxycycline is recommended 1.
• For outpatient adults with comorbidities, combination therapy with amoxicillin/clavulanate and a macrolide, such as azithromycin, is recommended 1.
• The dosage and duration of treatment should be individualized based on the specific infection, medical history, and other factors 1.

From the FDA Drug Label

For the 553 patients who were evaluated for clinical efficacy, the clinical success rate (i. e., cure plus improvement) at the Day 11 visit was 88% for azithromycin and 88% for the control agent (amoxicillin/clavulanate potassium). In a double-blind, controlled, randomized clinical study of acute otitis media in pediatric patients from 6 months to 12 years of age, azithromycin (10 mg/kg per day for 3 days) was compared to amoxicillin/clavulanate potassium (7:1) in divided doses q12h for 10 days A double blind, controlled, randomized trial was performed at nine clinical centers Pediatric patients from 6 months to 12 years of age were randomized 1:1 to treatment with either azithromycin (given at 30 mg/kg as a single dose on Day 1) or amoxicillin/clavulanate potassium (7:1), divided q12h for 10 days.

There is no direct information in the provided drug labels that supports the use of azithromycin with amoxicillin. The studies mentioned compare azithromycin to amoxicillin/clavulanate, not the combination of azithromycin with amoxicillin. The FDA drug label does not answer the question.

From the Research

Combination of Azithromycin and Amoxicillin

• The combination of azithromycin (AZI) and amoxicillin has been studied in various clinical settings, including the treatment of community-acquired pneumonia, acute sinusitis, and erythema migrans 2, 3, 4.
• A study published in the Journal of Chemotherapy found that azithromycin 1g once daily for 3 days was at least as effective as amoxicillin-clavulanate 875/125 mg twice daily for 7 days in the treatment of adult patients with community-acquired pneumonia 2.
• Another study published in the American Journal of Otolaryngology found that a 3-day course of azithromycin was as effective and well-tolerated as a 10-day course of amoxicillin/clavulanic acid in the treatment of acute sinusitis in adults 3.
• A study published in The Pediatric Infectious Disease Journal found that azithromycin was equally effective as amoxicillin in children with solitary erythema migrans 4.
• A retrospective study published in the Journal of Obstetrics and Gynaecology found that women who were prescribed amoxicillin and azithromycin for preterm premature rupture of the membranes had a longer median latency to delivery compared to those prescribed erythromycin monotherapy 5.

Safety and Tolerability

• The combination of azithromycin and amoxicillin has been found to be well-tolerated, with gastrointestinal symptoms being the most commonly reported adverse events 2, 3, 4.
• A study published in Drugs found that azithromycin had a similar safety profile to other macrolides, with gastrointestinal disturbances being the most common adverse events 6.

Clinical Implications

• The use of azithromycin and amoxicillin in combination may be considered in certain clinical settings, such as the treatment of community-acquired pneumonia or acute sinusitis, where the benefits of combination therapy outweigh the risks 2, 3.
• However, further studies are needed to determine the optimal dosing regimens and to fully evaluate the safety and efficacy of combination therapy in different patient populations 5.