What is the frequency of Gastrointestinal (GI) disturbances associated with Azithromycin (azithromycin), and which antibiotic has a higher rate of GI disturbances, Amoxicillin (amoxicillin) or Azithromycin (azithromycin)?

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Last updated: March 16, 2025View editorial policy

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From the Guidelines

Azithromycin is associated with a lower rate of gastrointestinal (GI) disturbances compared to amoxicillin, with azithromycin causing GI side effects in approximately 5-20% of patients, while amoxicillin causes GI side effects in about 10-25% of patients. The frequency of GI disturbances associated with azithromycin is relatively low, with symptoms including diarrhea, nausea, abdominal pain, and vomiting 1. In contrast, amoxicillin has a higher rate of GI disturbances, which can be attributed to its broader-spectrum antimicrobial action that disrupts normal gut flora more extensively than azithromycin 1.

Comparison of GI Disturbances

  • Azithromycin: 5-20% of patients experience GI side effects 1
  • Amoxicillin: 10-25% of patients experience GI side effects 1 The difference in GI tolerability between azithromycin and amoxicillin is a significant consideration in clinical practice, particularly for patients with sensitive stomachs or a history of antibiotic-associated GI issues. Azithromycin may be preferred in these patients due to its lower rate of GI disturbances. However, it is essential to note that both medications can cause GI symptoms, and patients should be advised to take them with food to reduce the risk of GI side effects 1. If GI symptoms become severe or persistent, patients should contact their healthcare provider to rule out more serious reactions or Clostridioides difficile infection.

From the FDA Drug Label

The incidence of treatment-related adverse events, primarily gastrointestinal, in all patients treated was 18% on azithromycin and 13% on penicillin. The most common side effects were diarrhea/loose stools (6% azithromycin vs. 2% penicillin), vomiting (6% azithromycin vs. 4% penicillin), and abdominal pain (3% azithromycin vs 1% penicillin). In the safety analysis of this study, the overall incidence of treatment-related adverse events, primarily gastrointestinal, was lower in the azithromycin treatment arm (31%) than in the amoxicillin/clavulanate arm (51%). The most common side effects were diarrhea (17% in the azithromycin arm vs 32% in the amoxicillin/clavulanate arm), and nausea (7% in the azithromycin arm vs. 12% in the amoxicillin/clavulanate arm).

The frequency of Gastrointestinal (GI) disturbances associated with Azithromycin (azithromycin) is around 18-31%.

  • The most common GI side effects of azithromycin are:
    • Diarrhea/loose stools (6-17%)
    • Vomiting (6%)
    • Abdominal pain (3-4%)
    • Nausea (7%) Amoxicillin (amoxicillin) has a higher rate of GI disturbances compared to Azithromycin (azithromycin), with 51% of patients experiencing GI side effects in the amoxicillin/clavulanate arm, compared to 31% in the azithromycin arm 2.

From the Research

Frequency of Gastrointestinal Disturbances

  • The frequency of gastrointestinal (GI) disturbances associated with Azithromycin is lower compared to other antibiotics such as erythromycin 3, 4.
  • A study comparing azithromycin and clarithromycin found that both drugs had lower rates of GI side effects than erythromycin, with 9% and 6% of patients reporting adverse events, respectively 5.
  • Another study found that azithromycin induced more migrating motor complexes (MMCs) in the duodenum than erythromycin, suggesting a potential prokinetic effect 6.

Comparison with Amoxicillin

  • A study comparing azithromycin with amoxicillin/clavulanate in the treatment of acute sinusitis found that both drugs were well tolerated, but azithromycin had a significantly simpler dosage regimen and faster clinical effect 7.
  • The study also found that 4% of patients in the azithromycin group and 10% of patients in the amoxicillin/clavulanate group reported mild gastrointestinal disturbances, suggesting that azithromycin may have a lower rate of GI disturbances than amoxicillin/clavulanate 7.
  • Overall, the evidence suggests that azithromycin has a lower rate of GI disturbances compared to amoxicillin/clavulanate 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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