Is there cross-reactivity between Erythromycin (a macrolide antibiotic) and Doxycycline (a tetracycline antibiotic)?

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Last updated: April 6, 2025View editorial policy

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From the Guidelines

There is no significant cross-reactivity between erythromycin and doxycycline, making doxycycline generally safe for patients with erythromycin allergies. These antibiotics belong to different structural classes - erythromycin is a macrolide while doxycycline is a tetracycline - with distinct chemical structures and mechanisms of action. Erythromycin works by binding to bacterial ribosomes at the 50S subunit, while doxycycline binds to the 30S ribosomal subunit. This structural difference means that an allergic reaction to one is unlikely to trigger a reaction to the other, as supported by the Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults 1.

Key points to consider:

  • Erythromycin and doxycycline have different mechanisms of action and chemical structures, reducing the likelihood of cross-reactivity.
  • The guidelines recommend doxycycline as a cost-effective alternative to macrolides like erythromycin for certain patients, indicating its safety and efficacy in patients who may have allergies to other classes of antibiotics.
  • When prescribing doxycycline to patients with a reported allergy to erythromycin, it is essential to characterize the nature of the reaction to better assess risk, but doxycycline would generally be considered a safe alternative.
  • Standard doxycycline dosing (typically 100mg twice daily for most infections) can be used without specific adjustments related to erythromycin allergy status, as per the guidelines 1.

In clinical practice, the primary concern is the patient's safety and the effectiveness of the treatment. Given the lack of significant cross-reactivity between erythromycin and doxycycline, doxycycline can be a viable option for patients with erythromycin allergies, considering the patient's overall health status and potential for other drug interactions or allergies.

From the Research

Erythromycin and Doxycycline Cross-Reactivity

  • There is limited information available on the cross-reactivity between erythromycin and doxycycline.
  • A study published in 1998 2 reported a case of a patient who developed generalized urticaria and tachycardia after administration of roxithromycin, and also had positive prick test reactions to erythromycin and clarithromycin, indicating cross-sensitization between these macrolides.
  • However, there is no direct evidence of cross-reactivity between erythromycin and doxycycline, which belongs to a different class of antibiotics (tetracyclines).
  • Other studies 3, 4, 5 discuss the properties and uses of macrolides, including erythromycin, azithromycin, and clarithromycin, but do not provide information on cross-reactivity with doxycycline.
  • A more recent study 6 reviews the classification, cross-reactivity, and collaboration related to antibiotic allergies, but does not specifically address the cross-reactivity between erythromycin and doxycycline.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Azithromycin and clarithromycin.

The Medical clinics of North America, 1995

Research

The new macrolides. Azithromycin and clarithromycin.

The Western journal of medicine, 1994

Research

The 3 Cs of Antibiotic Allergy-Classification, Cross-Reactivity, and Collaboration.

The journal of allergy and clinical immunology. In practice, 2017

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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