Are clarithromycin and co-trimoxazole (trimethoprim/sulfamethoxazole) safe in patients with a penicillin allergy?

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Last updated: April 19, 2025View editorial policy

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From the Guidelines

Yes, clarithromycin and co-trimoxazole (not contrixazole) are generally safe for patients with penicillin allergies. These medications belong to different antibiotic classes than penicillins and do not typically cause cross-reactivity in penicillin-allergic patients. Clarithromycin is a macrolide antibiotic, while co-trimoxazole is a combination of trimethoprim and sulfamethoxazole. The chemical structures of these medications differ significantly from penicillins, which is why allergic reactions to penicillins do not predict allergic reactions to these alternatives. However, any patient can develop an independent allergy to any medication. When prescribing these medications to penicillin-allergic patients, standard dosing can be used: for clarithromycin, typically 250-500 mg twice daily, and for co-trimoxazole, one double-strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) twice daily for most infections. It's essential to consider the side effect profiles and contraindications of these medications, as they can impact patient outcomes. According to the most recent guideline on antibiotic policy 1, there is no specific contraindication for using clarithromycin or co-trimoxazole in patients with penicillin allergies.

Some key points to consider when prescribing these medications include:

  • Clarithromycin is effective against a range of bacterial infections, including those caused by Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae 1.
  • Co-trimoxazole is effective against a range of bacterial infections, including those caused by Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli 1.
  • Both medications can cause gastrointestinal side effects, such as nausea and diarrhea, and can interact with other medications, such as warfarin and phenytoin.
  • Patients with a history of allergic reactions to sulfa medications should be cautious when taking co-trimoxazole, as it contains sulfamethoxazole.

In terms of morbidity, mortality, and quality of life, the use of clarithromycin and co-trimoxazole in patients with penicillin allergies can help to reduce the risk of complications and improve treatment outcomes. For example, a study on the treatment of community-acquired pneumonia found that the use of macrolide antibiotics, such as clarithromycin, was associated with improved outcomes and reduced mortality 1. Similarly, the use of co-trimoxazole has been shown to be effective in reducing the risk of complications and improving treatment outcomes in patients with skin and soft tissue infections 1.

Overall, the use of clarithromycin and co-trimoxazole in patients with penicillin allergies is a safe and effective treatment option, as long as the potential side effects and contraindications are carefully considered.

From the Research

Safety of Clarithromycin and Cotrimoxazole in Penicillin Allergy

  • Clarithromycin and cotrimoxazole are not β-lactam antibiotics, which are the class of antibiotics that include penicillin 2, 3.
  • The cross-reactivity between penicillin and other antibiotics is generally low, especially for non-β-lactam antibiotics like clarithromycin and cotrimoxazole 4, 5.
  • There is no significant evidence to suggest that clarithromycin and cotrimoxazole are contraindicated in patients with a penicillin allergy 2, 3, 6.
  • However, it is essential to note that patients with a penicillin allergy may still experience allergic reactions to other medications, including clarithromycin and cotrimoxazole, although this is not directly related to the penicillin allergy 2, 5.

Considerations for Antibiotic Selection

  • The selection of antibiotics in patients with a penicillin allergy should be based on the specific clinical situation and the suspected or confirmed pathogen 4, 3.
  • Clinicians should consider the patient's medical history, including any previous allergic reactions, and the potential for cross-reactivity with other antibiotics 2, 5.
  • In general, clarithromycin and cotrimoxazole can be considered as alternative antibiotics in patients with a penicillin allergy, but the decision should be made on a case-by-case basis 3, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Penicillin Allergy: Mechanisms, Diagnosis, and Management.

The Medical clinics of North America, 2024

Research

Understanding Penicillin Allergy, Cross-reactivity, and Antibiotic Selection in the Preoperative Setting.

The Journal of the American Academy of Orthopaedic Surgeons, 2022

Research

Penicillin allergy: A practical guide for clinicians.

Cleveland Clinic journal of medicine, 2015

Research

The Basics of Penicillin Allergy: What A Clinician Should Know.

Pharmacy (Basel, Switzerland), 2019

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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