Is cefdinir (Omnicef) safe to prescribe to a patient with a history of rash due to penicillin (Penicillin) allergy?

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Last updated: April 22, 2025View editorial policy

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From the Guidelines

Cefdinir can be considered for a patient with a penicillin allergy manifesting as a rash, but with caution and careful monitoring, as the cross-reactivity between penicillins and cephalosporins is estimated to be around 2-5%. The risk of cross-reactivity is higher with first-generation cephalosporins and lower with third-generation ones like cefdinir 1. For patients with mild penicillin allergies, cefdinir might be used, but for those with severe reactions, it should be avoided entirely. Alternative antibiotic classes with no cross-reactivity, such as macrolides (azithromycin, clarithromycin), fluoroquinolones, or tetracyclines, would be safer options depending on the infection being treated 1.

Key Considerations

  • The chemical structure of the cephalosporin determines the risk of cross-reactivity between specific agents 1.
  • Cefdinir, a third-generation cephalosporin, has a different chemical structure than penicillin and is less likely to cause cross-reactivity 1.
  • Skin testing or graded challenge may be considered to assess the patient's risk of reaction, especially for those with a history of severe penicillin allergy 1.

Recommendations

  • Carefully evaluate the patient's allergy history and consider alternative antibiotics with no cross-reactivity if possible.
  • If cefdinir is deemed necessary, monitor the patient closely for signs of an allergic reaction.
  • Consider consulting with an allergist about possible skin testing or graded challenge to assess the patient's risk of reaction.

From the FDA Drug Label

WARNINGS BEFORE THERAPY WITH CEFDINIR IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFDINIR, OTHER CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS IF CEFDINIR IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG β-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY.

Cefdinir is not absolutely contraindicated in patients who get a rash with penicillin, but caution should be exercised due to the possibility of cross-hypersensitivity among β-lactam antibiotics, which may occur in up to 10% of patients with a history of penicillin allergy 2. Careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cefdinir, other cephalosporins, penicillins, or other drugs.

From the Research

Cefdinir and Penicillin Allergy

  • Cefdinir is a third-generation cephalosporin, and its use in patients with a penicillin allergy is considered to be relatively safe 3, 4.
  • The overall cross-reactivity rate between penicillins and cephalosporins is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 3.
  • Third- or fourth-generation cephalosporins, such as cefdinir, or cephalosporins with dissimilar side chains than the offending penicillin, carry a negligible risk of cross allergy 3.
  • A study published in 2006 found that cefprozil, cefuroxime, cefpodoxime, ceftazidime, and ceftriaxone do not increase the risk of an allergic reaction in patients with penicillin allergy, but it did not specifically mention cefdinir 4.
  • However, it is essential to note that cefdinir is a third-generation cephalosporin, and its safety in patients with penicillin allergy is supported by the fact that cross-reactivity between penicillin and other beta-lactams is less common than previously thought 5, 6.

Key Considerations

  • The risk of cross-reactivity between penicillins and cephalosporins is lower than previously reported 3, 5.
  • Patients labeled as 'penicillin-allergic' may be able to tolerate penicillin after undergoing a complete evaluation by a board-certified allergist, including skin testing 5.
  • Mislabeling patients with penicillin allergy can lead to a higher utilization of second-line antimicrobial agents, potentially increasing costs and resistance 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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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