What is the treatment for an allergic reaction to penicillin?

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From the Guidelines

The treatment for an allergic reaction to penicillin depends on the severity of the reaction, and immediate action should be taken to prevent morbidity, mortality, and improve quality of life. For mild reactions like hives or itching, immediately stop taking the penicillin and take an antihistamine such as diphenhydramine (Benadryl) 25-50mg every 4-6 hours or cetirizine (Zyrtec) 10mg daily 1. For more severe reactions involving breathing difficulties, throat swelling, or a significant drop in blood pressure (anaphylaxis), immediate emergency treatment is necessary, including an epinephrine injection (EpiPen 0.3mg for adults, 0.15mg for children), followed by emergency medical care 1. In the hospital setting, treatment may include oxygen, intravenous antihistamines like diphenhydramine, corticosteroids such as methylprednisolone, and continued monitoring. After any penicillin allergic reaction, it's crucial to inform all healthcare providers about this allergy, wear a medical alert bracelet, and avoid all penicillin-class antibiotics in the future. These reactions occur because the immune system mistakenly identifies penicillin as harmful, releasing chemicals that cause allergy symptoms, with IgE antibodies playing a key role in this process. Some key points to consider in the management of penicillin allergy include:

  • The prevalence of a penicillin allergy label is higher in individuals who actively use healthcare, in females, in hospitalized patients, and increases with increasing age 1
  • Less than 5% of individuals labeled with a penicillin allergy are confirmed, with appropriate testing, to have either a currently active acute onset IgE-mediated penicillin allergy or a clinically significant delayed onset T-cell-mediated penicillin hypersensitivity 1
  • Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is of importance to improve antimicrobial stewardship practices worldwide 1
  • A proactive effort should be made to delabel patients with reported penicillin allergy, if appropriate, as this can lead to improved antibiotic selection and decreased use of broad-spectrum antibiotics 1.

From the FDA Drug Label

Emergency treatment of allergic reactions (Type I), including anaphylaxis, which may result from allergic reactions to insect stings, biting insects, foods, drugs, sera, diagnostic testing substances and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. Antihistaminic For amelioration of allergic reactions to blood or plasma, in anaphylaxis as an adjunct to epinephrine and other standard measures after the acute symptoms have been controlled, and for other uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated.

The treatment for an allergic reaction to penicillin includes:

  • Epinephrine (IM) for emergency treatment of allergic reactions (Type I), including anaphylaxis 2
  • Diphenhydramine (IV) as an adjunct to epinephrine and other standard measures after the acute symptoms have been controlled, for amelioration of allergic reactions 3

From the Research

Treatment for Allergic Reaction to Penicillin

The treatment for an allergic reaction to penicillin depends on the type and severity of the reaction. According to 4, treatments include:

  • Penicillin discontinuation
  • Epinephrine
  • Antihistamines
  • Glucocorticoids

Diagnosis and Management

Diagnosis of penicillin allergy involves skin testing, patch testing, and graded challenge 4. The selection of the type of testing depends on the clinical setting, equipment availability, and type of hypersensitivity reaction.

Desensitization

Desensitization may be used in some cases where treatment with penicillins is essential 4, 5, 6. However, desensitization has limitations, and tolerance is not permanent 6.

Cross-Reactivity with Other Antibiotics

Most beta-lactams may be safely used in penicillin-allergic patients, with the possible exception of first-generation and second-generation cephalosporins 4. Newer generation cephalosporins have demonstrated less cross-reactivity to penicillin than earlier generation ones 6. Aztreonam is the only semisynthetic penicillin that may safely be used in penicillin-allergic patients 5.

Evaluation and Management of Penicillin Allergy

Evaluation of penicillin allergy is important to identify patients who can tolerate penicillin and to avoid the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance 7. Penicillin skin testing carries a negative predictive value that exceeds 95% and approaches 100% when combined with amoxicillin challenge 7. Direct amoxicillin challenge is appropriate for patients with low-risk allergy histories, while moderate-risk patients can be evaluated with penicillin skin testing 7.

Classification of Reactions

Clinical presentation is key in classifying reactions as either mediated by or not mediated by immunoglobulin E (IgE), and in determining which patients may benefit from penicillin skin testing, graded-dose challenge, or desensitization 8.

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

Penicillin anaphylaxis: a review of sensitization, treatment, and prevention.

Journal of the Association for Academic Minority Physicians : the official publication of the Association for Academic Minority Physicians, 1992

Research

Overview of penicillin allergy.

Clinical reviews in allergy & immunology, 2012

Research

Penicillin allergy: A practical guide for clinicians.

Cleveland Clinic journal of medicine, 2015

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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