Can you have an allergic reaction to penicillin (antibiotic) the first time you take it?

From the Guidelines

Yes, you can have an allergic reaction to penicillin the first time you take it, as your immune system may have previously been exposed to substances with similar structures to penicillin, creating antibodies that cross-react with penicillin 1. This can trigger an allergic reaction when you take penicillin for the first time, with symptoms ranging from mild (rash, hives, itching) to severe (anaphylaxis with breathing difficulties, swelling, and drop in blood pressure) 1.

Key Points to Consider

• Allergic reactions to penicillin can be immediate, accelerated, or late, depending on the timing following contact with the compound 1.
• The mechanism for anaphylaxis is IgE-mediated, with risk factors including age, presence of allergic diseases, and multiple short courses of penicillin 1.
• Testing for penicillin allergy could be an approach to optimize antibiotic selection and improve patient safety by preventing allergic reactions, although routine testing is not usually recommended due to the very low rate of anaphylaxis 1.
• Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is important to improve antimicrobial stewardship practices worldwide, and can be done through oral administration of a low-dose penicillin in low-risk penicillin allergy patients or by clinical history taking alone 1.

Recommendations

• If you experience any symptoms after taking penicillin or any antibiotic, seek medical attention immediately 1.
• Always inform healthcare providers about any previous allergic reactions to medications 1.
• If you have a confirmed penicillin allergy, you should wear a medical alert bracelet and avoid all penicillin-class antibiotics including amoxicillin, ampicillin, and others unless cleared by an allergist through proper testing 1.

From the FDA Drug Label

Although the incidence of reactions to oral penicillins has been reported with much less frequency than following parenteral therapy, it should be remembered that all degrees of hypersensitivity, including fatal anaphylaxis, have been reported with oral penicillin The hypersensitivity reactions reported are skin eruptions (maculopapular to exfoliative dermatitis), urticaria and other serum sickness-like reactions, laryngeal edema and anaphylaxis.

Yes, you can have an allergic reaction to penicillin the first time you take it. The drug label reports that hypersensitivity reactions, including anaphylaxis, have been reported with oral penicillin, and it does not specify that previous exposure is required for these reactions to occur 2. Key points to consider include:

• Hypersensitivity reactions can be severe and potentially life-threatening
• Anaphylaxis is a possible reaction to penicillin, even with the first dose
• Skin eruptions, urticaria, and laryngeal edema are also possible hypersensitivity reactions to penicillin

From the Research

Allergic Reactions to Penicillin

• Allergic reactions to penicillin can occur, but clinically significant IgE-mediated or T lymphocyte-mediated penicillin hypersensitivity is uncommon, affecting less than 5% of the population 3.
• The rate of IgE-mediated penicillin allergies is decreasing, potentially due to decreased use of parenteral penicillins and rare severe anaphylactic reactions to oral amoxicillin 3.
• IgE-mediated penicillin allergy can wane over time, with 80% of patients becoming tolerant after a decade 3.

First-Time Allergic Reactions

• While most patients who report a positive history of a prior reaction to penicillin are not found to be allergic upon skin testing, it is possible for an allergic reaction to occur the first time penicillin is taken 4.
• Patients with a negative skin test to both major and minor determinants may generally be given penicillin, with a statistical risk of developing an allergic reaction similar to that observed in the general population 4.
• A graded challenge may be used in cases where the degree of suspicion is low, an allergic etiology is unproven, or there is a negative skin test 4.

Diagnosis and Management

• Penicillin allergy can occur via any of the 4 types of Gel-Coombs hypersensitivity reactions, producing distinct clinical histories and physical examination findings 5.
• Treatments include penicillin discontinuation, and depending on the type of reaction, epinephrine, antihistamines, and/or glucocorticoids 5.
• Penicillin testing includes skin testing, patch testing, and graded challenge, with the selection of the type of testing depending on the clinical setting, equipment availability, and type of hypersensitivity reaction 5.

Proactive Management

• Proactive evaluations of antibiotic allergies, particularly penicillin allergies, have been recommended by various specialty societies 6.
• The vast majority of patients with a penicillin allergy label are not allergic; however, this label results in increased morbidities and mortality 6.
• A variety of penicillin delabeling strategies can be used in both the outpatient and the inpatient settings, including direct penicillin challenge in patients at low risk 6.