From the FDA Drug Label
As with other penicillins, it may be expected that untoward reactions will be essentially limited to sensitivity phenomena. They are more likely to occur in individuals who have previously demonstrated hypersensitivity to penicillin and in those with a history of allergy, asthma, hay fever or urticaria A history of a previous hypersensitivity reaction to any of the penicillins is a contraindication.
Cross-reactivity between ampicillin and penicillin is likely, as individuals with a history of hypersensitivity to penicillin are more likely to experience adverse reactions to ampicillin.
- Hypersensitivity reactions such as anaphylaxis, skin rash, and urticaria have been reported with ampicillin use.
- A history of previous hypersensitivity reaction to any of the penicillins, including penicillin, is a contraindication for ampicillin use 1 1.
From the Research
Patients with a penicillin allergy should avoid ampicillin due to high cross-reactivity between these antibiotics, with approximately 90-100% cross-reactivity, as they share the same beta-lactam ring structure 2. Ampicillin is a semi-synthetic penicillin, and this high cross-reactivity means that if you are allergic to penicillin, you have a very high risk of experiencing a similar allergic reaction to ampicillin. The severity of the reaction depends on the nature of the original penicillin allergy, ranging from mild rashes to potentially life-threatening anaphylaxis. Some key points to consider include:
- The overall cross-reactivity rate between penicillins and cephalosporins is lower than previously reported, though there is a strong association between amoxicillin and ampicillin with first- and second-generation cephalosporins that share a similar R1 side chain 3.
- For patients with confirmed penicillin allergies who require antibiotic treatment, alternative non-beta-lactam antibiotics such as macrolides (azithromycin, clarithromycin), fluoroquinolones (ciprofloxacin, levofloxacin), or tetracyclines (doxycycline) should be considered.
- In cases where a beta-lactam is strongly indicated, penicillin allergy testing or desensitization protocols may be appropriate options under specialist supervision 4, 5.
- Always inform all healthcare providers about any penicillin allergy to ensure safe medication prescribing. It's also important to note that penicillin allergies are not always lifelong, and approximately 50% are lost over five years 5. Additionally, a reaction to penicillin during a childhood infection is unlikely to be a true allergy, and only 1–2% of patients with a confirmed penicillin allergy have an allergy to cephalosporins 5. Pharmacists play an essential role in inquiring about patient-specific reactions to presumed medication allergies and developing a further assessment plan, if needed, to determine if the medication allergy is real 6.