Penicillin Allergy: What to Know

Penicillin is perhaps the most well-known member of a group of antibiotics called beta-lactams, which refers to a particular structure in their chemical makeup. The structure is also shared by semi-synthetic penicillin (amoxicillin), cephalosporins, and other antibiotics, such as imipenem. Penicillins and cephalosporins are the antibiotics most commonly used to treat common bacterial infections.

Penicillins and cephalosporins are also the most common causes of drug allergy. About 10% of Americans report having an allergy to penicillin or a related antibiotic. In fact, though, the number of people who have a true penicillin allergy is much lower.

While penicillin allergy most frequently occurs in young adults, reactions can occur at any age. Women appear to be at higher risk than men. Reactions to penicillin may include hives, below-the-skin swelling, and asthma symptoms, as well as non-allergic symptoms such as serum sickness, certain forms of anemia, and rashes. In some cases a life-threatening reaction called anaphylaxis can occur.

This article will discuss how a true penicillin allergy is diagnosed, possible reactions, and what to do if you are allergic to penicillin but still need antibiotic treatment.

Mother Giving Penicillin Medicine to His Sick baby Boy
Onfokus / Getty Images

Family of Penicillin Antibiotics

The family of penicillin antibiotics includes:

  • Penicillin VK
  • Penicillin G
  • Dicloxacillin
  • Oxacillin
  • Nafcillin
  • Amoxicillin
  • Ampicillin
  • Augmentin (amoxicillin/clavulanate)
  • Unasyn (ampicillin/sulbactam)
  • Zosyn (pipercillin/tazobactam)

The family of cephalosporins includes:

  • Keflex (cephalexin)
  • Ancef (cefazolin)
  • Ceftin (cefuroxime)
  • Cefzil (cefprozil)
  • Omnicef (cefdinir)
  • Vantin (cefpodoxime)
  • Many other antibiotics beginning with “cef-“ or “ceph-“

How Is a Penicillin Allergy Diagnosed?

While many people report having an allergy to penicillin, less than 5% of the population actually has a true allergy to the drug. Some patients who have been labeled as "penicillin allergic" may in fact have experienced non-allergic reactions or side effects to the drug, such as gastrointestinal upset, headache, or nausea, and mistaken it for a true allergy. Furthermore, most people lose their penicillin allergy over time—even patients with a history of severe reactions, such as anaphylaxis.

An oral challenge, which involves administering small doses of the drug under medical supervision, is the best, most effective method for diagnosing a penicillin allergy. However, healthcare providers often perform skin testing first to avoid the risk of allergic reaction, particularly among those with a medical history of penicillin sensitivity.

An extract called Pre-Pen (benzylpenicilloyl polylysine injection) is the only FDA-approved skin test for the diagnosis of penicillin allergy. Penicillin skin testing identifies the presence or absence of IgE antibodies to this injection and identifies the majority of cases of true clinical penicillin allergy. This information will allow a healthcare provider to decide if penicillin or an alternative antibiotic should be given.

Testing usually takes about an hour to complete. The skin is injected with weak solutions of various preparations of penicillin and observed for a reaction. This may cause itching, although it is not painful.

A positive skin reaction is indicated by an itchy, red bump that forms within about 30 minutes. People with a positive test are usually advised to continue avoiding penicillins. Not every test that is positive represents a true penicillin allergy, however; there are false positives in penicillin skin testing.

It is important to identify who is truly allergic to penicillin and who is not, because patients who are labeled penicillin-allergic are more likely to receive broad-spectrum antibiotics. These are powerful drugs which kill both good and bad bacteria and have more side effects than more specialized antibiotics. People labeled as allergic to penicillin are also more likely to develop certain difficult-to-treat, resistant infections and require longer stays in hospitals, compared with patients who do not report a history of penicillin allergy.

How Is a Penicillin Allergy Treated?

Other than treating drug allergy symptoms, the main treatment for penicillin allergy is avoidance of future use of penicillin and related antibiotics. However, if penicillin is required, people with penicillin allergy can also be admitted to a hospital for a desensitization procedure.


Most patients with true penicillin allergy can tolerate cephalosporins, but there are some cases where both penicillin antibiotics and cephalosporins need to be avoided. Cephalosporins can cause allergic reactions in approximately 5% to 10% of people with a penicillin allergy, although rates may be higher in some people. Allergic reactions to cephalosporins can be severe and even life-threatening.

If you have a penicillin allergy, you should talk with your healthcare provider about whether you also need to avoid cephalosporins.

Similarly, ask your allergist about whether it is safe to take imipenem, another beta-lactam antibiotic, if you have a history of penicillin allergy. Most patients with a true penicillin allergy will be able to tolerate imipenem, but depending on your history, a medically supervised graded-dose challenge or other precautions may be recommended.

People with penicillin allergy are also at higher risk of developing an allergy to a different class of drugs called sulfa drugs, which include antibiotics as well as other medications.

Managing a Penicillin Allergy When Medically Necessary

There may be certain cases when a person with a penicillin allergy needs penicillin or cephalosporin to manage an infection. In these situations, an allergist can perform skin testing and, if the test is negative, can try an oral challenge.

A desensitization process can also be performed in a hospital. This entails giving small amounts of the drug and gradually increasing doses over several hours until the person can tolerate a full therapeutic dose.

Keep in mind that desensitization is temporary. It only works if you are taking the drug at least every day. Once you stop, you'll need to repeat the desensitization process.


Penicillin is one of the most commonly prescribed antibiotics. It is also the most common cause of drug allergy, along with comparable antibiotics such as cephalosporins. However, not everyone who reacts to penicillin has a true allergy.

A skin test can sometimes diagnose a true allergy, but a healthcare provider must do an oral challenge for an accurate diagnosis. There is no treatment for a penicillin allergy other than to avoid taking the medication.

A Word From Verywell

If you have any concerns about whether you are allergic to penicillin or a related drug, ask your healthcare provider about the possibility of being tested.

Frequently Asked Questions

  • What should you avoid if you're allergic to penicillin?

    If you are truly allergic to penicillin, you should avoid taking the drug. In some cases, you may need to avoid antibiotics in the same class, including cephalosporins and imipenem.

  • Can you outgrow a penicillin allergy?

    Yes, many people lose their allergy to penicillin as they age. However, it is unclear whether it was a true allergy in the first place or just a reaction from being sick that coincided with taking penicillin.

  • How can you tell if you're allergic to penicillin?

    If you have had a reaction after taking penicillin, including hives, asthma, or, in the worst case, symptoms anaphylaxis, you are probably allergic. However, only an allergist/immunologist can make an actual diagnosis.

6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. American Academy of Allergy, Asthma & Immunology. Penicillin allergy FAQ.

  2. Penicillin allergy-getting the label right. Drug Ther Bull. 2017;55(3):33-36. doi:10.1136/dtb.2017.3.0463

  3. Up to Date. Patient Education: Allergy to penicillin and related antibiotics (Beyond the Basics).

  4. National Institutes of Health. LiverTox Drug Record: Penicillin G and V.

  5. Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and Management of Penicillin Allergy: A Review. JAMA. 2019;321(2):188-199. doi:10.1001/jama.2018.19283

  6. Centers for Disease Control. Management of persons who have a history of penicillin allergy.

By Daniel More, MD
Daniel More, MD, is a board-certified allergist and clinical immunologist. He is an assistant clinical professor at the University of California, San Francisco School of Medicine and currently practices at Central Coast Allergy and Asthma in Salinas, California.