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Can you have a delayed allergic reaction to amoxicillin?

Hives and skin rashes may not appear right away if you’re allergic to amoxicillin
By | Jan. 10, 2025
A prescription bottle with an exclamation mark on it: Can you have a delayed allergic reaction to amoxicillin?

Key takeaways

  • Amoxicillin, a penicillin-type antibiotic, is one of the most commonly prescribed drugs and one of the most common to trigger an allergic reaction.

  • Allergic reactions to amoxicillin consist of both serious immediate hypersensitivity reactions and more limited delayed hypersensitivity reactions, which are distinct both in their immune mechanism and symptom complex.

  • Delayed allergic reactions often consist of rash alone, made up of red spots or bumps or occasionally hives, and they classically start hours to days after an amoxicillin dose and after having been on the antibiotic for a number of days.

  • Differentiating delayed from immediate hypersensitivity reactions is not always straightforward, and because immediate allergic reactions can include life-threatening anaphylaxis, the distinction must be left to healthcare professionals.

  • It’s critical to get urgent medical advice if you suspect an allergic reaction to amoxicillin.

In this article:

People of all ages can be prescribed amoxicillin for various types of infections, such as ear and sinus infections, pneumonia, and urinary tract infections. This member of the penicillin family of antibiotics falls under the subcategory of aminopenicillins along with ampicillin. Amoxicillin is one of the most popular prescriptions in the country because of its ability to kill a variety of bacteria and its usefulness in a multitude of medical scenarios. Unfortunately, it is also common to have an allergic reaction to amoxicillin, sometimes in a delayed fashion. What this means will be our thrust here.

Understanding allergic reactions to antibiotics

Antibiotics are foreign to our bodies, and our immune system can recognize antibiotics as foreign intruders and take action. Immune cells are capable of generating immunoglobulin E (IgE) antibodies, which trigger a cascading reaction, with hives, wheezing, swelling, abdominal pain, and drops in blood pressure all possible. Alternatively, the immune cells in our skin can react to the antibiotic, causing a skin rash of red spots and raised bumps.

Once sensitized, our immune system can be primed for another reaction if exposed to the antibiotic again. This is why it is so important to record and report any adverse reactions to your healthcare provider. Amoxicillin allergy is synonymous with penicillin allergy, which is reported by more than 10% of patients in some studies, a prevalence higher than that of any other drug family.

What is a delayed allergic reaction?

There are two primary types of allergic reactions: immediate and delayed hypersensitivity reactions. An immediate hypersensitivity reaction is mediated by IgE antibodies and can cause a spectrum of side effects ranging from hives to life-threatening anaphylaxis. The symptoms usually begin within an hour of taking a dose, oftentimes after the first dose of an antibiotic course but sometimes a few days into the treatment. After stopping the drug, the symptoms are typically gone within a day.

On the contrary, delayed hypersensitivity reactions are directed by immune cells in the skin and usually produce a rash with red spots or bumps without a life-threatening nature. Hives alone can sometimes occur in a delayed reaction. 

The timeframe of onset after dose is more variable for delayed reactions. It can begin a few hours or a few days after a medication dose and may persist for a week or two after discontinuing the drug. Most commonly, the reaction’s onset is not after the first drug dose. More allergic reactions are delayed-type than immediate.

What causes a delayed allergic reaction to amoxicillin?

When the body breaks down amoxicillin, it can couple with circulating proteins in our bloodstream, and the combination can be identified as foreign by our immune system. Our B and T-type white blood cells can work in tandem to produce a reaction fueled by IgE. This type of immediate hypersensitivity reaction is more common in young to middle-aged adults, particularly those who have had multiple exposures to amoxicillin over the years and have a family history of penicillin allergy.

T cells in the skin are thought to be the conductors of the immune response in delayed allergic reactions. Risk factors are not as well defined, but a concurrent viral infection seems to play a role in some cases. For example, amoxicillin use during Epstein-Barr virus (EBV), which causes mono, commonly causes rash. Viruses impact our immune system and may alter how it responds to antibiotics.

Symptoms of a delayed allergic reaction to amoxicillin

Children have a lot of viral infections and tend to get antibiotics like amoxicillin for secondary bacterial infections like sinus infections, ear infections, and pneumonia. They could also be prescribed an antibiotic inappropriately for a condition like the common cold that is viral in origin and not bacterial at all. Consequently, children are more likely to have delayed hypersensitivity reactions to amoxicillin. A delayed allergic reaction to amoxicillin in adults isn’t very common.

Children with delayed hypersensitivity reactions to amoxicillin tend to get red spots or bumps over wide areas of their body, termed a maculopapular amoxicillin rash. The drug reaction typically kicks in hours after a dose is taken, often in the later half of a treatment course or even days after the amoxicillin treatment has ended. Occasionally, the rash can consist of hives. However, the reaction generally does not include other systemic symptoms such as abdominal pain, vomiting, wheezing, swelling, or dizziness, and it doesn’t progress to anaphylaxis.

Rarely, delayed allergic reactions can be serious. Examples include Stevens-Johnson syndrome and toxic epidermal necrolysis—adverse drug reactions that involve blistering lesions and potentially life-threatening complications. Amoxicillin has rarely been implicated as a cause of these conditions.

Definitively differentiating a delayed versus immediate allergic reaction is not always straightforward. Making the distinction and final diagnosis should be left up to your healthcare provider. An allergist may need to weigh in and perform a skin prick test or intradermal skin test to identify an immediate-type IgE-mediated amoxicillin allergy.

How to treat an allergic reaction to amoxicillin

Immediate hypersensitivity reactions to amoxicillin require urgent medical attention. Antihistamines like oral or injected diphenhydramine, corticosteroids like injectable methylprednisolone, bronchodilator breathing treatments like albuterol, and (most importantly) epinephrine injections like EpiPen may all be necessary, depending on the specifics of the event. Anaphylaxis is a life-threatening immediate allergic reaction that can lead to shock and be fatal, so immediate allergic reactions to amoxicillin need to be treated as an emergency.

Delayed allergic reactions to amoxicillin are less severe and warrant less profound medical interventions. A simple rash may need no treatment other than stopping amoxicillin. A topical corticosteroid like triamcinolone or an oral antihistamine like Zyrtec (cetirizine) can be used, particularly if itching is bothersome. An oral steroid, such as prednisolone or prednisone, is an option for more severe itching or rash.

It can be helpful to learn more about rashes from amoxicillin. Most importantly, promptly contact your healthcare provider if you have a rash while taking amoxicillin and get their medical advice on treating it. If you come away with a new prescription, grab your SingleCare discount card to keep the cost in check.