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Drug Allergy or Side Effect: Distinguishing Similar Reactions

Written by Andrew Le, MD

UpdatedFebruary 29, 2024

A drug allergy is an adverse reaction to a medication that involves the body's immune system. However, distinguishing between a drug allergy and a mere side effect can confuse many individuals.

The line between a drug allergy and a side effect can be remarkably thin, often leading to misconceptions and unnecessary panic. According to the Centers for Disease Control and Prevention (CDC), 10% of the US population thinks they have a penicillin allergy, but only 1% actually do.

This comprehensive guide unveils the critical distinctions between drug allergies and side effects, giving you the knowledge to approach your healthcare regimen confidently and safely.

🔑 Key Takeaways

  • A drug allergy takes place when the immune system falsely identifies a drug as a threat, leading to the production of antibodies.
  • Common drugs known to cause allergic reactions include penicillin, chemotherapy drugs, cephalosporins, NSAIDs, anticonvulsants, sulfonamides, insulin, and radiocontrast media.
  • Allergic reactions may develop slowly, even days or weeks after taking a medication.
  • Sulfonamides, or "sulfa drugs," used to treat bacterial infections, may lead to allergic reactions in 3-8% of patients.
  • Allergic reactions to medications can range from mild symptoms like hives and itching to severe reactions like anaphylaxis.
  • Diagnostic procedures for drug allergies include skin tests, blood tests, and detailed patient history.
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Understanding Drug Allergies

Your immune system is designed to protect you from foreign invaders like viruses and bacteria. In the case of a drug allergy, the immune system falsely identifies a drug as a threat, leading to the production of antibodies.

These specialized proteins target the drug, causing inflammation and various symptoms. This reaction may occur upon initial exposure to the drug or after multiple administrations without issue.

Which Medicines Are Most Likely to Cause Allergic Reactions?

Now let's discuss different medicines that commonly trigger allergic reactions.

1. Penicillin

Penicillin is prescribed to treat a range of bacterial infections, including conditions like strep throat. However, penicillin and similar types of antibiotics are known to be common triggers of allergic responses.

Fortunately, there's a good chance you might outgrow it if you avoid the drug for several years. Experts estimated that around 80% of those with IgE-mediated penicillin allergies regain tolerance after 10 years.

2. Chemotherapy Drugs

Chemotherapy drugs are medications given to eliminate cancer cells. These drugs can trigger hypersensitivity reactions (HSRs) or allergies with varying frequencies. They're the third leading cause of fatal drug-induced allergies in the US.

According to a study, the majority of reactions stem from the following:

Platinum compounds
  • Carboplatin: The primary cause of HSRs. The risk rises with more exposure, affecting up to 46% of patients who receive at least seven infusions of the drug.
  • Oxaliplatin: Can cause HSRs ranging from 1% to 25% of cases, with severe reactions occurring in less than 1%.
  • Cisplatin: Responsible for about 5% of cases.

Taxanes can trigger HSRs in around 30% of patients, but the rate drops to under 5% with the use of steroids and antihistamines as premedication.


The occurrence of reactions to epipodophyllotoxins spans from 6.5% to 41%.


As per the Food and Drug Administration (FDA), roughly 20% of patients exhibit an allergic reaction to the asparaginase enzyme derived from E. coli bacteria.

💡 Did you know?

Breast cancer stands as the most prevalent form of cancer among women in the US. It accounts for roughly 30% of all newly diagnosed cases each year.

3. Cephalosporins

Cephalosporins are drugs employed to treat different types of bacterial infections. If you test positive for a penicillin allergy, there's a 2% chance of experiencing allergic reactions to first-generation cephalosporins.

First-generation cephalosporins include:

  • Cefazolin
  • Cephalothin
  • Cephapirin
  • Cefadroxil
  • Cephalexin
  • Cephradine

4. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Acetylsalicylic Acid (ASA), commonly known as Aspirin, and similar NSAIDs like ibuprofen or naproxen (found in Advil, Motrin, Aleve, and others) are commonly used to relieve pain and reduce fever. They're widely used by both children and adults.

Hypersensitivity to NSAIDs is estimated to affect around 0.5 to 1.9% of the overall population. Meanwhile, NSAIDs account for approximately 21 to 25% of all reported adverse reactions to drugs.

The primary types of NSAIDs are:

  • Ibuprofen
  • Naproxen
  • Diclofenac
  • Celecoxib
  • Indomethacin
  • Aspirin (low-dose aspirin is typically not classified as an NSAID)

5. Anticonvulsants

Anticonvulsants are used to treat conditions like epileptic seizures and bipolar disorder. However, a few anticonvulsants have been linked to causing Anticonvulsant Hypersensitivity Syndrome (AHS).

AHS is a serious syndrome that affects several organs and can lead to a mortality rate of 10–20%. It is estimated to happen in approximately one out of every 1000–10,000 instances of exposure. AHS has been observed in association with anticonvulsant drugs like:

  • Carbamazepine
  • Phenytoin
  • Phenobarbitone
  • Lamotrigine
  • Fosphenytoin
  • Primidone
  • Felbamate

6. Sulfonamides

Sulfonamides, also known as "sulfa drugs," are a category of medicines used to treat bacterial infections. They are available in various forms and can be taken orally, applied topically, used vaginally, or administered as eye medication.

In the general population, it is estimated that about 3–8% of patients may have a sulfa allergy. Additionally, studies showed that HIV-positive patients have a higher chance of experiencing skin reactions to sulfonamide antibiotics.

Here is a list of the most common sulfonamides:

  • Mafenide
  • Sulfacetamide
  • Sulfadiazine
  • Sulfadoxine
  • Sulfamethizole
  • Sulfanilamide
  • Sulfasalazine
  • Sulfisoxazole
  • Sulfamethoxazole/trimethoprim
  • Dapsone

While uncommon, a sulfa allergy can lead to serious issues, including anaphylaxis and Stevens-Johnson syndrome.

Source: PCDS

7. Insulin

Human insulin belongs to a group of drugs called hormones. It's used to manage blood sugar in individuals with type 1 diabetes (a condition where the body doesn't produce insulin) or type 2 diabetes (a condition where blood sugar is too high due to issues with insulin production or use).

However, receiving insulin injections can also sometimes result in an allergic reaction. Insulin allergy impacts around 0.1–3% of diabetics receiving insulin treatment.

8. Radiocontrast media

Radiocontrast media (RCM) are agents typically used for CT scan or other imaging technologies, which helps highlight blood vessels, organs, or tissues. This enhanced visibility is crucial for diagnosing a wide range of medical conditions and for guiding various medical procedures.

Some Radiocontrast agents include:

  • Lipiodol
  • Ethiodol
  • Gastrografin
  • Lymphazurin
  • Gadavist

RCMs are typically administered orally, intravenously, or rectally, depending on the specific type of imaging procedure being performed. Hypersensitivity reactions can involve both IgE and non-IgE triggered anaphylaxis.

Common Drug Allergy Symptoms

An allergic reaction to a medication usually starts shortly after you've taken it. The symptoms and their intensity can differ from person to person. Milder signs of a drug allergy may involve:

More severe symptoms of a drug allergy might include anaphylaxis. Anaphylaxis is a serious allergic reaction that can be life-threatening if not treated promptly. Severe signs may encompass:

  • Difficulty swallowing (dysphagia)
  • Trouble breathing
  • Feeling dizzy or light-headed
  • Swelling of the lips, tongue, or face
  • Low blood pressure
  • Faster heart rate
  • Feeling confused or anxious
  • Losing consciousness

An allergic reaction may develop slowly, even days or weeks after taking a medication. This reaction can also persist for days after stopping the medicine. These responses may involve:

  • Fever
  • Skin rashes
  • Joint pain or swelling
  • Low red blood cell count (anemia) or platelets (thrombocytopenia)
  • Unusual white blood cell count (leukocytosis or leukopenia) or eosinophil count (eosinophilia)
  • Kidney (nephritis) or liver (hepatitis) inflammation
  • Enlarged lymph nodes

💡 Did You Know?

Women have higher “allergy” incidence rates for all classes of antibiotics. Antibiotic “allergy” incidence in women is highest for sulfonamides, at 3.4%, compared with 1% to 1.5% for all other classes of antibiotics.

Allergy vs. Side Effects

It's crucial to distinguish between a drug allergy, which usually means stopping the medication, and a side effect, which generally doesn't require stopping unless it's serious. Unlike allergies, side effects do not impact the immune system. Sometimes, the benefit the drug brings to your health outweighs the risk of a side effect.

The label or package insert of the medication should outline any potential adverse effects. To help you differentiate drug allergy and side effects, here are some common drug side effects:

  • Tiredness
  • Hives
  • Feeling dizzy
  • Upset stomach
  • Throwing up
  • Loose stools
  • Trouble going to the bathroom
  • Getting bruises easily

Diagnostic Procedures

Diagnosing drug allergies can be challenging. A skin test is the definitive way to diagnose an allergy to penicillin-type drugs. However, some drug reactions, like rashes, hives, and asthma, can resemble certain diseases.

Your allergist might ask you the following questions:

  • Which drug do you suspect caused your reaction?
  • When did you start taking it, and have you stopped?
  • How soon after taking it did you notice symptoms, and what did you experience?
  • How long did your symptoms last, and how did you alleviate them?
  • Are you taking any other medications, prescription or over-the-counter?
  • Do you use herbal medications or take vitamins or mineral supplements? If so, which ones?

Your allergist will also inquire if you've had a reaction to any other drugs. If possible, bring the suspected drug with you, as it can assist the allergist in suggesting alternatives.

During a physical exam, your allergist will check for signs related to the drug reaction and other non-allergic causes of your symptoms.

Depending on the suspected drug, your allergist might recommend a skin test or, in rare cases, a blood test. A blood test can be useful in diagnosing a severe delayed reaction, particularly if there's concern about multiple organ system involvement. This uncommon reaction is known as "drug rash with eosinophilia and systemic symptoms" or, more commonly, "DRESS syndrome."

📕 Definition

DRESS syndrome is a severe reaction to a medication. It happens after a long period of time and shows various symptoms like fever, rash, swollen lymph nodes, high levels of a type of white blood cells called eosinophils, and a range of mild to severe body-wide issues.

Your allergist may suggest an oral drug challenge if a drug allergy is suspected. During this, you'll be monitored by medical staff as you take the suspected drug.

Management of Drug Allergies

Your healthcare provider might suggest the following to manage your drug allergies effectively:

  1. Stop using the medication: Your symptoms should improve as it clears from your system. If it's for a specific condition, your provider may prescribe an alternative medicine that won't cause an allergic reaction.
  2. Antihistamines: These medicines counteract the effects of histamine in your body.
  3. Corticosteroids: They're anti-inflammatory drugs that help lessen the production of chemicals causing inflammation.
  4. Bronchodilators: These medications can help ease symptoms affecting your lungs.
  5. Epinephrine auto-injector: Your provider might recommend this device if you have severe medication allergies. Epinephrine swiftly reverses symptoms of anaphylaxis. Your provider will explain when and how to use it.
  6. Allergy desensitization: Here, your provider administers small amounts of allergen-containing medications. This helps your immune system build tolerance. The dosage is gradually increased over hours or days until your body can tolerate the drug without reacting.

💡 Did you know?

Minoxidil was first sold as a pill for high blood pressure, but users discovered it also helped grow hair. Today, it's one of the top treatments for male-pattern baldness.

Seeking Professional Help

If you suspect you're experiencing a reaction to a medication, reach out to your healthcare provider.

If you have trouble breathing or show signs of severe asthma or anaphylaxis, go to the emergency room or call your local emergency number (like 911) immediately. These are urgent situations that require immediate attention.


Understanding the difference between a drug allergy and a side effect is really important. This knowledge helps you make smart decisions about your health. If there's any doubt about how your body reacts to a medicine, special tests like skin or blood tests can help figure it out.

Following your healthcare provider's advice is crucial if a drug allergy is confirmed. Taking medicine responsibly is a team effort between you and your healthcare provider.

By following these suggestions, you can safely handle drug allergies and side effects and ensure you're on the path to good health.

FAQs on Drug Allergy

Is it possible to prevent drug allergies?

Avoid medications with the allergen, including similar ones, to prevent a drug allergy reaction. Ensure your healthcare providers update your records to note the allergy, reducing the risk of future reactions.

How long does a drug allergy rash last?

A drug allergy rash might last a few days to a couple of weeks after you stop taking the medicine. Then, it will slowly go away. Usually, it starts disappearing from the top of your body and takes the longest to resolve in your legs and feet. As it gets better, your skin might peel a bit, like when you have a sunburn.

What does a drug allergy rash look like?

These are bumps or welts on the skin that are raised, swollen, and can be red or skin-colored. They come in various shapes and can be really itchy. They often appear in bunches and can cover large areas of the body.

Can a drug allergy develop over time?

Yes, a person can develop a drug allergy even if they have previously taken the medication without incident. The immune system can become sensitized over time, leading to an allergic reaction upon subsequent exposure.

Can I take other medications if I have a drug allergy?

If you have a known drug allergy, discussing alternative medications with your healthcare provider is important. They can recommend safe alternatives based on your specific allergy profile.

Illustration of a healthcare provider asking questions on a smart phone.
Allergy treatment - Online visit
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  • No video call or appointment necessary
  • Personalized treatment plan prescribed for your condition