The Difference Between an Adverse Drug Reaction, Drug Allergy, and Side Effect

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When you walk up to a pharmacy counter to drop off a new prescription, you may notice that the pharmacist or pharmacist technician always asks if you have any known allergies. Documenting allergies is important to prevent administering a medication that could cause an allergic reaction, which can range from a rash or hives to anaphylaxis. But did you know that many patients report their drug “allergies” that are actually just side effects? This could lead to unnecessarily withholding the medication. Read on to learn more about the difference between an adverse drug reaction, drug allergy, and side effect.

What is an adverse drug reaction?

An adverse drug reaction (ADR) can be defined as, “an unwanted, undesirable effect of a medication that occurs during usual clinical use.”  Adverse drug reactions are more serious than side effects. ADRs can be classified as two subtypes: Type A and Type B.

Type A ADRs are dose-dependent and predictable; they are augmentations of known pharmacologic effects of the drug and can be mild, moderate, or severe. Examples of type A ADRs include drug overdoses, secondary drug effects, and drug interactions. Type B ADRs are uncommon, unpredictable, and unrelated to the dose of the medication. Examples of type B ADRs include drug intolerances, and drug idiosyncrasies.

The drug classes most commonly responsible for ADRs in adults are adrenal corticosteroids, antibiotics, anticoagulants, antineoplastic and immunosuppressive drugs, cardiovascular drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), and opiates.

What is a drug allergy?

A drug allergy can be defined as an overreaction of the immune system to a harmless substance (in this case, a drug), which triggers an allergic reaction. Specifically, a drug allergy is a reaction mediated by Immunoglobulin E (IgE) antibodies. These antibodies travel to cells that release chemicals, causing an allergic reaction. This reaction usually causes symptoms in the nose, lungs, throat, or on the skin.


While any drug can cause an allergic reaction, there are some that are more likely to cause these types of problems than others, for example:

  • Antibiotics

  • Sulfa drugs

  • NSAIDs

  • Chemotherapy drugs

  • Monoclonal antibody therapy

  • HIV drugs

  • Insulin

  • Antiseizure drugs


The antibiotic penicillin is the most frequent drug allergy, affecting approximately 10% of patients. Plus, if you have an allergy to penicillin, that means there is a 20% possibility that you will be allergic to first-generation cephalosporins (i.e. Keflex). Second- or third-generation cephalosporins may be considered for treatment since the degree of cross reactivity with these agents and penicillin has been shown to be lower than with first-generation agents.

Allergic reactions to penicillin can range from breaking out in a rash to life-threatening anaphylaxis. However, there are new findings suggesting that breaking out in a rash may not indicate a true penicillin allergy. Rashes that involve hives (raised, intensely itchy spots that come and go over hours) or occur with other penicillin allergic symptoms (e.g. wheezing or swelling of the skin or throat) suggest a true penicillin allergy. Rashes that are flat, non-itchy, develop over days and do not change in appearance are less likely to represent a dangerous allergy.

Another common drug allergy is a sulfa allergy, which occurs when a person has an allergic reaction to drugs that contain chemicals called sulfonamides. Sulfonamides are found in a variety of medications, for instance, sulfonamide antibiotics (i.e. Bactrim), some diabetes medications (i.e. glyburide), sumatriptan (Imitrex), celecoxib (Celebrex), hydrochlorothiazide, furosemide (Lasix), and more. It’s important to note that there is a difference between sulfa and sulfite, despite their similar names. Sulfites are used as additives and preservatives in many types of processed foods and beverages. Both sulfa medications and sulfite can cause allergic reactions, but these two substances are not related. A patient who has a sulfa allergy will not necessarily have a sulfite allergy, so there is no cross-reactivity. Also, sulfa is different from sulfates and sulfur. Once again, if you have a sulfa drug allergy, there is no cross-reactivity with sulfates and sulfur.


What is a side effect?

A side effect can be defined as a secondary“ undesired effect that occurs when the medication is administered regardless of the dose.” Before a drug enters the market, the side effects of the drug are investigated and monitored extensively during clinical trials. Since side effects are mostly predictable, the patient is typically warned by the physician or pharmacist to be aware of the effects that could happen while on the therapy. Unlike drug allergies, side effects will often resolve on their own with time after taking the medication for several weeks.

An example of a very common side effect is nausea. Many patients believe they are allergic to a drug because they felt nauseous while taking the drug. As mentioned above, a drug allergy is caused by an overreaction of the immune system. The feeling of nausea has nothing to do with the immune system. There are different reasons as to why certain drugs cause nausea. For example, NSAIDs irritate the stomach lining and may cause nausea. In this case, the nausea can typically be alleviated by having something to eat before taking the medication.

Even though the definition of a side effect includes the statement “an undesired effect”, I’d like to point out that not all drug side effects are undesired. In fact, certain types of medication are even utilized due to their side effects. One example of this is the drug mirtazapine (Remeron), which is used in anorexic patients due to the drug’s potential to increase appetite and cause weight gain.


In summary

The term “adverse drug reaction” describes a broad range of dangerous effects that can occur with any type of medication during usual clinical use. It is important to recognize the difference between a true drug allergy and a side effect. Referring to side effects, such nausea or  headache, as allergies can lead to unnecessarily withholding a medication, which can lead to negative outcomes. When your physician or pharmacist asks about your drug allergies, it’s important to not only say the name of the drug you are allergic to, but also what kind of reaction you had to the drug.







References:

Pharmacy Times, “'Adverse Event,' Not the Same as 'Side Effect'” Feb 21, 2017

Am Fam Physician. 2003 Nov 1;68(9):1781-1791.

AAAAI, “Drug Allergy Definition”

AAAAI, “Immunoglobulin E (IgE) Definition”

ACCP, “Adverse Drug Reactions” 2015

Allergy Asthma Clin Immunol. 2011; 7(Suppl 1): S10.

The Pharmaceutical Journal, “Penicillin allergy: identification and management”, Sep 4 2015

Healthline, “What is a sulfa allergy”

Medscape, “Sulfa, Sulfur, Sulfate, Sulfite: Which Causes an Allergy?” October 19, 2016