Drug Reaction (Adverse Drug Reaction)

What counts as a drug reaction

An adverse drug reaction is a harmful response to a medicine used as intended. It is different from an overdose or a medication error, though all of these are "adverse drug events". Reactions can come from prescription drugs, over-the-counter medicines, vaccines, herbal products and supplements.

Doctors sort reactions into two main groups:

Other categories include delayed effects (for example, some cancers after chemotherapy), withdrawal reactions when a drug is stopped suddenly, and treatment failure caused by interactions.

Allergy vs side effect vs intolerance

Many people carry a label of "allergy" that is really a side effect. The difference matters: about 10% of Americans report a penicillin allergy, but more than 9 in 10 of them can take penicillin safely when tested.

• Side effect: an expected effect such as nausea from antibiotics or codeine, or diarrhea from amoxicillin-clavulanate. It is not an allergy and does not usually rule out the drug.
• Intolerance: a side effect at an unusually low dose, often because of how your body processes the drug.
• Allergy (hypersensitivity): the immune system reacts. Signs include hives, itching, swelling, wheezing, or specific rash patterns. Even a small dose can trigger it again.
• Pseudoallergy: looks allergic but bypasses antibodies. Examples are flushing with fast vancomycin infusions ("red man syndrome"), and hives or asthma flares from aspirin and other NSAIDs. See drug allergy for testing and desensitization.

Symptoms by timing

Immediate reactions (minutes to about 1 hour)

These are usually IgE antibody reactions:

• hives and itching
• angioedema: swelling of the lips, eyes, tongue or throat
• wheezing, a tight chest, vomiting, dizziness
• anaphylaxis, when several body systems are involved at once or blood pressure falls

Common triggers include penicillins and cephalosporins, neuromuscular blockers used in anesthesia, and some biologic medicines.

Delayed reactions (hours to weeks)

T-cell reactions start later and can begin after you have stopped the drug:

• Maculopapular (measles-like) rash: the most common drug eruption, appearing 4 to 14 days after starting a medicine.
• Fixed drug eruption: a round, dusky patch that recurs in the same spot each time.
• DRESS: rash, fever, swollen glands, facial swelling and liver or kidney damage 2 to 8 weeks after starting drugs such as allopurinol, carbamazepine or lamotrigine. See DRESS syndrome.
• Stevens-Johnson syndrome and TEN: painful red skin that blisters and peels, with sores on the lips, eyes and genitals. These are emergencies. See Stevens-Johnson syndrome.
• Serum sickness-like reactions: hives, joint pain and fever, often in children after cefaclor or amoxicillin.

Organ-specific reactions

Some reactions affect one organ: liver inflammation (drug-induced liver injury), kidney injury, low blood counts, lung inflammation, heart rhythm changes, photosensitive rashes or movement disorders.

Who is at higher risk

• Older adults and anyone taking five or more medicines
• Kidney or liver disease, which slow drug clearance
• Previous drug reactions
• Certain genes: for example HLA-B*58:01 raises the risk of severe reactions to allopurinol, and HLA-B*15:02 (more common in people of Southeast Asian descent) to carbamazepine
• HIV infection, which raises the risk of rashes from sulfonamide antibiotics
• Infections such as Epstein-Barr virus, which cause rashes with amoxicillin

How a drug reaction is diagnosed

Your doctor builds a timeline. Bring the names, doses and start dates of every medicine, supplement and herbal product.

1. History: what happened, how soon after the dose, how long it lasted, and whether you have taken the drug or a related one since.
2. Examination: skin, mouth, eyes, lymph nodes and vital signs.
3. Blood tests: a blood count (eosinophils), liver and kidney tests, and sometimes serum tryptase within a few hours of anaphylaxis.
4. Allergy testing: skin prick and intradermal tests for penicillin and some other drugs, patch tests for delayed rashes, and supervised drug challenges, where you take a test dose under observation. Challenges are never done after SJS, TEN or DRESS.

Treatment

• Anaphylaxis: epinephrine (adrenaline) injection in the thigh, then emergency care. Antihistamines alone are not enough.
• Stopping the drug: the main treatment for allergic and severe delayed reactions. Do not stop heart, seizure, transplant or blood-thinning medicines on your own for a mild side effect; call your prescriber first.
• Hives and itching: non-drowsy antihistamines (follow the label dose) and cool compresses.
• Rash: moisturizers and steroid creams prescribed for widespread itchy rashes.
• Severe skin or organ reactions: hospital care, sometimes in a burns unit, with fluids, wound care and specialist treatment.
• Type A reactions: often handled by lowering the dose, changing the timing, taking the drug with food, or switching to a similar medicine.

After a reaction

• Ask your clinician to record the drug, the reaction and the date in your record, and whether it was an allergy or a side effect.
• Carry an allergy card or medical alert ID after a severe reaction.
• Ask about allergy testing if a label such as "penicillin allergy" limits your treatment options.
• Report reactions to the FDA through MedWatch (or your country's equivalent); patients can report directly.
• Review your full medication list yearly, since polypharmacy raises the risk of reactions.

Frequently asked questions

How do I know if I am having a reaction to a medication?

Suspect a reaction when new symptoms start after beginning, changing or restarting a medicine. Immediate signs include hives, swelling and wheezing within an hour. Delayed rashes often appear 4 to 14 days in, and severe syndromes up to 8 weeks later. Check the leaflet for known side effects and call your pharmacist or doctor.

What is the difference between a drug allergy and a side effect?

A side effect comes from the drug's normal action and is usually predictable and dose-related, such as nausea or drowsiness. An allergy is an immune response that can occur at any dose, causes hives, swelling, wheezing or specific rashes, and usually means avoiding that drug and sometimes its relatives.

How long does a drug reaction last?

Most side effects ease within days of stopping or adjusting the medicine. Hives usually clear within 1 to 2 days, and a measles-like drug rash fades over 1 to 2 weeks after stopping. DRESS and liver reactions can take weeks to months to settle.

Can you suddenly become allergic to a medicine you have taken before?

Yes. Allergies need prior exposure to develop, so a reaction often appears on a second or later course. Your immune system can become sensitized at any time. Equally, some allergies fade: most people with penicillin allergy lose it within about 10 years.

What are the most common drugs that cause reactions?

Antibiotics (especially penicillins and sulfonamides), NSAIDs such as ibuprofen and aspirin, anticonvulsants, chemotherapy, blood thinners, insulin, opioids and blood pressure medicines account for most reactions. Older adults taking several of these together have the highest risk.