What Drug Makes You Break Out in Hives?

October 10, 2025 •

4 min read

Drug-induced urticaria (hives) is the second most common type of drug-induced skin eruption [1.2.1]. Answering 'What drug makes you break out in hives?' involves exploring a wide range of medications, from common pain relievers to antibiotics, and understanding how they can trigger this itchy reaction.

Quick Summary

Many medications can cause hives, a common skin reaction. The most frequent culprits include antibiotics like penicillin and non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen. This reaction can be allergic or non-allergic.

Key Points

Top Culprits: Antibiotics (like penicillin) and NSAIDs (like ibuprofen and aspirin) are the most common drugs that cause hives [1.3.2, 1.3.4].
Two Main Mechanisms: Hives can be caused by a true immune system (allergic) reaction or a non-allergic (pseudoallergic) reaction where the drug directly triggers histamine release [1.4.5].
NSAID Reaction: NSAIDs often cause hives by inhibiting the COX-1 enzyme, which is a pharmacological effect, not a true allergy [1.6.4].
ACE Inhibitors and Swelling: Blood pressure drugs known as ACE inhibitors are a primary cause of angioedema (deep swelling), which is related to hives but typically occurs without itching [1.10.1].
Treatment is Key: The most important step is to stop taking the causative drug under a doctor's supervision. Antihistamines are used to manage symptoms [1.5.1].
Anaphylaxis is an Emergency: If hives are accompanied by difficulty breathing, swelling of the throat, or dizziness, it may be anaphylaxis, which requires immediate emergency care [1.7.3, 1.8.1].
Diagnosis is History-Based: Identifying the drug responsible for hives usually relies on a careful review of your medication history with a doctor [1.5.3].

What is Drug-Induced Urticaria?

Urticaria, commonly known as hives, appears as raised, itchy welts on the skin. While many factors can trigger hives, medications are a frequent cause. Drug-induced urticaria is one of the most common skin reactions to medications, second only to morbilliform (measles-like) rashes [1.2.1]. It is estimated to affect 9% of patients who visit dermatology clinics for hives [1.2.2].

Hives can be part of a true allergic reaction, where the immune system mistakenly identifies a drug as a harmful substance [1.3.1]. In response, it releases histamine and other chemicals that cause skin swelling, itching, and redness [1.3.1]. However, some drugs can cause hives through a non-allergic mechanism, sometimes called a pseudoallergic reaction, by directly causing mast cells to release histamine or by other pathways [1.4.4, 1.4.5].

How Do Drugs Cause Hives?

The mechanisms behind drug-induced hives are complex and can be categorized into two main types:

Immunologic (Allergic) Reactions

This is a true allergic response involving the immune system. The first time you take a drug, your body may produce IgE antibodies against it without any symptoms [1.3.1]. Upon subsequent exposure, these antibodies recognize the drug and trigger immune cells like mast cells and basophils to release histamine, leading to hives [1.3.1]. This type of reaction can occur within minutes to hours of taking the drug and can sometimes lead to a severe, life-threatening reaction called anaphylaxis [1.8.1, 1.7.2]. Penicillin is a classic example of a drug that can cause IgE-mediated hives [1.3.1].

Non-Immunologic (Pseudoallergic) Reactions

These reactions mimic allergy symptoms but do not involve IgE antibodies [1.3.5]. The drug itself directly triggers the release of histamine from mast cells or interferes with biochemical pathways [1.4.4, 1.4.5].

Direct Mast Cell Activation: Some drugs, like opioids (morphine, codeine) and certain anesthetics, can directly cause mast cells to release their inflammatory contents [1.4.4, 1.2.2].
COX-1 Inhibition: Non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen are a major cause of pseudoallergic hives [1.2.2, 1.3.4]. They block the COX-1 enzyme, which shifts a metabolic pathway to produce more leukotrienes. These substances increase vascular permeability, leading to hives and swelling (angioedema) [1.6.4, 1.6.1]. This is considered a pharmacological side effect rather than a true allergy [1.2.2].

Common Medications That Cause Hives

A wide variety of drugs can induce urticaria. The most frequently implicated classes include:

Antibiotics: Penicillin and related drugs (like amoxicillin) are famously associated with allergic hives [1.3.1, 1.7.2]. Sulfa drugs, cephalosporins, and others can also be culprits [1.3.1, 1.3.4]. About 5-10% of children taking amoxicillin may develop a rash, though many are non-allergic viral rashes occurring concurrently [1.7.1].
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): This is one of the most common groups of drugs to cause hives, often through a non-allergic mechanism [1.3.4]. Aspirin, ibuprofen (Advil, Motrin), and naproxen (Aleve) are frequent triggers [1.3.2]. These reactions can be particularly common in patients with chronic urticaria [1.6.3].
ACE Inhibitors: These blood pressure medications (e.g., lisinopril, enalapril) are a leading cause of angioedema, a deeper swelling often affecting the lips, tongue, and face [1.10.1]. While classic hives (urticaria) are typically absent, the swelling is a related process. The mechanism involves the accumulation of bradykinin [1.10.2, 1.10.4].
Anesthetics: Both general and local anesthetics can cause hives and, in rare cases, severe allergic reactions [1.9.3, 1.3.3]. Reactions might be to the anesthetic itself or to preservatives like methylparaben in multi-dose vials [1.9.5].
Chemotherapy Drugs and Biologics: Many drugs used for cancer and autoimmune diseases can cause skin reactions, including hives [1.3.5, 1.8.1]. These can be immediate hypersensitivity reactions [1.8.1].
Opiates: Morphine and codeine are known to directly trigger histamine release, causing itching and hives [1.4.4, 1.2.2].
Radiocontrast Media: The dyes used in X-rays and CT scans can cause allergy-like reactions, including hives [1.3.1, 1.4.4].

Comparison of Common Drug Classes Causing Hives


Drug Class	Common Examples	Primary Mechanism	Onset of Reaction
Antibiotics	Penicillin, Amoxicillin, Sulfa drugs	Immunologic (IgE-mediated) [1.7.2]	Minutes to hours; can be delayed days [1.7.1, 1.7.2]
NSAIDs	Aspirin, Ibuprofen, Naproxen	Non-Immunologic (COX-1 inhibition) [1.6.4]	Minutes to hours [1.6.3]
ACE Inhibitors	Lisinopril, Enalapril	Non-Immunologic (Bradykinin-mediated) [1.10.4]	Can be immediate or occur months/years later [1.10.2]
Opiates	Morphine, Codeine	Non-Immunologic (Direct mast cell activation) [1.4.4]	Rapid
Anesthetics	Muscle relaxants, Novocaine	Immunologic or Non-Immunologic [1.9.3, 1.9.5]	Usually rapid/immediate [1.9.3]

Diagnosis and Management

Diagnosing drug-induced hives primarily involves a detailed medical history, focusing on all medications taken recently [1.5.3]. The most important step in management is to identify and discontinue the offending drug, after consulting with a doctor [1.5.1].

Symptoms are typically treated with:

Antihistamines: These are the first-line treatment to block the histamine causing the itching and swelling [1.5.1].
Corticosteroids: For more severe cases, oral or injected corticosteroids may be prescribed to reduce inflammation [1.5.1, 1.5.5].
Epinephrine: In cases of anaphylaxis (a severe reaction with difficulty breathing and a drop in blood pressure), an immediate injection of epinephrine is required [1.5.4].

It can take a few days or weeks for hives to completely disappear after stopping the medication [1.5.1].

Conclusion

Many different drugs can cause you to break out in hives, with antibiotics and NSAIDs being the most common offenders. The reaction can be a true allergy or a non-allergic hypersensitivity. If you develop hives after starting a new medication, it is crucial to contact your healthcare provider. They can help diagnose the cause, manage your symptoms, and find a safe alternative medication if needed. Never stop a prescribed medication without medical advice [1.5.1].

For more information on drug allergies, you can visit the Allergy & Asthma Network.

Frequently Asked Questions

The first signs often include skin reactions like hives, rash, or itching. Other early symptoms can include fever, swelling, shortness of breath, or a runny nose [1.7.2].

Hives from a drug allergy often appear within an hour, but reactions can be delayed by hours, days, or even weeks [1.7.2]. Non-allergic reactions, like those to NSAIDs, usually occur within minutes to hours [1.6.3].

Yes. An allergy can develop at any time. Your immune system may produce antibodies after the first time you take a medicine, causing a reaction on the next exposure [1.3.1].

Not necessarily. Hives (urticaria) are raised, itchy welts that can change location. Other drug rashes can be flat, blotchy spots (maculopapular rashes) [1.7.1, 1.8.1]. Hives are a specific type of rash.

Antibiotics, particularly penicillin and related drugs, and NSAIDs like aspirin and ibuprofen are among the most common causes of drug-induced hives [1.3.2, 1.3.4].

The primary treatment is to stop the medication causing the reaction (with a doctor's approval). Symptoms are then managed with antihistamines and, in severe cases, corticosteroids [1.5.1].

You should seek emergency help immediately if your hives are accompanied by swelling of the lips, tongue or throat, difficulty breathing, wheezing, or feeling faint, as these are signs of a severe reaction called anaphylaxis [1.8.1, 1.7.3].