NSAIDs, H2 Blockers, and Penicillin Linked to Greater Anaphylaxis Risk from Mild Drug Reactions

A study identified non-steroidal anti-inflammatory drugs (NSAIDs), H2 blockers, and penicillin as risk factors for anaphylaxis evolving from a non-severe drug hypersensitivity reaction.1

The study also showed that the intravascular route was associated with a lower risk of the progression of non‐severe hypersensitivity reactions to anaphylaxis.

“[This] may be attributed to the cautious prescription of intravascular drugs by physicians in hospital settings,” wrote investigators, led by Hyo‐In Rhyou, from the department of internal medicine at Inje University Haeundae Paik Hospital, Inje University College of Medicine, in Korea.

Patients who had a mild drug hypersensitivity reaction may experience more severe reactions upon re-exposure, although the reason behind this is poorly understood. Patients may get hives, a skin rash from morbilliform drug eruption, eosinophilia and systemic symptoms that affect the skin, liver, lungs, kidneys, and heart, and Stevens-Johnson Syndrome, which causes skin blistering all over the body.2 Investigators conducted a multicenter retrospective study to investigate the clinical characteristics and risk factors associated with the progression from non-severe drug hypersensitivity to anaphylaxis.1

“Our findings reveal that escalation from a non‐severe reaction to anaphylaxis upon re‐exposure occurred more commonly in daily life than within hospital settings,” investigators wrote. “This suggests that healthcare professionals may generally exercise caution when prescribing and administering drugs to patients with a history of [drug hypersensitivity reaction].”

Using 2015 – 2021 data from a drug-induced anaphylaxis registry across 10 university hospitals in Korea, the team collected information on culprit drugs, drug hypersensitivity reaction history, and the severity of reactions. They also collected data on age, gender, height, weight, and comorbidities (allergic rhinitis, asthma, atopic dermatitis, chronic urticaria, food allergy, and hypertension). The sample had a mean age of 55.9 ± 22.3 years and included 43.1% males. As for comorbidities, 6.9% had allergic rhinitis, 4.7% had asthma, and 1.2% had chronic urticaria.

Among 494 cases of drug-induced anaphylaxis, 84.4% occurred without and 15.6% with a prior history of drug hypersensitivity reaction.

Of those with a drug hypersensitivity reaction history, 43 cases reacted to a drug of the same class, and 34 cases reacted to drugs of other classes. The analysis saw anaphylaxis in daily life was significantly more frequent among participants who reacted with the same class as before vs those who reacted to a different class or had no prior reaction history (48.8% vs. 23.5% or 22.5%; P = .008 and P < .001, respectively).

Ultimately, the study identified several risk factors explaining the progression of non-severe drug hypersensitivity reactions to anaphylaxis. The most common culprit drugs responsible for drug-induced anaphylaxis was cephalosporins (n = 112), followed by iodinated contrast media (n = 109), NSAIDs (n = 56), platins‐based chemotherapy agents (n = 32), H2‐receptor antagonists and proton pump inhibitors (n = 29), acetylsalicylic acid and anilides (n = 20), monoclonal antibodies (n = 17), penicillins (n = 13), quinolones (n = 13), centrally acting muscle relaxants (n = 13), and taxanes and others (n = 13).

“…approximately one‐third of cases where hypersensitivity reaction progressed to anaphylaxis due to re‐exposure to the same drug occurred within a hospital,” investigators wrote.

These drugs included NSAIDs, ICM, penicillin, vancomycin, infliximab, ranitidine, and morphine. Investigators noted that physicians may decide to readminister drugs from the same class despite previous reactions due to symptoms not being severe or if the drug is essential for treatment.

“However, this practice carries the risk of hypersensitivity reactions escalating to anaphylaxis,” investigators wrote.1 “Therefore, it underscores the need for continued vigilance and caution in managing patients with a prior history of [drug hypersensitivity reaction].”

References

1. Rhyou HI, Kim SR, Jung JW, Kim SH, Lee JH, Park HJ, Park KH, Park HS, Chung EH, Choi GS, Kim S, Yang MS, Shim JY, Koh YI, Sim DW, Lee JH, Nam YH, Kang HR. Clinical characteristics and risk factors for escalation to anaphylaxis from non-severe drug hypersensitivity reaction. Clin Transl Allergy. 2025 Apr;15(4):e70047. doi: 10.1002/clt2.70047. PMID: 40263639; PMCID: PMC12014396.

2. Types of Drug Reactions & Hives. NYU Langone Health. https://nyulangone.org/conditions/drug-reactions-hives/types. Accessed May 8, 2025.