Single-dose oral challenge safely clears drug allergy labels in outpatients

Researchers report that 97 percent of patients given a direct oral drug challenge experienced no reaction at all, and the few reactions that did occur were mild.

The findings come from a prospective single-centre study conducted between May 2022 and January 2024 at a specialized allergy clinic. The study included patients aged 14 years or older who carried a drug allergy label. Patients with a history of anaphylaxis or severe cutaneous adverse drug reactions, as well as those who had already undergone skin testing with the suspected drug, were excluded from the study.

Instead of a graded protocol, the culprit drug was administered as a standard single dose during an outpatient hospital visit. This direct oral drug challenge approach has been adopted by numerous clinicians worldwide in the context of drug hypersensitivity, but drug allergy de-labelling has remained largely confined to inpatient or hospital-based outpatient care, and mostly for penicillins. The study set out to extend the approach to low-risk allergies involving drugs other than penicillin.

In total, 304 patients were included in the cohort. Penicillins were by far the most frequent culprit drugs, accounting for 228 patients, or 75 percent of the group. Nonsteroidal anti-inflammatory drugs were implicated in 31 patients (10.2 percent), other antibiotics in 15 patients (4.9 percent), cephalosporins in 10 patients (3.3 percent), analgesics in 7 patients (2.3 percent) and corticosteroids in 4 patients (1.3 percent).

Among the whole cohort, 295 patients, or 97.0 percent, had no reaction during the oral challenge. Nine patients presented with a mild reaction, including three with an immediate reaction and six with a delayed reaction. No severe reactions are reported in the study’s abstract.

The researchers conclude that allergy de-labelling for all drugs in patients with low-risk allergies can be safely conducted in outpatient visits. However, they caution that a risk stratification approach needs to be clarified with a validated tool for patient selection, meaning that careful identification of which patients qualify as low-risk remains an open task for the field.

The study was published as a Brief Report in the journal Allergy, Asthma & Clinical Immunology on 16 October 2026. As a single-centre prospective study with defined exclusion criteria, its results apply to the low-risk outpatient population described, and the authors themselves note that validated risk stratification is still needed before the approach can be generalized.

With 304 patients challenged and only nine mild reactions observed, the reported safety profile supports the feasibility of the outpatient model, while the call for a validated selection tool underscores that patient screening remains central to safe implementation.

Subject of Research: Direct oral drug challenge for outpatient de-labelling of low-risk drug allergies

Article Title: Drug allergy de-labelling with a direct oral challenge in outpatient hospital visits

Article References: Sekkai, N., Coco-Viloin, M., Calmels, M., & Guilleminault, L. (2026). Drug allergy de-labelling with a direct oral challenge in outpatient hospital visits. Allergy, Asthma & Clinical Immunology. https://doi.org/10.1186/s13223-026-01077-3

Image Credits: AI Generated

DOI: 10.1186/s13223-026-01077-3

Keywords: drug allergy, de-labelling, oral challenge, penicillin allergy, drug hypersensitivity, outpatient care, allergy clinic, NSAIDs, cephalosporins, risk stratification, adverse drug reactions, Drug