Presence of gluten and soy derived excipients in medicinal products and their implications on allergen safety and labeling

Abstract

Gluten and soy allergies are significant health concerns, particularly in individuals with celiac disease or soy sensitivity. While dietary sources of these allergens are well-studied, their presence in medicinal products remains under-explored. This study assessed the prevalence of gluten and soy-derived excipients in 308 medicinal products authorized for marketing in Portugal. A systematic search of the Summary of Product Characteristics (SmPC) database was conducted for 108 analgesics and antipyretics containing paracetamol, 85 NSAIDs containing ibuprofen, and 115 antiasthmatic and bronchodilator medicinal products. The study found significant associations between pharmacotherapeutic groups and the presence of these allergens (p < 0.001). Gluten was more prevalent in the group of analgesics and antipyretics (44.4%) than in NSAIDs (8.2%), whereas soy-derived excipients were more frequent in NSAIDs (14%) than in analgesics and antipyretics (6.5%). No excipients containing gluten or soy were identified in antiasthmatic and bronchodilator medicinal products. In analgesics and antipyretics, 51.2% of solid oral dosage forms and 40% of liquid oral formulations contained gluten. Within the NSAIDs group, gluten was mainly present in liquid oral dosage forms (26.7%). Soy-derived excipients were found in 30% of liquid oral formulations and in 33.3% of rectal dosage forms of analgesics and antipyretics. In the NSAIDs group, soy was more prevalent in liquid oral formulations (26.7%). These findings highlight the need for clearer labeling of allergens in medicinal products and underscore the importance of vigilance for patients with gluten or soy allergies. Further research is required to address gaps in allergen disclosure by pharmaceutical manufacturers and to promote safer medicinal product use for sensitive populations. Enhanced awareness among healthcare providers and patients is essential to mitigate the risk of allergic reactions associated with hidden excipients in medicinal products.

Introduction

Food allergies are an important public health problem that affects children and adults and their prevalence has increased in the past two to three decades1. Gluten, a protein found in wheat, barley and rye can trigger adverse reactions in susceptible individuals.

Gluten ingestion can cause three primary clinical disorders, celiac disease, wheat allergy, and gluten sensitivity, each with distinct characteristics and symptoms2,3. Celiac disease (CD) is one of the most prevalent chronic disorders worldwide, with an average prevalence of 1.4% when including individuals diagnosed by serological tests, and an overall prevalence of 0.7% based on biopsy findings4. CD causes nutrient deficiency due to impaired absorption of iron, calcium, zinc, vitamin B12, vitamin D, and folate5. Wheat allergies are common in children and are triggered by wheat proteins, particularly gluten6. Non-celiac gluten sensitivity mimics CD symptoms, but lacks an autoimmune component7.

Some excipients are used in various pharmaceutical forms such as starch, pregelatinized starch, sodium starch glycolate, and other excipients derived from wheat, oats, rye, and barley. Corn starch and potato starch may also appear, but these excipients are gluten-free and therefore safe for individuals with gluten-related disorders8. Starch, a by-product of gluten extraction, has a wide range of applications in the food and pharmaceutical industries9. As a common excipient in medicinal products, starch is the primary source of gluten and can be added to formulations with multiple functions, including gelling, thickening, adhesion, moisture retention, stabilisation, film formation, texturizing, and preventing staling8,10.

According to the Food and Agriculture Organization of the United Nations, soy is one of the top eight major food allergens, along with milk, eggs, fish, crustacean shellfish, tree nuts, peanuts and wheat11. Soy is considered an allergen by approximately 1.5% of the European population and is a frequent cause of allergies in children12. Indeed, soy allergy is the second most common food allergy in childhood (0.4% of children) and at the same time one of the allergies with the highest resolution rate, that is, 25% at the age of four, 45% at the age of six and 69% at the age of ten13,14,15. This allergy depends on the eating habits and the age at which soy is introduced into the diet. Patients with soybean allergies can tolerate other legumes16.

Soy contains various proteins with distinct characteristics that pose varying risks for severe allergic reactions. Soy allergies can result in manifestations such as oral allergy syndrome, urticaria, angioedema, rhinoconjunctivitis, asthma, and anaphylaxis16. However, according to a study by Savage et al. (2010), the most frequent symptoms after exposure are gastrointestinal symptoms (41%) and skin (28%) symptoms15.

Due to its solubility, elasticity, viscosity, adhesiveness, gelling, aggregation, absorption, and emulsification properties17, it is found in inhalers, tablets, suppositories, and cosmetic products18.

Currently, there is no cure for gluten or soy allergies. The best treatment is complete avoidance of these allergens, not only in diet but also in medicinal products, which requires vigilance in checking product labels for hidden allergen sources. Recent studies indicate that approximately 1.4% of the global population is affected by celiac disease, while soy allergies impact around 1% of Europeans, with higher prevalence observed in children19. However, specific prevalence rates for gluten and soy sensitivities in Portugal remain unexplored. To our knowledge, assessment of the presence of gluten and soy excipients in medicinal products is limited.

This study aimed to examine the prevalence of gluten and soy-derived ingredients used as excipients in selected medicinal products authorized for marketing in Portugal, focusing on three commonly used therapeutic classes (analgesics, antipyretics, non-steroidal anti-inflammatory drugs, and antiasthmatics).

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Materials

To identify gluten- and soy-derived excipients in medicinal products, a search was conducted using the Summary of Product Characteristics (SmPC) for human medications authorized for marketing in Portugal. The SmPCs were accessed through the online database INFOMED (https://extranet.infarmed.pt/INFOMED-fo/). The study’s inclusion criteria focused on therapeutic groups among the most prescribed for both children and adults, including analgesics and antipyretics containing paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) containing ibuprofen.These included analgesics and antipyretics containing paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) containing ibuprofen, and all antiasthmatics/bronchodilators approved and commercialized in Portugal, regardless of the active ingredient. The antiasthmatics/bronchodilators included in the study represented 19 different active ingredients, with the three most common being fluticasone (29.6%), salmeterol (19.2%), and budesonide (9.9%). According to IQVIA reports, paracetamol accounted for 74.3% of the total sales (in terms of units) within the N02B0 group (non-narcotic analgesics/antipyretics) in Portugal in February 2024, while ibuprofen ranked second, with 8.5% of the total sales. These groups were selected due to their widespread use in addressing common conditions such as pain, fever, inflammation, and respiratory issues, making the findings highly relevant to public health. All medicinal products included in the study required marketing authorization in Portugal, and an associated SmPC available in INFOMED. The study covered both generic and branded medicinal products, in all dosages and formulations, excluding injectables, and included prescription-only as well as over-the-counter medications for pediatric and adult use.

Table 1. List of excipients that have been researched in the summary of product characteristics (SmPC) and
which May contain gluten and soy derivatives.

Figueiredo, A., Auxtero, M.D., Brás, A. et al. Presence of gluten and soy derived excipients in medicinal products and their implications on allergen safety and labeling. Sci Rep 15, 10976 (2025). https://doi.org/10.1038/s41598-025-95525-6

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