Hidden Dangers: Recognizing Excipients as Potential Causes of Drug and Vaccine Hypersensitivity Reactions

Caballero, María Luisa; Krantz, Matthew S.; Quirce, Santiago; Phillips, Elizabeth

doi:10.1016/j.jaip.2021.03.002

Cited by 58 publications

(50 citation statements)

References 148 publications

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“…Excipients are necessary as support to the active ingredients in drug and play key role in drug's stability, preservation, appearance, pharmacokinetics and bioavilability. 42 However, excipients can trigger adverse events in patients. A small number of patients are allergic to drug excipients, food derivatives or dyes.…”

Section: Discussionmentioning

confidence: 99%

Predicting the Activities of Drug Excipients on Biological Targets using One-Shot Learning

Shukla

2021

Preprint

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Excipients are a major component of drugs and are used to improve drugs attributes such as stability and appearance. Excipients approved by Food and Drug Administration (FDA) are regarded as safe for human in allowed concentration, but their potential interaction with drug targets have not been investigated systematically, which might influence drugs efficacy. Deep learning models have been used for identification of ligands that could bind to the drug targets. However, due to the limited available data, it is challenging to reliably estimate the likelihood of a ligand-protein interaction. One-shot learning techniques provide a potential approach to address this low-data problem as these techniques require only one or a few examples to classify the new data. In this study, we apply one-shot learning models on datasets that include ligands binding to G-Protein Coupled Receptors (GPCRs) and Kinases. The predicted results suggest that one-shot learning models could be used for predicting ligand-protein interaction and the models attain better performance when protein targets contain conserved binding pockets. The trained models are also used to predict interactions between excipients and drug targets, which provides a potential efficient strategy to explore the activities of drug excipients. We find that a large number of drug excipients could interact with biological targets and influence their function. The results demonstrate how one-shot learning models can be used to make accurate prediction for excipient-protein interactions and these methods could be used for selecting excipients with limited drug-protein interactions.

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Section: Discussionmentioning

confidence: 99%

Predicting the Activities of Drug Excipients on Biological Targets using One-Shot Learning

Shukla

2021

Preprint

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“… 4 , 7 , 14 We did investigate excipients as a potential etiology, and found that he had tolerated these excipients in foods as well as medications such as eye drops, corticosteroids, antihistamines with no immediate or delayed reactions which reassured us that his reactions were not to the excipients. 17 …”

Section: Discussionmentioning

confidence: 99%

A case of delayed maculopapular eruption to ibuprofen and acute urticaria to acetaminophen

Wong

Sandoval

Naderi

2021

SAGE Open Medical Case Reports

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We present the unique case of a 33-year-old male referred to our clinic in search of analgesic options who was found to have a delayed hypersensitivity reaction to ibuprofen manifesting as a maculopapular rash and acute urticaria to acetaminophen. Non-steroidal anti-inflammatory drugs are associated with predictable reactions as well as immunoglobulin E-mediated reactions or T-cell mediated reactions. This case highlights the importance of knowledge of the different types of reactions to non-steroidal anti-inflammatory agents as well as the risk of cross reactivity. Delayed reaction to a single non-steroidal agent is rare; urticaria to acetaminophen is very rare. This is the first report we have found in the literature where one individual has a delayed reaction manifesting as rash to ibuprofen as well as urticaria to acetaminophen. We challenged our patient to aspirin which helped identify that his delayed reaction was only to ibuprofen and urticaria only to acetaminophen. The case also highlights the importance of an oral provocation challenge when no contraindications exist which helped us find that he could take celecoxib and avoid narcotics as initial therapy.

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“…Es más frecuente que estas reacciones se deban a excipientes, por ejemplo estabilizadores, adyuvantes, conservadores, antibióticos, sustancias residuales del medio de cultivo, látex. 19,20 Estabilizadores Gelatina (mediada por IgE) La gelatina es un producto derivado del colágeno parcialmente hidrolizado de mamíferos (porcinos o bovinos) o peces.…”

Section: Componentes De Las Vacunas Que Pueden Provocar Anafilaxiaunclassified

Anafilaxia causada por vacunas

Perea-Valle

Delgado-Aguirre²,

Villafuerte-Domínguez³

et al. 2022

RAM

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A pesar de la difícil situación que se enfrenta con la actual pandemia de COVID-19, la ciencia ha tenido un desarrollo exponencial. Si bien la inmunización contra esa enfermedad ha sido posible gracias a ello, desafortunadamente se ha acompañado de desinformación y mitos en torno a su fabricación y reacciones adversas. Por tal razón, es importante revisar una de las reacciones adversas a vacunas más temidas para el personal de salud y la población general, la anafilaxia. La anafilaxia se define como una reacción alérgica aguda y sistémica que puede poner en riesgo la vida; se asocia con distintos mecanismos inmunológicos, factores desencadenantes y manifestaciones clínicas. Su diagnóstico puede ser confuso, por lo que se han establecido diferentes criterios. Todas las inmunizaciones tienen el potencial de desencadenar anafilaxia, aunque este evento es poco frecuente. Respecto de las vacunas contra el coronavirus SARS-CoV-2, en Estados Unidos se ha reportado una tasa de anafilaxia de 1:200 000 para la vacuna Pfizer-BioNTech, y de 1:360 000 para la vacuna de Moderna. Al igual que un fármaco, las vacunas pueden presentar efectos adversos mediados por mecanismos de hipersensibilidad, pero a diferencia de lo que sucede con los medicamentos, el principio activo rara vez es el responsable; es más frecuente que las reacciones indeseadas se deban a los excipientes. La sospecha de una anafilaxia secundaria a su aplicación obliga a una oportuna referencia y a un correcto diagnóstico, tanto para el beneficio del paciente como para mejorar el perfil de seguridad de la vacuna.

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Hidden Dangers: Recognizing Excipients as Potential Causes of Drug and Vaccine Hypersensitivity Reactions

Cited by 58 publications

References 148 publications

Predicting the Activities of Drug Excipients on Biological Targets using One-Shot Learning

Predicting the Activities of Drug Excipients on Biological Targets using One-Shot Learning

A case of delayed maculopapular eruption to ibuprofen and acute urticaria to acetaminophen

Anafilaxia causada por vacunas

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