New Challenges in Drug Allergy: the Resurgence of Excipients

Abstract

Purpose of Review Allergy to excipients is a cause of multidrug allergy and if it is not taken into account, it can lead to unexpected severe reactions. If an excipient allergy is suspected, an accurate examination followed by algorithms is very important for a correct diagnosis and to give patients detailed information in order to avoid future reactions. Recent Findings In recent times, due to allergy COVID vaccine reactions, interest in excipients as polyethylene glycol derivatives (PEGs) has increased as a possible cause of drug and vaccine hypersensivity. In addition to PEGs many other excipients as gelatin, alpha-gal, protamine, benzalkonium chloride, and benzyl alcohol have been described as a cause of allergy to drugs and vaccines. For most excipients, the dilutions used for skin testing (ST) are not standardized and proper algorithms to reach a diagnosis are not available. Summary The purpose of this article is to review the excipients that may produce inmediate hypersensitivity drugs and vaccine reactions and update diagnostic procedures to reach an accurate diagnosis. We highlight the in vivo and in vitro diagnostic tests used in published reports and detail the dilution used for each excipient to perform ST in order to confirm this vital pathology and to prevent new reactions.

Antimicrobial Preservatives for Protein and Peptide Formulations: An Overview

“…m-Cresol immediate hypersensitivity was reported for insulin type medications, benzalkonium chloride for ophthalmic products and benzyl alcohol with parenteral medications [101][102][103] (see Caballero and Quirce (2020) and references cited therein [99]). A recent review paper by Díaz et al (2021) summarizes the current knowledge on drug allergy by also considering the used excipients [102]. Anaphylactic reactions were reported for vitamin B12 injections containing benzyl alcohol [104,105].…”

Allergological reappraisal of the Annex to the European Commission guideline on excipients (SANTE‐2017‐11,668)

“…cremophor) and PEG-propylene glycol copolymers (poloxamers) and povidone, all of them frequently implicated in immediate hypersensitivity reactions; and propylene glycol, which is the most commonly involved in delayed hypersensitivity reactions. [2][3][4][5] Furthermore, it should be noted that some pharmaceutical excipients are food or food-derived substances, such as casein, lysozyme and lactose (with potential milk proteins contaminating it, like ß-lactoglobulin, or alpha-gal related carbohydrate structures), which have been reported to be responsible for immediate hypersensitivity reactions, which could be a threat to patients with food allergy. 6 From the pharmaceutical point of view, an excipient is an inert substance, necessary as a support for the active principles in the formulation of almost all pharmacological or vaccine preparations, contributing to the stability, conservation, pharmacokinetics, bioavailability, appearance and acceptability by the patients, among other functions.…”

Disproportionate drug allergy labelling among middle-aged patients and barriers to excipient allergy testing from the Hong Kong Comprehensive Excipient and Drug Allergy Registry (CEDAR)

“…[7][8][9][10] Alternatively, mislabelled drug allergy can also be due to the possibility of missing hidden allergens found within drugs or vaccines such as in the case of excipient allergies. 11,12 Although an uncommon cause of drug allergy, excipient allergy can almost never be excluded in countries lacking in pharmaceutical legislations to mandate complete ingredient disclosure in registered medications. This can and has led to cases of missed-and mis-diagnoses with potentially lethal consequences.…”