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

J Allergy Clin Immunol Pract. 2021 Aug;9(8):2968-2982. doi: 10.1016/j.jaip.2021.03.002. Epub 2021 Mar 15.


Excipients are necessary as a support to the active ingredients in drugs, vaccines, and other products, and they contribute to their stability, preservation, pharmacokinetics, bioavailability, appearance, and acceptability. For both drugs and vaccines, these are rare reactions; however, for vaccines, they are the primary cause of immediate hypersensitivity. Suspicion for these "hidden dangers" should be high, in particular, when anaphylaxis has occurred in association with multiple chemically distinct drugs. Common excipients implicated include gelatin, carboxymethylcellulose, polyethylene glycols, and products related to polyethylene glycols in immediate hypersensitivity reactions and propylene glycol in delayed hypersensitivity reactions. Complete evaluation of a suspected excipient reaction requires detailed information from the product monograph and package insert to identify all ingredients that are present and to understand the function and structure for these chemicals. This knowledge helps develop a management plan that may include allergy testing to identify the implicated component and to give patients detailed information for future avoidance of relevant foods, drugs, and vaccines. Excipient reactions should be particularly considered for specific classes of drugs where they have been commonly found to be the culprit (eg, corticosteroids, injectable hormones, immunotherapies, monoclonal antibodies, and vaccines). We provide a review of the evidence-based literature outlining epidemiology and mechanisms of excipient reactions and provide strategies for heightened recognition and allergy testing.

Keywords: Allergy; Anaphylaxis; Biologic; Carboxymethylcellulose (CMC); Corticosteroid; Drug; Excipient; Gelatin; Inactive ingredient; Polyethylene glycol (PEG); Polysorbate; Vaccine; alpha-gal.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anaphylaxis* / diagnosis
  • Drug Hypersensitivity* / diagnosis
  • Excipients / adverse effects
  • Humans
  • Hypersensitivity*
  • Hypersensitivity, Immediate*
  • Polyethylene Glycols
  • Vaccines* / adverse effects


  • Excipients
  • Vaccines
  • Polyethylene Glycols