Hypersensitivity to Excipients in Drugs: An EAACI Position Paper

Drugs contain active pharmaceutical ingredients and excipients, compounds which enhance the pharmacokinetics, stability and palatability of the pharmaceutical formulation. While most drug hypersensitivity reactions (DHR) are caused by active ingredients, excipients may also be involved. Excipient-related DHR are easily overlooked and may lead to repeated anaphylaxis in patients exposed to pharmaceutical formulations containing different active ingredients. We performed an extensive review of the literature to provide practical recommendations on when to suspect and how to diagnose and manage excipient hypersensitivity. Where literature was limited, the collective experience of the authors was taken into consideration. Excipient hypersensitivity should be suspected in patients with a history of anaphylaxis to multiple drugs with chemically unrelated active ingredients and specific drug classes such as oral laxatives and injectable depot steroids or progestogens. Polyethylene glycol, methylcelluloses, gelatine, povidone and mannitol were identified as the most common culprits of DHR. DHR evaluation should include review of the product monograph to ascertain the presence of possible culprit excipients. Specific diagnostic tests for excipients should be performed when appropriate, including skin, in vitro and provocation testing with pure excipients and drugs with and without the excipient as controls. We provide consensus-based excipient-specific recommendations on diagnostic testing based on best available evidence.