Hypersensitivity reactions from additives in pharmaceuticals

Most drug allergic reactions are caused by the active principle of the drug or one of its metabolites. In allergic reactions which cannot be attributed to the active substance, additives have to be considered as potential causative agent. These so called excipients or additives are ingredients that do not account for the diagnostic or therapeutic effect of the drug. They include, among others, preservatives, antioxidants and colorants. Although they themselves are not the active principle for the advertised therapeutic effect they may well cause unwanted reactions, especially immediate type reactions, more rarely exanthematic reactions. This has been demonstrated for e.g. carboxymethylcellulose (E466), macrogols (polyethylenglycols), colorants such as patent blue V (E131) and fluorescein, as well as for preservatives and antioxidants. Some of those additives can play a role as active principle in other drug formulations. The pathomechanism of these hypersensitivity reactions is frequently unknown; in case of immunologically mediated reactions skin tests can occasionally be helpful. For some substances, IgE-assays or basophil activation tests have been described. Identification of an additive as allergen is important for the patient since they may be present in other drug formulations, such as topical, oral or systemic medications, as well as in foods. Some of the so called idiopathic anaphylactic reactions may be attributable to an additive as causative agent.