Nonimmediate drug hypersensitivity reactions (NI-DHR) are the most complex type of drug allergy, involving numerous substances. Both the original medicines and their reactive metabolites could be involved. Although the number of metabolites is modest for some medications, it is rather large for others, with more still to be identified. Diagnostic techniques are insufficient, and realistic approaches that mimic the diseased reaction are absent. A broader perspective has recently been taken into account, including many processes that may contribute to drug hypersensitivity reactions (DHR): the classical hapten hypothesis, the danger signal, and the pharmacological interaction. Monitoring the acute reaction gives useful information about the mechanisms involved, with the identification of a significant number of genes that can be over- or under-expressed during the acute phase of the response. HLA connections can validate the assessment of the risk of developing responses.

More information on these NI-DHRs, such as molecular genetics and transcriptome studies, has allowed for a better understanding and treatment of these reactions.