Abstract
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug hypersensitivities with high mortality. Typical over-the-counter drugs of cold medicines are suggested to be causative. As multiple ingredients are generally contained in cold medicines, it is of particular interest to investigate which ingredients are responsible for SJS/TEN. However, experimental examination of causal relationships between SJS/TEN and a particular drug molecule is not straightforward. Significant association between HLA-A*02:06 and SJS/TEN with severe ocular surface complications has been observed in the Japanese. In the present study, we have undertaken in silico docking simulations between various ingredients contained in cold medicines available in Japan and the HLA-A*02:06 molecule. We use the composite risk index (CRI) that is the absolute value of the binding affinity multiplied by the daily dose to assess the potential risk of the adverse reactions. The drugs which have been recognized as causative drugs of SJS/TEN in Japan have revealed relatively high CRI, and the association between SJS/TEN and HLA-A*02:06 has been qualitatively verified. The results have also shown that some drugs whose links to SJS/TEN have not been clinically recognized in Japan show the high CRI and suggested that attention should be paid to their adverse drug reactions.
Highlights
Adverse drug reactions (ADRs) are a serious public health problem
We examined all ingredients contained in four popular overthe-counter cold medicines available in Japan, that is, Lulu, Pabron, Contac, and Benza Block
Two alpha sites designated sites N and C were identified in the antigenic-peptide binding groove of the human leukocyte antigen (HLA)-A∗02:06 molecule and these two sites were considered in docking simulations
Summary
Adverse drug reactions (ADRs) are a serious public health problem. Drug hypersensitivity which constitutes a major category of ADRs is typically severe in nature. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug hypersensitivities with high mortality. Various drugs have been pointed out as causes of SJS/TEN. In addition to certain prescription drugs, typical over-the-counter drugs of cold medicines are suggested to be causative [1, 2]. These reactions often result in severe and definitive sequelae such as vision loss in some cases [2]. The reported incidence of ocular complications in SJS/TEN is 50– 68% [3]
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