Cross-reactivity among drugs: clinical problems

Cross-reactivity among drugs is either mediated by immunologic mechanisms or not. The former kind is usually explained by the presence of common antigenic determinants in the cross-reacting drugs. In the case of compounds provoking non-allergic hypersensitivity reactions, cross-reactivity is explained by a common pharmacological characteristic, such as the inhibitory effect of non-steroidal anti-inflammatory drugs on cyclooxygenase-1 and the capability of muscle relaxants or contrast media to release histamine through a non-immunologic mechanism. The main clinical problem deriving from cross-reactivity among drugs is the compelling need to choose a potentially cross-reactive compound and, therefore, to assess cross-reactivity by diagnostic tests. In choosing alternative compounds, skin testing has been used in evaluating IgE-mediated cross-reactivity between penicillins and cephalosporins, as well as among muscle relaxants. In assessing T cell-mediated cross-reactivity among contrast media, corticosteroids, anticonvulsants and heparins, delayed-reading intradermal tests and patch tests, together with lymphocyte transformation tests, can be performed. Because of the limited sensitivity of in vivo and in vitro testing, the most prudent way of establishing the tolerability of a compound of the same group in patients who especially require one is a graded challenge when other allergologic tests are negative.