Transdermal compositions, devices, and methods for the administration of a drug at reduced skin irritation levels are disclosed. More particularly, this invention relates to novel methods, compositions, and devices for the reduction or elimination of irritation or sensitization caused by an irritating or sensitizing drug when it is delivered transdermally. According to a preferred embodiment, transdermal administration of a drug salt of a non-zwitterionic drug is disclosed wherein the drug salt comprises a combination of surface activity and a low octanol-water partition coefficient. Such drug salts have been found to reduce irritation or sensitization to the drug being delivered while achieving therapeutically effective transdermal fluxes.