CYP3A4 and skin reaction: This could be partly explained by recent reports which showed that NVP was metabolically activated to quinone methidine, a toxic reactive metabolite, by CYP3A4, and, to a lesser extent, CYP2D6, CYP2C19, and CYP2A6 [22], and that this reactive metabolite was responsible for NVP-induced skin reactions [23].