Ketoconazole should not be given to a patient being treated with astemizole because:
Ketoconazole, erythromycin and clarithromycin are potent inhibitors of microsomal enzymes. Astemizole, terfenadine and cisapride are the drugs that can block cardiac K+ channels at high concentration. If administered along with microsomal enzyme inhibitors, these drugs can result in torsades de pointes, a serious polymorphic ventricular tachycardia.
Ketoconazole induces the metabolism of astemizole
Dangerous ventricular arrhythmias can occur
Astemizole inhibits the metabolism of ketoconazole
Astemizole antagonizes the antifungal action of ketoconazole
Histamine, 5-HT and PGs