Itraconazole and Nefazodone interaction

SSRIs, Tricyclics and Related Antidepressants Venlafaxine Monitor for adverse reactions.

Cardiac Dysrhythmias : Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients using certain drugs that are metabolized by human CYP450 enzymes concomitantly with oral itraconazole and/or other CYP3A4 inhibitors.

Cardiac Dysrhythmias Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients using drugs such as, pimozide, methadone, or quinidine concomitantly with oral itraconazole and/or other CYP3A4 inhibitors.

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug.

Similarly, there were no changes in the pharmacokinetic parameters of nefazodone or HO-NEF; however, the mean AUC levels of the nefazodone metabolites mCPP and triazole-dione increased by 3 to 6 fold and 1.3 fold, respectively.

There were also no changes in the pharmacokinetics of nefazodone or its triazole-dione metabolite, but the AUC and C max of mCPP increased by 44% and 48%, respectively, while the AUC of HO-NEF decreased by 19%.

When the two drugs were coadministered, there were no changes in the steady-state pharmacokinetics of either lithium, nefazodone, or its metabolite HO-NEF; however, there were small decreases in the steady-state plasma concentrations of two nefazodone metabolites, mCPP and triazole-dione, which are considered not to be of clinical significance.

Similar reductions in the C max and AUC of HO-NEF were also observed (85% and 94%), while the reductions in C max and AUC of mCPP and triazole-dione were more modest (13% and 44% for the former and 28% and 57% for the latter).