However, with multiple dosing, this difference is much smaller. It is recommended that these patients be started at one-half the initial dose and titrated as normally indicated. The safe and effective use of nefazodone in adults under 18 years of age has not been established. Nefazodone has been shown to have an effect on the pharmacokinetics of digoxin. Nefazodone's pharmacokinetics were not affected by digoxin.
Nefazodone inhibits the reuptake of serotonin and, to a lesser extent, norepinephrine.
Although severe reactions have been seen when drugs with a similar pharmacological profile were used with MAOI therapy, no controlled trials have been done with nefazodone. At least 2 weeks should elapse between the discontinuation of MAOI therapy and the start of nefazodone therapy, or vice versa. Inhibition of this enzyme by nefazodone results in increased plasma concentrations of both terfenadine and astemizole. Increased plasma concentrations of terfenadine or astemizole are associated with QT prolongation and rare cases of serious cardiovascular adverse events, including death due to torsade de pointes. 2-fold for triazolam and alprazolam, respectively.