Nefazodone drug administration

A number of SSRIs and SNRIs were tested for their effects on cognitive function in repeated-dose studies in healthy, non-depressed volunteers. Studies with SSRIs before 1999 have been reviewed by Lane and O Hanlon (1999) and some more recent reports deal with nefazodone. paroxetine and sertraline (Furlan et al., 2001 Schmitt et al., 2001 van Laar et al.. 2002). However, considering the populations studied in these trials (non-depressed subjects), the duration of drug administration (1 2 weeks) and the mostly low drug doses used, the relevance of these studies for a clinical situation may be questioned. 

Nefazodone presentation to the Food and Drug Administration Psychopharmacology Advisory Committee. Washington, DC, July 1993. 

Nefazodone is an inhibitor of the CYP3A4 isoenzyme, so it can raise the level and thus exacerbate adverse effects of many 3A4-dependent drugs. For example, triazolam levels are increased by concurrent administration of nefazodone such that a reduction in triazolam dosage by 75% is recommended. Likewise, administration of nefazodone with simvastatin has been associated with 20-fold increase in plasma levels of simvastatin. 

Nefazodone is a weak inhibitor of CYP2D6, but a potent inhibitor of CYP3A4, and increases plasma concentrations of drugs that are substrates of CYP3A4, such as triazolam, alprazolam, ciclosporin, astemizole, cisapride, terfenadine, and carbamazepine (26). Co-administration with terfenadine, astemizole, or cisapride should be avoided, because of the risk of cardiac dysrhythmias (SEDA-20, 9). 

The use of cisapride and its benefit to harm balance in children has been reviewed (25). Overall it is well tolerated. The most common adverse effects are diarrhea, abdominal cramps, borborygmi, and colic. Serious adverse events are rare and include isolated cases of extrapyramidal reactions, seizures in epileptic patients, cholestasis, QT interval prolongation and ventricular dysrhythmias, anorexia, and enuresis. Interactions of cisapride with other drugs are similar to those reported in adults. Co-administration of drugs that inhibit CYP3A4, such as imidazoles, macrolide antibiotics, the antidepressant nefazodone, and protease inhibitors such as ritonavir, are contraindicated. Furthermore, co-administration of anticholinergic drugs can compromise the beneficial effects of cisapride. 

Carbamazepine should not be used in patients with a history of previous bone m arrow depression, or known hypersensitivity to carbamazepine or tricyclic compounds. It is contraindicated with concomitant use of an MAOI or within 14 days of discontinuing an MAOI. Co-administration of carbamazepine and nefazodone may result in insufficient plasma concentrations of nefazodone and decreased drug effectiveness. Coadministration of carbamazepine with nefazodone is contraindicated. 

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