Nefazodone CYP3A4 substrates

Nefazodone is a phenylpiperazine structurally related to trazodone. Both nefazodone and trazodone block the reuptake of serotonin at presynaptic neurones and block aj-adrenoceptors, but have no apparent effect on dopamine. Unlike trazodone, nefazodone blocks the reuptake of noradrenaline. Compared to the tricyclics, neither drug has very significant antimuscarinic effects, but trazodone also has marked sedative properties. Nefazodone is an inhibitor of the cytochrome P450 isoenzyme CYP3A4 and therefore it will inhibit the metabolism of drugs by this route. For a list of CYP3A4 substrates see Table 1.4 , (p.6). Note that, nefazodone has largely been withdrawn due to adverse hepatic effects. 

Nefazodone is a weak inhibitor of CYP2D6 but a potent inhibitor of CYP3A4 and it increases plasma concentrations of drugs that are substrates of CYP3A4, such as alprazolam, astemizole, carbamazepine, ciclosporin, cisapride, terfenadine, and triazolam. 

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