Nefazodone Ciclosporin

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. 

Nefazodone can alter blood ciclosporin concentrations (276,277). In one case there was nearly a 10-fold increase in whole-blood ciclosporin concentrations in a cardiac transplant patient shortly after the addition of nefazodone (278). 

Four cases of raised ciclosporin levels have been seen in patients taking nefazodone and ciclosporin, one with raised creatinine levels and tremor, and one with raised liver enzymes. A small study found no evidence of an interaction between fluoxetine and ciclosporin although one case of increased ciclosporin levels has been seen with fluoxetine. Fluvoxamine may inhibit the metabolism of ciclosporin and one case of increased ciclosporin levels has been reported with fluvoxamine. The serotonin syndrome has... 

A 53-year-old man taking ciclosporin following a renal transplant developed the serotonin syndrome 5 days after starting to take sertraline 50 mg daily. Ciclosporin is known to increase serotonin turnover within the brain, and so the reaction was attributed to an interaction between sertraline and ciclosporin. One report briefly mentions that a patient taking ciclosporin had her antidepressant medication switched from nefazodone to sertraline, because sertraline did not affect ciclosporin levels. ... 

Fluvoxamine and nefazodone are inhibitors of the cytochrome P450 isoenzyme CYP3A4, the main isoenzyme by which ciclosporin is metabolised. Concurrent use can therefore lead to increased ciclosporin levels. Fluoxetine may interact similarly. Citalopram and sertraline do not usually signifrcantly inhibit CYP3A4 and would therefore not be expected to interact. 

Although the evidence is limited, it appears that nefazodone can cause a marked rise in ciclosporin levels, with an increase in adverse effects. Alternative antidepressants should probably be used, or concurrent therapy very well monitored. Similar caution would seem prudent with fluvoxamine, and possibly fluoxetine. Citalopram, and sertraline do not appear to alter ciclosporin levels and may therefore be suitable alternatives. Serotonin syndrome is a rare adverse effect, usually associated with the use of more than one serotonergic drug (see The serotonin syndrome , (p.9)). 

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