Fluoxetine Ciclosporin

Imidazoles, grapefruit juice, ciclosporin, macrolides, fluoxetine, etc. inhibit 3A4 ... 

SSRIs-FLUOXETINE IMMUNOMODULATING DRUGS-CICLOSPORIN t plasma concentrations of cidosporin with risk of nephrotoxicity, myelosuppression and neurotoxicity Inhibition of CYP3A4-mediated metabolism of cidosporin these inhibitors vary in potency Monitor plasma cidosporin levels to prevent toxicity... 

Fluvoxamine and fluoxetine have been involved in isolated cases of increased blood ciclosporin concentrations, but fluoxetine was not confirmed to affect ciclosporin concentrations significantly in 13 patients (SEDA-20, 345) (SEDA-22, 385-386). In an analysis of changes in ciclosporin clearance and systemic availability obtained from the medical records of 100 transplant patients, sertraline altered ciclosporin pharmacokinetics (228). 

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 small, retrospective study in 9 liver transplant and 4 heart transplant patients found no evidence that fluoxetine 5 to 20 mg daily increased ciclosporin blood levels. However, the ciclosporin blood levels of a heart transplant patient were doubled by fluoxetine 20 mg daily for 10 days. They fell when the ciclosporin dosage was reduced and needed to be increased again when the fluoxetine was stopped. ... 

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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