INTERACTIONS BETWEEN CYCLOSPORINE AND NEWER ANTIDEPRESSANT MEDICATIONS

The favorable safety profile of the newer antidepressant drugs recentl y introduced has lead to their increased use in transplant recipients, These new agents are a chemically diverse group of compounds that hav e selective serotonin reuptake inhibitory properties. Most of these me dications inhibit one or more hepatic microsomal cytochrome p450 isoen zymes, Because cyclosporine is metabolized predominantly by CYP3A3/4 i soenzymes, inhibition of this system can lead to the buildup of toxic levels, Two case reports of cyclosporine toxicity attributable to inte ractions with the novel antidepressants nefazodone and fluvoxamine are presented, The serum creatinine and whole blood cyclosporine levels w ere found to be elevated at a routine clinic visit, Although it was su bsequently possible to reduce the dose of cyclosporine by between 33% and 50%, the frequency of blood draws and consultations was greatly in creased in both patients over several weeks, resulting in considerable patient anxiety, Interestingly, both nefazodone and fluvoxamine are k nown to potently inhibit the CYP3A3/4 isoenzymes, It is concluded that the introduction of a novel antidepressant to a cyclosporine-treated allograft recipient may be complicated by cyclosporine toxicity, Inten sive monitoring of the serum creatinine and cyclosporine level is indi cated under such circumstances, with dose reductions performed as indi cated, (C) 1998 by the National Kidney Foundation, Inc.