Nefazodone Tacrolimus

Drugs that affect nefazodone include general anesthetics, sibutramine, sumatriptan, buspirone, carbamazepine, and propranolol. Drugs that may be affected by nefazodone include alcohol, benzodiazepines, buspirone, carbamazepine, cisapride, digoxin, haloperidol, HMG-CoA reductase inhibitors, MAOIs, propranolol, St. John s wort, cyclosporine, and tacrolimus. 

Drugs that may affect tacrolimus include nephrotoxic agents (aminoglycosides, amphotericin B, cisplatin, cyclosporine), antifungals, bromocriptine, calcium channel blockers, cimetidine, clarithromycin, danazol, diltiazem, erythromycin, methylprednisolone, metoclopramide, carbamazepine, phenobarbital, phenytoin, rifamycins, cisapride, chloramphenicol, metronidazole, nefazodone, omeprazole, protease inhibitors, macrolide antibiotics, fosphenytoin, and St. John s wort. 

The catabolism of lovastatin, simvastatin, and atorvastatin proceeds chiefly through CYP3A4, whereas that of fluvastatin and rosuvastatin is mediated by CYP2C9. Pravastatin is catabolized through other pathways, including sulfation. The 3A4-dependent reductase inhibitors tend to accumulate in plasma in the presence of drugs that inhibit or compete for the 3A4 cytochrome. These include the macrolide antibiotics, cyclosporine, ketoconazole and its congeners, HIVprotease inhibitors, tacrolimus, nefazodone, fibrates, and others (see Chapter 4). Concomitant use of reductase inhibitors with amiodarone or verapamil also causes an increased risk of myopathy. 

Campo JV, Smith C, Perel JM. Tacrolimus toxic reaction associated with the use of nefazodone paroxetine as an alternative agent. Arch Gen Psychiatry 1998 55(ll) 1050-2. 

Olyaei AJ, deMattos AM, Norman DJ, Bennett WM. Interaction between tacrolimus and nefazodone in a stable renal transplant recipient. Pharmacotherapy 1998 18 1356-1359. 

A4 Amiodarone, azole antifungals, cimetidine, clarithromycin, cyclosporine, erythromycin, fluoroquinolones, grapefruit juice, HIV protease inhibitors, metronidazole, quinine. SSRIs, tacrolimus Antiarrhythmics, antidepressants, azole antifungals, benzodiazepines, calcium channel blockers, cyclosporine, delavirdine, doxorubicin, efavirenz, erythromycin, estrogens, HIV protease inhibitors, nefazodone. paclitaxel, proton pump inhibitors, HMG-CoA reductase inhibitors, rifabutin, rifampin, sildenafil, SSRIs, tamoxifen, trazodone, vinca anticancer agents... 

Marked increases in tacrolimus levels and toxicity were observed when three patients were also given nefazodone. In theory, flu-voxamine may increase tacrolimus levels. Paroxetine and sertraline may not interact, but the situation is not clear. 

A kidney transplant patient taking prednisone, azathioprine and tacrolimus 5 mg daily for 2 years experienced headache, confusion and grey areas in her vision within one week of starting nefazodone 50 mg twice daily in place of sertraline, for depression. Her serum creatinine had risen from 132 to 195 micromol/Land her trough tacrolimus level was greater than 30 nanograms/niL. Nefazodone was replaced by sertraline, and tacrolimus was withheld for 4 days. Signs oftacrolimus-induced neurotoxicity disappeared within 36 hours and serum creatinine and tacrolimus levels returned to pretreatment levels within 2 weeks. ... 

Another patient developed raised liver enzymes and raised tacrolimus levels after taking nefazodone and tacrolimus for 2 weeks. When the nefazodone was stopped his liver enzymes normalised over the next 5 days, and his tacrolimus levels fell from 23 to 9.5 nanograms/mL over 10 days. ... 

Tacrolimus is metabolised by the cytochrome P450 isoenzyme CYP3A4, which is inhibited by nefazodone, concurrent use therefore results in increased levels of tacrolimus. Paroxetine and sertraline do not have significant effects on CYP3A4 and are therefore not expected to interact with tacrolimus. 

Information appears to be limited but what is known indicates that tacrolimus levels or at least signs of toxicity should be well monitored if nefazodone is also given. In view of the narrow therapeutic index of tacrolimus, it may be advisable to avoid concurrent nefazodone. 

Garton T, Nefazodone and CYP450 3A4 interactions with cyclosporine and tacrolimus. Transplantation (2002) 74, 745. 

Fexofenadine Imatinib Irinotecan Loperamide Methadone Midazolam Nefazodone Nevirapine Omeprazole Paroxetine oral contraceptives Phenprocoumon Setraline Simvastine Tacrolimus Theophylline Tolbutamide Voriconazole Warfarin... 

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