Tacrolimus with itraconazole

The interactions of tacrolimus with itraconazole and ketoconazole also appear to be established, and the manufacturer states that nearly all patients will require tacrolimus dose reductions when given these drugs. Information about clotrimazole is limited, but on the basis of the case report and study it would be prudent to monitor tacrolimus levels, and adjust the dose as necessary. 

A patient taking tacrolimus 0.085 mg/kg bd with itraconazole 200-400 mg/day developed ketoacidosis, neutropenia, and thrombocytopenia, requiring the withdrawal of both drugs (114). 

A 34-year-old renal transplant recipient taking a stable regimen of tacrolimus and methylprednisolone was given itraconazole 100 mg bd for a yeast infection of the urinary tract (115). Concomitant therapy with itraconazole led to a marked increase in tacrolimus trough concentrations on the second day of therapy (from 13 to 21 ng/ml) and an increase in serum creatinine concentrations, necessitating dosage reduction of tacrolimus by 50%. 

A 17-year-old man with cystic fibrosis who took itraconazole after a lung-Uver transplant had high trough concentrations of tacrolimus, despite the relatively low dosage (0.1-0.3 mg/kg/day) (113). 

The inhibitory effect of itraconazole occurred quickly, while the time of disappearance was much longer, which is important for clinical management. Thus, during co-administration of itraconazole with tacrolimus, close... 

A 30-year-old man with a renal transplant had a more than two-fold increase in blood tacrolimus concentrations after starting to take itraconazole 200 mg/day, accompanied by a reduced glomerular filtration rate and biopsy-proven tacrolimus-associated tubulopathy (120). 

Clinically important, potentially hazardous interactions with alfentanil, aminophylline, amisulpride, amoxicillin, ampicillin, anticonvulsants, astemizole, atorvastatin, benzodiazepines, bromocriptine, buprenorphine, bupropion, carbamazepine, cilostazol, ciprofloxacin, cisapride, clindamycin, colchicine, cyclosporine, dasatinib, digoxin, dihydroergotamine, diltiazem, disopyramide, enoxacin, eplerenone, ergotamine, eszopiclone, everolimus, fluconazole, fluoxetine, fluvastatin, gatifloxacin, HMG-CoA reductase inhibitors, imatinib, itraconazole, ketoconazole, lomefloxacin, lorazepam, lovastatin, methadone, methylprednisolone, methysergide, midazolam, mizolastine, moxifloxacin, nitrazepam, norfloxacin, ofloxacin, paroxetine, pimozide, pravastatin, quinolones, ranolazine, repaglinide, rupatadine, sertraline, sildenafil, simvastatin, sparfloxacin, sulpiride, tacrolimus, terfenadine, triazolam, troleandomycin, vardenafil, verapamil, vinblastine, warfarin, zaleplon, zolpidem, zuclopenthixol... 

Clinically important, potentially hazardous interactions with abacavir, atorvastatin, bepridil, bupropion, carbamazepine, clarithromycin, cyclosporine, dexamethasone, digoxin, felodipine, fluticasone propionate, fosamprenavir, itraconazole, ketoconazole, lovastatin, methadone, midazolam, nicardipine, nifedipine, phenobarbital, phenytoin, rifabutin, simvastatin, sirolimus, St John s wort, systemic lidocaine, tacrolimus, tenofovir, trazodone, vinblastine, vincristine, voriconazole, warfarin, zidovudine... 

Clinically important, potentially hazardous interactions with atazanavir, azithromycin, bosentan, cholestyramine, clarithromycin, cyclosporine, darunavir, delavirdine, erythromycin, exenatide, fenofibrate, fosamprenavir, gemfibrozil, grapefruit juice, imatinib, itraconazole, red rice yeast, tacrolimus, telithromycin, tipranavir, tolvaptan, verapamil... 

Clinically important, potentially hazardous interactions with amiodarone, amprenavir, anisindione, antacids, anticoagulants, aprepitant, atazanavir, atovaquone, beclomethasone, buprenorphine, corticosteroids, cortisone, cyclosporine, cyproterone, dabigatran, dapsone, darunavir, delavirdine, dexamethasone, dicumarol, digoxin, eszopiclone, flunisolide, fosamprenavir, gadoxetate, gestrinone, halothane, imatinib, isoniazid, itraconazole, ketoconazole, lapatinib, lorcainide, methylprednisolone, midazolam, nelfinavir, nifedipine, oral contraceptives, phenylbutazone, prednisone, protease inhibitors, pyrazinamide, ramelteon, ritonavir, saquinavir, solifenacin, sunitinib, tacrolimus, telithromycin, temsirolimus, tipranavir, tolvaptan, trabectedin, triamcinolone, triazolam, voriconazole, warfarin, zaleplon... 

When tacrolimus is given orally, its serum levels are considerably increased by oral fluconazole, and tacrolimus dose reductions may be needed. Itraconazole, ketoconazole, posaconazole, voriconazole, and oral clotrimazole, also raise tacrolimus levels. There is some evidence that the levels of intravenous tacrolimus are minimally affected by fluconazole and ketoconazole. In theory it is possible that miconazole oral gel may also interact with tacrolimus. 

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