Voriconazole Tacrolimus

Voriconazole is started in the patient along with 1 mg/kg per day of methylprednisolone to control the graft-versus-host disease. Her tacrolimus dose was also decreased by 70% with the addition of voriconazole and a recent tacrolimus blood level of 1 0 ng/mL. Unfortunately, the patient remains febrile with worsening respiratory pain. A repeat CT scan of the lung demonstrates new nodules, and pleural effusion in the right lung. 

Drugs affected by voriconazole include the following benzodiazepines, calcium channel blockers, cisapride, coumarin anticoagulants, cyclosporine, ergot alkaloids, HMG-CoA reductase inhibitors, NNRTIs, phenytoin, protease inhibitors, pimozide, proton pump inhibitors, quinidine, prednisolone, rifabutin, sirolimus, sulfonylureas, tacrolimus, vinca alkaloids. 

Prednisolone Progesterone Protease Inlaibitors Quinidine (1 )-Warfarin Rifampin Sertraline Sirolimus Simvastatin Tacrolimus Testosterone Trazadone Triazolam Voriconazole ... 

In a patient who took tacrolimus after hver transplant, co-administration of voriconazole resulted in raised trough tacrolimus concentrations (nearly 10-fold) there were no changes in another patient, who took a placebo (123). Voriconazole inhibits the metabohsm of tacrolimus in liver microsomes by 50% in vitro. 

Venkataramanan R, Zang S, Gayowski T, Singh N. Voriconazole inhibition of the metabolism of tacrolimus in a liver transplant recipient and in human hver micro-somes. Antimicrob Agents Chemother 2002 46(9) 3091-3. 

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 amiodarone, anisindione, anticoagulants, azithromycin, corticosteroids, cyclosporine, dapsone, delavirdine, dicumarol, fosamprenavir, lapatinib, lopinavir, midazolam, oral contraceptives, ritonavir, solifenacin, tacrolimus, temsirolimus, tolvaptan, voriconazole... 

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. 

Fluconazole, itraconazole, ketoconazole, posaconazole and voriconazole inhibit the metabolism of the tacrolimus by the gut wall and/or liver by the cytochrome P450 isoenzyme CYP3A4, and/or inhibit the activity of P-glycoprotein so that more tacrolimus is absorbed.Therefore, intravenous tacrolimus is little affected." ... 

The manufacturers of voriconazole advise reducing the tacrolimus dose to one-third when starting voriconazole, closely monitoring tacrolimus levels throughout, and increasing the tacrolimus dose in response to levels obtained when voriconazole is stopped. However, greater reductions in tacrolimus dose may be needed in some patients, and raised tacrolimus levels requiring a total 90% tacrolimus dose reduction were reported in one patient. ... 

Wood N, Tan K, Allan R, Fieldii A, Nichols DJ. Effect of voriconazole on the pharmacokinetics of tacrolimus. Intersci Corf Antimicrob Agents Chemother 200 )4, 2. 

Tintillier M, Kirch L, Goffin E, Cuvelier C, Pochet J-M Interaction between voriconazole and tacrolimus in a kidney-transplanted patient. Nephrol Dial Transplant (2005) 20,664-5. 

Tacrolimus An interaction of voriconazole with tacrolimus has been described [22 ]. 

Chang HH, Lee NY, Ko WC, Lee HC, Yang YH, Wu CJ, Chang CM. Voriconazole inhibition of tacrolimus metabolism in a kidney transplant recipient with fluconazole-resistant cryptococcal meningitis. Int J Infect Dis 2010 14(4) e348-50. 

TrifUio SM, Scheetz MH, Pi J, Mehta J. Tacrolimus use in adult allogeueic stem cell trausplaut redpieuts receiving voriconazole preemptive dose modification and therapeutic drug monitoring. Bone Marrow Transplant 2010 45(8) 1352-6. 

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

Tacrolimus A study and a case report describing DDIs with tacrolimus and fluconazole or voriconazole, respectively have been described [60, 61 ]. 

A 58-year-old man with acute liver failure received tacrolimus (3 mg b.i.d) 8 days after liver transplantation [61 ]. On day 11 after transplantation, A. fumigatus was cultured from broncho-alveolar lavage and voriconazole started. At the same time tacrolimus dose was reduced to 30% to avoid toxicity. Oral voriconazole was started on day 21 to avoid nephrotoxicity, which... 

Spriet 1, Grootaert V, Meyfroidt G, Debaveye Y, Willems L. Switching from intravenous to oral tacrolimus and voriconazole leads to a more pronounced drug-drug interaction. Eur J Qin Pharmacol 2013 69(3) 737-8. 

The oral dose of voriconazole does not have to be adjusted in patients who have renal impairment. However, intravenous administration of voriconazole should be avoided in these patients as the carrier vehicle sulfobu-tyl ether P-cyclodextrin sodium can accumulate in these patients. Dosage adjustment is required in patients who have chronic hepatic impairment. As voriconazole is a substrate for a number of cytochrome P450 enzymes, a number of clinically important dmg interactions occur with dmgs including ciclospotin, tacrolimus, phenytoin, warfarin, HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors. 

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