Voriconazole Cyclosporine

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. 

Significant drug interactions include cyclosporins (increased cyclosporine levels), phenytoin, rifampin, and rifabutin (decreased voriconazole levels). Because of its low toxicity profile, this drug may gain importance in the chronic treatment of infections with invasive dimorphic fungi and resistant Candida spp. 

Drugs that may inhibit cytochrome P450 metabolism of other drugs include amiodarone, androgens, atazanavir, chloramphenicol, cimetidine, ciprofloxacin, clarithromycin, cyclosporine, delavirdine, diltiazem, diphenhydramine, disulfiram, enoxacin, erythromycin, fluconazole, fluoxetine, fluvoxamine, furanocoumarins (substances in grapefruit juice), indinavir, isoniazid, itraconazole, ketoconazole, metronidazole, mexile-tine, miconazole, nefazodone, omeprazole, paroxetine, propoxyphene, quinidine, ritonavir, sulfamethizole, verapamil, voriconazole, zafirlukast, and zileuton. 

Sirolimus is metabolized by CYP2A4 and is a substrate of the P-glycoprotein drug efflux pump drugs like voriconazole, itraconazole, fluconazole and erythromycin increase its blood concentration. Conversely, the inducers of CYP3A4 will decrease blood levels of sirolimus. Cyclosporine increases the bioavailability of sirolimus, possibly due to P-GP inhibition and competition for CYP3A4. The bioavailability is more than 30-40% when the two drugs are administered 4 h apart and is more than... 

Micafungin Topical 0.1% solution 1 drop ql h while awake Side effects include pulmonary edema, blood dyscrasias, hypercalcemia, hepatotoxicity (rare), gastrointestinal symptoms, headache, fever, chills, anemia, eosinophilia, hypokalemia, liver function test elevations, infusion site reactions. Drug interaction with cyclosporine and additional voriconazole. Pregnancy category C lactation safety unknown. Coadministration of caspofungin is contraindicated with multiple antiretrovirals (refer to Table 11-3) Topical not commercially available... 

Romero AJ, Pogamp PL, Nilsson LG, Wood N. Effect of voriconazole on the pharmacokinetics of cyclosporine in renal transplant patients. Clin Pharmacol Ther 2002 71(4) 226-34. 

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... 

Clinically important, potentially hazardous interactions with alfentanil, alfuzosin, alprazolam, amiodarone, amprenavir, aprepitant, astemizole, atazanavir, bepridil, buprenorphine, bupropion, carbamazepine, chlordiazepoxide, ciclesonide, clozapine, conivaptan, cyclosporine, cyproterone, dasatinib, diazepam, dihydroergotamine, ergot alkaloids, estazolam, eszopidone, etravirine, ezetimibe, fentanyl, fesoterodine, flecainide, flurazepam, fluticasone, halazepam, ivabradine, ixabepilone, ketoconazole, lapatinib, levothyroxine, meperidine, meptazinol, methysergide, midazolam, nifedipine, nilotinib, oral contraceptives, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quazepam, quinidine, ranolazine, rifabutin, rifampin, rifapentine, rimonabant, rivaroxaban, saquinavir, sildenafil, silodosin, simvastatin, solifenacin, St John s wort, tadalafil, temsirolimus, trabectedin, triazolam, vardenafil, voriconazole, zolpidem... 

Clinically important, potentially hazardous interactions with cyclosporine, hemophilus B vaccine, itraconazole, micafungin, St John s wort, telithromycin, voriconazole, zotarolimus... 

Coadministration with rifampin, rifabutin, or ritonavir is contraindicated because of accelerated voriconazole metabolism. Efavirenz and perhaps other normucleoside reverse transcriptase inhibitors (NNRTIs) significantly increase voriconazole metabolism and slow the metabolism of the NNRTI. When given with phenytoin, the voriconazole dose should be doubled. Drugs that significantly accumulate in patients receiving voriconazole include cyclosporine,... 

Observational studies A retrospective survey reported life-threatening complications associated with cyclosporine A and azole antimycotes itraconazole and voriconazole in 10 out of 104 (9.6%) cases [12 ]. Six patients developed fatal acute graft-versus-host disease and another four patients presented fatal neurological complications. The authors suggest avoiding azole antimycotics during cyclosporine A treatment. 

Kikuchi T, Mori T, Yamane A, Kato J, Kohashi S, Okamoto S. Variable magnitude of drug interaction between oral voriconazole and cyclosporine A in recipients of allogeneic hematopoietic stem cell transplantation. Clin Transplant September-October 2012 26(5) E544-8. PubMed PMID 23061764. Epub 2012/10/16. eng. 

Adefovir, amlodipine, busulfan, cefaclor, cefdinir, cefixime, citalopram, cyclosporine, fenofibric acid, hydrocodone, hydromorphone, lonafarnib, nalmefene, rosuvastatin voriconazole... 

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