Voriconazole drug interactions

Many experts now consider voriconazole as the initial drug of choice for invasive aspergillosis in patients without significant contraindications (e.g., drug interactions or preexisting liver dysfunction) to azole therapy. 

Is voriconazole an acceptable option in this patient Are there any drug interaction concerns ... 

Voriconazole 6 mg/kg IV loading dose every 12 hours on day 1 followed by 4 mg/kg PO/IV every 12 hours Dosage adjustment in hepatic dysfunction IV formulation contraindicated if creatinine clearance less than 50 mDminute multiple drug interactions. 

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. 

Etravirine is a substrate as well as an inducer of CYP3A4 and an inhibitor of CYP2C9 and CYP2C19 it has many therapeutically significant drug-drug interactions (Tables 49-3 and 49-4). Some of the interactions are difficult to predict. For example, etravirine may decrease itraconazole and ketoconazole concentrations but increase voriconazole... 

ITRACONAZOLE, FLUCONAZOLE, MICONAZOLE, VORICONAZOLE SULPHONYLUREAS t risk of hypoglycaemic episodes Inhibition of CYP2C9-mediated metabolism of these sulphonylureas Watch for and warn patients about symptoms of hypoglycaemia >- For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia... 

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... 

Voriconazole is contraindicated in patients with known hypersensitivity to voriconazole or its components. There is no information regarding cross-sensitivity between voriconazole and other azole antifungal agents. Caution should be used when prescribing voriconazole to patients with hypersensitivity to other azoles. Refer to Table 11-14 for drug interactions. 

Voriconazole has a half-life of about 6 hours and undergoes complex hepatic metabolism. There is wide intersubject variability in the disposition of voriconazole, which is at least partly related to a CYP2C19 polymorphism. Voriconazole has the potential for drug-drug interactions mediated by CYP3A4, CYP2C9, and CYP2C19. 

Ullmann AJ. Review of the safety, tolerability, and drug interactions of the new antifungal agents caspofungin and voriconazole. Curr Med Res Opin 2003 19(4) 263-71. 

In more advanced esophageal disease, oral azoles may be ineffective. Until recently, intravenous amphotericin B deoxycholate has been the alternative for patients with endoscopically proven disease who have failed fluconazole or itraconazole therapy.22 2" Moderate disease may be treated adequately with low- to moderate-dose amphotericin B for 10 days, although higher doses may be necessary for patients with AIDS or advanced disease. " Voriconzole, a new triazole antifungal available in both oral and intravenous preparations, produces comparable clinical response to fluconazole. Voriconazole has been associated with more side effects and multiple pharmacokinetic drug interactions. " ... 

Petraitis V et al. Combination therapy in treatment of experimental pulmonary aspergillosis in vitro and in vivo correlations of the concentration and dose-dependent interactions between anidulafungin and voriconazole by Bliss independence drug interaction analysts. Antimicrobial Agents and Chemotherapy. 

Drug-drug interactions Fluconazole and voriconazole The kinetic and dynamic interactions of diazepam 5 mg with variable doses of fluconazole and voriconazole have been evaluated in a randomized controlled study in 12 healthy volunteers [1(T]. Both voriconazole and fluconazole markedly increased exposure to diazepam. After voriconazole, the plasma diazepam concentration increased 2.2-fold and the mean half-life was prolonged from 31 to 61 hours. After fluconazole, the plasma diazepam concentration increased 2.5-fold, and the mean half-life was prolonged from 31 to 73 hours. The peak plasma diazepam concentration was unchanged by voriconazole and fluconazole. The pharmacodynamics of diazepam showed only minor changes. Caution should be taken during concurrent administration of diazepam with these medications. 

Kato J, Mori T, Nakamura Y, Sakurai M, Aisa Y, Ikeda Y, Okamoto S. Hypotension due to the drug interaction of voriconazole with eplerenone and nifedipine. Eur J Clin Pharmacol 2009 65 323-4. 

Drug-drug interactions The lack of voriconazole-mediated effect on the plasma concentrations of arunavir/ritonavir and etravirine has been reported [35 ]. 

Aouri M, Decosterd LA, Buclin T, Hirschel B, Calmy A, livio F. Drug interactions between voriconazole, darunavir/ritonavir and etravirine in an HIV-infected patient with Aspergillus pneumonia. AIDS 2012 26(6) 776-8. 

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 drug interaction between oral voriconazole 400 mg and a stable dose of oral ciclosporin A (CsA) was compared in a prospective trial of 20 adult recipients of haematopoietic stem cell transplantation (HSCT). With concurrent therapy, the median concentration/dose (C/D) ratio of CsA increased significantly from 64.1 to 114.3(ng/mL)/(mg/kg) (p<0.01) [4 ]. 

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. 

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