Hepatic Safety of Voriconazole after Allogeneic Hematopoietic Stem Cell Transplantation

Department of Medicine, Service of Infectious Disease, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation (Impact Factor: 3.35). 01/2010; 16(1):46-52. DOI: 10.1016/j.bbmt.2009.08.015
Source: PubMed

ABSTRACT Voriconazole is increasingly used in allogeneic hematopoietic stem cell transplantation (HSCT) for prophylaxis and treatment of fungal infections. Hepatic dysfunction is common in patients undergoing HSCT and may have an impact on the clinical decision to institute voriconazole. We conducted a retrospective review of all adult and pediatric HSCT recipients who received >2 consecutive doses of voriconazole between January 2005 and February 2008. Clinical hepatotoxicity was defined as the subjective attribution of liver enzyme elevation (even a mild one) to hepatotoxicity because of voriconazole by the treating physician and leading to discontinuation of voriconazole. Biochemical hepatotoxicity was defined as an elevation in one or more liver enzymes to >3 times the upper limit of normal or >3 times the baseline value if abnormal at baseline. Liver enzymes assessed included aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin. Simple and multiple logistic regressions were used to define the risks for hepatic dysfunction. The Wilcoxon signed-rank test was used to assess the differences in liver function test values before, during, and after the use of voriconazole. Sixty-eight of 200 patients (34%) developed hepatotoxicity while on voriconazole. The median duration of voriconazole therapy was 72 days (range, 1-804 days). Biochemical hepatotoxicity occurred in 51 patients (75%); clinical hepatotoxicity, in 17 patients (25%). Thirty-five (51%) of the patients with hepatotoxicity required discontinuation of therapy. In simple logistic regression, acute graft-versus-host disease (GVHD) was a risk factor for hepatotoxicity, and receipt of a T-cell depleted allograft was protective. In multiple logistic regression, acute GVHD (P = .002) remained significant. There were no cases of liver failure or death attributed to voriconazole. In this cohort of patients undergoing allogeneic HSCT, the rate of hepatotoxicity while on voriconazole was 34%. In general, the hepatic dysfunction was mild and reversible. Voriconazole therapy with monitoring appears to be reasonably safe for use in HSCT recipients at high risk for invasive fungal infections.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We aimed to investigate the role of several host factors as predictors of mortality in non-neutropenic patients with invasive pulmonary aspergillosis (IPA). Contribution of respiratory galactomannan (GM) index was evaluated as well. In this retrospective study we examined 27 patients with “proven” and “probable” IPA. Outcome measured was death within 6-week from diagnosis of possible IPA. Overall mortality was 33.3%. At univariate analysis, Nonsurvivors were statistically more likely to be affected with cirrhosis. No independent variables predicting mortality were identified in the multivariate model. Mean BAL GM index value in the nonsurvivor group was significantly higher. A GM index cutoff value ≥ 2.0 is able to classify patients with a poor outcome with a sensitivity of 100% and a specificity of 77%. Liver cirrhosis is a predictor of mortality in patients with IPA. GM index in BAL might be considered as a valuable tool in classifying patients at risk of poor outcome.
    Diagnostic Microbiology and Infectious Disease 05/2014; DOI:10.1016/j.diagmicrobio.2014.05.015 · 2.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Invasive fungal disease (IFD) causes significant morbidity and mortality among children undergoing allo-SCT. In this prospective pilot study, we analyze voriconazole as primary antifungal prophylaxis. From October 2004 to July 2010, 56 children <18 years of age were enrolled in this study. Patients received voriconazole doses of 5 mg/kg per 12 h (n=23) or 7 mg/kg per 12 h (n=33), with a limiting dose of 200 mg/12 h, from day -1 to day +75 or later in patients with active acute GVHD. Patients were followed up for IFD for 6 months. In this series, 37 (66.1%) patients successfully completed treatment (85.7% during neutropenic period) without empirical or preemptive antifungal therapy, adverse effects or IFD. Nine (16.1%) children needed preemptive (n=2) or empirical (n=7) antifungal therapy, and one (1.8%) of them developed a fatal probable IFD during the study period. A total of 10 (17.8%) children developed adverse effects related to voriconazole prophylaxis, leading to definitive withdrawal on median day 26.5 (in 7 patients after granulocytic recovery). The most frequent adverse effect was persistent elevation of hepatic enzymes in seven (12.5%) children. There were no differences between doses of 5 and 7 mg/kg per 12 h. Our results suggest that voriconazole can be safely used as primary antifungal prophylaxis in children undergoing allo-SCT.
    Bone marrow transplantation 05/2011; 47(4):562-7. DOI:10.1038/bmt.2011.111 · 3.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Skin toxicity due to voriconazole is well recognized. Recently, several series have reported skin cancer, particularly cutaneous squamous cell carcinoma (C-SCC), following photosensitivity reactions among patients receiving long-term voriconazole (>12 months). Almost all patients were immunosuppressed, including stem cell and solid organ transplant recipients. A case-control study of lung transplant recipients identified long-term voriconazole (median cumulative dose: 76 grams) and residence in areas of strong sun exposure as independent risk factors for C-SCC. The mechanism(s) by which voriconazole may predispose to skin cancer is not clear. Moreover, the relative contribution of voriconazole and other factors such as immunosuppression, ultraviolet exposure, advanced age and skin type is unknown. Until further data are available, voriconazole should be used carefully for durations >6-9 months, particularly among patients with risk factors for skin cancer. In patients requiring prolonged voriconazole, diligent skin examinations, avoidance of excess sunlight, and liberal use of UV protectants are advisable.
    Current Infectious Disease Reports 12/2011; 13(6):536-43. DOI:10.1007/s11908-011-0220-x


Available from