Fatal Acute Hepatic Necrosis Due to Dose‐Dependent Fluconazole Hepatotoxicity

Bronstein, Jean‐Ariel; Gros, Philippe; Hernandez, Éric; Larroque, P; Molinié, C

doi:10.1086/516975

Cited by 37 publications

(22 citation statements)

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“…Long-term maintenance therapy may be needed in those with severe and persistent immunosuppression or those who have relapsed after discontinuation of a 1-year course of Flu. Patients receiving high doses of Flu should be monitored closely for toxic effects, including measurement of Flu concentrations, hepatic enzymes, and bilirubin [29]. grant from the National Institutes of Health that much needed assistance was provided.…”

Section: Discussionmentioning

confidence: 99%

Amphotericin B Combined with Itraconazole or Fluconazole for Treatment of Histoplasmosis

et al. 2000

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To investigate the efficacy of combined treatment with fluconazole (Flu) and amphotericin B (AmB) for Histoplasma capsulatum meningitis, MICs were determined for 10 clinical isolates, following National Committee for Clinical Laboratory Standards guidelines. Weak synergy was observed for 6 of the 10 isolates. For the in vivo models, mice either were sham treated or were given Flu (75 mg/kg/day), AmB (2 mg/kg every other day), itraconazole (Itra; 75 mg/kg/day), AmB+Flu, or AmB+Itra. Following infection with 5x105 yeasts, Flu antagonized AmB's reduction of fungal burden without reducing its effect on survival. When in vivo antagonism was reproduced following infection with 1x104 yeasts, a higher fungal burden was observed in the lungs. Itra had no effect on AmB's activity and was more effective than Flu for clearance of fungal burden. These findings caution against use of AmB+Flu for treatment of histoplasmosis, but studies of the effect of treatment on the fungal burden in the brain are needed to assess combination therapy for meningitis.

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Section: Discussionmentioning

confidence: 99%

Amphotericin B Combined with Itraconazole or Fluconazole for Treatment of Histoplasmosis

et al. 2000

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“…In addition to being potent inhibitors of CYP3A4, fluconazole can cause mild to moderate serum aminotransferase elevations in up to 5% of treated patients. Fluconazole, as well as the other azole antifungals (itraconazole, voriconazole, ketoconazole), can also rarely lead to severe acute hepatocellular injury with jaundice (139, 140). …”

Section: Direct Acting Antivirals In the Pipelinementioning

confidence: 99%

Drug-drug interactions with oral anti-HCV agents and idiosyncratic hepatotoxicity in the liver transplant setting

Tischer

Fontana

2014

Journal of Hepatology

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Preliminary studies of boceprevir and telaprevir based antiviral therapy in liver transplant (LT) recipients with hepatitis C have demonstrated dramatic increases in tacrolimus, cyclosporine, and the mTOR inhibitor exposure. In addition to empiric dose reductions, daily monitoring of immunosuppressant blood levels is required when initiating as well as discontinuing the protease inhibitors to maximize patient safety. Although improved suppression of HCV replication is anticipated, 20 to 40% of treated subjects have required early treatment discontinuation due to various adverse events including anemia (100%), infection (30%), nephrotoxicity (20%) and rejection (5 to 10%). Simeprevir and faldepravir are 2nd generation protease inhibitors which may have improved efficacy and tolerability profiles but potential drug interactions with other OATP1B1 substrates and unconjugated hyperbilirubinemia are expected. In contrast, sofosbuvir and daclatasvir based therapies are not expected to lead to clinically significant drug-drug interactions in LT recipients but confirmatory studies are needed. Liver transplant recipients may also be at increased risk of developing drug induced liver injury (DILI). Establishing a diagnosis of DILI in the transplant setting is very difficult with the variable latency, laboratory features and histopathological manifestations of hepatotoxicity associated with a given drug, the need to exclude competing causes of allograft injury, and the lack of an objective and verifiable confirmatory test. Nonetheless, a heightened awareness of the possibility of DILI is warranted in light of the large number of medications used in LT recipients and the potential adverse impact that DILI may have on patient outcomes.

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“…While it is always tempting to attribute causality to newer or unfamiliar compounds, we believe that the authors have not considered another more familiar cause. From our assessment, the most likely cause is fluconazole-induced hepatotoxicity, which has been reported previously [2][3][4].…”

mentioning

confidence: 54%

Reported Case of Severe Hepatotoxicity Likely due to Fluconazole and <i>Not</i> Desloratadine

Kim¹,

Bindslev‐Jensen²

2004

Acta Haematol

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Fatal Acute Hepatic Necrosis Due to Dose‐Dependent Fluconazole Hepatotoxicity

Abstract: PhagocytosisOxidative burst suggesting a synergistic effect by adding tetracycline (2 g/d) [1, 4], there have been no controlled studies comparing the efficacy agents.

Cited by 37 publications

References 2 publications

Amphotericin B Combined with Itraconazole or Fluconazole for Treatment of Histoplasmosis

Amphotericin B Combined with Itraconazole or Fluconazole for Treatment of Histoplasmosis

Drug-drug interactions with oral anti-HCV agents and idiosyncratic hepatotoxicity in the liver transplant setting

Reported Case of Severe Hepatotoxicity Likely due to Fluconazole and <i>Not</i> Desloratadine

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