Hepatic Failure Related to Itraconazole Use Successfully Treated by Corticosteroids

Itraconazole (ITZ) belongs to the triazole group of antifungals with potent keratinophilic and lipophilic features. Hepatotoxicity is one of its most remarkable features. Silibinin (SIL) is a plant used worldwide which is used in the treatment of many liver diseases and it is especially very well known for its hepatoprotective-cytoprotective effect. The aim of our study was to research the protective effect of SIL in ITZ-induced hepatotoxicity using biochemical and pathological tests. Liver enzymes and antioxidant enzyme activities were measured spectrophotometrically by using commercial kits. ALT and AST levels in ITZ group were significantly increased compared to the group, while the activities of GSH-Px and SOD had decreased (p < 0.05). When ITZ group was compared to ITZ + SIL group, AST, ALT, and levels of NO and MPO were significantly decreased, while the activities of GSH-Px and SOD were increased (p < 0.05). Histopathological evaluation showed that SIL significantly decreased periportal inflammation and parenchymal hepatocyte apoptosis in ITZ and ITZ + SIL groups (p < 0.05). Eventhough not statistically significant, partial improvement with the use of SIL has been detected (p > 0.05) in hepatocyte degeneration and multinuclear giant cell formation. According to the evaluation performed with comet assay method, ITZ leads to DNA damage, and the use of SIL significantly decreases DNA damage (p < 0.05). We have detected that the use of ITZ increases oxidative stress (MPO, NO), decreases antioxidant activity (SOD and GSH-Px), and leads to DNA damage and histopathological liver damage, whereas the use of SIL has a cytoprotective effect on the liver by increasing the antioxidant effect (SOD, GSH-Px) and by decreasing the oxidative stress (NO, MPO). ITZ causes the generation of ROS and leads to DNA damage and liver damage. SIL has a cytoprotective effect on the liver by increasing antioxidant enzyme activities, preventing the formation of ROS.

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“…All parameters were semiquantitatively scored. (Scoring system: 0: Absent, 1: Mild, 2: Moderate, 3: Severe) [27,28].…”

Section: Histopathological Evaluationmentioning

confidence: 99%

Evaluation of the Protective Effect of Silibinin in Rats with Liver Damage Caused by Itraconazole

Sözen

Çelik

Çetin

et al. 2014

Cell Biochem Biophys

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“…These products were selected because they have substantial exposure, well-characterized risks, and allow for within-indication comparisons. We noted established associations between terbinafine and itraconazole and risk of liver disease [ 32 , 33 ] and allergic reaction [ 34 , 35 ]. Itraconazole and both diabetes drugs carry black box warnings for congestive heart failure on the U.S. FDA approved product labeling .…”

Section: Methodsmentioning

confidence: 99%

Drug Adverse Event Detection in Health Plan Data Using the Gamma Poisson Shrinker and Comparison to the Tree-based Scan Statistic

et al. 2013

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Background: Drug adverse event (AE) signal detection using the Gamma Poisson Shrinker (GPS) is commonly applied in spontaneous reporting. AE signal detection using large observational health plan databases can expand medication safety surveillance. Methods: Using data from nine health plans, we conducted a pilot study to evaluate the implementation and findings of the GPS approach for two antifungal drugs, terbinafine and itraconazole, and two diabetes drugs, pioglitazone and rosiglitazone. We evaluated 1676 diagnosis codes grouped into 183 different clinical concepts and four levels of granularity. Several signaling thresholds were assessed. GPS results were compared to findings from a companion study using the identical analytic dataset but an alternative statistical method—the tree-based scan statistic (TreeScan). Results: We identified 71 statistical signals across two signaling thresholds and two methods, including closely-related signals of overlapping diagnosis definitions. Initial review found that most signals represented known adverse drug reactions or confounding. About 31% of signals met the highest signaling threshold. Conclusions: The GPS method was successfully applied to observational health plan data in a distributed data environment as a drug safety data mining method. There was substantial concordance between the GPS and TreeScan approaches. Key method implementation decisions relate to defining exposures and outcomes and informed choice of signaling thresholds.

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“…151 Some instances of clinically apparent DILI (mainly hepatocellular) and fatal injuries have been reported. 152,153 Itraconazole has rarely been associated with hepatocellular, 154 mixed, 155,156 and reversible cholestatic injury. 157 Instances of cholestasis progressing to VBDS have been described.…”

Section: Antifungalsmentioning

confidence: 99%

Drug-Induced Liver Injury Due to Antimicrobials, Central Nervous System Agents, and Nonsteroidal Anti-Inflammatory Drugs

Devarbhavi

Andrade

2014

Semin Liver Dis

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Antimicrobial agents including antituberculosis (anti-TB) agents are the most common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced liver failure across the world. Better molecular and genetic biomarkers are acutely needed to help identify those at risk of liver injury particularly for those needing antituberculosis therapy. Some antibiotics such as amoxicillin-clavulanate and isoniazid consistently top the lists of agents in retrospective and prospective DILI databases. Central nervous system agents, particularly antiepileptics, account for the second most common class of agents implicated in DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine, phenytoin, and phenobarbital are often associated with hypersensitivity features, whereas newer antiepileptic drugs have a more favorable safety profile. Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of significant liver injury, but their prolific use make them important causes of DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays of minimizing hepatotoxicity.

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Hepatic Failure Related to Itraconazole Use Successfully Treated by Corticosteroids

Cited by 5 publications

References 19 publications

Evaluation of the Protective Effect of Silibinin in Rats with Liver Damage Caused by Itraconazole

Evaluation of the Protective Effect of Silibinin in Rats with Liver Damage Caused by Itraconazole

Drug Adverse Event Detection in Health Plan Data Using the Gamma Poisson Shrinker and Comparison to the Tree-based Scan Statistic

Drug-Induced Liver Injury Due to Antimicrobials, Central Nervous System Agents, and Nonsteroidal Anti-Inflammatory Drugs

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