Idiosyncratic drug-induced liver injury: an update on the 2007 overview

Hussaini, S. H.; Farrington, Elizabeth

doi:10.1517/14740338.2013.828032

Cited by 56 publications

(40 citation statements)

References 133 publications

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“…A hypersensitivity syndrome with fever and rash as clinical manifestations, as well as with autoantibodies and eosinophilia, and a short latency period (1-6 weeks) point to a predominantly immunoallergic pathophysiological mechanism [43], whereas a lack of hypersensitivity syndrome and a longer latency period (i.e. 1 month to 1 year) points to an idiosyncratic metabolic mechanism [44]. …”

Section: Hepatotoxicity and Hypersensitivity Reactionsmentioning

confidence: 99%

The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature

Carvalho

Sharma²,

Brunoni³

et al. 2016

Psychother Psychosom

451

286

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Newer generation antidepressant drugs (ADs) are widely used as the first line of treatment for major depressive disorders and are considered to be safer than tricyclic agents. In this critical review, we evaluated the literature on adverse events, tolerability and safety of selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, bupropion, mirtazapine, trazodone, agomelatine, vilazodone, levomilnacipran and vortioxetine. Several side effects are transient and may disappear after a few weeks following treatment initiation, but potentially serious adverse events may persist or ensue later. They encompass gastrointestinal symptoms (nausea, diarrhea, gastric bleeding, dyspepsia), hepatotoxicity, weight gain and metabolic abnormalities, cardiovascular disturbances (heart rate, QT interval prolongation, hypertension, orthostatic hypotension), genitourinary symptoms (urinary retention, incontinence), sexual dysfunction, hyponatremia, osteoporosis and risk of fractures, bleeding, central nervous system disturbances (lowering of seizure threshold, extrapyramidal side effects, cognitive disturbances), sweating, sleep disturbances, affective disturbances (apathy, switches, paradoxical effects), ophthalmic manifestations (glaucoma, cataract) and hyperprolactinemia. At times, such adverse events may persist after drug discontinuation, yielding iatrogenic comorbidity. Other areas of concern involve suicidality, safety in overdose, discontinuation syndromes, risks during pregnancy and breast feeding, as well as risk of malignancies. Thus, the rational selection of ADs should consider the potential benefits and risks, likelihood of responsiveness to the treatment option and vulnerability to adverse events. The findings of this review should alert the physician to carefully review the appropriateness of AD prescription on an individual basis and to consider alternative treatments if available.

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Section: Hepatotoxicity and Hypersensitivity Reactionsmentioning

confidence: 99%

The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature

Carvalho

Sharma²,

Brunoni³

et al. 2016

Psychother Psychosom

451

286

View full text Add to dashboard Cite

show abstract

“…More than 1100 medicines, natural products, vitamins, dietary supplements, recreational and illicit compounds have been reported to cause DILI, and the list is constantly growing. Antibiotics, anticonvulsants, and antidepressant therapy remain the commonest causes of DILI in the Western Hemisphere [1] . Among others, tumor necrosis factor-alpha antagonists, fluoroquinolones, tyrosine kinase inhibitors, statins and food supplements are gaining appreciation [2] .…”

Section: Definition Of Dilimentioning

confidence: 99%

“…The quest for highly predictive biomarkers has been underway for years and remains an ongoing challenge [21] . Although some genetic associations (e.g., flucloxacillin and HLA-B 1 5701) have been identified, the clinical utility of genetic polymorphisms associated with drug-specific DILI appears still limited [1] . In addition, there are at least 3 groups of individuals showing different pattern of hepatic response: tolerates (the vast majority of patients without significant changes in liver biochemical tests), susceptibles (showing progressive increase in ALT level that continues to increase and evolves into clinically significant liver damage with signs and symptoms) and adaptors (showing transient increase in enzyme levels, which eventually return to baseline despite continuation of the drug) [19] .…”

Section: Issues In Drug Developmentmentioning

confidence: 99%

Assessing liver injury associated with antimycotics: Concise literature review and clues from data mining of the FAERS database

Raschi¹,

Poluzzi²,

Koci³

et al. 2014

WJH

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AIM: To inform clinicians on the level of hepatotoxic risk among antimycotics in the post-marketing setting, following the marketing suspension of oral ketoconazole for drug-induced liver injury (DILI). METHODS:The publicly available international FAERS database (2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011) was used to extract DILI cases (including acute liver failure events), where antimycotics with systemic use or potential systemic absorption were reported as suspect or interacting agents. The reporting pattern was analyzed by calculating the reporting odds ratio and corresponding 95%CI, a measure of disproportionality, with time-trend analysis where appropriate. RESULTS:From 1687284 reports submitted over the 8-year period, 68115 regarded liver injury. Of these, 2.9% are related to antimycotics (1964 cases, of which 112 of acute liver failure). Eleven systemic antimycotics (including ketoconazole and the newer triazole derivatives voriconazole and posaconazole) and terbinafine (used systemically to treat onychomicosis) generated a significant disproportionality, indicating a post-marketing signal of risk. CONCLUSION:Virtually all antimycotics with systemic action or absorption are commonly reported in clinically significant cases of DILI. Clinicians must be aware of this aspect and monitor patients in case switch is considered, especially in critical poly-treated patients under chronic treatment.

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“…For example, one could invoke idiosyncratic drug-induced liver injury (IDILI). Recently-published reviews place its frequency at 19 per 100,000 treated individual [47], and IDILI can manifest in multiple fashions. It accounts for up to 13% of acute liver failure in the United States.…”

Section: Alternative Explanation For Unwanted Effects Of Bace1 Inhibimentioning

confidence: 99%

Lessons from a BACE1 inhibitor trial: Off‐site but not off base

Lahiri

Maloney

Long

et al. 2014

Alzheimer's & Dementia

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Alzheimer's disease (AD) is characterized by neuritic plaque formation, which is primarily composed of a small filamentous protein called amyloid-β peptide (Aβ). The rate-limiting step in the production of Aβ is the processing of Aβ precursor protein (APP) by a β-site APP-cleaving enzyme (BACE1). Hence, BACE1 activity plausibly plays a significant role in the generation of potentially toxic Aβ within brain and the development of AD, thereby making it an interesting drug target. A phase 2 trial of the promising LY2886721 inhibitor of BACE1 was suspended in June of 2013 by Eli Lilly and Company due to apparent liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of β-galactoside α-2,6-sialyltransferase I (STGal6 I). In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespans of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. In summary, we present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening and testing programs might prevent such failures in the future.

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Idiosyncratic drug-induced liver injury: an update on the 2007 overview

Cited by 56 publications

References 133 publications

The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature

The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature

Assessing liver injury associated with antimycotics: Concise literature review and clues from data mining of the FAERS database

Lessons from a BACE1 inhibitor trial: Off‐site but not off base

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