Severe liver injury after initiating therapy with atomoxetine in two children

Lim, Joel R; Faught, Philip R.; Chalasani, Naga; Molleston, Jean P.

doi:10.1016/j.jpeds.2006.01.035

Cited by 60 publications

(33 citation statements)

References 14 publications

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“…We found four studies and two case reports that reported hepatic effects [18,30,[48][49][50][51][52]. The results are compatible with the rarity of reports of liver injury highlighted in the European SPC.…”

Section: Findings In the Predefined Literature Searchsupporting

confidence: 85%

“…Similarly, two case reports describe hepatitis in three girls (aged 8-12 years, treated for between 37 days and nearly 1 year with atomoxetine at doses of 25-40 mg/day [1.0 mg/ kg/day in each case]). The hepatitis improved following withdrawal of atomoxetine for one girl [49] and, for two girls, with additional supportive care [50] or additional immunosuppressive therapy for autoimmune hepatitis [49].…”

Section: Findings In the Predefined Literature Searchmentioning

confidence: 98%

See 1 more Smart Citation

The Safety of Atomoxetine for the Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Comprehensive Review of Over a Decade of Research

et al. 2016

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Atomoxetine is a noradrenergic reuptake inhibitor prescribed for attention-deficit/hyperactivity disorder (ADHD) that first gained approval in the USA in 2002 and has been authorized in 97 countries worldwide. The aim of this paper is to comprehensively review publications that addressed one or more of seven major safety topics relevant to atomoxetine treatment of children and adolescents (aged ≥6 years) diagnosed with ADHD. While the review focuses on children and adolescents, publications in which data from patients aged >18 years and from 6 to 18 years were analyzed in the same dataset were included. Using a predefined search strategy, including agreement of two reviewers when selecting papers, reduced the potential for bias. Using this process, we identified 70 eligible papers (clinical trials, epidemiological studies, and case reports) across the seven topics. We also referred to the European Summary of Product Characteristics (SPC) and US label. We found 15 papers about suicidality, three about aggression/hostility, seven about psychosis/mania, six about seizures, seven about hepatic effects, 29 about cardiovascular effects, and 28 about growth and development. The main findings (i.e., those from the largest and most well-conducted studies/analyses) are as follows. A large register-based study of pediatric and adult patients (6818 received atomoxetine) calculated a hazard ratio of 0.96 for suicide-related events during treatment with atomoxetine, and a meta-analysis of 23 placebo-controlled studies (N = 3883), published in 2014, found no completed suicides and no statistically significant association between atomoxetine and suicidality. The frequency of aggression/hostility was not statistically significantly higher with atomoxetine, e.g., experienced by 1.6 % (N = 21/1308) of atomoxetine-treated patients versus 1.1 % (N = 9/806) of placebo-treated patients in one meta-analysis. Symptoms of psychosis and mania were mainly observed in patients with comorbid bipolar disorder/depression. Based on spontaneous reports, during a 2-year period when 2.233 million adult and pediatric patients were exposed to atomoxetine, the reporting rate for seizures was 8 per 100,000 patients. In the manufacturer's database, atomoxetine was a "probable cause" of three hepatic adverse events (AEs) (all reversible hepatitis), and 133 hepatic AEs had possible confounding factors and were "possibly related" to atomoxetine, during 4 years when atomoxetine exposure had reached about 4.3 million patients. Rare cases of severe liver injury are described in the US label and European SPC; a case requiring liver transplantation is described in the US label. In a comprehensive review of a clinical trials database (N = 8417 received atomoxetine), most pediatric patients experienced modest increases in heart rate and blood pressure, and 8-12 % experienced more pronounced changes (≥20 bpm, ≥15 to 20 mmHg). However, in three long-term analyses (≥2 years), blood pressure was within age norms, and few patients discontinued due to cardiovascular AE...

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Section: Findings In the Predefined Literature Searchsupporting

confidence: 85%

Section: Findings In the Predefined Literature Searchmentioning

confidence: 98%

The Safety of Atomoxetine for the Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Comprehensive Review of Over a Decade of Research

et al. 2016

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“…Less frequently, clinical and histologic features mimicking diseases such as autoimmune hepatitis may manifest. Although nitrofurantoin, minocycline, and methyldopa are prototypical to cause autoimmune-like DILI, it recently became clear that many other compounds (e.g., atomoxetine, statins) may present with acute liver injury that is indistinguishable from classic autoimmune hepatitis [6][7][8]. Therefore, it is critical to consider the role of medications when evaluating a new case of autoimmune liver disease.…”

Section: Clinical Presentation and Predisposing Factorsmentioning

confidence: 99%

“…Several potential therapies have been attempted, including steroids. The use of steroids may be justified when evidence exists of hypersensitivity reaction (rash, fever, and eosinophilia) or if drug-induced autoimmune hepatitis is suspected [6,7].…”

Section: Current Therapiesmentioning

confidence: 99%

Idiosyncratic Drug-Induced Liver Injury: A Clinical Update

Maddur

Chalasani

2010

Curr Gastroenterol Rep

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Drug-induced liver injury (DILI) is a rare but potentially devastating adverse drug reaction. Its presentation can range from asymptomatic elevation in liver biochemistries to fulminant liver failure. Over the past decade, clinical and research interest in the field of idiosyncratic DILI has been intense, and several new findings have been reported. In this article, we provide an update on implicated agents, clinical features, outcomes, and the results of recently reported genetic studies.

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“…gov/medwatch/SAFETY/2004/Strattera_PI.pdf, accessed May 2007), based on a teenager and an adult who were treated for several months and who recovered after discontinuation of the drug. Since then three children were reported to develop hepatitis after atomoxetine treatment (Lim et al 2006;Stojanovski et al 2007).…”

Section: Introductionmentioning

confidence: 99%