OBJECTIVE: This study describes and assesses potential hepatobiliary events related to atomoxetine therapy, as reported in clinical trials and as spontaneous adverse event reports post-launch in 2002. METHODS: Case reports that contained potential hepatobiliary events were identified by a computerized search of the Eli Lilly and Company atomoxetine spontaneous adverse events and clinical trials databases. All cases were reviewed by at least two company physicians, one with expertise in hepatology, to determine the relevance of the information in respect of potential liver toxicity. RESULTS: Of 7961 paediatric and adult patients treated with atomoxetine in clinical trials, 41 were identified as having hepatobiliary events requiring additional analysis. Most of these events were mild increases in ALT and AST levels. None of these cases met Hy's rule criteria or progressed to liver failure. During the 4 years after market launch, 351 spontaneous reports of adverse events were related to the liver, of which 69 had other explanations unrelated to atomoxetine. Of the remaining 282 cases, 133 contained possible confounding factors (and were deemed to be possibly related), 146 presented too little information to assess, and three suggested atomoxetine as a probable cause of liver injuries. One of the three had a positive rechallenge. All three patients recovered after discontinuation of the drug. CONCLUSIONS: Since the launch of atomoxetine therapy, three spontaneously reported cases of reversible drug-induced liver injury were deemed probably related to it. Atomoxetine should be discontinued in patients with jaundice or laboratory evidence of liver injury and should not be restarted.
OBJECTIVE: This study describes and assesses potential hepatobiliary events related to atomoxetine therapy, as reported in clinical trials and as spontaneous adverse event reports post-launch in 2002. METHODS: Case reports that contained potential hepatobiliary events were identified by a computerized search of the Eli Lilly and Company atomoxetine spontaneous adverse events and clinical trials databases. All cases were reviewed by at least two company physicians, one with expertise in hepatology, to determine the relevance of the information in respect of potential liver toxicity. RESULTS: Of 7961 paediatric and adult patients treated with atomoxetine in clinical trials, 41 were identified as having hepatobiliary events requiring additional analysis. Most of these events were mild increases in ALT and AST levels. None of these cases met Hy's rule criteria or progressed to liver failure. During the 4 years after market launch, 351 spontaneous reports of adverse events were related to the liver, of which 69 had other explanations unrelated to atomoxetine. Of the remaining 282 cases, 133 contained possible confounding factors (and were deemed to be possibly related), 146 presented too little information to assess, and three suggested atomoxetine as a probable cause of liver injuries. One of the three had a positive rechallenge. All three patients recovered after discontinuation of the drug. CONCLUSIONS: Since the launch of atomoxetine therapy, three spontaneously reported cases of reversible drug-induced liver injury were deemed probably related to it. Atomoxetine should be discontinued in patients with jaundice or laboratory evidence of liver injury and should not be restarted.
Authors: Lenard A Adler; Virginia K Sutton; Rodney J Moore; Anthony P Dietrich; Frederick W Reimherr; R Bart Sangal; Keith E Saylor; Kristina Secnik; Douglas K Kelsey; Albert J Allen Journal: J Clin Psychopharmacol Date: 2006-12 Impact factor: 3.153
Authors: Chad J Swanson; Kenneth W Perry; Susanne Koch-Krueger; Jason Katner; Kjell A Svensson; Frank P Bymaster Journal: Neuropharmacology Date: 2006-01-19 Impact factor: 5.250
Authors: Christopher J Kratochvil; David Michelson; Jeffrey H Newcorn; Margaret D Weiss; Joan Busner; Rodney J Moore; Dustin D Ruff; Janet Ramsey; Ruth Dickson; Atilla Turgay; Keith E Saylor; Stephen Luber; Brigette Vaughan; Albert J Allen Journal: J Am Acad Child Adolesc Psychiatry Date: 2007-09 Impact factor: 8.829
Authors: David Michelson; Lenard Adler; Thomas Spencer; Frederick W Reimherr; Scott A West; Albert J Allen; Douglas Kelsey; Joachim Wernicke; Anthony Dietrich; Denái Milton Journal: Biol Psychiatry Date: 2003-01-15 Impact factor: 13.382
Authors: Mark L Wolraich; Joseph F Hagan; Carla Allan; Eugenia Chan; Dale Davison; Marian Earls; Steven W Evans; Susan K Flinn; Tanya Froehlich; Jennifer Frost; Joseph R Holbrook; Christoph Ulrich Lehmann; Herschel Robert Lessin; Kymika Okechukwu; Karen L Pierce; Jonathan D Winner; William Zurhellen Journal: Pediatrics Date: 2019-10 Impact factor: 7.124
Authors: Daniel A Gorman; David M Gardner; Andrea L Murphy; Mark Feldman; Stacey A Bélanger; Margaret M Steele; Khrista Boylan; Kate Cochrane-Brink; Roxanne Goldade; Paul R Soper; Judy Ustina; Tamara Pringsheim Journal: Can J Psychiatry Date: 2015-02 Impact factor: 4.356
Authors: Paul Hammerness; Anna Georgiopoulos; Robert L Doyle; Linsey Utzinger; Mary Schillinger; Marykate Martelon; Kerry Brodziak; Joseph Biederman; Timothy E Wilens Journal: J Child Adolesc Psychopharmacol Date: 2009-10 Impact factor: 2.576
Authors: Victoria A Reed; Jan K Buitelaar; Ernie Anand; Kathleen Ann Day; Tamás Treuer; Himanshu P Upadhyaya; David R Coghill; Ludmila A Kryzhanovskaya; Nicola C Savill Journal: CNS Drugs Date: 2016-07 Impact factor: 5.749