Hepatic events associated with atomoxetine treatment for attention-deficit hyperactivity disorder.
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.
Bangs
Mark E
ME
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. bangsme@lilly.com
Jin
Ling
L
Zhang
Shuyu
S
Desaiah
Durisala
D
Allen
Albert J
AJ
Read
Holly A
HA
Regev
Arie
A
Wernicke
Joachim F
JF
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D002648:Child; D005260:Female; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D011437:Propylamines / Q000009:adverse effects* / Q000627:therapeutic use
D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase