Drug-induced liver injury following positive drug rechallenge.
Drug rechallenge (or reinitiation), following an event of drug-induced liver injury, can lead to serious or fatal liver injury. A retrospective review of a large pharmaceutical safety database was conducted to assess clinical outcomes of positive drug rechallenge following possible drug-induced liver injury. Positive rechallenge with suspect drug was reported in 770 of 36,795 hepatic adverse events. A total of 88 cases met inclusion criteria for analysis. Mean age was 44 years (range 0.5-83) and 56% were male. A broad spectrum of suspect drugs were identified. Many patients exhibited hepatitis symptoms or jaundice on the initial and rechallenge liver event. Twelve patients (14%) exhibited clinically worrisome severe hepatocellular injury and jaundice on either initial or rechallenge event and two died, reflecting a 2.3% fatality rate in those with positive rechallenge. The two fatalities developed severe hepatocellular injury with jaundice only upon rechallenge. Liver injury recurred in most rechallenges. Improved identification and communication of possible drug-induced liver injury is needed to avoid potentially serious and/or fatal drug rechallenges. Clinicians should generally avoid such rechallenges.
Papay
Julie I
JI
Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, RTP, NC 27709, USA. julie.i.papay@gsk.com
Clines
Dawn
D
Rafi
Rezvan
R
Yuen
Nancy
N
Britt
Susan D
SD
Walsh
John S
JS
Hunt
Christine M
CM
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007565:Jaundice / Q000139:chemically induced / Q000453:epidemiology; D017093:Liver Failure / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D011446:Prospective Studies; D012189:Retrospective Studies; D012720:Severity of Illness Index
D004364:Pharmaceutical Preparations