The evaluation of drug rechallenge: the casopitant Phase III program.

Journal Article (Clinical Trial, Phase III;Journal Article;Multicenter Study)

Drug rechallenge (or reinitiation), following an event of drug-induced liver injury, is associated with 13% mortality in prospective series. Rechallenge generally results in much more rapid injury than the initial liver event. The neurokinin-1 antagonist casopitant or its placebo was administered cyclically with ondansetron and dexamethasone in two randomized chemotherapy-induced nausea and vomiting clinical trials in nearly 3000 subjects. Grade 3 ALT elevations were observed in up to 2% of subjects receiving casopitant or placebo treatment. Similar rates of positive rechallenge were observed in the casopitant 8/29 (28%) and placebo groups 2/8 (25%), with no Grade 4 ALT elevations, hypersensitivity or liver-related serious adverse events. Publishing available rechallenge data (positive and negative) will advance our clinical understanding. Rechallenge should only be considered when the potential drug benefit exceeds the risk.

Full Text

Duke Authors

Cited Authors

  • Hunt, CM; Papay, JI; Rich, DS; Abissi, CJ; Russo, MW

Published Date

  • December 2010

Published In

Volume / Issue

  • 58 / 3

Start / End Page

  • 539 - 543

PubMed ID

  • 20932869

Electronic International Standard Serial Number (EISSN)

  • 1096-0295

Digital Object Identifier (DOI)

  • 10.1016/j.yrtph.2010.09.014


  • eng

Conference Location

  • Netherlands