title: Hepatotoxicity with Vismodegib: An MD Anderson Cancer Center and Research on Adverse Drug Events and Reports Project.
abstract: BACKGROUND
  On 30 January 2012, the US FDA approved vismodegib (Erivedge®, Genentech, CA, USA) for the management of both metastatic and locally advanced basal cell carcinoma.
  
  
  OBJECTIVE
  Our objective was to identify evidence of hepatotoxicity with vismodegib in the FDA Adverse Event Reporting System (FAERS) in treated patients in two National Cancer Institute Comprehensive Cancer Centers.
  
  
  METHODS
  FAERS was searched for reports dated 1 January 2009 through 31 December 2015 using terms including hedgehog pathway and vismodegib and hepatic-related terms such as liver, jaundice, and hepatitis, among others. Disproportionality analyses with estimates of proportional reporting ratio and empirical Bayesian geometric mean were conducted. A comprehensive literature review was conducted, and the clinical databases at the University of Texas MD Anderson Cancer Center and Robert H. Lurie Comprehensive Cancer Center of Northwestern University were searched.
  
  
  RESULTS
  Two cases of severe liver dysfunction were published (Common Terminology Criteria for Adverse Events [CTCAE] class III), and 94 reports of adverse events (AEs) were detected in FAERS, 35 of which were serious AEs. Safety notifications related to hepatotoxicity have not been issued by the manufacturer or the FDA, although vismodegib is listed in LiverTox and the European Medicines Agency website.
  
  
  CONCLUSIONS
  We identified a detectable safety signal for hepatotoxicity for vismodegib within 4 years of FDA approval. Vismodegib should be used in patients with severe liver disease only after careful consideration, and concomitant hepatotoxic medications should be avoided. Rapid dissemination of such safety concerns is expected to result in fewer serious hepatotoxic AEs and more optimal outcomes for patients with cancer receiving vismodegib.
authors.affiliation: Department of General Internal Medicine, University of Texas MD Anderson Cancer Center, 1400 Pressler Dr., Unit # 1465, Houston, TX, 77030, USA. BEdwards@mdanderson.org.
authors.forename: Beatrice J
authors.initials: BJ
authors.lastname: Edwards
authors.affiliation: College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Raisch
authors.affiliation: Department of General Internal Medicine, University of Texas MD Anderson Cancer Center, 1400 Pressler Dr., Unit # 1465, Houston, TX, 77030, USA.
authors.forename: Smita S
authors.initials: SS
authors.lastname: Saraykar
authors.affiliation: Department of General Internal Medicine, University of Texas MD Anderson Cancer Center, 1400 Pressler Dr., Unit # 1465, Houston, TX, 77030, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Dermatology, Northwestern University, Chicago, IL, USA.
authors.forename: Josh A
authors.initials: JA
authors.lastname: Hammel
authors.affiliation: Thoracic, Head and Neck Medical Oncology Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hai T
authors.initials: HT
authors.lastname: Tran
authors.affiliation: Department of General Internal Medicine, University of Texas MD Anderson Cancer Center, 1400 Pressler Dr., Unit # 1465, Houston, TX, 77030, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Wehr
authors.affiliation: College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Rasha
authors.initials: R
authors.lastname: Arabyat
authors.affiliation: Department of Dermatology, Northwestern University, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
authors.forename: Dennis P
authors.initials: DP
authors.lastname: West
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000813:Anilides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; C538724:HhAntag691; D011725:Pyridines