PMID- 28063021
OWN - NLM
STAT- MEDLINE
DCOM- 20170503
LR  - 20181113
IS  - 1179-6901 (Electronic)
IS  - 1174-5886 (Print)
IS  - 1174-5886 (Linking)
VI  - 17
IP  - 1
DP  - 2017 Mar
TI  - Hepatotoxicity with Vismodegib: An MD Anderson Cancer Center and Research on 
      Adverse Drug Events and Reports Project.
PG  - 211-218
LID - 10.1007/s40268-016-0168-2 [doi]
AB  - BACKGROUND: On 30 January 2012, the US FDA approved vismodegib (Erivedge((R)), 
      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. 
      CONCLUSION: 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.
FAU - Edwards, Beatrice J
AU  - Edwards BJ
AD  - Department of General Internal Medicine, University of Texas MD Anderson Cancer 
      Center, 1400 Pressler Dr., Unit # 1465, Houston, TX, 77030, USA. 
      BEdwards@mdanderson.org.
FAU - Raisch, Dennis W
AU  - Raisch DW
AD  - College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
FAU - Saraykar, Smita S
AU  - Saraykar SS
AD  - Department of General Internal Medicine, University of Texas MD Anderson Cancer 
      Center, 1400 Pressler Dr., Unit # 1465, Houston, TX, 77030, USA.
FAU - Sun, Ming
AU  - Sun M
AD  - Department of General Internal Medicine, University of Texas MD Anderson Cancer 
      Center, 1400 Pressler Dr., Unit # 1465, Houston, TX, 77030, USA.
FAU - Hammel, Josh A
AU  - Hammel JA
AD  - Department of Dermatology, Northwestern University, Chicago, IL, USA.
FAU - Tran, Hai T
AU  - Tran HT
AD  - Thoracic, Head and Neck Medical Oncology Research, University of Texas MD 
      Anderson Cancer Center, Houston, TX, USA.
FAU - Wehr, Nathaniel
AU  - Wehr N
AD  - Department of General Internal Medicine, University of Texas MD Anderson Cancer 
      Center, 1400 Pressler Dr., Unit # 1465, Houston, TX, 77030, USA.
FAU - Arabyat, Rasha
AU  - Arabyat R
AD  - College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
FAU - West, Dennis P
AU  - West DP
AD  - Department of Dermatology, Northwestern University, Chicago, IL, USA.
AD  - Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, 
      IL, USA.
LA  - eng
PT  - Journal Article
PL  - New Zealand
TA  - Drugs R D
JT  - Drugs in R&D
JID - 100883647
RN  - 0 (Anilides)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (HhAntag691)
RN  - 0 (Pyridines)
SB  - IM
MH  - *Adverse Drug Reaction Reporting Systems
MH  - Anilides/administration & dosage/*adverse effects/therapeutic use
MH  - Antineoplastic Agents/administration & dosage/*adverse effects/therapeutic use
MH  - Chemical and Drug Induced Liver Injury/*pathology/physiopathology
MH  - Humans
MH  - Liver/*drug effects/*pathology/physiopathology
MH  - Liver Neoplasms/*drug therapy/metabolism/pathology
MH  - Pyridines/administration & dosage/*adverse effects/therapeutic use
MH  - Retrospective Studies
PMC - PMC5318336
COIS- FUNDING: University of Texas MD Anderson Cancer Center. CONFLICT OF INTEREST: 
      BJE, DWR, SSS, MS, JAH, HTT, NW, RA, and DPW have no conflicts of interest.
EDAT- 2017/01/08 06:00
MHDA- 2017/05/04 06:00
PMCR- 2017/01/06
CRDT- 2017/01/08 06:00
PHST- 2017/01/08 06:00 [pubmed]
PHST- 2017/05/04 06:00 [medline]
PHST- 2017/01/08 06:00 [entrez]
PHST- 2017/01/06 00:00 [pmc-release]
AID - 10.1007/s40268-016-0168-2 [pii]
AID - 168 [pii]
AID - 10.1007/s40268-016-0168-2 [doi]
PST - ppublish
SO  - Drugs R D. 2017 Mar;17(1):211-218. doi: 10.1007/s40268-016-0168-2.