Table 1.
Cases of hepatotoxicity attributed to vismodegib in the FDA Adverse Event Reporting System
| Report date | Agea (sex) | Cancer type | Concomitant drugs with hepatic metabolism | Co-morbidities | Adverse events | CTCAE | Outcomes | Vismodegib administration time course (days) |
|---|---|---|---|---|---|---|---|---|
| 2012 | 83 (F) | BCC | Lanoxin, Lasix, Theophylline | NA | Hepatocellular injury | 4 | Hospitalization, life threatening | NA |
| 2012 | 84 (M) | BCC | NA | NA | Hepatitis | 4 | Life threatening | 47 |
| 2012 | 63 (F) | BCC | Cymbalta, Levothyroxine | NA | Hepatotoxicity | 3 | Hospitalization | 55 |
| 2012 | 58 (NA) | Pancreatic carcinoma metastatic | Oxycontin | NA | Ascites | 5 | Death, hospitalization | 218 |
| 2012 | 59 (M) | Adenocarcinoma pancreas | NA | NA | Ascites | 3 | Hospitalization | 5 |
| 2012 | 41 (F) | BCC | NA | NA | Hepatitis | 3 | Hospitalization | 60 |
| 2013 | NA (F) | BCC | NA | NA | DILI | NA | Other | NA |
| 2013 | 50 (M) | BCC | NA | NA | Hepatitis | 4 | Hospitalization, life threatening | NA |
| 2013 | 76 (M) | BCC | Uroxatral, Zocor, Zyloprim | NA | Hepatotoxicity | 4 | Hospitalization | NA |
| 2013 | 59 (F) | BCC | Advair, Premarin | Asthma | Hepatitis | 3 | Hospitalization | NA |
| 2013 | 68 (F) | NA | Diovan, Vibramycin | NA | DILI | NA | Other | NA |
| 2013 | NA | NA | NA | NA | Liver disorder | NA | Other | NA |
| 2014 | 75 (M) | BCC | NA | NA | Hepatocellular injury | 4 | Disability other | 52 |
| 2014 | 79 (F) | AML | Augmentin, Diovan, Dulcolax, Hydrea, Hydrochlorothiazid, Lipitor, Nystatin, Tenormin, Zyloprim | Autoimmune thyroiditis, hyperlipidemia, hypertension | Hepatic infection | 3 | Hospitalization | NA |
| 2014 | 98 (F) | BCC | NA | NA | DILI | NA | Other | 48 |
| 2014 | 90 (M) | BCC | Amoxicillin, Aspirin, Kerlone, Lotensin, Lozol, Norvasc, Rutinoscorbin, Tricor, Ultracet, Vinpocetine, Zocor | Hypercholesterolemia, hyperlipidemia, hypertension | DILI | 3 | Hospitalization | 66 |
| 2014 | 72 (M) | BCC | Cialis, Diovan, Norvasc | Cholestatic liver injury | 3 | Hospitalization | NA | |
| 2014 | 68 (M) | BCC | Amaryl, Bactrim, Capoten, Cardizem, Coumadin, Glucophage, Jentadueto, Lantus, Pravachol, Ranexa, Xarelto | Hyperlipidemia, hypertension, T2DM | Acute hepatic failure | 5 | Hospitalization, disability, death | 217 |
| 2014 | 88 (M) | BCC | NA | NA | Hepatitis cholestatic | 3 | Hospitalization | NA |
| 2015 | 70 (M) | NA | NA | NA | Hepatotoxicity | NA | Other | NA |
| 2015 | 72 (M) | BCC | NA | NA | Liver injury | NA | Other | NA |
| 2015 | 48 (F) | NA | NA | NA | Hepatic failure | NA | Other | NA |
| 2015 | 0 (F) | NA | NA | NA | Liver disorder | NA | Other | NA |
| 2015 | 56 (M) | NA | NA | NA | Hepatobiliary disease | 5 | Hospitalization, death | 18 |
| 2015 | 70 (F) | BCC | Diosmectite, Elavil, Hexaquine, Miralax, Nexium, Tylenol, Ultracet, Ultram, Vitabact | DM | Ascites | 3 | Hospitalization | 853 |
| 2015 | 68 (M) | NA | Capoten, Cardizem, Colace, Diabeta, Eliquis, Glucophage, Jentadueto, Lantus, Lasix, Lopressor, Nitroglycerin, Plavix, Pravachol, Protonix, Ranexa, Sulfamethoxazole | NA | Acute hepatic failure | 5 | Hospitalization, life threatening, death | 240 |
| 2015 | 83 (F) | BCC | NA | NA | Hepatocellular injury | NA | Other | 81 |
| 2015 | 0 (F) | NA | NA | NA | Hepatotoxicity | NA | Other | NA |
| 2015 | 0 (M) | NA | Diovan, Fusidic Acid, Glucophage, Januvia, Lipitor, Robaxacet, Sectral, Symbicort, Ventolin, Veramyst, Voltaren | NA | Hepatitis | 3 | Hospitalization | NA |
| 2015 | 76 (F) | NA | Enbrel, Hyzaar | NA | Hepatitis toxic | 3 | Hospitalization | 21 |
| 2015 | 89 (F) | NA | NA | NA | Hepatitis | NA | Other | NA |
| 2015 | 0 (NA) | NA | NA | NA | Liver disorder | 3 | Hospitalization | NA |
| 2015 | 71 (F) | BCC | NA | NA | Hepatitis acute | NA | Other | NA |
| 2015 | 57 (M) | BCC | NA | NA | Hepatic failure | 5 | Death | NA |
| 2015 | 0 (M) | BCC | NA | NA | Hepatitis cholestatic | NA | Other | NA |
Assessment based on FAERS summary data. Since FAERS case data are often incomplete, missing data are shown as ‘NA’
AML acute myeloid leukemia, BCC basal cell carcinoma, CTCAE Common Terminology Criteria for Adverse Events, Version 4.0, DILI drug-induced liver injury, DM diabetes mellitus, F female, M male, NA not available, T2DM type 2 diabetes mellitus
aAge is presented in years