Table 1.
31 KIs tested in the present study
| Drug name | Approval date as a new molecular entity | Cmax (µM) | Recommended daily dose (mg/day) | DILI potential (based on labeling) | labeling for DILI |
|---|---|---|---|---|---|
| Imatinib | 10-May-01 | 2.00 | 600 | 1 | W&P: fatal DILI |
| Gefitinib | 5-May-03 | 0.27 | 250 | 1 | W&P: fatal DILI |
| Erlotinib | 18-Nov-04 | 3.44 | 150 | 1 | W&P: fatal DILI |
| Sorafenib | 20-Dec-05 | 4.30 | 400 | 1 | W&P: fatal DILI |
| Sunitinib | 26-Jan-06 | 0.12 | 44 | 1 | BBW: fatal DILI |
| Dasatinib | 28-Jun-06 | 0.18 | 120 | 0 | NA |
| Lapatinib | 13-Mar-07 | 4.18 | 1375 | 1 | BBW: fatal DILI |
| Nilotinib | 29-Oct-07 | 4.27 | 700 | 1 | W&P: ALT↑/monitoring |
| Pazopanib | 19-Oct-09 | 132.80 | 800 | 1 | BBW: fatal DILI |
| Vandetanib | 6-Apr-11 | 1.80 | 300 | 0 | NA |
| Vemurafenib | 17-Aug-11 | 0.13 | 960 | 1 | W&P: hepatic impairment/ALT monitoring |
| Crizotinib | 26-Aug-11 | 0.91 | 500 | 1 | W&P: fatal DILI |
| Ruxolitinib | 16-Nov-11 | 1.20 | 25 | 0 | NA |
| Axitinib | 27-Jan-12 | 0.07 | 10 | 1 | W&P: ALT↑/monitoring |
| Bosutinib | 4-Sep-12 | 0.38 | 500 | 1 | W&P: ALT↑/monitoring |
| Regorafenib | 27-Sep-12 | 8.08 | 160 | 1 | BBW: fatal DILI |
| Tofacitinib | 6-Nov-12 | 0.09 | 10 | 1 | W&P: ALT↑/monitoring |
| Cabozantinib | 29-Nov-12 | 2.58 | 100 | 0 | NA |
| Ponatinib | 14-Dec-12 | 0.14 | 45 | 1 | BBW: fatal DILI |
| Trametinib | 29-May-13 | 0.04 | 2 | 0 | NA |
| Dabrafenib | 29-May-13 | 2.84 | 300 | 0 | NA |
| Afatinib | 12-Jul-13 | 0.04 | 40 | 1 | W&P: ALT↑/monitoring |
| Ibrutinib | 12-Feb-14 | 0.37 | 490 | 0 | NA |
| Ceritinib | 29-Apr-14 | 1.81 | 750 | 1 | W&P: ALT↑/monitoring |
| Idelalisib | 23-Jul-14 | 4.64 | 300 | 1 | BBW: fatal DILI |
| Nintedanib | 15-Oct-14 | 0.06 | 300 | 1 | W&P: ALT↑/monitoring |
| Palbociclib | 3-Feb-15 | 0.24 | 125 | 0 | NA |
| Lenvatinib | 13-Feb-15 | 0.68 | 24 | 1 | W&P: fatal DILI |
| Cobimetinib | 10-Nov-15 | 0.51 | 60 | 1 | W&P: ALT↑/monitoring |
| Osimertinib | 13-Nov-15 | 0.50 | 80 | 0 | NA |
| Alectinib | 11-Dec-15 | 1.37 | 1200 | 1 | W&P: ALT↑/monitoring |
W&P warnings and precautions, BBW black box warnings, ALT alanine aminotransferase, NA not available. The 31 drugs are all FDA approved KIs for human use. Definition of DILI potential: 1, BBW and/or W&P indicated that the drug cased DILI; 0, no DILI information available in the labeling. The six KIs with a BBW for hepatotoxicity are highlighted in red