Table 7.
Effects of ALK-TKIs on the Exposure of Other Drugs
| Drugs | CYP Substrates | Change of CYP Substrates | Clinically Significant | Recommendations | |
|---|---|---|---|---|---|
| AUCR | CmaxR | ||||
| Crizotinib13,69 | Midazolam | 3.65 | 2.02 | Yes | Avoiding concomitant use of crizotinib with CYP3A substrates. If concomitant use is unavoidable, reduce the dose of CYP3A substrates. |
| Ceritinib15,30 | Midazolam | 5.40 | 1.80 | Yes | Avoiding coadministration of ceritinib with sensitive CYP3A and CYP2C9 substrates. If concomitant use is unavoidable, consider dose reduction of the CYP3A and CYP2C9 substrates. |
| Warfarin | 1.54 | 1.0 | Yes | ||
| Alectinib18,19,32 | Midazolam | 0.97 | 0.92 | No | No dose adjustments are required when alectinib is co-administered with CYP3A substrates. |
| Brigatinib20,21 | NA | NA | NA | NK | Coadministration of brigatinib with CYP3A substrates with a narrow therapeutic index should be avoided. |
| Lorlatinib22,23 | Midazolam | 0.36 | 0.50 | Yes | Avoiding concomitant use of lorlatinib with CYP3A substrates. |
| Entrectinib24,25 | Midazolam | 1.50 | 0.79 | No | Dose adjustment is not needed for sensitive CYP3A substrates when coadministered with entrectinib. |
Abbreviations: NK, not known; NA, not applicable/not available.