DABRAFENIB IS PRIMARILY METABOLIZED BY CYP2C8 AND CYP3A4. IF CONCOMITANT USE OF STRONG INHIBITORS (E.G., KETOCONAZOLE, NEFAZODONE, CLARITHROMYCIN, GEMFIBROZIL) OR STRONG INDUCERS (E.G., RIFAMPIN, PHENYTOIN, CARBAMAZEPINE, PHENOBARBITAL, ST JOHN'S WORT) OF CYP3A4 OR CYP2C8 IS UNAVOIDABLE, MONITOR PATIENTS CLOSELY FOR ADVERSE REACTIONS WHEN TAKING STRONG INHIBITORS OR LOSS OF EFFICACY WHEN TAKING STRONG INDUCERS.
DABRAFENIB INDUCES CYP3A4 AND CYP2C9. DABRAFENIB DECREASED THE SYSTEMIC EXPOSURES OF MIDAZOLAM, WARFARIN. MONITOR INTERNATIONAL NORMALIZED RATIO (INR) LEVELS MORE FREQUENTLY IN PATIENTS RECEIVING WARFARIN DURING INITIATION OR DISCONTINUATION OF DABRAFENIB. COADMINISTRATION OF TAFINLAR WITH OTHER SUBSTRATES OF THESE ENZYMES, INCLUDING DEXAMETHASONE OR HORMONAL CONTRACEPTIVES, CAN RESULT IN DECREASED CONCENTRATIONS AND LOSS OF EFFICACY.