Drug Interactions between Braftovi and Cuvrior

GENERALLY AVOID: Coadministration with potent or moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of encorafenib, which is primarily metabolized by the isoenzyme. When a single 50 mg dose of encorafenib (equivalent to 0.1 times the recommended dose) was administered with posaconazole, a potent CYP450 3A4 inhibitor, encorafenib peak plasma concentration (Cmax) increased by 68% and systemic exposure (AUC) increased by 3-fold. When the same dose of encorafenib was administered with diltiazem, a moderate CYP450 3A4 inhibitor, encorafenib Cmax increased by 45% and AUC increased by 2-fold. Increased exposure to encorafenib may increase the risk of serious and life-threatening adverse effects such as hemorrhage, uveitis, QT prolongation, hepatotoxicity, dermatologic reactions, and new malignancies.

MANAGEMENT: Concomitant use of encorafenib with grapefruit or grapefruit juice should generally be avoided. If coadministration is required, the manufacturer recommends reducing the encorafenib dose to one-third of the dose used prior to addition of a potent CYP450 3A4 inhibitor or one-half of the dose used prior to addition of a moderate CYP450 3A4 inhibitor. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, the encorafenib dose that was taken prior to initiating the inhibitor may be resumed.

ADJUST DOSING INTERVAL: The gastrointestinal absorption of trientine may be decreased in the presence of food, resulting in reduced therapeutic effects.

MANAGEMENT: Trientine should be administered on an empty stomach, at least one hour before or two hours after meals and at least one hour apart from any other food, drug, or milk.

GENERALLY AVOID: Concurrent oral administration of mineral supplements or mineral-containing products may block the absorption of trientine, and vice versa. The mechanism is trientine chelation of polyvalent metal ions resulting in a nonabsorbable complex.

MANAGEMENT: In general, mineral supplements or mineral-containing products (e.g., antacids) should not be used in patients treated with trientine. If concomitant use is unavoidable, separation of administration times by at least two hours is advisable.