Drug Interactions between Braftovi and Voxzogo

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.

MONITOR: Vosoritide may cause transient decreases in blood pressure. In clinical trials, 13% of patients treated with vosoritide experienced a transient decrease in blood pressure compared to 5% of patients on placebo. The median time to onset from injection was 31 (18 to 120) minutes with resolution within 31 (5 to 90) minutes. Two out of 60 (3%) vosoritide-treated patients each had one symptomatic episode of decreased blood pressure with vomiting and/or dizziness compared to 0 of 61 (0%) patients on placebo.

MANAGEMENT: To reduce the risk of low blood pressure and its associated signs and symptoms, patients should have adequate food intake before vosoritide administration and should drink approximately 240 to 300 mL of fluid within the hour prior to vosoritide administration. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their doctor if they experience fatigue, nausea, dizziness, or lightheadedness.