Drug Interactions between encorafenib and quetiapine

ADJUST DOSE: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of quetiapine, which is primarily metabolized by the isoenzyme. In 18 psychiatric patients receiving quetiapine 300 mg twice daily, addition of the potent CYP450 3A4 inducer carbamazepine (200 mg three times daily) decreased mean quetiapine peak plasma concentration (Cmax) and systemic exposure (AUC) by 80% and 87%, respectively, and increased oral clearance (Cl/F) by 7.5-fold compared to quetiapine administered alone. The interaction has also been reported with phenytoin, another potent CYP450 3A4 inducer. In ten subjects with various affective disorders, coadministration of quetiapine (250 mg orally three times a day) with phenytoin (100 mg orally three times a day) decreased the mean steady-state Cmax, trough plasma concentration (Cmin) and AUC of quetiapine by 66%, 89% and 80%, respectively. The mean oral clearance increased by 5.5-fold.

MANAGEMENT: Increased dosages of quetiapine may be required during chronic treatment (greater than 7 to 14 days) with potent CYP450 3A4 inducers. The manufacturer recommends an increase of up to 5-fold the original dosage of quetiapine. Further adjustments should be made based on clinical response and tolerance. The safety of dosages above 800 mg/day has not been established in clinical trials. Continued treatment at higher dosages should only be considered following careful consideration of risks and benefits. When the CYP450 3A4 inducer is discontinued, the dosage of quetiapine should be reduced to the original level within 7 to 14 days.