Drug Interaction Report

MONITOR: Drugs that alter the pH of the upper gastrointestinal tract may affect the solubility of dabrafenib and reduce its bioavailability. The interaction has not been formally studied with H2-receptor antagonists or antacids; however, the solubility of dabrafenib is known to be pH-dependent. It has been reported to be very slightly soluble at pH 1 and practically insoluble above pH 4 in aqueous media.

MANAGEMENT: Until more information is available, caution is advised if dabrafenib is used in combination with H2-receptor antagonists or antacids. The potential for diminished therapeutic effects of dabrafenib should be considered, and pharmacologic response should be closely monitored.

ADJUST DOSING INTERVAL: Food may reduce as well as delay the absorption of dabrafenib. In study subjects, administration of dabrafenib with a high-fat meal decreased peak plasma concentration (Cmax) and systemic exposure (AUC) by 51% and 31%, respectively, and delayed median Tmax by approximately 3.6 hours compared to administration in the fasted state.

MANAGEMENT: Dabrafenib should be taken at least 1 hour before or 2 hours after a meal.