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.

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.