Drug Interactions between pazopanib and Prepopik

GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of pazopanib and reduce its concentrations in plasma. The solubility of pazopanib is pH-dependent, thus an increase in pH may interfere with its absorption. According to the product labeling, pazopanib is very slightly soluble at pH 1 and practically insoluble above pH 4 in aqueous media. When pazopanib (800 mg once daily in the morning) was coadministered with esomeprazole (40 mg once daily in the evening) for 5 days in 12 patients with advanced solid tumors, mean steady-state pazopanib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 40% each. The AUCs of three metabolites were also decreased. Mean steady-state trough concentration of pazopanib was reduced to 17.3 mcg/mL, which is close to the reported threshold of >=15 mcg/mL for clinical efficacy as suggested by a phase I trial of pazopanib. However, the potential for subtherapeutic pazopanib exposure in some patients cannot be excluded.

MANAGEMENT: Concomitant use of pazopanib with drugs that increase gastric pH should generally be avoided. If acid-suppression therapy is required, short-acting antacids should be considered, with dosing separated by several hours from pazopanib dosing. Some experts recommend administering pazopanib at least 1 hour before or 2 hours after antacids.

MONITOR: The use of bowel cleansing preparations may increase the risk of ventricular arrhythmia, particularly torsade de pointes, in patients treated with drugs that prolong the QT interval. Severe and potentially fatal cases of electrolyte disorders and arrhythmias have been reported in elderly patients using bowel cleansing products. Electrolyte disturbances including hypokalemia and hypomagnesemia are known risk factors for torsade de pointes associated with QT interval prolongation.

MANAGEMENT: Caution is advised when bowel cleansing preparations are prescribed in patients treated with drugs that prolong the QT interval. Monitoring of baseline and posttreatment serum electrolyte levels is recommended, particularly in the elderly. Patients should be instructed to drink plenty of clear liquids before, during, and after the bowel preparation process. Consideration should be given to consumption of 36 to 48 fluid ounces of a carbohydrate-electrolyte solution in the six hours before the first dose. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.