Drug Interactions between pazopanib and tacrolimus

GENERALLY AVOID: Coadministration with potent inhibitors of P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) may significantly increase the plasma concentrations and risk of toxicity of pazopanib. The proposed mechanism involves inhibition of P-gp- or BCRP-mediated transporters of pazopanib metabolism. Although not studied, the interaction may increase the risk of QT interval prolongation and torsade de pointes arrhythmia as well as severe and fatal hepatotoxicity associated with the use of pazopanib. In a pharmacokinetic study, ketoconazole (400 mg daily), a P-gp inhibitor, increased pazopanib (400 mg daily) systemic exposure (AUC) and peak plasma concentration (Cmax) by 66% and 45%, respectively. Similarly, in another study, concomitant use of lapatinib (1500 mg), another P-gp inhibitor, with pazopanib (800 mg) led to an increase in both the AUC and Cmax of pazopanib by an average of 50% to 60%. The extent to which other, less potent inhibitors of P-gp or BCRP may interact with pazopanib is unknown.

MANAGEMENT: Concomitant use of pazopanib with potent inhibitors of P-gp or BCRP should generally be avoided. Selection of an alternate concomitant medication with no or minimal potential to inhibit P-gp or BCRP should be considered. Patients should have liver function tests (ALT, AST, bilirubin), electrocardiograms, and serum electrolyte levels performed at baseline and regular intervals as recommended in the product labeling. Patients should be advised to notify their physician if they experience signs and symptoms of hepatotoxicity such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. In addition, they should seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope.