Approved October 19, 2009

PAZOPANIB HYDROCHLORIDE
(FDA Category 1)

VOTRIENT(TM) (GlaxoSmithKline, Pharmaceuticals). is a multi-tyrosine kinase inhibitor.

DOSING INFORMATION: The recommended dose is 800 mg orally once daily without food.

PHARMACOKINETICS: Do not crush tablet since bioavailability and rate of absorption are increased. Administer on empty stomach due to increased systemic exposure (2-fold increase in AUC and Cmax) when administered with fat-containing meal. Protein binding is greater than 99%. Pazopanib is hepatically metabolized via CYP3A4, CYP1A2 and CYP2C8 with extensive elimination primarily via feces (less than 4% renal elimination). Clearance decreased by 50% in moderate hepatic impairment. Hemodialysis is not expected to enhance the elimination. Following oral administration the mean half-life is 30.9 hours.

CAUTIONS: Severe and fatal hepatotoxicity has occurred; monitor hepatic function and interrupt, reduce, or discontinue dosing as needed. Moderate hepatic impairment requires dose adjustment. Avoid use of strong CYP3A4 inhibitors, strong CYP3A4 inducers, and grapefruit juice. Concomitant use with narrow therapeutic index substances metabolized by CYP3A4, CYP2D6, and CYP2C8 are not recommended. Cautious use in patients with increased risk or with a history of arterial thrombotic events, QT prolongation, and hypertension. Hemorrhagic events and gastrointestinal perforation or fistula, some cases fatal, have been reported. Discontinue therapy at least 7 days prior to scheduled surgery. Hypertension, hypothyroidism, and proteinuria have been reported.

FDA APPROVED INDICATIONS: Pazopanib hydrochloride is indicated for the treatment of advanced renal cell carcinoma in adults.