Indications

Pazopanib is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). Pazopanib is indicated for the treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy. The efficacy of Pazopanib for the treatment of patients with adipocytic STS or gastrointestinal stromal tumors has not been demonstrated.

Composition

Pharmacology

Pazopanib is a multi-tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR 2, VEGFR-3, platelet-derived growth factor receptor (PDGFR)-α and -β, fibroblast growth factor receptor (FGFR)-1 and -3, cytokine receptor (Kit), interleukin-2 receptor-inducible T-cell kinase (Itk), lymphocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms). In vitro, Pazopanib inhibited ligand-induced autophosphorylation of VEGFR-2, Kit, and PDGFR-β receptors. Absorption : Pazopanib is absorbed orally with median time to achieve peak concentrations of 2 to 4 hours after the dose. Daily dosing at 800 mg results in geometric mean AUC and C max of 1,037 mcg/mL and 58.1 mcg/mL (equivalent to 132 µM), respectively. There was no consistent increase in AUC or C max at Pazopanib doses above 800 mg. Distribution : Binding of Pazopanib to human plasma protein in vivo was greater than 99% with no concentration dependence over the range of 10 to 100 mcg/mL. In vitro, studies suggest that Pazopanib is a substrate for P-gp and BCRP. Metabolism : In vitro studies demonstrated that Pazopanib is metabolized by CYP3A4 with a minor contribution from CYP1A2 and CYP2C8. Elimination : Pazopanib has a mean half-life of 30.9 hours after administration of the recommended dose of 800 mg. Elimination is primarily via feces with renal elimination accounting for less than 4% of the administered dose.

Dosage & Administration

The recommended starting dose of Pazopanib is 800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal). The dose of Pazopanib should not exceed 800 mg. Tablets should not be crushed due to the potential for increased rate of absorption which may affect systemic exposure. If a dose is missed, it should not be taken if it is less than 12 hours until the next dose. Or, as directed by the registered physicians.

Contraindications

It is contraindicated in patients with known hypersensitivity to Pazopanib or any other components of this product.

Side Effects

Common side effects of Pazopanib include: Hepatic Toxicity and Hepatic Impairment QT Prolongation and Torsades de Pointes Cardiac Dysfunction Hemorrhagic Events Arterial and Venous Thromboembolic Events Thrombotic Microangiopathy Gastrointestinal Perforation and Fistula Interstitial Lung Disease/Pneumonitis Reversible Posterior Leukoencephalopathy Syndrome Hypertension Hypothyroidism Proteinuria Tumor Lysis Syndrome Infection Increased Toxicity with Other Cancer Therapy

Pregnancy & Lactation

Pazopanib can cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform a drug-associated risk. Pregnant women or women should be advised of the childbearing potential of the potential risk to a fetus. There is no information regarding the presence of Pazopanib or its metabolites in human milk, or their effects on the breastfed infant, or on milk production. Because of the potential for serious adverse reactions in breastfed infants from Pazopanib, a lactating woman should be advised not to breastfeed during treatment with Pazopanib and for 2 weeks after the final dose.

Precautions & Warnings

Hepatic Toxicity and Hepatic Impairment : In clinical trials with Pazopanib, hepatotoxicity, manifested as increases in serum transaminases (alanine transferase [ALT], aspartate aminotransferase [AST]) and bilirubin, was observed. This hepatotoxicity can be severe and fatal. Patients older than 65 years are at greater risk for hepatotoxicity. Transaminase elevations occur early in the course of treatment (92.5% of all transaminase elevations of any grade occurred in the first 18 weeks). QT Prolongation and Torsades De Pointes : In the RCC trials of Pazopanib, QT prolongation (greater than or equal to 500 msec) was identified on routine electrocardiogram (ECG) monitoring in 2% (11/558) of patients. Torsades de pointes occurred in less than 1% (2/977) of patients who received Pazopanib in the monotherapy trials. Pazopanib should be used with caution in patients with a history of QT interval prolongation, in patients taking antiarrhythmics or other medications that may prolong QT interval, and those with relevant pre-existing cardiac disease. When using Pazopanib, baseline and periodic monitoring of ECGs and maintenance of electrolytes (e.g., calcium, magnesium, potassium) within the normal range should be performed.

Therapeutic Class

Storage Conditions

Store below 30° C in a cool and dry place, away from sunlight. Keep out of reach of children.