Overview
11 DESCRIPTION Pazopanib is a kinase inhibitor. Pazopanib is presented as the hydrochloride salt, with the chemical name 5-[[4-[(2,3-Dimethyl-2 H -indazol-6-yl)methylamino]pyrimidin-2-yl]amino]-2-methylbenzenesulfonamide monohydrochloride. It has the molecular formula C 21 H 23 N 7 O 2 S·HCl and a molecular weight of 473.98 g/mol.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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)-ɑ 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. In vivo, pazopanib inhibited VEGF-induced VEGFR-2 phosphorylation in mouse lungs, angiogenesis in a mouse model, and the growth of some human tumor xenografts in mice. 12.
Indications
- 1 INDICATIONS AND USAGE Pazopanib tablets are a kinase inhibitor indicated for the treatment of adults with: advanced renal cell carcinoma (RCC). ( 1.1 ) advanced soft tissue sarcoma (STS) who have received prior chemotherapy. ( 1.2 ) Limitations of Use: The efficacy of pazopanib tablets for the treatment of patients with adipocytic soft tissue sarcoma or gastrointestinal stromal tumors has not been demonstrated. 1.1 Renal Cell Carcinoma Pazopanib tablets are indicated for the treatment of adults with advanced renal cell carcinoma (RCC). 1.
Common Doses
- 800 mg
- 200 mg
- 400 mg
- 600 mg
Dosage
2 DOSAGE AND ADMINISTRATION Recommended Dosage: 800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal). ( 2.1 ) Moderate Hepatic Impairment: 200 mg orally once daily. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage of pazopanib tablets is 800 mg (four 200 mg tablets) orally once daily without food (at least 1 hour before or 2 hours after a meal) until disease progression or unacceptable toxicity [see Clinical Pharmacology ( 12.3 )].
Black Box Warning
WARNING: HEPATOTOXICITY Severe and fatal hepatotoxicity has been observed in clinical trials. Monitor hepatic function and interrupt, reduce, or discontinue dosing as recommended [see Warnings and Precautions ( 5.1 )] . WARNING: HEPATOTOXICITY See full prescribing information for complete boxed warning. Severe and fatal hepatotoxicity has been observed in clinical trials. Monitor hepatic function and interrupt, reduce, or discontinue dosing as recommended. ( 5.1 )
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are elsewhere in the labeling: Hepatic Toxicity [see Warnings and Precautions ( 5.1 )] QT Prolongation and Torsades de Pointes [see Warnings and Precautions ( 5.2 )] Cardiac Dysfunction [see Warnings and Precautions ( 5.3 )] Hemorrhagic Events [see Warnings and Precautions ( 5.4 )] Arterial Thromboembolic Events [see Warnings and Precautions ( 5.5 )] Venous Thromboembolic Events [see Warnings and Precautions ( 5.6 )] Thrombotic Microangiopathy (TMA) [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors: Avoid coadministration of pazopanib tablets with strong CYP3A4 inhibitors. If coadministration cannot be avoided, reduce the dose of pazopanib tablets. ( 2.4 , 7.1 ) Strong CYP3A4 Inducers: Consider an alternate concomitant medication with no or minimal enzyme induction potential. Pazopanib tablets are not recommended if chronic use of strong CYP3A4 inducers cannot be avoided. ( 2.4 , 7.