Pazopanib Hydrochloride (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- PAZOPANIB HYDROCHLORIDE
- VOTRIENT
Boxed Warning
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)].
Contraindications
None.
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 (5.7)] Gastrointestinal Perforation and Fistula [see Warnings and Precautions (5.8)] Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.9)] Posterior Reversible Encephalopathy Syndrome (PRES) [see Warnings and Precautions (5.10)] Hypertension [see Warnings and Precautions (5.11)] Hypothyroidism [see Warnings and Precautions (5.13)] Proteinuria [see Warnings and Precautions (5.14)] Tumor Lysis Syndrome [see Warnings and Precautions (5.15)] Infection [see Warnings and Precautions (5.16)]
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)-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. 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.
Overdosage
Dose-limiting toxicity (Grade 3 fatigue) and Grade 3 hypertension were each observed in 1 of 3 patients dosed at 2,000 mg daily (2.5 times the recommended dose) and 1,000 mg daily (1.25 times the recommended dose), respectively. Provide general supportive measures to manage an overdose. Hemodialysis is not expected to enhance the elimination of pazopanib tablets because pazopanib is not significantly renally excreted and is highly bound to plasma proteins.