Pazopanib is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3), platelet-derived growth factor receptors (PDGFR-α and PDGFR-β), fibroblast growth factor receptor (FGFR-1 and FGFR-3), cytokine receptor (Kit), interleukin-2 receptor inducible T-cell kinase (Itk), leukocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms). It is a cornerstone in the management of advanced renal cell carcinoma (RCC) and advanced soft tissue sarcoma (STS) in the Indian oncology setting.
Adult: 800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal). The recommended starting dose is 800 mg. For the 400mg tablet, this equates to two 400mg tablets taken together once daily.
Note: Swallow tablet whole with water. Do not crush or break. Must be taken on an empty stomach, at least 1 hour before or 2 hours after a meal. If a dose is missed, it should not be taken if it is less than 12 hours until the next dose. Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole) should be avoided; if unavoidable, reduce pazopanib dose to 400 mg daily. Concomitant use of strong CYP3A4 inducers (e.g., rifampin) should be avoided as they may decrease pazopanib efficacy.
Pazopanib is a potent and selective multi-targeted receptor tyrosine kinase inhibitor that blocks the ATP-binding sites of specific receptors involved in tumor angiogenesis, tumor growth, and metastatic progression. Its primary anti-tumor effect is mediated through inhibition of VEGFR-2, which is critical for endothelial cell proliferation and new blood vessel formation (angiogenesis) required for tumor survival and growth.
Pregnancy: Category D. Based on animal studies and mechanism of action, pazopanib can cause fetal harm when administered to a pregnant woman. It is contraindicated. Women of childbearing potential must use effective contraception during and for at least 2 weeks after therapy.
Driving: Patients should be cautioned about the potential for fatigue, dizziness, and weakness, which may impair the ability to drive or operate machinery.
| Strong CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole, Clarithromycin, Ritonavir) | Significantly increase pazopanib plasma concentration, increasing risk of toxicity. | Major |
| Strong CYP3A4 Inducers (e.g., Rifampin, Carbamazepine, Phenytoin, St. John's Wort) | Significantly decrease pazopanib plasma concentration, reducing efficacy. | Major |
| CYP3A4/5/2C8 Substrates (e.g., Simvastatin) | Pazopanib may increase concentrations of these drugs. | Moderate |
| CYP2D6 Substrates (e.g., Debrisoquine) | Pazopanib is a weak inhibitor of CYP2D6; monitor for increased effects. | Moderate |
| P-gp Substrates (e.g., Digoxin) | Pazopanib may increase digoxin concentration; monitor serum levels. | Moderate |
| Antihypertensives | Pazopanib-induced hypertension may necessitate adjustment of antihypertensive therapy. | Moderate |
| Drugs that Prolong QT Interval (e.g., Class Ia/III antiarrhythmics, Moxifloxacin) | Additive risk of QT prolongation and cardiac arrhythmias. | Major |