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

Pazopanib is a multi-target tyrosine kinase inhibitor that acts on vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3), platelet-derived growth factor receptors (PDGFR-α and PDGFR-β), fibroblast growth factor receptors (FGFR-1 and FGFR-3), and other receptors including c-Kit, Itk, Lck, and c-Fms. In vitro studies show inhibition of ligand-induced autophosphorylation of VEGFR-2, Kit, and PDGFR-β.

Absorption: Pazopanib is absorbed orally, reaching peak plasma concentration within 2–4 hours after dosing. A daily dose of 800 mg produces mean AUC of 1,037 mcg·h/mL and Cmax of 58.1 mcg/mL. No further increase in exposure is seen above 800 mg.

Distribution: Plasma protein binding is greater than 99%, with no concentration dependency. It is a substrate of P-gp and BCRP transporters.

Metabolism: Pazopanib is mainly metabolized by CYP3A4, with minor contributions from CYP1A2 and CYP2C8.

Elimination: The mean elimination half-life is approximately 30.9 hours. It is mainly excreted in feces, with less than 4% eliminated through urine.

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.

Drugs that inhibit or induce CYP3A4 enzymes: In vitro studies show that Pazopanib is mainly metabolized by CYP3A4, with minor contributions from CYP1A2 and CYP2C8. Therefore, drugs that inhibit or induce CYP3A4 may alter Pazopanib levels.

CYP3A4 inhibitors: Strong inhibitors (e.g., Ketoconazole, Ritonavir, Clarithromycin) increase Pazopanib exposure and should be avoided. If unavoidable, a reduced dose of 400 mg should be considered. Grapefruit and grapefruit juice should also be avoided as they inhibit CYP3A4 and may increase drug levels.

CYP3A4 inducers: Drugs such as Rifampin may reduce Pazopanib plasma concentration. Concomitant use with strong inducers should be avoided; if not possible, Pazopanib should generally not be used.

Transporter inhibitors: Pazopanib is a substrate of P-glycoprotein (P-gp) and BCRP. Drugs affecting these transporters may alter absorption and elimination. Strong inhibitors should be avoided due to increased exposure risk.

Effect on CYP substrates: Pazopanib weakly inhibits CYP3A4, CYP2C8, and CYP2D6 in vivo. It has no significant effect on CYP1A2, CYP2C9, or CYP2C19. Concomitant use with drugs having a narrow therapeutic index metabolized by CYP3A4, CYP2D6, or CYP2C8 is not recommended.

Simvastatin interaction: Concomitant use with Simvastatin increases the risk of ALT elevation. If liver enzymes increase, dose adjustment or discontinuation of either drug should be considered.

Pazopanib is contraindicated in patients with known hypersensitivity to Pazopanib or any of its components.

Common adverse effects include:

• Hepatic toxicity and liver impairment
• QT prolongation and torsades de pointes
• Cardiac dysfunction
• Hemorrhagic events
• Arterial and venous thromboembolism
• Thrombotic microangiopathy
• Gastrointestinal perforation and fistula
• Interstitial lung disease/pneumonitis
• Reversible posterior leukoencephalopathy syndrome
• Hypertension
• Hypothyroidism
• Proteinuria
• Tumor lysis syndrome
• Infections
• Increased toxicity with other cancer therapies

Pazopanib can cause fetal harm if used during pregnancy. There are no adequate human data. Women of reproductive potential should be informed of the potential risk. It is unknown whether Pazopanib or its metabolites are present in human milk. Due to potential serious adverse effects in infants, breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose.

Hepatic toxicity: Severe and potentially fatal liver toxicity may occur, especially within the first 18 weeks of treatment. Elderly patients are at higher risk. Regular monitoring of liver enzymes is required.

QT prolongation: QT interval prolongation and rare cases of torsades de pointes have been reported. ECG monitoring and electrolyte correction are recommended, especially in at-risk patients.

Females: Effective contraception is required during treatment and for at least 2 weeks after stopping therapy.

Males: Male patients with partners of reproductive potential should use condoms during treatment and for at least 2 weeks after the last dose.

Pediatric use: Safety and efficacy have not been established in children.

Doses up to 2000 mg have been studied. Overdose may cause severe fatigue and hypertension. Management is supportive; no specific antidote exists. Hemodialysis is not effective due to high protein binding and low renal elimination.

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