Instructions for Pazopanib

1. Generic name: Pazopanib

Product name:VOTRIENT

All names: pazopanib tablets, pazopanib, pazopanib, Vitant

2. Indications:

1. Renal cell carcinoma (RCC): Pazopanib is suitable for the treatment of advanced renal cell carcinoma in adults.

2. Soft tissue sarcoma (STS):

Pazopanib is suitable for the treatment of adult patients with advanced soft tissue sarcoma(STS) who have previously received chemotherapy.

Limitations of use: The efficacy of this product in patients with adipocytic soft tissue sarcoma or gastrointestinal stromal tumors has not been proven.

3. Usage and dosage:

1. Recommended dose: The recommended dose of pazopanib is 800 mg (four 200 mg tablets ) once daily, without food, or at least 1 hour before or 2 hours after meals, until disease progression or unacceptable toxicity occurs. Do not crush tablets as this may increase absorption, thereby affecting systemic exposure.

2. Dose adjustment: If patients experience adverse reactions during pazopanib treatment, the dose should be adjusted under the guidance of a doctor. For patients with renal cell carcinoma, the first dose is reduced to 400 mg orally once a day, and for the second time, the dose is reduced to 200 mg orally once a day; for patients with soft tissue sarcoma, the first dose is reduced to 600 mg orally once a day, and for the second time, the dose is reduced to 400 mg orally once a day. Pazopanib should be permanently discontinued in patients who are unable to tolerate the second dose reduction.

(1) Liver function damage:

For patients with moderate hepatic impairment[total bilirubin >1.5-3 times the upper limit of normal (ULN) and any alanine aminotransferase (ALT) value], consider alternatives to pazopanib. If pazopanib is used in patients with moderate hepatic impairment, reduce the oral dose to 200 mg once daily. Pazopanib is not recommended in patients with severe hepatic impairment (total bilirubin >3 × ULN and any ALT value).

(2) Combined medication:

If coadministration of a strong CYP3A4 inhibitor is necessary, reduce the pazopanib dose to 400 mg. Pazopanib is not recommended for patients in whom long-term use of strong CYP3A4 inducers cannot be avoided. If concomitant use of acid-reducing agents cannot be avoided, consider using short-acting antacids instead of proton pump inhibitors (PPIs) and H2-receptor antagonists, spacing the administration of short-acting antacids and vitamin E by several hours.

4. Adverse reactions:

In clinical studies of renal cell carcinoma, the common adverse reactions of pazopanib (≥20%) were diarrhea, hypertension, hair color change, nausea, fatigue, anorexia and vomiting. In clinical studies of soft tissue sarcoma, common adverse reactions (≥20%) were fatigue, diarrhea, nausea, weight loss, hypertension, decreased appetite, vomiting, tumor pain, hair color changes, musculoskeletal pain, headache, dysgeusia, dyspnea, and skin hypopigmentation. PazopanibAdverse reactions that have occurred after marketing include polycythemia, retinal detachment/tear, pancreatitis, tumor lysis syndrome, arterial (including aortic) aneurysm, dissection and rupture.

5. Storage:

Pazopanib is typically stored at 20°C to 25°C (68°F to 77°F), with tolerances between 15°C and 30°C (59°F to 86°F).

6. Special groups:

1. Female:. Due to the potential for serious adverse reactions in breastfed infants, women are advised not to breastfeed during treatment with pazopanib and for at least 2 weeks after the last dose; women of childbearing potential use effective contraception during treatment with pazopanib and for at least 2 weeks after the last dose.

2. Men: It is recommended that men with female partners of reproductive potential (including men who have had vasectomy) use condoms during treatment with pazopanib and for at least 2 weeks after the last dose of the drug.

3. Liver function impairment: Pazopanib is not recommended for patients with moderate (total bilirubin >1.5-3×ULN and any ALT value) and severe (total bilirubin >3×ULN and any ALT value) liver impairment.

7. Mechanism of action:

Pazopanibis a vascular endothelial growth factor receptorPolytyrosine kinase inhibitor of (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 inhibits ligand-induced autophosphorylation of VEGFR-2, Kit and PDGFR-β receptors. In vivo, pazopanib inhibits VEGF-induced VEGFR-2 phosphorylation in mouse lungs, angiogenesis in mouse models, and the growth of some human tumor xenografts in mice.