Uses of Votrient Tablet: - Kidney cancer - Soft tissue sarcoma Renal cell carcinoma, soft tissue sarcoma Hypersensitivity.

Targeted Cancer Therapy

Pazopanib is a multi-tyrosine kinase inhibitor of vascular endothelial growth factorreceptor (VEGFR)- 1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR)-α and -β, fibroblast growth factor receptor (FGFR)-1 and -3, cytokinereceptor (Kit), interleukin-2 receptor-inducible T-cell kinase (Itk), leukocyte-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.

How to use Pazopanib Hydrochloride: Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Pazopanib Hydrochloride is to be taken empty stomach. Administration: Should be taken on an empty stomach: Take at least 1 hr before or 2 hr after meals. Swallow whole, do not break/crush. Adult Dose: Advanced Renal Cell Carcinoma 800 mg PO qDay on empty stomach Soft Tissue Sarcomas 800 mg PO qDay on empty stomach Hepatic Impairment Billirubin <1.5 x ULN or ALT >ULN: No dosage adjustment required Billirubin >1.5-3 x ULN: Decreased dose to 200 mg PO qDay Billirubin >3 x ULN: Not recommended Child Dose: Safety and efficacy not established; not indicated for use in pediatric patients Renal Dose: Renal impairment: No dosage adjustment required

Co-administration w/ CYP3A4 (eg, itraconazole, clarithromycin, atazanavir, idinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice), P-gp & BCRP inhibitors, high-/low-fat food increases exposure & conc of pazopanib. Co-administration w/ CYP3A4 (eg, rifampicin) inducers may decrease plasma pazopanib conc. P-gp & BCRP inducers may alter exposure & distribution of pazopanib. Pazopanib may alter exposure &/or distribution of CYP3A4 substrates (eg, midazolam), CYP2C8 substrates (eg, paclitaxel) & UGT1A1 substrates (eg, irinotecan & its active metabolite SN-38). Pazopanib may increase the ratio of dextrometrophan to dextrophan conc after administration of dextrometrophan. Proton-pump inhibitors (eg, esomeprazole) & other agents that increase gastric pH may decrease bioavailability of pazopanib. Concomitant use w/ simvastatin & other statins may lead to ALT elevations.

Hypersensitivity.

Common - Headache - Nausea - Vomiting - Musculoskeletal (bone, muscle or joint) pain - Fatigue - Change in color of hair - Diarrhea - High blood pressure - Decreased appetite - Weight loss - Taste change - Abnormal skin pigmentation - Hair discoloration - Tumor pain - Breathlessness >10% ALT (SGPT) level raised (all grades, 53%; grade 3, 10%; grade 4, 2% ) AST/SGOT level raised (all grades, 53%; grade 3, 7%; grade 4, less than 1% ) Diarrhea (52%),Increased glucose (41%),Hypertension (40%),Hair depigmentation (38%) Leukopenia (all grades, 37%; grade 3, 0%; grade 4, 0% ) Increased bilirubin level (all grades, 36%; grade 3, 3%; grade 4, less than 1% ) Neutropenia (all grades, 34%; grade 3, 1%; grade 4, less than 1% ) Phosphorous decreased (34%) Thrombocytopenia (all grades, 32%; grade 3, less than 1%; grade 4, less than 1% ) Lymphocytopenia (all grades, 31%; grade 3, 4%; grade 4, less than 1% ) Sodium decreased (31%),Magnesemium decreased (26%),Nausea (26%),Weakness (22%),Vomiting (21%),Anorexia (22%),Fatigue (19%),Bradycardia (19%) Hemorrhage (all grades, 13% to 16%; grade 3 to 5, 2%) Myocardial dysfunction (ie, >15% decline in LVEF from baseline or ≥10% with baseline below normal) (11-13%) Abdominal pain (11%) 1-10% (select) Headache (10%),Proteinuria (9%),Weight loss (9%),Alopecia (8%),Dysgeusia (8%),Rash (8%),Hypothyroidism (4% to 7% ),Palmar-plantar erythrodysesthesia (6%),Chest pain (5%),Dyspepsia (5%),Skin depigmentation (3%),Prolonged QT interval (<2%),Hepatotoxicity (1%-2%),Facial edema (1%),Rectal hemorrhage (1%),Transient ischemic attack (1%),Hemorrhagic death (0.9%-1%) <1% Cardiac dysfunction (eg, decreased LVEF, CHF) (0.6%) Congestive heart failure (0.5%),Torsades de pointes,Cerebrovascular accident,Pancreatitis Frequency Not Defined Myocardial infarction,Gastrointestinal fistula,Gastrointestinal perforation

Pazopanib can cause fetal harm when administered to a pregnant woman. Based on its mechanism of action, Pazopanib is expected to result in adverse reproductive effects. In pre-clinical studies in rats and rabbits, pazopanib was teratogenic, embryotoxic, fetotoxic, and abortifacient.There are no adequate and well-controlled studies of Pazopanib in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while taking Pazopanib

Precaution: Hepatic Toxicity and Hepatic Impairment, QT Prolongation, Cardiac Dysfunction, Hemorrhagic Events, Thromboembolic Events, Gastrointestinal Perforation and Fistula, Hypertension, Hypothyroidism, Pregnancy. Lactation: Unknown whether distributed in breast milk, do not nurse

Pazopanib doses up to 2000 mg have been evaluated in clinical trials. Dose-limiting toxicity (Grade 3 fatigue) and Grade 3 hypertension were each observed in 1 of 3 patients dosed at 2000 mg daily and 1000 mg daily, respectively. Treatment of overdose with Pazopanib should consist of general supportive measures. There is no specific antidote for overdosage of Pazopanib. Hemodialysis is not expected to enhance the elimination of Pazopanib because Pazopanib is not significantly renally excreted and is highly bound to plasma proteins.

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

Multikinase inhibitor (including VEGF & PDGF receptor tyrosine kinases) some of which are implicated in tumor growth, angiogenesis, & metastasis

Pazopanib can cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform a drug-associated risk. Pregnant women or women should be advised of the childbearing potential of the potential risk to a fetus. There is no information regarding the presence of Pazopanib or its metabolites in human milk, or their effects on the breastfed infant, or on milk production. Because of the potential for serious adverse reactions in breastfed infants from Pazopanib, a lactating woman should be advised not to breastfeed during treatment with Pazopanib and for 2 weeks after the final dose.