Generic
Pazopanib Hydrochloride
4 brands available in the market
At a glance
Pazopanib Hydrochloride is a multi-tyrosine kinase inhibitor used for the treatment of advanced renal cell carcinoma (RCC) and advanced soft tissue sarcoma (STS) who have received prior chemotherapy.
Description
Pazopanib is a multi-tyrosine kinase inhibitor that inhibits VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-α and -β, FGFR-1 and -3, Kit, Itk, Lck, and c-Fms. In vitro, Pazopanib inhibited ligand-induced autophosphorylation of VEGFR-2, Kit, and PDGFR-β receptors. It works by inhibiting tyrosine kinase receptors involved in tumor growth, angiogenesis, and metastasis.
Indications
- Advanced Renal Cell Carcinoma (RCC)
- Advanced Soft Tissue Sarcoma (STS) with prior chemotherapy
Therapeutic class
Antineoplastic Drugs
Pharmacological class
Tyrosine Kinase Inhibitor (TKI)
Pharmacology
Pazopanib is a multi-tyrosine kinase inhibitor that inhibits VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-α and -β, FGFR-1 and -3, Kit, Itk, Lck, and c-Fms. It prevents tumor growth and angiogenesis by inhibiting tyrosine kinase receptors involved in tumor proliferation and new blood vessel formation.
Mechanism of action
Inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and other tyrosine kinase receptors to prevent tumor growth and angiogenesis.
Dosage
Adult Dose (Oral):
- Recommended dose: 800 mg once daily on an empty stomach (at least 1 hour before or 2 hours after a meal)
- Dose should not exceed 800 mg
- Do not crush tablets (may affect absorption rate)
- Hepatic impairment: Bilirubin >1.5-3 x ULN: Decrease dose to 200 mg/day; Bilirubin >3 x ULN: Not recommended
Pediatric Dose: Safety and efficacy not established.
Administration
- Take on an empty stomach (at least 1 hour before or 2 hours after a meal)
- Swallow tablet whole; do not chew, crush or break
- Take at the same time each day
- Missed dose: Do not take if less than 12 hours until next dose
Missed dose
If you miss a dose, take it as soon as you remember; skip if less than 12 hours until next dose; do not double the dose.
Side effects
Common Side Effects:
- Hepatotoxicity (elevated ALT, AST, bilirubin)
- QT prolongation
- Cardiac dysfunction
- Hemorrhagic events
- Arterial and venous thromboembolic events
- Hypertension
- Hypothyroidism
- Proteinuria
- Diarrhea
- Nausea
- Vomiting
- Fatigue
- Headache
- Decreased appetite
- Weight loss
- Taste changes
- Hair discoloration
- Abnormal skin pigmentation
Precautions & warnings
- Hepatotoxicity can be severe and fatal; patients >65 years at greater risk; transaminase elevations occur within first 18 weeks
- QT prolongation and Torsades de Pointes; caution with history; monitor electrolytes
- May decrease alertness, affect vision, or cause sleepiness and dizziness; do not drive if these occur
- May cause serious bleeding problems; inform doctor if blood in urine or stools
- May affect wound healing; inform doctor before surgery
- Do not use during pregnancy or breastfeeding; use effective contraception
Contraindications
- Hypersensitivity to pazopanib or any of its components
Drug interactions
- CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, clarithromycin): Increase pazopanib concentrations; avoid; if warranted, reduce dose to 400 mg
- CYP3A4 inducers (e.g., rifampin): Decrease pazopanib concentrations; avoid
- P-gp or BCRP inhibitors: Increase pazopanib exposure; avoid
- Simvastatin: Increased incidence of ALT elevations; follow dosing guidelines or discontinue simvastatin if ALT elevations occur
- Proton pump inhibitors (e.g., esomeprazole): Decrease pazopanib bioavailability
- Avoid grapefruit or grapefruit juice (inhibits CYP3A4)
Food interactions
Take on an empty stomach (1 hour before or 2 hours after a meal); high/low-fat food increases exposure.
Use in pregnancy
Use in Pregnancy: Can cause fetal harm when administered to a pregnant woman; advise women of potential risk to the fetus.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: No information on presence of pazopanib or metabolites in human milk; due to potential serious adverse reactions in breastfed infants, advise not to breastfeed during treatment and for 2 weeks after the final dose.
Pediatric use
Safety and effectiveness not established in pediatric patients.
Geriatric use
Elderly patients (≥65 years) are at greater risk for hepatotoxicity; caution required.
Renal / hepatic impairment
Renal Impairment: Safe in kidney disease; no dose adjustment recommended.
Hepatic Impairment: Caution in liver disease; Bilirubin >1.5-3 x ULN: 200 mg/day; >3 x ULN: Not recommended.
Overdose effects
Overdose (up to 2000 mg evaluated): Dose-limiting toxicity (Grade 3 fatigue) and Grade 3 hypertension observed. Treatment: General supportive measures; no specific antidote; hemodialysis is not expected to be effective (high protein binding and low renal excretion).
Storage conditions
Store below 30°C in a cool and dry place, away from sunlight; keep out of reach of children.
Chemical structure
Pazopanib Hydrochloride