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Votrient

pazopanib
Multi-Kinase Inhibitor (VEGFR/PDGFR/KIT) Novartis FDA Approved 2009
Indications Dosing Forms Contraindications Warnings Adverse Reactions Pharmacology Clinical Studies Tumor Types
1. Indications and Usage

Advanced renal cell carcinoma (RCC); Advanced soft tissue sarcoma (STS) — previously treated with chemotherapy.

2. Dosage and Administration

800 mg orally once daily on empty stomach (at least 1 hour before or 2 hours after a meal)
Do not crush tablets (increases rate of absorption and toxicity)
Dose reductions: 400 mg, then 200 mg
Moderate hepatic impairment: 200 mg daily
Severe hepatic impairment: Not recommended

3. Dosage Forms and Strengths

Tablets: 200 mg

4. Contraindications

Severe hepatic impairment.

5. Warnings and Precautions
⚠ Boxed Warning
HEPATOTOXICITY: Severe and fatal hepatotoxicity has been observed. Monitor hepatic function and interrupt, reduce, or discontinue per recommendations.
  • Hepatotoxicity: Fatal hepatotoxicity in 0.3%. ALT >3× ULN in 53%, >8× ULN in 9%. Monitor LFTs every 4 weeks × 4 months, then periodically. D/C if ALT >8× ULN.
  • QT Prolongation and Torsades de Pointes: Monitor ECGs and electrolytes. Avoid with other QT-prolonging drugs.
  • Cardiac Dysfunction: MI, cardiac dysfunction in 2%. Monitor BP and LVEF.
  • Hemorrhage: Fatal hemorrhage (including pulmonary, GI, GU). Do not use if history of hemoptysis.
  • Arterial/Venous Thromboembolic Events
  • GI Perforation/Fistula: Fatal cases. Monitor for symptoms.
  • Hypertension: In 42%. Monitor BP weekly first 8 weeks.
  • Wound Healing: Withhold ≥1 week pre-surgery.
  • Hypothyroidism: In 7%. Monitor TSH.
  • Proteinuria: In 9%. Monitor with urinalysis.
6. Adverse Reactions
Most Common Adverse Reactions

Diarrhea (52%), hypertension (42%), hair color change (38%), nausea (26%), decreased appetite (22%), fatigue (19%), vomiting (21%), AST/ALT elevation (53%), weight decrease (9%), stomatitis (8%)

AST/ALT elevation
53%
Diarrhea
52%
Hypertension
42%
Hair Color Change
38%
Nausea
26%
Decreased Appetite
22%
Vomiting
21%
Fatigue
19%
Weight Decrease
9%
Stomatitis
8%

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

12. Clinical Pharmacology
Mechanism of Action

Pazopanib is a multi-kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-α, PDGFR-β, FGFR-1, FGFR-3, c-KIT, IL-2 inducible T-cell kinase (Itk), leukocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms). Inhibition of VEGFR and PDGFR suppresses tumor angiogenesis; KIT inhibition has direct anti-tumor effects in KIT-driven sarcomas.

Pharmacokinetics

Tmax: 2-4 hours. Half-life: 30.9 hours. Protein binding: >99%. Metabolized by CYP3A4 (minor: CYP1A2, CYP2C8). Excreted primarily in feces (>80%). Food increases AUC ~2-fold (take fasting). Steady-state by Day 7-8.

14. Clinical Studies

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

Pivotal Clinical Trials
Additional Resources
📋 All Pazopanib Trials on ClinicalTrials.gov ↗ 📚 PubMed: Pazopanib Clinical Trials ↗
Approved Tumor Types
Kidney Cancer Sarcoma