Pazopanib — Drug Monograph

Brand names: Votrient

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Pazopanib is a multi-target tyrosine kinase inhibitor that primarily targets VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-alpha, PDGFR-beta, and fibroblast growth factor receptors (FGFR-1 and FGFR-3). It also inhibits the stem cell factor receptor (c-KIT). By blocking these pathways, it inhibits angiogenesis, cell proliferation, and survival in susceptible tumors. This broad inhibition disrupts the blood supply to the tumor and directly interferes with oncogenic signaling.

FDA Indications

• Treatment of patients with advanced renal cell carcinoma (RCC)
• Treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy

Common Side Effects

• Diarrhea
• Hypertension
• Hair color changes (depigmentation)
• Nausea
• Anorexia
• Vomiting
• Fatigue
• Asthenia
• Abdominal pain
• Headache
• Dysgeusia

Clinical Pearl

A unique and common side effect of pazopanib is hair depigmentation (lightening), which is reversible upon discontinuation. Unlike many other TKIs, pazopanib absorption is significantly affected by gastric pH; PPIs should be avoided, and if an acid-reducer is needed, short-acting antacids should be spaced from the pazopanib dose. Hepatotoxicity usually occurs within the first 4 months of therapy, necessitating intensive early monitoring. It is generally not recommended for adipocytic soft…

Related Therapies & Mechanisms

• Axitinib (Inlyta) — Tyrosine Kinase Inhibitor · RCC
• Cabozantinib (Cabometyx) — Tyrosine Kinase Inhibitor · RCC
• Imatinib (Gleevec) — Tyrosine Kinase Inhibitor · Sarcoma
• Lenvatinib (Lenvima) — Tyrosine Kinase Inhibitor · RCC