Drug Detail

Information about Votrient

Generic Name	Pazopanib
IND	GW786034B
Brand Name (US)	Votrient
Manufacturer	GlaxoSmithKline
Drug Type	Tyrosine Kinase Inhibitor
Delivery	Oral
Approval Status	Approved for a non-GIST cancer
Indications	Renal cell carcinoma (RCC) and Soft-tissue Sarcoma (but not GIST) in the U.S.
Overall Strategy	KIT Protein Based
Strategy	Block KIT + Block blood vessel growth
Drug Category	KIT/PDGFRA inhibitor+ VEGF inhibitor (TKI)

Pazopanib is a multi-tyrosine kinase inhbitor that inhibits the VEGF receptors (1,2 & 3) as well as KIT and PDGFRA and PDGFRB. In this respect it is similar to Sutent and Nexavar. At higher concentrations, it appears to inhibit Aurora A kinase. It is unknown whether it inhibits Aurora A at clinically achievable concentrations.
On October 19, 2009, pazopanib was approved in the US for renal cell carcinoma (kidney cancer). In 2012, it was approved for soft-tissue sarcoma. It is not approved for GIST. Pazopanib is in phase 2 trials for GIST (2012).
Severe liver toxicity has been noted in some patients and regular monitoring of liver function is important. Drug-related deaths were observed in 2.2% of 593 patients and included hepatic failure (n=2), hemorrhage (n=6),arterial thrombotic events (n=3) and perforation (n=2). See link below about changes to liver monitoring frequency.
In RCC patients, the recommended dose of pazopanib is 800 mg orally once daily without food (at least1 hour before or 2 hours after a meal). The dose of pazopanib should not exceed 800 mg. Do not crush tablets due to the potential for increased rate of absorption which may affect systemic exposure. The prescribing information (US), indicates a starting dose of 200 mg/day for patients with moderate liver impairment. Pazopanib is not recommended for patients with severe liver impairment.
If a dose is missed, it should not be taken if it is less than 12 hours until the next dose.