The medication is used to treat clear cell renal cell carcinoma, the most common histological subtype.
The treatment phase is continuing treatment beyond three months.
The patient has been issued an authority prescription for pazopanib.
The patient must have stable or responding disease according to the Response Evaluation Criteria In Solid Tumours (RECIST).
This treatment must be the sole tyrosine kinase inhibitor subsidised for this condition.
Pazopanib has also demonstrated initial therapeutic properties in patients withaggressive fibromatosis (desmoid tumor),[9] ovarian and non-small cell lung cancer.[10][unreliable medical source?] However, plans to apply to the EMA for a variation to include advanced ovarian cancer have been withdrawn and a license will not be sought in any country.[11][12]
Haematologic parameter alterations have been reported in 31–37% of patients.
Events of cardiac dysfunction (decreased left ventricularejection fraction and congestiveheart failure) have been observed.
Fatal haemorrhage, arterial and venous thrombotic events and perforations in thegastrointestinal tract have been observed in randomized clinical trials.
It has oneboxed warning by the US FDA, namely severe hepatotoxicity including fatalities.[2][3]
The most common side effects of pazopanib are nausea, vomiting, diarrhoea (occurs in about half of patients), changes in hair colour, hypertension (which usually occurs during the first few weeks of treatment), appetite loss,hyperglycaemia,hypoglycaemia, electrolyte abnormalities (includinghypocalcaemia,hypomagnesemia,hypophosphatemia), laboratory anomalies (including increasedAST,ALT and protein in the urine), oedema, hair loss or discolouration, taste changes, abdominal pain, rash, fatigue andbone marrow suppression (includingleucopenia,neutropenia,thrombocytopenia andlymphopenia).[13] It has been associated with a low, but real risk of potentially fatal liver damage.[13]
Co-administration with strong inhibitors of the liver enzymeCYP3A4 (e.g.ketoconazole,ritonavir,clarithromycin, grapefruit juice) may increase pazopanib serum levels as it is a CYP3A4 substrate.
Pazopanib is a multiple kinase inhibitor that limits tumor growth bytargeting angiogenesis via inhibition of enzymes including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor(PDGFR),c-KIT andFGFR.[2][13][16][17][18][19]
After oral intake of a single tablet, pazopanib has abioavailability of 21% with a range of 14–39% between people. It reaches highest concentrations in theblood plasma aftermedian 3.5 hours; the range in studies was 1.0 to 11.9 hours. When taken regularly, thearea under the curve (AUC) increases 1.23- to 4-fold as compared to a single dose. Taking the drug together with food approximately doubles the AUC as well as thehighest plasma concentrations (Cmax); and crushing the tablet increases the AUC 1.46-fold, as well doubling the Cmax.[1][4]
When in the bloodstream, more than 99.5% of the substance are bound toplasma proteins. The liver enzyme mainly responsible for metabolizing the drug is CYP3A4; and there are minor contributions fromCYP1A2 andCYP2C8. Metabolites identified in tests with humanliver cells andmicrosomes include varioushydroxyl derivatives and possibly acarboxylic acid. Only 6% of the circulating substance is in the form of metabolites, and all but one of them are 10- to 20-fold less active than pazopanib itself. Consequently, the metabolites are not considered important for the drug's therapeutic effect.[1][4]
Pazopanib is eliminated with abiological half-life of 30.9±4 hours on average (range 21–51 hours) mainly via the faeces. Less than 4% are eliminated via the urine.[1][4]
^abcZivi A, Cerbone L, Recine F, Sternberg CN (September 2012). "Safety and tolerability of pazopanib in the treatment of renal cell carcinoma".Expert Opinion on Drug Safety.11 (5):851–859.doi:10.1517/14740338.2012.712108.PMID22861374.S2CID2178331.
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