Advanced renal cell carcinoma.
Pazopanib is a multi-kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor-α and-β, fibroblast growth factor receptor-1, and -3, cytokine receptor, interleukin-2 receptor inducible T-cell kinase, leukocyte-specific protein tyrosine kinase, and transmembrane glycoprotein receptor tyrosine kinase.
Pazopanib was evaluated in a placebo-controlled Phase 3 study involving 435 patients with renal cell carcinoma. Patients were randomized (2:1) to receive pazopanib 800mg or placebo once daily. In this trial, the overall median progression free survival (PFS) was 9.2 months with pazopanib and 4.2 months with placebo. Treatment-naive patients who received pazopanib experienced 11.1 months of median PFS vs 2.8 months with placebo. Additionally, patients who had previously received cytokine-based treatment achieved 7.4 months of median PFS with pazopanib vs 4.2 months with placebo.
Take on an empty stomach. Swallow whole. 800mg once daily. Hepatic impairment: moderate: 200mg once daily; severe: not recommended. Concomitant strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir, clarithromycin): avoid; if warranted, reduce dose of pazopanib to 400mg; may reduce further if toxicity occurs. Concomitant strong CYP3A4 inducers (eg, rifampin): avoid.
Monitor liver tests before starting and at least once every 4 weeks for at least the first 4 months of treatment, then periodically. If ALT between 3xULN and 8xULN continue therapy with weekly monitoring until ALT returns to Grade 1 or baseline. If ALT >8xULN interrupt therapy until ALT returns to Grade 1 or baseline; may consider reintroducing at a reduced dose, measure liver tests weekly for 8 weeks; if ALT>3xULN recurs, permanently discontinue. Permanently discontinue if ALT>3xULN and bilirubin >2xULN. Gilbert’s syndrome (see literature). History of QT prolongation. Cardiac disease. Monitor ECG, electrolytes (eg, calcium, magnesium, potassium), thyroid, urinalysis. History of hemoptysis, cerebral, or clinically significant GI hemorrhage in the past 6 months: not recommended. Risk of arterial thrombotic events (within previous 6 months: not recommended). Discontinue if severe and persistent hypertension (despite antihypertensive therapy and dose reduction) or if Grade 4 proteinuria occurs. Stop therapy at least 7 days before surgery; discontinue in patients with wound dehiscence. Pregnancy (Cat.D), nursing mothers: not recommended.
See Adult dosing: Potentiated by strong CYP3A4 inhibitors, grapefruit juice. Antagonized by strong CYP3A4 inducers. Concomitant drugs with narrow therapeutic windows metabolized by CYP3A4, CYP2D6, or CYP2C8: not recommended. Caution with concomitant drugs that prolong QT interval (eg, antiarrhythmics).
Diarrhea, hypertension, hair color changes, nausea, anorexia, vomiting; hepatotoxicity (may be severe or fatal), QT prolongation, hemorrhagic events, arterial thrombotic events (eg, MI, angina, ischemic stroke, TIA), GI perforation or fistula, impaired wound healing, hypothyroidism, proteinuria.
Tabs 200mg—30, 90, 120