PAZOPANIB HYDROCHLORIDE

The recommended dosage of 800 mg once daily results in mean AUC of 1,037 mcg

• h/mL and C max of 58.1 mcg/mL. There was no consistent increase in AUC or C max at pazopanib doses above 800 mg. Administration of a single 400-mg crushed tablet increased AUC 0-72h by 46% and C max by approximately 2-fold and decreased T max by approximately 2 hours compared with administration of the whole tablet [see Dosage and Administration (2.1) ] .

AbsorptionThe median time to achieve peak concentrations was 2 h...

14.1 Renal Cell Carcinoma The efficacy of pazopanib was evaluated in VEG105192, a randomized, double-blind, placebo-controlled, multicenter trial ( NCT00387764 ). Patients with locally advanced and/or metastatic RCC who had received either no prior therapy or one prior cytokine-based systemic therapy were randomized (2:1) to receive pazopanib 800 mg once daily or placebo once daily. Eligible subjects were stratified according to the following 3 stratification factors: baseline ECOG performance status 0 versus 1; prior nephrectomy yes versus no; and prior systemic therapy for advanced RCC: trea...

The following clinically significant adverse reactions are elsewhere in the labeling: Hepatic Toxicity [see Warnings and Precautions (5.1) ] QT Prolongation and Torsades de Pointes [see Warnings and Precautions (5.2) ] Cardiac Dysfunction [see Warnings and Precautions (5.3) ] Hemorrhagic Events [see Warnings and Precautions (5.4) ] Arterial Thromboembolic Events [see Warnings and Precautions (5.5) ] Venous Thromboembolic Events [see Warnings and Precautions (5.6) ] Thrombotic Microangiopathy (TM...

None. None. ( 4 )

Hepatic Toxicity : Severe and fatal hepatotoxicity has occurred. Monitor liver tests at baseline, regularly during treatment and as clinically indicated. Withhold pazopanib and resume at reduced dose with continued weekly monitoring for 8 weeks, or permanently discontinue with weekly monitoring until resolution based on severity of hepatotoxicity. ( 2.2 , 5.1 ) QT Prolongation and Torsades de Pointes : Monitor patients who are at significant risk of developing QT interval prolongation. Monitor e...

7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors: Avoid co-administration of pazopanib with strong CYP3A4 inhibitors. If co-administration cannot be avoided, reduce the dose of pazopanib. ( 2.4 , 7.1 ) Strong CYP3A4 Inducers: Consider an alternate concomitant medication with no or minimal enzyme induction potential. Pazopanib is not recommended if chronic use of strong CYP3A4 inducers cannot be avoide...