Votrient

Pazopanib HCl

Advanced renal cell carcinoma (RCC). Advanced soft tissue sarcoma (STS) who have received prior chemotherapy.

800 mg once daily. Moderate hepatic impairment 200 mg daily.

Should be taken on an empty stomach: Take at least 1 hr before or 2 hr after meals. Swallow whole, do not chew/crush. Avoid grapefruit juice.

Monitor liver function. Perform serum liver tests before treatment initiation at wk 3, 5, 7 & 9, then at mth 3 & 4, w/ additional tests as indicated, & periodically continue testing after mth 4. Treatment may be continued in patients w/ isolated ALT elevations between 3 & 8x ULN w/ wkly monitoring of liver function until Grade 1 (NCI CTCAE) or baseline. Interrupt until patients return to Grade 1 (NCI CTCAE) or baseline if ALT is >8x ULN. Permanently discontinue if ALT elevations >3x ULN occur concurrently w/ bilirubin elevations >2x ULN. Concomitant use w/ simvastatin; other anti-cancer agents (eg, pemetrexed, lapatinib); strong CYP3A4 inhibitors, P-gp or breast cancer resistance (BCRP). BP should be well-controlled prior to treatment initiation. Monitor patients for HTN early after starting treatment (no longer than 1 wk after starting treatment) & frequently thereafter; pulmonary symptoms indicative of ILD/pneumonitis; signs or symptoms of CHF. Permanently discontinue in patients developing posterior reversible encephalopathy syndrome (PRES)/reversible posterior leukoencephalopathy syndrome (RPLS); ILD/pneumonitis; thrombotic microangiopathy. Monitor BP & manage promptly using combination of anti-hypertensive therapy. Perform baseline & periodic evaluation of left ventricular ejection fraction (LVEF) in patients at risk of cardiac dysfunction; baseline & periodic monitoring of ECG & maintenance of electrolytes (Ca, Mg, K) w/in normal range; baseline & periodic urinalyses during treatment & monitor for worsening proteinuria. History of QT interval prolongation, those taking antiarrhythmics or other medications that may prolong QT interval, or those w/ relevant preexisting cardiac disease. Patients at increased risk of thrombotic events or who have had history of thrombotic events; risk of hemorrhage; GI perforations & fistula. Venous thromboembolic events. Stop treatment at least 7 days prior to scheduled surgery. Proactively monitor thyroid function tests. Infections. Females of reproductive potential should be advised to use effective contraception during & for at least 2 wk after last dose. Male patients should use condoms while taking & for at least 2 wk after last dose. Pregnancy & lactation. Ped patients <2 yr.

Tumour pain; anorexia, decreased wt; dizziness, dysgeusia, headache; asymptomatic bradycardia; HTN; cough, dyspnoea; abdominal pain, diarrhoea, nausea, stomatitis, vomiting; increased AST & ALT; alopecia, exfoliative rash, hair depigmentation, palmar-plantar erythrodysaesthesia syndrome, skin depigmentation; musculoskeletal pain, myalgia; asthenia, chest pain, fatigue, peripheral oedema. Neutropenia, thrombocytopenia; hypothyroidism; insomnia; transient ischemic attack; cardiac dysfunction (eg, decrease in ejection fraction & CHF), MI, myocardial ischaemia, QT prolongation; epistaxis, GI haemorrhage, haematuria, pulmonary haemorrhage, venous thromboembolic events; dysphonia, pneumothorax; dyspepsia, lipase elevations; abnormal hepatic function, hyperbilirubinaemia; dry skin, nail disorder, rash; proteinuria; chills, blurred vision.

Metabolism may be altered by CYP3A4 inhibitors & inducers. Increased plasma conc w/ strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), other P-gp & BCRP inhibitors (eg, lapatinib) & grapefruit juice. Decreased plasma conc w/ CYP3A4 inducers (eg, rifampin). Increase mean AUC & C_max of midazolam, paclitaxel. Dextromethorphan. Increase conc of drugs primarily eliminated through UGT1A1 & OATP1B1. Increased incidence of ALT elevations w/ simvastatin. 2-fold increase in AUC & C_max w/ high- or low-fat meal. Decreased bioavailability w/ esomeprazole.

Targeted Cancer Therapy

L01EX03 - pazopanib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

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