Votrient

Pazopanib HCl

1st-line treatment of advanced renal cell carcinoma in adults & for patients who received prior cytokine therapy for advanced disease. Treatment of selective subtypes of advanced soft tissue sarcoma in adults who have received prior chemotherapy for metastatic disease or who have progressed w/in 12 mth after (neo) adjuvant therapy.

Adult 800 mg once daily. Dose modification should be in 200 mg decrements or increments in a step-wise fashion based on individual tolerability. Max: 800 mg. Patient w/ moderate hepatic impairment 200 mg once 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. Do not eat/drink grapefruit products.

Hypersensitivity.

Reports of hepatic failure. Increased risk of pazopanib-associated ALT elevations in patients who carry the HLA-B*57:01 allele. Perform serum liver tests before treatment initiation, at wk 3, 5, 7 & 9, then at mth 3 & 4, w/ additional tests as clinically indicated, & continue periodically after mth 4. Risk of HTN & hypertensive crisis. BP should be well controlled prior to treatment initiation. Monitor for HTN no longer than 1 wk after treatment initiation & frequently thereafter. Caution in patients w/ moderate to severe heart failure or those w/ below normal left ventricular ejection fraction (LVEF). Baseline & periodic LVEF evaluation is recommended in patients at risk of cardiac dysfunction. Risk of QT prolongation & torsade de pointes. Caution in patients w/ history of QT interval prolongation, in patients taking antiarrhythmics or other medicinal products that may prolong QT interval & in patients w/ relevant pre-existing cardiac disease. Baseline & periodic ECG monitoring & electrolyte maintenance w/in normal range is recommended. Risk of MI, myocardial ischaemia, ischaemic stroke & transient ischaemic attack. Caution in patients at increased risk or w/ history of thrombotic events. Reports of haemorrhagic events. Caution in patients w/ significant risk of haemorrhage. May promote formation of aneurysms &/or artery dissections in patients w/ or w/o HTN. Caution in patients at risk for GI perforation or fistula. May impair wound healing. Discontinue in patients w/ wound dehiscence. Risk of hypothyroidism. Baseline & periodic monitoring of thyroid function is recommended. Reports of proteinuria. Baseline & periodic urinalysis during treatment is recommended. Discontinue if patient develops nephrotic syndrome. Reports of posterior reversible encephalopathy syndrome/reversible posterior leukoencephalopathy syndrome; ILD/pneumonitis; thrombotic microangiopathy; serious infections (w/ or w/o neutropenia). Risk of venous thromboembolic events; tumour lysis syndrome; pneumothorax. Concomitant use w/ other systemic anti-cancer therapies (eg, pemetrexed, lapatinib, pembrolizumab); uridine diphosphate glucuronosyl transferase 1A1 substrates (eg, irinotecan). Avoid concomitant use w/ strong inhibitors of CYP3A4, P-gp or BRCP; CYP3A4 inducers; grapefruit juice. Patients w/ CrCl <30 mL/min; mild or moderate hepatic impairment. Not recommended in patients w/ severe hepatic impairment. Pregnancy. Advise women of childbearing potential to use adequate contraception during treatment & for at least 2 wk after the last dose & to avoid becoming pregnant while on treatment. Male patients (including those vasectomized) should use condoms during sexual intercourse while on treatment & for at least 2 wk after the last dose to avoid potential exposure for pregnant partners & female partners of reproductive potential. Discontinue breast-feeding during treatment. Do not use in childn <2 yr. Childn 2-18 yr. Elderly ≥65 yr.

Diarrhoea, hair colour change, skin hypopigmentation, exfoliative rash, HTN, nausea, headache, fatigue, anorexia, vomiting, dysgeusia, stomatitis, decreased wt, pain, elevated ALT & AST.

Increased plasma conc w/ ketoconazole (strong CYP3A4 & P-gp inhibitor); strong CYP3A4 inhibitors (eg, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole); grapefruit juice; lapatinib (CYP3A4, P-gp & BCRP inhibitor); potent P-gp or BCRP inhibitors; high- or low-fat meal. Decreased plasma conc w/ CYP3A4 inducers (eg, rifampin). Altered exposure & distribution w/ potent P-gp or BCRP inducers. Increased AUC & C_max of midazolam (CYP3A4 substrate); paclitaxel (CYP3A4 & CYP2C8 substrate). Increased dextromethorphan/dextrorphan conc ratio in urine after oral administration of dextromethorphan (CYP2D6 substrate). Increased systemic exposure of SN-38 (active metabolite or irinotecan, UGT1A1 substrate). Increased incidence of ALT elevations w/ simvastatin. May affect pharmacokinetics of other statins (eg, atorvastatin, fluvastatin, pravastatin, rosuvastatin). Decreased bioavailability w/ esomeprazole. Avoid co-administration w/ medicines that increase gastric pH.

Targeted Cancer Therapy

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

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