Lanib 4

Patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated, thyroid cancer. In combination with everolimus for the treatment of patients with, advanced renal cell carcinoma, following 1 prior vascular endothelial growth factor-targeted therapy.

Swallow capsule whole May take with or without food Take at the same time each day

Adult Differentiated thyroid cancer (DTC) 24 mg once daily. Renal cell carcinoma (RCC) 18 mg in combination w/ everolimus 5 mg once daily. Patient w/ severe hepatic impairment Initially 14 mg once daily for DTC. 10 mg once daily for RCC.

Patient w/ severe renal impairment Initially 14 mg once daily for DTC. 10 mg once daily for RCC.

Hypersensitivity. Lactation.

Receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4) Also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet-derived growth factor receptor alpha (PDGFR-alpha), KIT, and RET

Monitor BP after 1 wk of treatment then every 2 wk for the 1st 2 month & monthly thereafter. Monitor urine protein regularly. Actively managed GI toxicity to reduce the risk of development of renal impairment/renal failure. Monitor for clinical symptoms or signs of cardiac decompensation. Posterior reversible encephalopathy syndrome/reversible posterior leucoencephalopathy syndrome. Monitor liver function tests before initiation of treatment, then every 2 wk for the 1st 2 month & monthly thereafter during treatment. Adjust initial dose in patients w/ severe renal or hepatic impairment. Serious tumour-related bleeds including fatal haemorrhagic events, GI perforation & fistula formation may occur. Patients w/ arterial thromboembolic event w/in the previous 6 month. Consider periodic monitoring of ECG & electrolytes during treatment. Monitor TSH levels. Discontinue use in the event of persistence of GI perforation or fistula & grade 4 diarrhoea. Patients of ethnic origin other than Caucasian or Asian. Not recommended in patients w/ end-stage renal disease. May affect the ability to drive or operate machinery. Women of childbearing potential must use highly effective contraception while taking & 1 month after stopping treatment. Do not use during pregnancy. Do not use in child <2 yr. Elderly >75 yr. Lactation Unknown if distributed in human breast milk; advise women to discontinue breastfeeding during treatment because of the potential for serious adverse reactions in nursing infants Lenvatinib and its metabolites are excreted in rat milk at concentrations higher than in maternal plasma (approximately 2 times higher [based on AUC] in milk compared with maternal plasma

>10% Percentages are for all grades of adverse effects unless otherwise noted Hypertension (73%),Diarrhea (67%),Fatigue (67%),Arthralgia/myalgia (62%),Decreased appetite (54%),Weight decreased (51%),Nausea (47%),Hypertension, grades 3-4 (44%),Stomatitis (41%),Headache (38%),Vomiting (36%),Proteinuria (34%),Palmar-plantar erythrodysesthesia (32%),Abdominal pain (31%),Dysphonia (31%),Constipation (29%),Oral pain (25%),Cough (24%),Peripheral edema (21%),Rash (21%),Dysgeusia (18%),Dry mouth (17%),Dizziness (15%),Dyspepsia (13%),Alopecia (12%),Epistaxis (12%),Insomnia (12%),Urinary tract infection (11%) 1-10% Percentages are for all grades of adverse effects unless otherwise noted Dental infections (10%) Hypotension (9%) Diarrhea, grades 3-4 (9%) Dehydration (9%) Prolonged QT interval (9%) Hypocalcemia (9%) Decreased appetite, grades 3-4 (7%) Hyperkeratosis (7%) Hypokalemia (6%) AST increased (5%) ALT increased (4%) Lipase increased (4%) Creatinine increased (3%) Nausea, grades 3-4 (2%) Platelet count decreased (2%)

Decreased exposure w/ oral CYP3A4/Pgp substrates [eg, astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil or ergot alkaloids (ergotamine, dihydroergotamine)]. May reduce effectiveness of oral hormonal contraceptives.