レンバチニブ

Breast Feeding; Lactation; Milk, Human; Antineoplastic Agents; Enzyme Inhibitors; Protein Kinase Inhibitors; Signal Transduction Inhibitors; Tyrosine Kinase Inhibitors

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

Warning

H302 (50%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

In large clinical trials of lenvatinib, elevations in serum aminotransferase levels were common, occurring in 52% of patients. Values greater than 5 times the upper limit of normal (ULN), however, occurred in only 3% to 5% of recipients. Serum alkaline phosphatase elevations were also common occurring in 28% of patients and were above 3 times ULN in 2%. In addition, fatal hepatic failure was reported in 3 of 1160 patients treated in preregistration clinical trials and another patient developed symptomatic but self-limited acute hepatitis with jaundice. The degree of relatedness of these events to lenvatinib therapy, however, was not defined. In the product label for lenvatinib, serum ALT, AST and alkaline phosphatase elevations are listed as adverse reactions, and acute hepatitis is mentioned as a rare occurrence. Monitoring of serum enzymes before, every 2 weeks for 2 months and monthly thereafter during treatment is recommended with dose reduction or discontinuation depending upon the degree and persistence of the abnormalities.

The most frequently observed adverse reactions of lenvatinib (≥30% of patients) include hypertension, fatigue, diarrhea, myalgia/arthralgia, reduced appetite, reduced body weight, stomatitis, headache, nausea, vomiting, abdominal pain, dysphonia, proteinuria, palmar-plantar erythrodysesthesia/hand-foot syndrome. Hypertension is one of the most common adverse effects of lenvatinib and is more prominent in subjects aged older than 75. During the phase III SELECT trials for radioactive iodine-refractory DIC, patients from the treatment group reported fistula formation causing bleeding from the tumor. Adverse effects from therapy should be managed supportively with dosing adjustments and discontinuation of treatment if necessary. Other reported adverse effects include the following. The description of severe adverse events includes:

Fetal harm was observed in animal trials during the administration of lenvatinib at a dosage below the recommended range. No reproductive studies have been conducted to analyze the toxicity in humans. Pregnant women should be counseled and advised of possible toxicity to the fetus. Lenvatinib may be present during lactation, and halting breastfeeding is recommended for 1 week following the last dosage.

L01XE29

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Based on x-ray crystallography and kinetic interaction studies, lenvatinib binds to the adenosine 5'-triphosphate binding site of VEGFR2 and to a neighbouring region via a cyclopropane ring and thereby inhibits tyrosine kinase activity and associated signalling pathways.

Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib 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 (PDGFRα), KIT, and RET.

EE083865G2

LENVATINIB

Established Pharmacologic Class [EPC] - Kinase Inhibitor

Mechanisms of Action [MoA] - Receptor Tyrosine Kinase Inhibitors

Lenvatinib is a Kinase Inhibitor. The mechanism of action of lenvatinib is as a Receptor Tyrosine Kinase Inhibitor.

LENVATINIB

Substances that inhibit or prevent the proliferation of NEOPLASMS.

Agents that inhibit PROTEIN KINASES.

Time to peak plasma concentration occurred from 1 to 4 hours post­dose. Administration with food did not affect the extent of absorption, but decreased the rate of absorption and delayed the median Tmax from 2 hours to 4 hours.

Following administration of a radiolabeled dose, approximately 64% and 25% of the radiolabel were eliminated in the feces and urine, respectively.