Lenvatinib (unofficial Chinese translation: 乐伐替尼/Lenvatinib/Lenvatinib), sold under the brand names Lenvima and others, is an anti-cancer drug used to treat certain types of thyroid cancer and other cancers. It was developed by Eisai, an Eisai company, and is a multiple kinase inhibitor that targets VEGFR1, VEGFR2, and VEGFR3 kinases.
Levatinib is approved (since 2015) for the treatment of differentiated thyroid cancer that is locally recurrent or metastatic, progressive, and unresponsive to radioiodine therapy.
In May 2016, the U.S. Food and Drug Administration (FDA) approved its use in combination with everolimus for the treatment of advanced renal cell carcinoma that had received one prior anti-angiogenic therapy.
The drug is also approved in the U.S. and EU for the treatment of hepatocellular carcinoma that cannot be surgically removed in patients not receiving oral or injectable cancer therapy.
Hypertension (high blood pressure) was the most common side effect in the study (73% of patients compared to 16% in the placebo group), followed by diarrhea (67% vs. 17%) and fatigue (67% vs. 35%). Other common side effects included decreased appetite, hypotension (low blood sugar), thrombocytopenia (low platelet count), nausea, and muscle and bone pain.
Because levatinib modestly prolongs QT time, the addition of other drugs with this property may increase the risk of one abnormal rhythm, torsade de pointes. No interactions with enzyme inhibitors and inducers are expected to be relevant.
Levautinib acts as a multi-kinase inhibitor. It inhibits the three major vascular endothelial growth factor receptors VEGFR1, 2 and 3, as well as fibroblast growth factor receptor (FGFR) 1, 2, 3 and 4, platelet-derived growth factor receptor (PDGFR) alpha, c-Kit and the RET proto-oncogene. Some of these proteins play a role in oncogenic signaling pathways. inhibition of VEGFR2 is thought to be the main cause of hypertension, the most common side effect.
Levautinib is rapidly absorbed from the intestine, reaching peak plasma concentrations after 1 to 4 hours (3 to 7 hours if taken with food). Bioavailability is estimated to be about 85%. The substance is almost completely (98-99%) bound to plasma proteins, mainly albumin.
Lenvatinib is metabolized by the hepatic enzyme CYP3A4 to demethyl-lenvatinib (M2). m2 and lenvatinib itself are oxidized by aldehyde oxidase (AO) to substances called M2′ and M3′,[7] which are the major metabolites in the feces. Another metabolite, also mediated by the CYP enzyme, is N-oxide M3. non-enzymatic metabolism also occurs, leading to a low potential for interaction with enzyme inhibitors and inducers.
The terminal half-life is 28 hours and about two-thirds is excreted in the feces and one-fourth in the urine.
The drug is available in Bangladesh under the trade name Lenvanix.