|Trade names||Lenvima, Kisplyx, others|
|Drug class||Tyrosine kinase inhibitor|
|Main uses||Thyroid cancer, renal cell cancer, hepatocellular carcinoma|
|Side effects||High blood pressure, diarrhea, weight loss, nausea, inflammation of the mouth, headache, rash|
|Metabolism||CYP3A4, aldehyde oxidase, non-enzymatic|
|Metabolites||Desmethyl-lenvatinib (M2) and others|
|Elimination half-life||28 hours|
|Excretion||~65% feces, 25% urine|
|Chemical and physical data|
|Molar mass||426.86 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Lenvatinib, sold under the brand name Lenvima among others, is medication used to treat certain types of thyroid cancer, renal cell cancer, and hepatocellular carcinoma. For thyroid cancer, it is used when radioactive iodine is not effective. It is taken by mouth.
Common side effects include high blood pressure, diarrhea, weight loss, nausea, inflammation of the mouth, headache, and rash. Other side effects may include kidney problems, heart failure, blood clots, bleeding in the brain, and liver problems. Use in pregnancy may harm the baby. It is a tyrosine kinase inhibitor against VEGFR1, VEGFR2 and VEGFR3.
Lenvatinib was approved for medical use in the United States and Europe in 2015. In the United Kingdom it costs the NHS about £1,400 at a dose of 10 mg per day for a month as of 2021. In the United States this amount is about 21,300 USD.
Lenvatinib is approved (since 2015) for the treatment of differentiated thyroid cancer that is either locally recurrent or metastatic, progressive, and did not respond to treatment with radioactive iodine (radioiodine).
In May 2016, the U.S. Food and Drug Administration (FDA) approved it (in combination with everolimus) for the treatment of advanced renal cell carcinoma following one prior anti-angiogenic therapy.
The drug is also approved in the US and in the European Union for hepatocellular carcinoma that cannot be removed surgically in patients who have not received cancer therapy by mouth or injection.
It is used at a dose of 8 mg to 24 mg once per day.
Hypertension (high blood pressure) was the most common side effect in studies (73% of patients, versus 16% in the placebo group), followed by diarrhoea (67% vs. 17%) and fatigue (67% vs. 35%). Other common side effects included decreased appetite, hypotension (low blood pressure), thrombocytopenia (low blood platelet count), nausea, muscle and bone pain.
As lenvatinib moderately prolongs QT time, addition of other drugs with this property could increase the risk of a type of abnormal heart rhythm, namely torsades de pointes. No relevant interactions with enzyme inhibitors and inducers are expected.
Mechanism of action
Lenvatinib acts as a multiple kinase inhibitor. It inhibits the three main vascular endothelial growth factor receptors VEGFR1, 2 and 3, as well as fibroblast growth factor receptors (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 roles in cancerogenic signalling pathways. VEGFR2 inhibition is thought to be the main reason for the most common side effect, hypertension.
Lenvatinib is absorbed quickly from the gut, reaching peak blood plasma concentrations after one to four hours (three to seven 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 liver enzyme CYP3A4 to desmethyl-lenvatinib (M2). M2 and lenvatinib itself are oxidized by aldehyde oxidase (AO) to substances called M2' and M3', the main metabolites in the feces. Another metabolite, also mediated by a CYP enzyme, is the N-oxide M3. Non-enzymatic metabolization also occurs, resulting in a low potential for interactions with enzyme inhibitors and inducers.
In February 2015, the U.S. FDA approved lenvatinib for treatment of progressive, radioiodine refractory differentiated thyroid cancer. In May 2015, European Medicines Agency (EMA) approved the drug for the same indication.
In August 2018, the FDA approved lenvatinib for the first-line treatment of people with unresectable hepatocellular carcinoma (HCC).
In Bangladesh under the trade name Lenvanix.
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- "Summary of the European public assessment report (EPAR) for Lenvima". European Medicines Agency.
- "Lenvatinib mesylate". Drug Information Portal. U.S. National Library of Medicine.