Approval Date: February 13, 2015
- Lenvatinib , a kinase inhibitor, is the mesylate salt of lenvatinib. Its chemical name is 4-[3chloro-4-(N’-cyclopropylureido)phenoxy]-7-methoxyquinoline-6-carboxamide methanesulfonate.
- The molecular formula is C21H19ClN4O4 • CH4O3S, and the molecular weight of the mesylate salt is 522.96. The chemical structure of lenvatinib mesylate is:
————————————–Mechanism of Action————————————-
- 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.
- Metabolism: CYP3A is one of the main metabolic enzymes of lenvatinib. The main metabolic pathways for lenvatinib in humans were identified as enzymatic (CYP3A and aldehyde oxidase) and non-enzymatic processes.
————————-DOSAGE AND ADMINISTRATION——————————–
Discontinue for Grade 4 hemorrhage
- Recommended dose: 24 mg orally, once daily
- Impairment of Thyroid Stimulating Hormone Suppression: Monitor TSH
- In patients with severe renal or hepatic impairment, the dose is 14 mg once levels monthly and adjust thyroid replacement medication as needed in daily.
- Capsules: 4 mg and 10 mg.
————————–WARNINGS AND PRECAUTIONS——————————–
- Hypertension: Control blood pressure prior to treatment with LENVIMA Withhold LENVIMA for Grade 3 hypertension despite optimal hypertensive therapy. Discontinue for life-threatening hypertension.
- Cardiac Failure: Monitor for clinical symptoms or signs of cardiac decompensation. Withhold LENVIMA for Grade 3 cardiac dysfunction
Discontinue for Grade 4 cardiac dysfunction.
- Arterial Thromboembolic Events: Discontinue LENVIMA following arterial thromboembolic event.
- Hepatotoxicity: Monitor liver function tests before initiation of LENVIMA and periodically throughout treatment. Withhold LENVIMA for Grade 3 or greater liver impairment. Discontinue for hepatic failure
- Proteinuria: Monitor for proteinuria before initiation of, and periodically throughout, treatment with LENVIMA. Withhold LENVIMA for ≥2 grams of proteinuria for 24 hours. Discontinue for nephrotic syndrome
- Renal Failure and Impairment: Withhold LENVIMA for Grade 3 or 4 renal failure.
- Gastrointestinal Perforation and Fistula Formation:
- QT Interval Prolongation
- Hypocalcemia: Monitor blood calcium levels at least monthly and replace as needed.
- Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Withold
LENVIMA for RPLS until fully resolved.
- Hemorrhagic Events: Withhold LENVIMA for Grade 3 hemorrhage.
- Impairment of Thyroid Stimulating Hormone Suppression; Monitor thyroid level monthly & replace as needed.
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