Lanib-10mg (Lenvatinib)

Description

COMPOSITION: Lanib-4: Each capsule contains Lenvatinib 4mg as Lenvatinib Mesylate INN.
Lanib-10: Each capsule contains Lenvatinib 10mg as Lenvatinib Mesylate INN.
CLINICAL PHARMACOLOGY
Mechanism of Action: Lenvatinib is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth
factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib inhibits other kinases 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; platelet derived growth factor
receptor alpha (PDGFR ), KIT, and RET. Lenvatinib also exhibited antiproliferative activity in hepatocellular carcinoma
cell lines dependent on activated FGFR signaling with a concurrent inhibition of FGF-receptor substrate 2� (FRS2 )
phosphorylation.In syngeneic mouse tumor models, Lenvatinib decreased tumor-associated macrophages, increased
activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal
antibody compared to either treatment alone.The combination of Lenvatinib and Everolimus showed increased
antiangiogenic and antitumor activity as demonstrated by decreases in human endothelial cell proliferation, tube
formation, and VEGF signaling in vitro, and by decreases in tumor volume in mouse xenograft models of human renal
cell cancer that were greater than those with either drug alone.
Pharmacokinetics: Absorption The time to peak plasma concentration (Tmax) typically occurred from 1 to 4 hours
post-dose. Food Effect: Administration with a high fat meal (approximately 900 calories of which approximately 55%
were from fat, 15% from protein, and 30% from carbohydrates) did not affect the extent of absorption, but decreased
the rate of absorption and delayed the median Tmax from 2 hours to 4 hours.
Distribution In vitro binding of Lenvatinib to human plasma proteins ranged from 98% to 99% at concentrations of 0.3
to 30 μg/mL. The blood-to-plasma concentration ratio ranged from 0.59 to 0.61 at concentrations of 0.1 to 10 μg/mL in
vitro.
Elimination : The terminal elimination half-life of Lenvatinib was approximately 28 hours. Metabolism: The main
metabolic pathways for Lenvatinib in humans were identified as enzymatic (CYP3A and aldehyde oxidase) and
non-enzymatic processes. Excretion: Ten days after a single administration of radiolabeled Lenvatinib, approximately
64% and 25% of the radiolabel were eliminated in the feces and urine, respectively.
INDICATIONS
Differentiated Thyroid Cancer : Lenvatinib is indicated for the treatment of patients with locally recurrent or
metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC).
Renal Cell Carcinoma : Lenvatinib is indicated in combination with everolimus for the treatment of patients with
advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy.
Hepatocellular Carcinoma : Lenvatinib is indicated for the first-line treatment of patients with unresectable
hepatocellular carcinoma (HCC).
Endometrial Carcinoma : Lenvatinib, in combination with Pembrolizumab, is indicated for the treatment of patients
with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient
(dMMR), who have disease progression following prior systemic therapy and are not candidates for curative surgery or
radiation. This indication is approved under accelerated approval based on tumor response rate and durability of
response. Continued approval for this indication may be contingent upon verification and description of clinical benefit
in the confirmatory trial.
DOSAGE AND ADMINISTRATION : Important Dosage Information
• The dose reduction is needed for certain patients with renal or hepatic impairment.
• Lenvatinib should be taken once daily, with or without food, at the same time each day. If a dose is missed and
cannot be taken within 12 hours, skip that dose and take the next dose at the usual time of administration.
Recommended Dosage for Differentiated Thyroid Cancer (DTC) : The recommended dosage of Lenvatinib is 24
mg orally once daily until disease progression or until unacceptable toxicity.
Recommended Dosage for Renal Cell Carcinoma (RCC) : The recommended dosage of Lenvatinib is 18 mg in
combination with 5 mg Everolimus orally once daily until disease progression or until unacceptable toxicity. Refer to
Everolimus prescribing information for recommended Everolimus dosing information.
Recommended Dosage for Hepatocellular Carcinoma (HCC) : The recommended dosage of Lenvatinib is based on
actual body weight:
• 12 mg for patients greater than or equal to 60 kg or
• 8 mg for patients less than 60 kg.
Lenvatinib should be taken orally once daily until disease progression or until unacceptable toxicity.
Recommended Dosage for Endometrial Carcinoma : The recommended dosage of Lenvatinib is 20 mg orally once
daily, in combination with Pembrolizumab 200 mg administered as an intravenous infusion over 30 minutes every 3
weeks, until unacceptable toxicity or disease progression. Refer to the Pembrolizumab prescribing information for
recommended Pembrolizumab dosing information.
Dosage Modifications for Adverse Reactions : Recommendations for Lenvatinib dose interruption, reduction and
discontinuation for adverse reactions are listed in Table 1. Table 2 lists the recommended dosage reductions of
Lenvatinib for adverse reactions