Lenvaxen 4 mg, containing Lenvatinib, is an oral kinase inhibitor used in the treatment of multiple advanced cancers:

• Differentiated Thyroid Cancer (DTC): For patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC.

• Renal Cell Carcinoma (RCC): In combination with Everolimus, for advanced RCC following prior anti-angiogenic therapy.

• Hepatocellular Carcinoma (HCC): First-line treatment for unresectable HCC.

• Endometrial Carcinoma: In combination with Pembrolizumab, for advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), after prior systemic therapy and for patients ineligible for curative surgery or radiation.

Mode of Action

Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that blocks multiple pathways involved in tumor growth and angiogenesis:

• Inhibits VEGFR1, VEGFR2, VEGFR3, reducing abnormal blood vessel formation in tumors.

• Inhibits FGFR1–4, PDGFRα, KIT, and RET, which are involved in cancer progression and proliferation.

• Exhibits antiproliferative effects in cancer cells dependent on FGF signaling, reducing tumor growth.

By targeting these pathways, Lenvatinib restricts tumor vascularization and proliferation, improving disease control in advanced cancers.

Pharmacology

• Absorption: Peak plasma concentration (Tmax) occurs 1–4 hours post-dose; high-fat meals delay Tmax but do not affect overall absorption.

• Distribution: 98–99% plasma protein bound; blood-to-plasma ratio 0.59–0.61.

• Metabolism: Primarily via CYP3A and aldehyde oxidase; also non-enzymatic pathways.

• Excretion: 64% feces, 25% urine; terminal half-life ~28 hours.

Dosage & Administration

• DTC: 24 mg orally once daily.

• RCC: 18 mg orally once daily with 5 mg Everolimus once daily.

• HCC: ≥60 kg: 12 mg orally once daily; <60 kg: 8 mg orally once daily.

• Endometrial Carcinoma: 20 mg orally once daily with Pembrolizumab 200 mg IV every 3 weeks.

Capsules can be swallowed whole or dissolved in 1 tablespoon of water or apple juice, stirred for 3 minutes, left for 10 minutes, then consumed with an additional tablespoon of liquid.

Dose modifications are recommended for renal or hepatic impairment, and treatment should continue until disease progression or unacceptable toxicity.

Drug Interactions

• QT Interval Prolongation: Avoid co-administration with drugs known to prolong QT/QTc.

• CYP3A4 Substrates/Inhibitors/Inducers: Monitor or adjust dose due to potential effects on plasma concentration.

Contraindications

• Hypersensitivity to Lenvatinib or any excipients.

Side Effects

Common and serious adverse effects include:

• Hypertension, cardiac dysfunction, arterial thromboembolic events

• Hepatotoxicity, renal impairment, proteinuria

• Diarrhea, gastrointestinal perforation, fistula formation

• QT prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome

• Thyroid dysfunction, wound healing complications

Precautions & Warnings

• Monitor blood pressure, liver and renal function, thyroid function, electrolytes, and ECG regularly.

• Dose adjustment or discontinuation may be required for severe adverse events.

• Withhold prior to surgery and resume based on wound healing.

• Permanently discontinue in cases of arterial thromboembolism, gastrointestinal perforation, or severe fistula.

Pregnancy & Lactation

• May cause fetal harm; effective contraception is required during treatment and for 30 days after the last dose.

• Breastfeeding should be avoided during treatment and for at least one week after the last dose.

Pediatric Use

• Safety and efficacy in pediatric patients are not established. Dose adjustments are recommended for severe renal or hepatic impairment based on the specific cancer type.

Therapeutic Class

Targeted Cancer Therapy / Multi-kinase Inhibitor

Storage Conditions

Store in a dry place below 30°C, protected from light, and out of reach of children.