lenvatinib BEACON Lenvanix 4

[Drug Name]

Generic Name: Lenvatinib Capsules

English Name: Lenvatinib

Specification: 4 mg × 30 capsules/box

Manufacturer: Beacon Pharmaceuticals

[Active Ingredient] "Lenvatinib Mesylate. Chemical Name: 4-[3-chloro-4-(N'-cyclopropylureido)phenoxy]-7-methoxyquinoline-6-carboxamide mesylate"

[Drug Introduction] Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that inhibits VEGFR2 and VEGFR3 (vascular endothelial growth factor receptors). It is indicated for the treatment of unresectable, locally advanced or metastatic, symptomatic or progressive medullary thyroid carcinoma. Lenvatinib also inhibits tumor-associated pathological angiogenesis, thereby inhibiting tumor growth and disease progression.

[Drug Highlights] Lenvatinib is an oral multi-target inhibitor of vascular endothelial growth factor receptors 1–3 (VEGFR 1-3), fibroblast growth factor receptors 1–4 (FGFR 1-4), platelet-derived growth factor receptor alpha (PDGFRα), RET, and KIT. It has currently received FDA approval for the treatment of differentiated thyroid carcinoma and advanced renal cell carcinoma. New data indicate that as a first-line treatment for unresectable hepatocellular carcinoma (uHCC), lenvatinib is non-inferior to sorafenib in terms of overall survival (OS); specifically within the Asia-Pacific population, first-line lenvatinib treatment for liver cancer demonstrated superior OS benefits compared to sorafenib. Furthermore, as a first-line treatment regimen for uHCC, lenvatinib demonstrated significantly superior progression-free survival (PFS), time to progression (TTP), and overall response rate (ORR) compared to sorafenib.

[Dosage and Administration]

Recommended Dosage: For patients weighing <60 kg, the recommended daily dose is 8 mg (two 4 mg capsules), taken once daily; for patients weighing ≥60 kg, the recommended daily dose is 12 mg (three 4 mg capsules), taken once daily. Treatment should be continued until disease progression or the occurrence of intolerable toxicity. Administration Method: Oral. This product should be taken at a fixed time each day; it may be taken either on an empty stomach or with food. The product should be swallowed whole. Alternatively, the product (without opening or crushing it) may be mixed with one tablespoon of water or apple juice in a glass to form a suspension. The capsule must remain in the liquid for at least 10 minutes and be stirred for at least 3 minutes to dissolve the capsule shell; the resulting suspension should then be swallowed. After drinking the suspension, an equal amount of water or apple juice (one tablespoon) must be added to the glass, stirred several times, and the entire contents of the glass consumed. If a patient misses a dose and is unable to take it within 12 hours of the scheduled time, the missed dose should not be made up; the patient should simply resume the regular dosing schedule for the next scheduled dose. Before adjusting the dosage of this product (e.g., by suspending or reducing the dose), adverse reactions such as nausea, vomiting, and diarrhea should be actively treated; gastrointestinal toxicities should be actively managed to minimize the risk of renal insufficiency or renal failure (see [Precautions]). Monitoring, Dosage Adjustment, and Discontinuation: It may be necessary to suspend administration, adjust the dosage, or discontinue treatment with this product to manage certain adverse reactions. Mild to moderate adverse reactions (e.g., Grade 1 or 2) generally do not require suspension of administration, unless the patient remains intolerant despite active treatment. Severe (e.g., Grade 3) or intolerable adverse reactions require suspension of administration until the adverse reaction improves to Grade 0–1 or returns to baseline. Detailed information regarding dosage adjustments based on adverse reactions, as well as details on monitoring, dosage adjustment, and discontinuation, can be found in the accompanying tables.

[Precautions]

1) Take the medication at the same time each day.

2) If a dose is missed, and more than 12 hours remain before the next scheduled dose, take the missed dose immediately.

3) If less than 12 hours remain before the next scheduled dose, do not take the missed dose; simply proceed with the next scheduled dose at the usual time and dosage.

4) Continue taking the medication until disease progression occurs or until intolerable toxic side effects develop. [Indications]

1) Lenvatinib is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioiodine-refractory differentiated thyroid cancer.

2) Lenvatinib, in combination with everolimus, is indicated for the treatment of advanced renal cell carcinoma following one prior anti-angiogenic therapy.

[Adverse Reactions]

The most common side effects of Lenvatinib include hypertension, fatigue, diarrhea, arthralgia/myalgia (joint/muscle pain), decreased appetite, vomiting, proteinuria (excess protein in the urine), palmar swelling and pain/redness of the hands and/or soles of the feet (Hand-Foot Syndrome), abdominal pain, and changes in voice (dysphonia).

Lenvatinib can cause serious side effects, including heart failure, blood clots (arterial thromboembolic events), liver injury (hepatotoxicity), kidney injury (renal failure/impairment), gastrointestinal perforation or abnormal connections between the stomach or intestines (fistula formation), changes in electrical heart activity (QT interval prolongation), hypocalcemia, headaches accompanied by seizures and visual changes (Reversible Posterior Leukoencephalopathy Syndrome [RPLS]), severe bleeding (hemorrhage), risks to the unborn child if used during pregnancy, and suppressive effects on thyroid-stimulating hormone (TSH) production.

[Precautions]

1) Hypertension: Control blood pressure prior to initiating treatment. Withhold Lenvatinib for Grade 3 hypertension despite optimized antihypertensive therapy; discontinue Lenvatinib for life-threatening hypertension.

2) Heart Failure: Monitor for clinical signs and symptoms of cardiac decompensation. Withhold Lenvatinib for Grade 3 cardiac dysfunction; discontinue Lenvatinib for Grade 4 cardiac dysfunction.

3) Discontinue Lenvatinib following a single arterial thromboembolic event.

4) Hepatotoxicity: Monitor liver function tests periodically during treatment. Withhold Lenvatinib for Grade 3 or greater liver impairment; discontinue Lenvatinib for hepatic failure. 5) Proteinuria: Monitor for proteinuria periodically during treatment. Withhold Lenvatinib for 24-hour urine protein levels ≥ 2 g; discontinue the drug in cases of nephrotic syndrome.

6) Renal Failure and Impairment: Withhold Lenvatinib for Grade 3 or 4 renal failure or impairment.

7) Discontinue the drug in patients who develop gastrointestinal perforation or life-threatening fistula.

8) Withhold Lenvatinib for Grade 3 or greater QT interval prolongation.

9) Hypocalcemia: Monitor blood calcium levels and administer calcium supplementation as needed.

10) Withhold Lenvatinib in patients with Reversible Posterior Leukoencephalopathy Syndrome (RPLS) until complete resolution.

11) Hemorrhagic Events: Withhold Lenvatinib for Grade 3 hemorrhage or significant blood loss requiring transfusion; discontinue the drug for Grade 4 hemorrhage, or for blood loss resulting in debilitating symptoms, retinal or cerebral ischemia, or severe shock.

12) Impairment of Thyroid-Stimulating Hormone (TSH) Suppression: Monitor TSH levels monthly in patients with Differentiated Thyroid Carcinoma (DTC), and adjust thyroid replacement therapy as necessary.

13) Embryo-Fetal Toxicity: May cause fetal harm.

[Use in Specific Populations] Lactation: Discontinue breastfeeding.

[Pediatric Use] No initial dose adjustment is required based on age; data regarding patients aged ≥ 75 years are limited. [Pharmacokinetics] Currently, there are no clinical data available regarding the use of this product in pediatric or adolescent patients under 18 years of age; therefore, its use is not recommended in this population.

[Storage] Store at a temperature not exceeding 30°C.

[Packaging] 30 capsules/box.

[Shelf Life] 48 months.

Product Specifications

Product Name: Lenvatinib Capsules 4 mg × 30 capsules (lenvatinib) — BEACON Lenvanix 4 / Levima

Common Name: Lenvatinib Capsules

Active Ingredient: Lenvatinib

Dosage Form: Capsules

Specification: 4 mg × 30 capsules/box

Manufacturer: Beacon Pharmaceuticals

Indications:

1. Hepatocellular Carcinoma (HCC): For the treatment of patients with unresectable HCC.

2. Differentiated Thyroid Carcinoma (DTC): As monotherapy for patients with locally recurrent or metastatic, progressive, radioiodine-refractory DTC.

3. Renal Cell Carcinoma (RCC): In combination with everolimus, for the treatment of patients with advanced RCC who have previously received anti-angiogenic therapy (targeting vascular endothelial growth factor).

Dosage and Administration: Recommended Dosage: For patients weighing less than 60 kg, the recommended daily dose is 8 mg (two 4 mg capsules), taken once daily. For patients weighing 60 kg or more, the recommended daily dose is 12 mg (three 4 mg capsules), taken once daily. Treatment should be continued until disease progression or the occurrence of intolerable toxicity. Method of Administration: Oral use. This product should be taken at the same time each day; it may be taken with or without food. The capsules should be swallowed whole. Alternatively, the capsules (which must not be opened or crushed) may be mixed with one tablespoon of water or apple juice in a glass to form a suspension. The capsules must remain in the liquid for at least 10 minutes and be stirred for at least 3 minutes to dissolve the capsule shells; the resulting suspension should then be swallowed. After ingestion, an equal amount of water or apple juice (one tablespoon) must be added to the glass; stir several times, and then consume all the liquid remaining in the glass. If a patient misses a dose and is unable to take it within 12 hours, the missed dose should be skipped, and the next dose should be taken at the regularly scheduled time. Prior to adjusting the dosage of this product (e.g., temporary interruption or dose reduction), adverse reactions such as nausea, vomiting, and diarrhea should be actively treated; gastrointestinal toxicities should be actively managed to minimize the risk of developing renal insufficiency or renal failure (see [Precautions]). Monitoring, Dose Adjustment, and Discontinuation: It may be necessary to temporarily interrupt administration, adjust the dosage, or discontinue treatment with this product to manage certain adverse reactions. Mild to moderate adverse reactions (e.g., Grade 1 or 2) generally do not require temporary interruption of administration, unless the patient remains intolerant despite active treatment. Severe (e.g., Grade 3) or intolerable adverse reactions require temporary interruption of administration until the adverse reaction improves to Grade 0–1 or returns to baseline. For detailed information regarding dose adjustments based on adverse reactions, please refer to the relevant table.