Lenvaxen Lenvatinib capsules 4mg/10mg

[Key Drug Information]

Chinese Name: Lenvatinib Mesylate Capsules

Brand Name: Lenvima / Lenvaxen

Chinese Aliases: Lenvatinib, Lefatinib

Dosage Form & Strength: Oral Capsules

Specifications: 4 mg × 30 capsules/box; 10 mg × 30 capsules/box

Manufacturer: Everest Pharma Ltd (Bangladesh)

Pharmacological Action: Inhibits multiple targets—including vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), platelet-derived growth factor receptor alpha (PDGFRα), RET, and KIT—thereby inhibiting tumor angiogenesis and tumor cell proliferation.

[Indications]

1. Hepatocellular Carcinoma (HCC)

Indicated for the treatment of adult patients with unresectable hepatocellular carcinoma. This is one of the core indications for Lenvatinib and may be used as a first-line treatment option.

2. Differentiated Thyroid Cancer (DTC)

Indicated for the treatment of adult patients with locally recurrent or metastatic, radioiodine-refractory differentiated thyroid cancer.

3. Renal Cell Carcinoma (RCC)

In combination with Everolimus, indicated for the treatment of adult patients with advanced renal cell carcinoma who have previously received vascular endothelial growth factor (VEGF)-targeted therapy.

4. Endometrial Carcinoma (EC)

In combination with Pembrolizumab, indicated for the treatment of adult patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have had disease progression following prior systemic therapy and are not candidates for curative surgery or radiation.

[Dosage and Administration]

Indication: Recommended Dosage (Oral, Once Daily) | Key Notes

1. Hepatocellular Carcinoma (HCC): Dosing based on body weight: 12 mg for patients ≥ 60 kg; 8 mg for patients < 60 kg.

Used as a first-line treatment for unresectable hepatocellular carcinoma. 2. Differentiated Thyroid Cancer (DTC): 24 mg (e.g., two 10 mg capsules + one 4 mg capsule).

Indicated for locally recurrent or metastatic, progressive DTC that is refractory to radioactive iodine.

3. Renal Cell Carcinoma (RCC): Combination Therapy: 18 mg when used in combination with everolimus; 20 mg when used in combination with pembrolizumab.

①. In combination with everolimus, indicated for advanced RCC following prior anti-angiogenic therapy.

②. Latest Update (2024): In combination with pembrolizumab, now established as a first-line treatment for advanced non-clear cell RCC (nccRCC).

4. Endometrial Carcinoma (EC): 20 mg (in combination with pembrolizumab).

Indicated for the subsequent treatment of specific types (pMMR or non-MSI-H) of advanced EC.

General Administration Instructions:

Method of Administration: Take orally once daily at a fixed time; may be taken with or without food. Capsules should be swallowed whole; for patients with difficulty swallowing, the capsules may be dissolved in a small amount of water or apple juice before administration.

Missed Dose: If a dose is missed and less than 12 hours have elapsed, take the missed dose as soon as possible; if more than 12 hours have elapsed, skip the missed dose and resume the regular schedule with the next planned dose. Do not take a double dose to make up for a missed dose.

Pre- and Post-Surgery: Discontinue use at least 1 week prior to elective surgery; resume use at least 2 weeks after major surgery, provided that the surgical wound has substantially healed.

[Important Warnings and Precautions (Dose Adjustment Guidelines)]

Lenvatinib may cause severe adverse reactions; patients require close monitoring, and management should be guided by the table below:

Adverse Reaction/Condition | Management and Dose Adjustment Recommendations (Graded by Severity)

Hypertension: Very common; blood pressure must be controlled prior to treatment and monitored regularly thereafter. Grade 3 hypertension (persisting despite optimal antihypertensive therapy) requires temporary interruption of treatment; resume at a reduced dose once blood pressure is controlled. Grade 4 hypertension requires permanent discontinuation.

Cardiac Dysfunction: Monitor for signs and symptoms of heart failure during treatment. Grade 3 events require temporary interruption and evaluation; Grade 4 events require permanent discontinuation.

Hepatotoxicity: Monitor liver function prior to and periodically throughout treatment. Grade 3–4 Hepatotoxicity: Suspend treatment; after assessment, decide whether to reduce the dose or discontinue the drug. In cases of hepatic failure, permanently discontinue the drug.

Proteinuria: Monitor urinary protein levels prior to and during treatment. If 24-hour urinary protein excretion is ≥ 2 g, suspend treatment; once resolved, resume at a reduced dose. If nephrotic syndrome develops, permanently discontinue the drug.

Gastrointestinal Perforation or Fistula: In the event of gastrointestinal perforation of any grade, or a Grade 3–4 fistula, permanently discontinue the drug.

Arterial Thromboembolic Events: In the event of an arterial thromboembolic event of any grade, permanently discontinue the drug.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): If symptoms occur (e.g., headache, seizures, confusion), suspend treatment; once symptoms have completely resolved, consider resuming treatment at a reduced dose or discontinuing the drug.

QT Interval Prolongation: Monitor ECG and electrolytes during treatment (particularly in patients at risk). If the QTc interval exceeds 500 ms or increases by > 60 ms from baseline, suspend treatment; once resolved, resume at a reduced dose.

Hemorrhagic Events: For Grade 3 hemorrhage, suspend treatment; for Grade 4 hemorrhage, permanently discontinue the drug.

Impaired Wound Healing: The drug may impair wound healing; suspend treatment as required before and after surgical procedures.

Osteonecrosis of the Jaw: A dental examination is recommended prior to treatment; avoid invasive dental procedures during treatment.

Embryo-Fetal Toxicity: The drug poses a definitive risk of harm to the fetus. Women and men of reproductive potential must use effective contraception during treatment and for at least 30 days (for women) or 1 week (for men) following the last dose.

[Adverse Reactions]

Most Common Adverse Reactions: Hypertension, fatigue/asthenia, diarrhea, arthralgia/myalgia, decreased appetite, weight loss, nausea, vomiting, proteinuria, hand-foot skin reaction, abdominal pain, dysphonia, etc.

Serious but Uncommon Reactions Requiring Vigilance: In addition to the warnings listed above, these include severe diarrhea, hypothyroidism, hypocalcemia, pancreatitis, renal failure, etc. [Drug Interactions]

1.  With Food and Other Medications: Food does not affect absorption; the drug may be co-administered with CYP3A4 inducers or inhibitors without the need for dose adjustment.

2.  Combinations to Avoid: Co-administration with medications known to prolong the QT interval should be avoided.

[Use in Specific Populations]

Hepatic/Renal Impairment: For mild to moderate impairment, dose adjustment is generally not required. For severe impairment (Child-Pugh Class C or severe renal impairment), the dosage for renal cell carcinoma and thyroid carcinoma should be reduced to 10 mg/day; for hepatocellular carcinoma, please refer to specific dose reduction protocols.

Elderly Patients: Compared to younger patients, no significant differences in overall safety have been observed, although the incidence of certain adverse reactions may be higher.

Children and Adolescents: Safety and efficacy have not been established.

Pregnant Women: Contraindicated, based on its established embryo-fetal toxicity.

Breastfeeding Women: Breastfeeding should be discontinued during treatment and for at least one week following the final dose.

[Storage]

Store below 30°C; keep container tightly closed.

[Important Note]

This package insert synthesizes official drug information and is intended to serve as a comprehensive reference; it does not substitute for the prescription and guidance of a qualified physician. All treatment decisions—particularly those involving combination therapy or complex dose adjustments—must be made by an oncologist following a thorough assessment of the individual patient's specific condition.