lenvatinib Lenvat 10mg Capsules, Natco

Lenvatinib (Lenvima), developed by Eisai Co., targets receptors such as VEGFR-1, VEGFR-2, VEGFR-3, FGFR1, PDGFR, cKit, and Ret. Its currently approved indications include hepatocellular carcinoma (liver cancer), thyroid cancer, and renal cell carcinoma (kidney cancer). In China, it is approved for the treatment of patients with unresectable hepatocellular carcinoma who have not previously received systemic therapy.

【Specification】 10 mg × 30 capsules (calculated based on C21H19ClN4O4)

【Dosage and Administration】

Once daily.

Take one hour before a meal or two hours after a meal.

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

2) If a dose is missed: if 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 resume the regular dosing schedule and dosage at the usual time.

4) Continue treatment until disease progression occurs or until intolerable toxic side effects develop.

Differentiated Thyroid Cancer

24 mg, orally, once daily.

In actual clinical practice, most patients with thyroid cancer take 20 mg per day (i.e., two 10 mg capsules).

Renal Cell Carcinoma

18 mg Lenvatinib + 5 mg Everolimus, orally, once daily.

Hepatocellular Carcinoma (Liver Cancer)

The dosage of Lenvatinib for the treatment of hepatocellular carcinoma is based on the patient's body weight:

Body weight ≥ 60 kg: 12 mg/day; Body weight < 60 kg: 8 mg/day; orally, once daily.

Most patients can take 10 mg per day.

Sarcoma

Generally, a dosage of 20 mg or 18 mg is recommended.

A dosage of 14 mg may also be taken, depending on the individual patient's physical condition.

Indications:

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

2. Differentiated Thyroid Cancer: As monotherapy for patients with locally recurrent or metastatic, progressive differentiated thyroid cancer that is refractory to radioactive iodine.

3. Renal Cell Carcinoma: In combination with Everolimus, for the treatment of patients with advanced renal cell carcinoma who have previously received vascular endothelial growth factor (VEGF)-targeted therapy. Administration

Oral use. This product should be taken at a fixed time each day, 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 suspension should then be swallowed. After drinking, the same 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, the missed dose should not be taken; the next dose should be taken at the regularly scheduled time.

Prior to 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 reduce the risk of developing renal insufficiency or renal failure (see [Precautions]).

Monitoring, Dosage Adjustment, and Discontinuation: Management of certain adverse reactions may require temporary suspension of administration, dosage adjustment, or discontinuation of treatment with this product.

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 can be found in Table 1.

Detailed information regarding monitoring, dosage adjustment, and discontinuation can be found in Table 2.

Special Populations

Patients aged 75 years and older, Caucasian patients, female patients, or patients with more severe hepatic impairment appear to have lower tolerability to this product. With the exception of patients with moderate to severe hepatic impairment or severe renal impairment, all patients with hepatocellular carcinoma should initiate treatment at a recommended starting dose of 8 mg (two 4 mg capsules for patients weighing <60 kg) or 12 mg (three 4 mg capsules for patients weighing ≥60 kg); subsequent dose adjustments should be made based on individual tolerability.

Patients with Hepatic Impairment

Among patients enrolled in clinical studies for hepatocellular carcinoma, no dose adjustment based on hepatic function is required for patients with mild hepatic impairment (Child-Pugh A). Currently, data regarding patients with moderate hepatic impairment (Child-Pugh B) are limited; patients with mild to moderate hepatic impairment should use this product with caution under medical supervision and undergo close monitoring of hepatic function. No data are currently available for patients with severe hepatic impairment (Child-Pugh C); therefore, use of this product is not recommended in patients with severe hepatic impairment.

Patients with Renal Impairment

For patients with mild or moderate renal impairment, no dose adjustment based on renal function is required. Currently, no data are available for patients with severe renal impairment; therefore, use of this product is not recommended in patients with severe renal impairment.

Pediatric Patients

Currently, no clinical data are available regarding the use of this product in children or adolescents under 18 years of age; therefore, use of this product is not recommended in this population.

Geriatric Patients

No adjustment to the starting dose is required based on age; however, data regarding patients aged ≥75 years are limited.

[Contraindications]

Patients with a known hypersensitivity to any component of this product.

Breastfeeding women (see [Use in Pregnant and Breastfeeding Women]).

[Use in Pregnant and Breastfeeding Women]

Contraception

Women of childbearing potential should avoid pregnancy and employ highly effective contraceptive measures during treatment with Lenvatinib and for at least one month following the completion of treatment. It is currently unknown whether Lenvatinib reduces the efficacy of hormonal contraceptives; therefore, women using oral hormonal contraceptives should utilize an additional barrier method of contraception.

Pregnancy

Currently, there are no data regarding the use of Lenvatinib in pregnant women. Lenvatinib has demonstrated embryotoxicity and teratogenicity when administered to rats and rabbits (see [Pharmacology and Toxicology]). Lenvatinib should not be used during pregnancy unless clearly necessary and after careful consideration of the mother's needs versus the risks to the fetus.

Lactation

It is not known whether lenvatinib is excreted in human milk. Lenvatinib and its metabolites are excreted in the milk of rats (see [Pharmacology and Toxicology]). Because a risk to the newborn or infant cannot be excluded, lenvatinib is contraindicated during breastfeeding; breastfeeding should not be resumed until one week after discontinuing the drug (see [Contraindications]).

Fertility

The effect on human fertility is unknown. However, testicular and ovarian toxicity were observed in rats, dogs, and monkeys (see [Pharmacology and Toxicology]). Fertility may be impaired in men and women of reproductive potential.

[Storage]

Store at no more than 30°C.