LuciGefi Gefitinib tablets

[Product Name] Gefitinib Tablets

[Other Name] Iressa

[English Name] Gefitinib Tablets

[Specification] 250 mg × 30 tablets/box

[Manufacturer] Lucius Pharmaceutical (Laos) Co., Ltd.

[Drug Approval Number] 09 L 1215/24

[Indications]

The indications for Gefitinib Tablets primarily include the following:

Non-Small Cell Lung Cancer (NSCLC)

First-line treatment: Indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors harbor activating mutations of the epidermal growth factor receptor (EGFR) gene.

Second-line and subsequent treatment: Indicated for patients with locally advanced or metastatic non-small cell lung cancer who have previously received chemotherapy. Specifically, this applies to patients whose disease has progressed following treatment with platinum-based agents and docetaxel; the use of Gefitinib Tablets can help continue to control tumor growth, prolong patient survival, and improve quality of life.

[Dosage and Administration]

Administration

Method of Administration: Gefitinib Tablets are typically administered orally. They may be taken with or without food. Generally, it is recommended to take the medication at a fixed time each day to maintain a stable drug concentration in the body and maximize therapeutic efficacy.

Special Circumstances: If a patient has difficulty swallowing, the tablet may be dispersed in half a glass of drinking water (non-carbonated). No other liquids should be used. Drop the tablet into the water—do not crush it—and stir until it is completely dispersed (this takes approximately 10 minutes). Drink the liquid immediately. Rinse the glass with another half-glass of water and drink the remaining liquid. The medication may also be administered via a nasogastric tube.

Dosage

Standard Dose: The recommended dose is 250 mg (1 tablet) once daily.

Dosage Adjustment

Adjustments for Adverse Reactions: If a patient experiences intolerable diarrhea or skin-related adverse reactions, these may be managed by temporarily suspending treatment (for up to 14 days), followed by resuming the daily dose of 250 mg. If the adverse reactions persist without improvement or worsen, a further dose reduction may be required—for example, reducing the dose to 125 mg (half a tablet) once daily. **Hepatic and Renal Impairment:** For patients with mild hepatic impairment (e.g., hepatic dysfunction resulting from liver metastases), no dose adjustment is required. However, the safety and efficacy of gefitinib tablets in patients with moderate to severe hepatic impairment have not yet been established; therefore, the drug should be administered with caution and under close monitoring. Regarding patients with renal impairment, since gefitinib is primarily metabolized by the liver, dose adjustment is generally not required for those with mild to moderate renal impairment; however, patients with severe renal impairment also require cautious administration and close observation.

The safety and efficacy of this drug in pediatric patients have not been established; therefore, its use is not recommended in this population. No significant pharmacokinetic differences have been observed between elderly and younger patients; thus, dose adjustment is generally not required for the elderly. However, elderly patients may present with a higher incidence of comorbidities and age-related declines in hepatic or renal function; consequently, a careful assessment should be conducted when administering the drug to this population.

**[Mechanism of Action]**

**Action on EGFR**

**Binding to EGFR:** A protein known as the Epidermal Growth Factor Receptor (EGFR) is present on the surface of human cells; in certain tumor cells, EGFR is either overexpressed or mutated. Gefitinib is a selective Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) that specifically binds to the intracellular tyrosine kinase domain of EGFR.

**Blocking ATP Binding:** Activation of EGFR requires the binding of Adenosine Triphosphate (ATP) to the tyrosine kinase domain to provide the necessary energy, thereby initiating intracellular signal transduction pathways. Upon binding to EGFR, gefitinib occupies the ATP-binding site, preventing ATP from binding to the EGFR tyrosine kinase domain. This action blocks the phosphorylation process of EGFR and, consequently, inhibits its activation.

**Effects on Tumor Cells**

**Inhibition of Tumor Cell Proliferation:** Under normal physiological conditions, EGFR activation triggers a cascade of intracellular signal transduction pathways—such as the RAS-RAF-MEK-ERK pathway and the PI3K-AKT pathway—which promote cell proliferation, differentiation, and survival. By inhibiting EGFR activation, gefitinib blocks the transmission of these signaling pathways. This action inhibits the mitosis of tumor cells, preventing them from entering the S phase of the cell cycle to undergo DNA replication, and thereby suppresses tumor cell proliferation. Induction of Tumor Cell Apoptosis: Gefitinib can induce apoptosis in tumor cells by modulating intracellular apoptosis-related proteins and signaling pathways. It downregulates the expression of anti-apoptotic proteins (such as Bcl-2, Bcl-xL, etc.) while simultaneously upregulating the expression of pro-apoptotic proteins (such as Bax, Bad, etc.). This enhances intracellular apoptotic signals, prompting tumor cells to initiate the apoptotic program and ultimately leading to tumor cell death.

Inhibition of Tumor Angiogenesis: Tumor growth and metastasis depend on the supply of nutrients and oxygen provided by newly formed blood vessels. Activation of the EGFR signaling pathway promotes the secretion of angiogenic factors—such as Vascular Endothelial Growth Factor (VEGF)—by tumor cells, thereby inducing tumor angiogenesis. By inhibiting the EGFR signaling pathway, Gefitinib reduces the secretion of these angiogenic factors. Consequently, it inhibits the proliferation and migration of tumor endothelial cells, impedes the formation of tumor blood vessels, severs the tumor's supply of nutrients and metastatic pathways, and ultimately suppresses tumor growth and metastasis.

[Adverse Reactions]

Common Adverse Reactions: Adverse reactions with an incidence rate of over 20% include diarrhea and skin reactions (rash, acne, dry skin, pruritus). These typically manifest within the first month of treatment and are generally reversible.

Serious Adverse Reactions: Approximately 10% of patients experience serious adverse drug reactions (NCI CTC Grade 3 or 4), and approximately 3% of patients discontinue treatment due to adverse reactions. Reports include cases of interstitial lung disease, hepatic failure, gastrointestinal perforation, and severe ocular disorders.

[Contraindications]

Patients with a known history of severe hypersensitivity reactions to the active substance or to any of the excipients contained in this product.

[Precautions]

Genetic Testing: Prior to treatment, it is recommended to perform EGFR mutation testing on tumor tissue samples. If the tumor specimen is not evaluable, circulating tumor DNA (ctDNA) testing using blood (plasma) specimens may be utilized.

Interstitial Lung Disease (ILD): Patients undergoing treatment may develop interstitial lung disease. If respiratory symptoms worsen, treatment should be interrupted to allow for diagnostic evaluation; if ILD is confirmed, the drug should be permanently discontinued and appropriate treatment initiated. Hepatotoxicity: Abnormalities in liver function tests may occur; hepatitis is observed occasionally, and fatal cases of liver failure have been reported. Periodic monitoring of liver function is recommended. Caution should be exercised in patients with mild to moderate elevations in liver transaminases; discontinuation of the medication should be considered if these elevations worsen.

Other: Conditions such as severe and persistent diarrhea, gastrointestinal perforation, or ocular symptoms require appropriate clinical management and medical attention. Drug interactions may occur; caution is advised when co-administering with other medications, such as CYP3A4 inducers or inhibitors, warfarin, or vinorelbine. The medication may impair the ability to drive or operate machinery.