Gefitinib Tablets

1. Gefitinib is a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, which is usually expressed in solid tumors of epithelial origin. 2. Gefitinib widely inhibits the growth of human tumor cells transplanted into nude mice, inhibits their angiogenesis, and in vitro, it can increase the apoptosis of human tumor cell-derived lines and inhibit the invasion and secretion of angiogenic factors. In animal experiments or in vitro studies, it has been confirmed that gefitinib can enhance the anti-tumor activity of chemotherapy, radiotherapy and hormone therapy.

Gefitinib

Brown, round, film-coated tablets; printed with "IRESSA250" on one side. The other side is smooth.

This product is indicated for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) that has previously received chemotherapy.

The recommended dose is 250 mg (1 tablet) once daily, taken on an empty stomach or with food. It is not recommended for children or adolescents, and the safety and efficacy of this patient group have not been studied. If swallowing is difficult, the tablets can be dispersed in half a cup of drinking water (non-carbonated beverages), and no other liquids should be used. Drop the tablet into the water without crushing it, stir until it is completely dispersed (about 10 minutes), and drink the solution immediately. Rinse the cup with half a cup of water and drink it. The solution can also be given through a nasogastric tube. There is no need to adjust the dosage due to the following conditions: age, weight, sex, race, renal function, moderate to severe liver damage caused by liver metastasis. Dose adjustment: When patients experience intolerable diarrhea or skin adverse reactions, they can be resolved by short-term suspension of treatment (up to 14 days), followed by resumption of the daily dose of 250 mg.

1. The most common (incidence rate of more than 20%) adverse drug reactions (ADRs) are diarrhea and skin reactions (including rash, acne, dry skin and itching), which are generally seen within the first month after taking the drug and are usually reversible. Approximately 8% of patients experience serious adverse drug reactions (CTC standard grade 3 or 4). About 3% of patients discontinued treatment due to ADR. 2. Adverse events occurring in each body system are arranged in descending order of frequency (more common: >10%; common: >1% and 0.1% and 0.01% and <0.1%; extremely rare: <0.01%) (1) Based on data from clinical studies conducted globally, expanded use/compassionate use and post-marketing use, the overall incidence of interstitial lung disease outside of Japan

Patients with known severe allergic reaction to the active substance or any of the excipients of this product.

Precautions for children: There is currently no data on the safety and efficacy of this product for children or adolescent patients, so it is not recommended. Precautions for pregnancy and lactation: 1. Use during pregnancy There is currently no data on the use of this product in pregnant women. When gefitinib is given during the organogenesis period at doses that can produce maternal toxicity, an increased incidence of osteogenesis imperfecta was observed in rats and a decrease in fetal weight was observed in rabbits. No malformations were observed in rats, and malformations were only observed in rabbits at doses that produce severe maternal toxicity. During treatment with this product, women of childbearing age should be advised to avoid pregnancy. 2. Use during lactation (1) During treatment with this product, nursing mothers should be advised to stop breastfeeding. (2) There is currently no data on the use of this product in lactating women. It is not known whether gefitinib or its metabolites are secreted into human milk, but when lactating rats were given 5 mg/kg gefitinib orally (0.2 times the clinical dose based on body surface area), gefitinib and certain metabolites were extensively secreted into breast milk. (3) When gefitinib was administered to rats during pregnancy and delivery at a dose of 20 mg/kg/day (0.7 times the clinical dose based on body surface area), the survival rate of the pups was reduced. Precautions for the elderly: Not yet determined.

In vitro studies on human liver microsomes confirmed that gefitinib is primarily metabolized by CYP3A4 of the hepatic cytochrome P-450 system. Therefore, gefitinib may interact with drugs that induce, inhibit, or are metabolized by the same hepatic enzyme. Animal studies have shown that gefitinib has little enzyme induction effect, and in vitro studies have shown that gefitinib can inhibit CYP2D6 to a limited extent. The following is a list of drugs or drug classes that have or may have clinically significant drug interactions with gefitinib: 1. Drugs that affect gefitinib (1) Proven interactions Drugs that inhibit CYP3A4 In healthy volunteers, when gefitinib was co-administered with itraconazole (a CYP3A4 inhibitor), the mean AUC of gefitinib increased by 80%. Because adverse drug reactions are dose- and exposure-related, this increase may be clinically significant. Although studies on interactions with other CYP3A4 inhibitors have not been conducted, drugs in this class, such as ketoconazole, clotrimazole, and ritonavir, may also inhibit the metabolism of gefitinib. Drugs that increase gastric pH Clinical studies in healthy volunteers have shown that co-administration of drugs that can significantly and continuously increase gastric pH to ≥5 can reduce the mean AUC of gefitinib by 47%, which may reduce the efficacy of gefitinib. Rifampicin When gefitinib was co-administered with rifampicin (a known strong CYP3A4 inducer) in healthy volunteers, the mean AUC of gefitinib was reduced by 83% compared with that when taken alone. (2) Theoretically, there may be interactions with other drugs (3) Other CYP3A4 inducers Substances that induce CYP3A4 activity can increase the metabolism of gefitinib and reduce its plasma concentration. Therefore, co-administration with CYP3A4 inducers (such as phenytoin, carbamazepine, barbiturates, or St. John's wort) may reduce the efficacy. 2. Effects of gefitinib on other drugs (1) Proven interactions Drugs metabolized by CYP2D6 In a clinical trial, the co-administration of gefitinib and metoprolol (a CYP2D6 substrate) increased the exposure of metoprolol by 35%, which was considered not clinically relevant. Co-administration of gefitinib with other drugs metabolized by CYP2D6 may increase the latter's blood concentration. (2) Drugs that may theoretically interact Warfarin: Although no formal drug interaction studies have been conducted to date, increased INR and/or bleeding events have been reported in some patients taking warfarin. Patients taking warfarin should be regularly monitored for changes in their prothrombin time or INR (see Precautions). Vinorelbine: In a Phase II clinical study, the co-administration of this product with vinorelbine showed that this product may exacerbate the neutropenia caused by vinorelbine.

Store below 30°C.

0.25 g

24 months.