GEFTINAT吉非替尼片剂说明书全文(中英对照翻译)

易瑞沙(GEFTIB)使用说明书【药品名称】通用名：吉非替尼片英文名：Gefitinib Tablet、ZD1839商品名：国内进口易瑞沙 — 英国阿斯利康进口印度吉非替尼GEFTIB — GLENMARK生产印度吉非替尼GEFTINAT — NATCO生产印度吉非替尼GEFTILON — CELON生产【适应症】吉非替尼主要适用于治疗局部晚期或转移性非小细胞肺癌(NSCLC)。

既往接受过化学治疗的或不适于化疗、未经化疗的患者均可使用。

临床确诊为小细胞肺癌的患者不适宜服用本品。

吉非替尼不仅对晚期非小细胞肺癌有效，可以改善疾病相关的症状，而且对其他实体瘤也具有抗肿瘤活性，包括前列腺癌、乳腺癌、头颈部肿瘤、胃癌、肠癌等，还可以提高化疗、放疗及激素治疗的抗肿瘤活性。

目前，对其他肿瘤的疗效的Ⅱ期／Ⅲ期临床研究还在进行当中。

易瑞沙（吉非替尼）是一种新型的小分子量肿瘤治疗药物，其作用机制主要是通过抑制EGFR自身磷酸化而阻滞传导，抑制癌细胞的增殖，实现靶向治疗。

临床主要用于治疗既往接受过化学治疗的局部晚期或转移性非小细胞肺癌，尤其对肺腺癌疗效显著，对鳞癌的疗效较腺癌和肺泡癌的低，但临床大量资料表明：根据肺癌患者的实际情况选用易瑞沙（吉非替尼）治疗后，仍有部分肺鳞癌和其它非小细胞肺癌的患者效果比较明显，且具有良好的耐受性。

服用易瑞沙如果有效建议长时间不间断服用，用药物抑制病情进展。

停药超过14天病情即有可能会进展。

易瑞沙是由英国阿斯利康公司研发，2005年2月在中国上市，从国外进口药片，在国内包装销售，价格相对比较高，每片是550元，一个月需要16500元。

长时间服用经济压力会很大。

阿斯利康和中华慈善总会共同推出了赠药活动，服用半年即可申请免费赠药。

赠药需要符合一定条件，如果申请赠药请务必了解清楚每一个环节和细节条件，防止像有些患者一样虽然服用半年但最终却申请不到赠药。

印度产易瑞沙属于仿制药，是被印度法律允许并保护的，但不被中国法律允许，和假药、盗版药不是一个概念。

GEFTINAT吉非替尼片剂说明书全文（中英对照翻译）Hepatic Impairment: The influence of hepatic metastases with elevation Table 1: Demographic and Disease Characteristics INDICATIONS AND USAGE For the use only of a Cancer Specialist or a Hospital or an Institution of serum aspartate aminotransferase (AST/SGOT), alkaline phosphatase, Gefitinib Dose GEFITINAT is indicated as monotherapy for the treatment of patients GEFTINAT* and bilirubin has been evaluated in patients with normal (14 patients), 250 mg/day 500 mg/day with locally advanced or metastatic non-small cell lung cancer after (Gefitinib Tablets IP) moderately elevated (13 patients) and severely elevated (4 patients) Characteristic N=66(%) N=76(%) failure of both platinum-based and docetaxel chemotherapies. levels of one or more of these biochemical parameters. Patients with --------------------------------------------------------------------------- The effectiveness of Gefitinib is based on objective response rates (see Composition moderately and severely elevated biochemical liver abnormalities had Age Group CLINICAL PHARMACOLOGY - Clinical Studies section). There are no Each film coated tablet contains: Gefitinib IP 250 mg gefitinib pharmacokinetics similar to individuals without liver 18-64controlled trials demonstrating a clinical benefit, such as improvement years 43 (65) 43 (57) abnormalities (see PRECAUTIONS section). in disease-related symptoms or increased survival. 64-74 years 19 (29) 30 (39) DESCRIPTION Results from two large, controlled, randomized trials in first- line 75 years andabove 4 (6) 3 (4) GEFTINAT (gefitinib tablets IP) contain 250 mg of gefitinib IP and are Renal Impairment: No clinical studies were conducted with Gefitinib in Sex treatment of non-small cell lung cancer showed no benefit from adding available as reddish brown film-coated tablets engraved with GEFTINAT patients with severely compromised renal function (see PRECAUTIONS Male 38 (58) 41 (54) GEFTINAT to doublet, platinum-based chemotherapy. Therefore, on one side and 250 on another side tor daily oral administration. section). Gefitinib and its metabolites are not significantly excreted via GEFTINAT is not indicated for use in this setting. Female 28 (42) 35(46) Gefitinib is an anilinoquinazoline with the chemical name 4-Quinazolin the kidney(<4%). Race amine, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-4-morpholin] CONTRAINDICATIONS White 61 (92) 68(89) propoxy]. It has the molecular formula C22H24C1F4O3,a relative Drug-Drug Interactions: In human liver microsome studies, gefitinib had Black 1 (2) 2 (3) GEFTINAT is contraindicated in patients with severe hypersensitivity to molecular mass of 446.9 and is a white-colored powder. Gefitinib is a noinhibitory effect on CYPIA2, CYP2C9, and CYP3A4 activities atAsian/Oriental 1 (2) 2 (3) gefitinib or to any other component of GEFTINAT. free base. concentrations ranging from 2-5000 ng/ mL. At the highest concentration Hispanic 0 (0) 3 (4) studied (5000 ng/mL),gefitinib inhibited CYP2C19 by 24% and WARNINGS Other 3 (5) 1 (1) CLINICAL PHARMACOLOGY CYP2D6 by 43%. Exposure to metoprolol, a substrate of CYP2D6, was Pulmonary Toxicity Smoking History Mechanism of Action:The mechanism of the clinical antitumor action of increased by 30% when it was given in combination with gefitinib (500 Yes (Previous or current smoker) 45 (68) 62 (82) Cases of interstitial lung disease (ILD) have been observed in patients gefitinib is not fully characterized.Gefitinib inhibits the intracellular mg daily for 28 days) in patients with solid tumors. Rifampicin, an No (Never smoked) 21 (32) 14 (18) receiving Gefitinib at an overall incidence of about 1%. Approximately phosphorylation of numerous tyrosine kinases associated with inducer of CYP3A4, reduced mean AUC of gefitinib by 85% in healthy Baseline WHO Performance Status 1/3 of the cases have been fatal. The reported incidence of ILD was transmembrane cell surface receptors, including the tyrosine kinases male volunteers (see PRECAUTIONS-Drug Interactions and DOSAGE about 2% in the Japanese post-marketing experience, about 0.3% in 0 14 (21) 9(12) associated with the epidermal growth factor receptor (EGFRTK). EGFR AND ADMINISTRATION-Dosage Adjustment sections). approximately 23,000 patients treated with Gefitinib in a US expanded 1 36 (55) 53(70) is expressed on the cell surface of many normal cells and cancer cells. Concomitant administration of itraconazole (200 mg QD for 12 days), an access program and about 1% in the studies of first-line use in NSCLC 2 15 (23) 14 (18) No clinical studies have been performed that demonstrate a correlation inhibitor of CYP3A4, with gefitinib (250 mg single dose) to healthy Not Recorded 1(2) 0(0) (but with similar rates in both treatment and placebo groups). Reports between EGFR receptor expression and response to gefitinib. male volunteers,increased mean gefitinib AUC by 88% (see Tumor Histology have described the adverse event as interstitial pneumonia, pneumonitis PRECAUTIONS-Drug Interactions section). Co-administration of high and alveolitis. Patients often present with the acute onset of dyspnea, Squamous 9(14) 11 (14) Pharmacokinetics : Gefitinib is absorbed slowly after oral administration doses of ranitidine with sodium bicarbonate (to maintain the gastric pH sometimes associated with cough or low-grade fever, often becoming Adenocarcinoma 47(71) 50 (66) with mean bioavailability of 60%. Elimination is by metabolism above pH 5.0) reduced mean gefitinib AUC by 44% (see severe within a short time and requiring hospitalization. ILD has Undifferentiated 6(9) 4 (5) (primarily CYP3A4) and excretion in feces. The elimination halt-life is PRECAUTIONS-Drug Interactions section). Large Cell 1 (2) 2(3) occurred in patients who have received prior radiation therapy (31% of about 48 hours. Daily oraladministration of gefitinib to cancer patients International Normalized Ratio (INR) elevations and/or bleeding events Squamous and Adenocarcinoma 3 (5) 7 (9) reported cases), prior chemotherapy (57% of reported patients), and no resulted in a 2- fold accumulation compared to single dose have been reported in some patients taking warfarin while on Gefitinib Not Recorded 0 (0) 2 (3) previous therapy (12% of reported cases). Patients with concurrent administration. Steady state plasma concentrations are achieved within therapy. Patients taking warfarin should be monitored regularly for idiopathic pulmonary fibrosis whose condition worsens while receiving Current DIsease Status 10 days.changes in prothrombin time or INR (see PRECAUTIONS-Drug Gefitinib have been observed to have an increased mortality compared to Locally Advanced 11 (17) 5 (7) Interactions and ADVERSE REACTIONS sections). Metastatic 55 (83) 71 (93) those without concurrent idiopathic pulmonary fibrosis. Absorption and Distribution: --------------------------------------------------------------------------- In the event of acute onset or worsening of pulmonary symptoms Gefitinib is slowly absorbed, with peak plasma levels occurring 3-7 Clinical Studies : Non-Small Cell Lung Cancer (NSCLC) - A multicenter Table 2 shows tumor response rates and response duration. The overall (dyspnea, cough, fever), Gefitinib therapy should be interrupted and a hours after dosing and mean oral bioavailability of 60%. Bioavailability clinical trial in the United States evaluated the tumor response rate of prompt investigation of these symptoms should occur. If interstitial response rate for the 250 and 500 mg doses combined was 10.6% (95% is not significantly altered by food. Gefitinib is extensively distributed Gefitinib 250 and 500 mg/day in patients with advanced non-small cell lung disease is confirmed, Gefitinib should be discontinued and the Cl: 6%, 16.8%). Response rates appeared to be highly variable in throughout the body with a mean steady state volume of distribution of lung cancer whose disease had progressed after at least two prior patient treated appropriately (see PRECAUTIONS-Information for subgroups of the treated population: 5.1% (4/79) in males, 17.5% (11/63) 1400L following intravenous administration. Invitro binding of gefitinib chemotherapy regimens including a platinumdrug and docetaxel. in females, 4.6% (5/108) in previous or current smokers, 29.4% (10/34) Patients, ADVERSE REACTIONS and DOSAGE AND to human plasma proteins (serum albumin and al-acid glycoprotein) is Gefitinib was taken once daily at approximately the same time each day.in nonsmokers, 12.4% (12/97) with adenocarcinoma histology, and 6.7% ADMINISTRATION-Dosage Adjustment sections). 90% and is independent of drug concentrations. Two hundred and sixteen patients received Gefitinib, 102 (47%) and 114 (3/45) with other NSCLC histologies. Similardifferences in response (53%) receiving 250 mg and 500 mg daily doses, respectively. Study Pregnancy Category D were seen in a multinational study in patients who had received 1 or 2 Metabolism and Elimination: Gefitinib undergoes extensive hepatic patient demographics and disease characteristics are summarized in Gefitinib may cause fetal harm when administered to a pregnant woman. prior chemotherapy regimens, at least1 of which was platinum-based. In metabolism in humans, predominantly by CYP3A4. Three sites of Table 1. Forty-one percent of the patients had received two prior responders, the median time from diagnosis to study randomization was A single dose study in rats showed that gefitinib crosses the placenta biotransformation have been identified: metabolism of the N-propoxy treatment regimens, 33% three prior treatment regimens, and 25% four 16.7 months (range 8 to 34 months). after an oral dose of 5 mg/kg (30 mg/m2 , about 1/5 the recommended morpholino-group, demethylation of the methoxy-substituent on the or more prior treatment regimens. Effectiveness of Gefitinib as third line human dose on a mg/m2basis). When pregnant rats were treated with 5 Table 2 : EfficacyResults quinazoline, and oxidative defluorination of the halogenated phenyl therapy was determined in the 142 evaluable patients with documented mg/kg from the beginning of organogenesis to the end of weaning gave --------------------------------------------------------------------------- group. Five metabolites were identified in human plasma. Only disease progression on platinum and docetaxel therapies or who had had birth, there was a reduction in the number of offspring born alive. This Avaliable Patients O-desmethyl gefitinib has exposure comparable to gefitinib. Although unacceptable toxicity on these agents. 250 mg 500 mg Combined effect was more severe at 20 mg/kg and was accompanied by high this metabolite has similar EGFR-TK activity to gefitinib in theisolated (N=66) (N=76) (N=142) neonatal mortality soon after parturition, In this study a dose of 1 enzyme assay, it had only l/14 of the potency of gefitinib in one of the Objective Tumor Response 13.6 7.9 10.6 mg/kg caused no adverse effects. cell- based assays. Rate (%) In rabbits, a dose of 20 mg/kg/day (240 mg/m2 , about twice the Gefitinib is cleared primarily by the liver, with total plasma clearance recommended dose in humans on 1 mg/m2 basis) caused reduced fetal 95% Cl (%) 6.4-24.3 3.0-16.4 6.0-16.8 and elimination half-life values of 595 mL/min and 48 hours, Median Duration of Objective weight. There are no adequate and well-controlled studies in pregnant respectively, after intravenous administration. Excretion is Response(months) 8.9 4.5 7.0 women using Gefitinib. If Gefitinib is used during pregnancy or if the predominantlyvia the feces (86%), with renal elimination of drug and Range (months) 4.6-18.6+ 4.4-7.6 4.4-18.6+ patient becomes pregnant while receiving this drug, she should be metabolites accounting for less than 4% of the administered dose. --------------------------------------------------------------------------- apprised of the potential hazard to the fetus or potential risk for loss of +=data are ongoing the pregnancy. Special Populations: In population based data analyses, no relationships Non-Small Cell Lung Cancer (NSCLC); Studies of First-line Treatment were identified between predicted steady state trough concentration and in patient age, body weight, gender, ethnicity or creatinine clearance. Combination with Chemotherapy- Two large trials were conducted in Pediatric: There are no pharmacokinetic data in pediatric patients. chemotherapy-naive patients with stage III and IV non-small cell lung cancer. Two thousand one hundred thirty patients were randomized to receive Gefitinib 250 mg daily, Gefitinib 500 mg daily, or placebo in combination with platinum-based chemotherapy regimens. The chemotherapies given in these first-line trials were gemcitabine andcis-platinum (N=1093) or carboplatin and paclitaxel (N=1037). The addition of Gefitinib did not demonstrate any increase, or trend toward such an increase, in tumor response rates, time to progression, or overall survival.PRECAUTIONS Pregnancy Table 4 - Drug Related Adverse Events 5% at 250 mg OVERDOSAGE Hepatotoxicity Pregnancy Category D (see WARNINGS and PRECAUTIONS- dose by Worst CTC Grade (n=102) The acute toxicity ofGefitinib up to 500 mg in clinical studies has Asymptomatic increases in liver transaminases have been observed in Information for Patients sections). % of patients been low. In non-clinical studies, a single dose of 12,000 mg/m2 (about Gefitinib treated patients; therefore, periodic liver function --------------------------------------------------------------------------- 80 times the recommended clinical dose on a mg/m2 basis) was lethal to (transaminases, bilirubin, and alkaline phosphatase) testing should be Nursing Mothers Adverse ALL CTC CTC CTC CTC rats. Half this dose caused no mortality in mice. considered. Discontinuation of Gefitinib should be considered if changes It is not known whether Gefitinib is excreted in human milk. Following Event Grades Grade 1 Grade 2 Grade 3 Grade 4 There is no specific treatmentfor an GEFTINAT overdose and possible are severe. oral administration of carbon-14 labeled gefitinib to rats 14 days --------------------------------------------------------------------------- symptoms of overdose are not established. However, in phase l clinical postpartum, concentrations of radioactivity in milk were higher than in Diarrhea 48 41 6 1 0 trials, a limited number of patients were treated with daily doses of up to Patients with Hepatic Impairment blood. Levels of gefitinib and its metabolites were 11-to-19-fold higher Rash 43 39 4 0 0 1000 mg. An increase in frequency and severity of some adverse In vitro and in vivo evidence suggest that gefitinib is cleared primarily in milk than in blood, after oral exposure of lactating rats to a dose of 5 Acne 25 19 6 0 0 reactions was observed, mainly diarrhea and skin rash. Adversereactions by the liver. Therefore, gefitinib exposure may be increased in patients mg/kg. Because many drugs are excreted in human milk and because of Dry Skin 13 12 1 0 0 associated with overdose should be treated symptomatically; in with hepatic dysfunction. In patients with liver metastases and the potential for serious adverse reactions in nursing infants, women Nausea 13 7 5 1 0 particular, severe diarrhea should be managed appropriately. moderately to severely elevated biochemical liver abnormalities, should be advised against breast-feeding while receiving Gefitinib Vomiting 12 9 2 1 0 however, gefitinib pharmacokinetics were similar to the therapy. Pruritus 8 7 1 0 0 DOSAGE AND ADMINISTRATION pharmacokinetics of individuals without liver abnormalities(see Anorexia 7 3 4 0 0 The recommended daily dose of GEFITINIB is one 250 mg tablet with CLINICAL PHARMACOLOGY/Pharmaco kinetics - Special Pediatric Use Asthenia 6 2 2 1 1 or without food. Higher doses do not give a better response and cause Populations section). The influence of non-cancer related hepatic Safety and effectiveness of Gefitinib in pediatric patients have not been --------------------------------------------------------------------------- increased toxicity. impairment on the pharmacokinetics of gefitinib has not been evaluated. studied. Other adverse events reported at an incidence of <5% in patients who received either 250 mg or 500 mg as monotherapy for treatment of Dosage Adjustment Information for Patients Geriatric Use NSCLC (along with their frequency at the 250 mg recommended dose) Patients with poorly tolerated diarrhea (sometimesassociated with Patients should be advised to seek medical advice promptly if they Of the total number of patients participating in trials of second- and include the following: peripheral edema (2%), amblyopia (2%), dyspnea dehydration) or skin adverse drug reactions may be successfully develop third-line Gefitinib treatment of NSCLC, 65% were aged 64 years or less, (2%), conjunctivitis (1%), vesiculobullous rash (1%), and mouth managed by providing a brief (up to 14 days) therapy interruption 1) severe or persistent diarrhea, nausea, anorexia, or vomiting, as these 30.5% were aged 65 to 74 years, and 5% of patients were aged 75 years ulceration (1%). followed by reinstatement of me 250 mg daily dose. have sometimes been associated with dehydration; or older. No differences in safety or efficacy were observed between In the event of acute onset or worsening of pulmonary symptoms 2) an onset or worsening of pulmonary symptoms, ie, shortness of breath younger and older patients. Interstitial Lung Disease (dyspnea, cough, fever), GEFTINAT therapy should be interrupted and or cough; Cases ofinterstitial lung disease (ILD) have been observed in patients a prompt investigation of these symptoms should occur and appropriate 3) an eye irritation; or, Patients with Severe Renal Impairment receivingGefitinib at an overall incidence of about l%. Approximately treatment initiated. If interstitial lung disease is confirmed, GEFTINAT 4) any other new symptom (see WARNINGS- Pulmonary Toxicity, The effect ofsevere renal impairment on the pharmacokinetics of 1/3 0f the cases have been fatal. The reported incidence of ILD was should be discontinued andthe patient treated appropriately (see ADVERSE REACTIONS and DOSAGE AND gefitinib is not known. Patients with severe renal impairment should be about 2% in the Japanese post-marketing experience, about 0.3% in WARNINGS- Pulmonary Toxicity, PRECAUTIONS-Information for ADMINISTRATION-Dosage Adjustment sections). treated with caution when given GEFTINAT. approximately 23,000 patients treated with Gefitinib in a US expanded Patients and ADVERSE REACTIONS sections). Women of childbearing potential must be advised to avoid becoming access program and about l% in the studies of first-line use in NSCLC Patients who develop onset of new eye symptoms such as pain should be pregnant (see WARNINGS-Pregnancy Category D). ADVERSE REACTIONS (but with similar rates in both treatment and placebo groups). Reports medically evaluated and managed appropriately, The safety database includes 941 patients from clinical trials and have described the adverse event asinterstitial pneumonia, pneumonitis including GEFTINAT therapy interruption and removal of an aberrant Drug Interactions approximately 23,000 patients in the Expanded Access Program. Table 3 and alveolitis. Patients often present with the acute onset of dyspnea, eyelash if present. After symptoms and eye changes have resolved, the Substances that are inducers of CYP3A4 activity increase the includes drug-related adverse events with an incidence of 5% for the 216 sometimes associated with cough or low-grade fever, often becoming decision should be made concerning reinstatement of the 250 mg daily metabolism of gefitinib and decrease its plasma concentrations. In patients who received either 250mg or 500 mg of Gefitinib monotherapy severe within a short time and requiring hospital ization. ILD has dose (see PRECAUTIONS- Information for Patients and ADVERSE patients receiving a potent CYP3A4 inducer such as rifampicin or for treatment of NSCLC. The most common adverse events reported at occurred in patients who have received prior radiation therapy (31% of REACTIONS sections), phenytoin, a dose increase to 500 mg daily should be considered in the the recommended 250 mg daily dose were diarrhea, rash, acne, dry skin, reported cases), prior chemotherapy (57% of reported patients), and no In patients receiving a potent CYP3A4 inducer such as rifampicin or absence of severe adverse drug reaction, and clinical response and nausea, and vomiting (see PRECAUTIONS- Information for Patients and previous therapy (12% of reported cases). Patients with concurrent phenytoin, a dose increase to 500 mg daily should be considered in the adverse events should be carefully monitored (see CLINICAL DOSAGE AND ADMINISTRATION- Dosage Adjustment sections). idiopathic pulmonary fibrosis whose condition worsens while receiving absence of severe adverse drug reaction, and clinical response and PHARMACOLOGY- Pharmacokinetics-Drug-Drug Interactions and The 500 mg dose showed a higher rate for most of these adverse events. Gefitinib have been observed to have an increased mortality compared to adverse events should be carefully monitored (see CLINICAL DOSAGE AND ADMIN-ISTRATION- Dosage Adjustment sections). Table 4 provides drug-related adverse events with an incidence of 5% by those without concurrent idiopathic pulmonary fibrosis. PHARMACOLOGY-Pharmacokinetics- Drug DrugInteractions and International Normalized Ratio (INR) elevations and/or bleeding events CTC grade for the patients who received the 250 mg/day dose of PRECAUTIONS-Drug Interactions sections). have been reported in some patients taking warfarin while on Gefitinib Gefitinib monotherapyfor treatment of NSCLC. Only 2% of patients In the event of acute onset or worsening of pulmonary symptoms No dosage adjustment is required on the basis of patient age, body therapy. Patients taking warfarin should be monitored regularly for stopped therapy due to an adverse drug reaction (ADR). The onset of (dyspnea, cough, fever), GEFITINIB therapy should be interrupted and a weight, gender, ethnicity, or renal function; or in patients with moderate changes in prothrombin time or INR (see CLINICAL these ADRs occurred within the first month of therapy. prompt investigation of these symptoms should occur. If interstitial lung to severe hepatic impairment due to liver metastases (see CLINICAL PHARMACOLOGY-Pharmacokinetics-Drug-Drug Interactions and disease is confirmed, Gefitinib should be discontinued and the patient PHARMACOLOGY-Pharmacokinetics- Special Populations section). ADVERSE REACTIONS sections). Table 3 - Drug-Related Adverse Events With an Incidence treated appropriately(see WARNINGS-Pulmonary Toxicity, Keepthis medication out of reach and sight of children. Substances that are potent inhibitors of CYP3A4 activity (eg, of 5% in either 250 mg or 500 mg Dose Group PRECAUTIONS- Information for Patients and DOSAGE AND ketoconazole and itraconazole) decrease gefitinib metabolism and ---------------------------------------------------------------------------ADMINISTRATION- Dosage Adjustment sections). HOW SUPPLIED increase gefitinib plasma concentra-tions. This increase may be clinically Number (%) of Patients In patients receiving Gefitinib therapy, there were reports of eye pain and 30 Tablets packed in tamper evident HDPE container. One container and relevant as adverse experiences are related to dose and exposure; --------------------------------------------------------------------------- corneal erosion/ulcer, sometimes in association with aberrant eyelash literature housed in a carton. therefore, caution should be used when administering CYP3A4 inhibitors Drug-related 250 mg/day 500 mg/day growth (see PRECAUTIONS Information for Patients section). There 10 Tablets packed in a blister. 3 blisters and literature housed in a with GEFTINAT (see CLINICAL adverse event @ (N=102) (N=114) were also rare reports of pancreatitis and very rare reports of corneal carton. PHARMACOLOGY-Pharmacokinetics-Drug-Drug Interactions and % % membrane sloughing, ocular ischemia/hemorrhage, toxic epidermal ADVERSE REACTIONS sections). Diarrhea 49 (48) 76 (67) necrolysis, erythema multiforme, and allergic reactions, including Storage Drugs that cause significant sustained elevation in gastric pH (histamine Rash 44 (43) 61 (54) angioedema and urticaria. Store in a cool, dry place, protected from light and moisture. H 2 -receptor antagonists such as ranitidine or cimetidine) may reduce Acne 25 (25) 37 (33) International Normalized Ratio (INR) elevations and/or bleeding events plasma concentrations of Gefitinib and therefore potentially may reduce Dry skin 13 (13) 30 (26) have been reported in some patientstaking warfarin while on Gefitinib Made in India by: efficacy (see CLINICAL PHARMACOLOGY- Drug-Drug Interactions Nausea 13 (13) 20 (18) therapy. Patients taking warfarin should be monitored regularly for NATCO section). Vomiting 12 (12) 10 (9) changes in prothrombin time or INR (see CLINICAL PHARMA LIMITED, Carcinogenesis, Mutagenesis, Impairment of Fertility Gefitinib has been Pruritus 8 (8) 10 (9) PHARMACOLOGY-Drug-Drug Interactions and PRECAUTIONS-Drug Regd. Office: NATCO HOUSE, ROAD No. 2, tested for genotoxicity in a series of in vitro [bacterial mutation, mouse Anorexia 7 (7) 11 (10) Interactions sections). BANJARA HILLS, HYDERABAD-500 033. lymphoma, and human lymphocyte) assays and an in vivo rat Asthenia 6 (6) 5 (4) Data from non-clinical (in vitro and in vivo) studies indicate that micronucleus test. Under the conditions of these assays, gefitinib did not Weight loss 3 (3) 6 (5) gefitinib has the potential to inhibit the cardiac action potential NATCO cause genetic damage. --------------------------------------------------------------------------- repolarization process (eg, OT interval). The clinical relevance of these Carcinogenicity studies have not been conducted with gefitinib. *A patient may have had more than 1 drugrelated adverse event. findings is unknown.对于只使用一个肿瘤专科医院或机构肝功能不全:在正常的患者(14例)，中度升高(13例)和严重升表1:人口和疾病特征适应症吉非替尼剂量 GEFTINAT* 高(4例肝转移血清谷草转氨酶(AST/SGOT)，碱性磷酸酶和胆红GEFITINAT表示作为单药治疗铂类为基础和多西紫杉醇化疗失败后 250毫克/天 500毫克/天。

GEFTINAT中文说明书原产地英文商品名:Geftinat原产地英文药品名:吉非替尼( Gefitinib )中文参考商品译名:易瑞沙( IRESSA )艾瑞沙包装规格及销售价:0.25g/片*30片/瓶计价单位:瓶适应症:局部晚期或转移性非小细胞肺癌扩大适应症:其他实体癌【成分】吉非替尼Gefitinib【包装/剂型】薄膜衣片0.25g x 30 片【性状】【化学名】N-(3-氯-4-氟苯基)-7-甲氧基-6-(3-吗啉丙氧基)喹唑啉-4-胺，分子式为:C22H24ClFN4O3，分子量为:446.90。

本药为褐色圆形薄膜衣片;一面印有"IRESSA 250"。

【药理作用】吉非替尼是一种选择性表皮生长因子受体(EGFR)酪氨酸激酶抑制剂，该酶通常表达于上皮来源的实体瘤。

吉非替尼广泛抑制异种移植于裸鼠的人肿瘤细胞的生长，抑制其血管生成。

在体外，可增加人肿瘤细胞衍生系的凋亡，并抑制血管生成因子的侵入和分泌。

在动物试验或体外研究中已证实，吉非替尼可提高化疗、放疗及激素治疗的抗肿瘤活性。

适应症本品适用于治疗既往接受过化学治疗的局部晚期或转移性非小细胞肺癌(NSCLC)。

既往化学治疗主要是指铂剂和多西紫杉醇治疗。

对于化学治疗失败的局部晚期或转移性非小细胞肺癌患者的疗效，是基于客观反应率指标而确立的，尚无对照性的研究显示改善疾病相关症状和延长生存期方面的临床受益。

本品用于非小细胞肺癌二线治疗的现有数据仅基于非对照的临床研究，尚待设计良好的对照的临床试验进一步证实。

对于非小细胞肺癌的一线治疗，两个大型的随机对照临床试验结果表明:基于铂剂的二联化疗方案合用本品治疗后未显示任何受益，因此，吉非替尼不适用于此种治疗。

【用法用量】本品的成人推荐剂量为250 mg(1片)，1日1次，口服，空腹或与食物同服。

如果有吞咽困难，可将片剂分散于半杯饮用水中(非碳酸饮料)，不得使用其他液体。

将片剂丢入水中，无需压碎，搅拌至完全分散(约需10分钟)，即刻饮下药液。

肺癌一代靶向药易瑞沙吉非替尼片中文说明书本文由印康源整理提供。

易瑞沙是迄今为止研究最为广泛的口服小分子EGFR酪氨酸激酶抑制剂，其作用机制是：通过与ATP竞争性结合胞外的配体结合位点，阻断分子内酪氨酸的自身磷酸化，阻断酪氨酸激酶活化，阻断EGFR信号传导系统，将位于下游的ras/raf/MAPK系统功能封闭，从而阻断EGF诱导的肿瘤细胞生长，促进凋亡，同时减少血管内皮生长因子，中性成纤维生长因子和TGFA含量，抗血管生成，达到靶向治疗的目的，已作为单一治疗药物用于晚期NSCLS。

目前除了英国版易瑞沙，还有孟加拉和印度版本，微信：yinkangyuan1首次服用易瑞沙半个月左右出现效果？对于首次服用易瑞沙的患者,如果患者症状比较明显，且易瑞沙对其有效果，一般在半个月左右，会有明显的症状和精神上的改善，快的话三五天就能有明显感觉。

最多四十天如果没有任何改善，且病情有明显进展，应该认定易瑞沙，对于该患者个体是没有效果的，应该停药。

患者可以在服药两个月的时候，做一个肺部的检查，观察肿块是否有明显的缩小。

服药两个月患者症状没有明显恶化，或者比服药前恶化速度减慢，也应该认定该药是有效的。

什么是易瑞沙？易瑞沙是转移性EGFR和非小细胞肺癌患者的靶向治疗药易瑞沙是一种有针对性的治疗手段——每天服用一片药片，这是专门为非小细胞癌（NSCLC）已经蔓延到肺部以外并有某种类型的表皮生长因子受体（EGRF）基因异于常人的患者研发的药物。

你的医生将进行测试，以确保IRESSA适合您。

易瑞沙是怎样起作用的？您的医生会使用活体检测或者组织样本来检测EGFR突变的存在。

EGFR是一种在人体细胞表面发现的蛋白质。

突变的EGFR通过发出使细胞生长和分裂的信号而参与癌细胞生长。

但是IRESSA可能会对你有所帮助。

原理是，IRESSA附着在你的肺癌细胞上的某些异常类型的EGFR蛋白上。

实践证明这样做能够减慢这些细胞的生长并可能有助于减小肿瘤的大小。

吉非替尼Gefitinib说明书【药品名称】通用名称：吉非替尼片商品名称：吉非替尼片(易瑞沙)拼音全码：JiFeiTiNiPian(YiRuiSha)【主要成份】吉非替尼Gefitinib 化学名：N-(3-氯-4-氟苯基)-7-甲氧基-6-(3-吗啉丙氧基)喹唑啉-4-胺分子式：C22H24ClFN4O 分子量：446.90【性状】褐色，椭圆形或圆形（不同国家上市的药形状不一样），双凸面，薄膜衣片；一面印有&ldquo;250&rdquo;，每片含吉非替尼250mg。

【适应症/功能主治】吉非替尼适用于治疗既往接受过化学治疗或不适于化疗的局部晚期或转移性非小细胞肺癌(NSCLC)。

【规格型号】0.25g*10s【用法用量】推荐剂量为250mg(1片)每日1次，空腹或与食物同服。

不推荐用于儿童或青少年，对于这一患者群的安全性和疗效尚未进行研究。

如果有吞咽困难，可将片剂分散于半杯饮用水中(非碳酸饮料)，不得使用其他液体。

将片剂丢入水中，无需压碎，搅拌至完全分散(约需10分钟)，即刻饮下药液。

以半杯水冲洗杯子，饮下。

也可通过鼻-胃管给予该药液。

无需因下述情况不同调整给药剂量：年龄、体重、性别、种族，肾功能，因肝转移而引起的中至重度肝功能损害。

剂量调整：当患者出现不能耐受的腹泻或皮肤不良反应时，可通过短期暂停治疗(最多14天)解决，随后恢复每天250 mg的剂量。

【不良反应】最常见(发生率20％以上)的药物不良反应为腹泻、皮疹、瘙痒、皮肤干燥和痤疮，一般见于服药后的第1个月内，通常是可逆性的。

大约8％的患者出现严重的药物不良反应(CTC标准3或4级)。

因不良反应停止治疗的患者仅有1％。

各身体系统发生的不良事件按发生频率以降序排列(多见：≥(greaterthanorequalto)10％；常见：≥(greaterthanorequalto)1％且<10%；少见：≥(greaterthanorequalto)0.1％且<1％；罕见：≥(greaterthanorequalto)0.01％且<0.1％；极罕见：<0.01％)。

易瑞沙中文说明书易瑞沙中文说明书【药品名称】: 通用名:吉非替尼片英文名:Gefitinib Tablet、Iressa、ZD1839 【性状】褐色，椭圆形，双凸面，薄膜衣片;一面印有“250”，另一面“geftinat”。

每片含吉非替尼 250mg。

【药理毒理】 1、药物动力学特性吉非替尼是一种选择性表皮生长因子受体(EGFR)酪氨酸激酶抑制剂，该酶通常表达于上皮来源的实体瘤。

对于 EGFR 酪氨酸激酶活性的抑制可妨碍肿瘤的生长，转移和血管生成，并增加肿瘤细胞的凋亡。

在体内，吉非替尼广泛抑制异种移植于裸鼠的人肿瘤细胞衍生系的肿瘤生长，并提高化疗、放疗及激素治疗的抗肿瘤活性。

在临床实验中已证实吉非替尼对局部晚期或转移性非小细胞肺癌具客观的抗肿瘤反应并可改善疾病相关的症状。

2、药物代谢动力学特性静脉给药后，吉非替尼迅速廓清，分布广泛，平均清除半衰期为 48 小时。

癌症患者口服给药后，吸收较慢，平均终末半衰期为 41 小时吉非替尼每天给药 1 次出现 2-8 倍蓄积，经7-10 天的给药后达到稳态。

24 小时间隔用药，循环血浆药物浓度一般维持在 2-3 倍之间。

3、吸收口服给药后，吉非替尼的血浆峰浓度出现在给药后的3 到 7 小时。

癌症患者。

进食对吉非替尼吸收的影响不明显。

在一项健康志愿的平均吸收生物利用度为 59者的实验中，当 pH值维持在 pH5 以上时，吉非替尼的吸收减少 47(见 4.4 和 4.5 节)。

4、分布在吉非替尼稳态时的平均分布容积为 1400L，分布广泛。

血浆蛋白结合率近 90。

吉非替尼与血清白蛋白及αl—酸性糖蛋白结合。

5、代谢体外研究数据表明参与吉非替尼氧化代谢的 P450 同工酶只有 CYP3A4。

体外研究显示吉非替尼可能有限的抑制 CYP2D6 酶。

在一项临床试验中，吉非替尼与metoprolol(美多心安，一种 CYP2D6 酶底物)合用使该组的作用有少量的增高(35)，其实际临床意义尚未估计。

吉非替尼说明书（注意是易瑞沙，不是印度产的）∙通用名称：∙吉非替尼片∙功能主治：∙本品适用于治疗既往接受过化学治疗的局部晚期或转移性非小细胞肺癌(NSCLC)。

既往化学治疗主要是指铂剂和多西紫杉醇治疗。

本品对于既往接受过化学治疗的局部晚期或转移性非小细胞肺癌患者的疗效，是基于大规模安慰剂对照临床试验预设亚洲亚组的生存优势(注：该试验总体人群中未显示改善疾病相关症状和延长生存期)及中国非对照临床试验的生存数据而确立的。

两个大型的随机对照临床试验结果表明：吉非替尼联合含铂化疗方案一线治疗局部晚期或转移性NSCLC未显示出临床获益，所以不推荐此类联合方案。

∙用法用量：∙本品的推荐剂量为250mg(1片)，一日1次，口服，空腹或与食物同服。

如果有吞咽困难，可将片剂分散于半杯饮用水中(非碳酸饮料)。

不得使用其他液体。

将片剂丢入水中，无需压碎，搅拌至完全分散(约需10分钟)，即刻饮下药液。

以半杯水冲洗杯子，饮下。

也可通过鼻-胃管给予该药液。

无需因下述情况不同调整给药剂量：年龄、体重、性别、种族、肾功能、因肝转移而引起的中至重度肝功能损害。

剂量调整：当患者出现不能耐受的腹泻或皮肤不良反应时，可通过短期暂停治疗(最多14天)解决，随后恢复每天250mg的剂量 (见不良反应)。

儿童中使用目前尚无本品用于儿童或青少年患者安全性与疗效的资料，故不推荐使用。

∙不良反应：∙最常见(发生率20%以上)的药物不良反应( ADRs )为腹泻和皮肤反应(包括皮疹、痤疮、皮肤干燥和瘙痒)，一般见于服药后的第一个月内，通常是可逆性的。

大约8%的患者出现严重的药物不良反应(CTC标准3或4级)。

因ADR停止治疗的患者有约3%。

各身体系统发生的不良事件按发生频率以降序排列(多见：>10%;常见：>1%且<10%;少见：>0.1%且<1%;罕见：>0.01%且<0.1%;极罕见：<0.01%)。