易瑞沙(GEFTIB)使用说明书
易瑞沙
吉非替尼（易瑞沙）【规格】250mg/片【适应症】用于晚期或转移性非小细胞肺癌。
【禁忌症】对本品有严重超敏反应者禁用。
【用法用量】空腹或与食物同服，250mg 口服，每日1 次。
【不良反应】1、消化道反应：腹泻多见，主要为轻度，少为中度，个别严重者有伴脱水的腹泻；轻度恶心；呕吐常见，主要为轻中度；轻中度食欲不振；口腔黏膜炎，多为轻度；口腔溃疡；继发脱水；少见胰腺炎。
2、皮肤和附件反应：皮疹、皮肤瘙痒多见，皮肤反应主要为轻中度，红斑有时伴有皮肤干燥和发痒，可出现脓疱性皮疹、多形性红斑，极罕见有中毒性表皮坏死松懈症，过敏反应包括血管性水肿和荨麻疹。
指甲异常常见。
3、肝功能异常：主要为轻中度转氨酶异常。
4、全身症状：轻度乏力，脱发，体重下降，外周性水肿。
5、眼：常见结膜炎和眼睑炎，主要为轻度，弱视少见，有可逆的角膜糜烂，有时伴有睫毛生长异常，极罕见有角膜脱落、眼部缺血和出血。
6、血液和淋巴系统：出血，如常见鼻出血和尿血。
少见在服用华法林患者有时出现INR（国际标准化比值）升高和出血，出血性膀胱炎。
7、呼吸系统：常见表现为呼吸困难。
少见发生间质性肺病，常较严重（3、4度）。
【注意事项】1.定期胸部X 线检查，观察呼吸，监测血氧饱和度的变化。
2.病人出现不能耐受的腹泻或皮肤不良反应时，暂停用药（最多14 天），随后恢复用药。
3.定期检查肝功能。
4.用清水洗脸，不用碱性肥皂等避免刺激皮肤，避免出现皮疹。
5.服用华法林病人，定期查凝血功能。
6.服药期间出现不可解释的气短、咳嗽，应及时进行影像学检查以排除急性间质性肺炎。
7.本品与其他化疗药物并用不能增加疗效。
GEFTINAT吉非替尼片剂说明书全文(中英对照翻译)
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。
易瑞沙(Gefitinib)中文说明书
最常见的药物不良反应（ADRs）为腹泻、皮疹、瘙痒、皮肤干燥和痤疮，发生率20%以上，一般见于服药后一个月内，通常是可逆性的。大约8%的患者出现严重的ADRs（CTC标准3或4级）。因ADRs停止治疗的患者仅有1%。
可出现的ADRs总结如下：
非常常见（>10%）消化系统：皮肤及附件：腹泻，主要为轻度（CTC1级），少有中度（CTC2级），个别报道严重腹泻伴脱水者（CTC3级）。恶心，主要为轻度（CTC1级）。皮肤反应，主要为轻或中度（CTCl或2级）多泡状突起的皮疹，在红斑的基础上有时伴皮肤干燥发痒。
常见（>1-≤10%）消化系统：代谢和营养：皮肤及附器：全身：眼科：呕吐，主要为轻度或中度（CTC1或2级）。厌食，轻或中度（CTCl或2级）。口腔粘膜炎，多数轻微（CTC1级）。继发于腹泻、恶心、呕吐或厌食引起的脱水。肝功能异常，主要包括无症状性轻或中度转氨
酶升高（CTCl或2级）。指甲毒性。脱发、乏力，多为轻度（CTC1级）结膜炎和睑炎，主要为轻度（CTC1级）。
不常见（>0.1-≤1%）血液和淋巴：眼科：呼吸：在服用华法令的一些患者中出现国际正常值（INR）升高及/或出血事件角膜糜烂，可逆，有时伴异常睫毛生长。间质性肺病，常较严重（CTC3-4）级，已有致死性病历的报道。
应告诫患者当以下情况加重时即刻就医：
"任何眼部症状
"严重或持续的腹泻、恶心、呕吐或厌食
这些症状应按临床需要进行处理（见可能出现的不良反应节）。
同时见妊娠和哺乳和对驾驶及操纵机器能力的影响节。
对驾驶及操纵机器能力的影响：
在治疗期间，可出现乏力的症状，这些患者在驾驶或操纵机器时应给与提醒。
药物说明书drins-吉非替尼-阿斯利康
妊娠期使用目前尚无本品用于妊娠期女性的资料。在器官发生期给予可产生母体毒性剂量的吉非替尼，在大鼠中可观察到成骨不全的发生率升高，在家兔中可观察到胎儿体重下降。在大鼠中未观察到畸型，仅在产生严重母体毒性的剂量下可在家兔中观察到畸型。在接受本品治疗期间，要劝告育龄女性避免妊娠。哺乳期使用在接受本品治疗期间，应建议哺乳母亲停止母乳喂养。目前尚无本品用于哺乳期女性的资料。尚不知吉非替尼或其代谢产物是否会分泌入人乳，但当给予哺乳大鼠口服5mg/kg吉非替尼 (按体表面积计为临床用药剂量的0.2倍) ，吉非替尼及某些代谢产物广泛分泌入乳汁。在大鼠妊娠及分娩期间给于吉非替尼20mg/kg/天 (按体表面积计为临床用药剂量的0.7倍) 的剂量，可减少幼鼠的存活率。
【毒理研究】
毒理学研究非临床 (体外) 研究资料表明吉非替尼具有抑制心脏动作电位复极化过程 (如QT间期) 的可能性。但由临床研究和上市后监测获得的安全性资料未提示吉非替尼对心脏有任何不良作用。致癌，致畸和生殖毒性在基因突变分析 (细菌和体外哺乳动物细胞) 和裂解试验 (体外哺乳动物细胞和体内大鼠微核试验) 中，吉非替尼未显示基因毒性作用。在交配前4周至妊娠7天期间给予吉非替尼20mg/kg/天 (按体表面积计为临床用药剂量的0.7倍) ，可对雌鼠排卵产生影响 ，导致黄体量下降。在器官发生期给予可产生母体毒性剂量的吉非替尼，在大鼠中可观察到成骨不全的发生率升高，在家兔中可观察到胎儿体重下降。在大鼠中未观察到畸型，仅在产生严重母体毒性的剂量下可在家兔中观察到畸型。当给予哺乳大鼠口服5mg/kg吉非替尼 (按体表面积计为临床用药剂量的0.2倍) ，吉非替尼及某些代谢产物广泛分泌入乳汁。在大鼠妊娠及分娩期间给于吉非替尼20mg/kg/天 (按体表面积计为临床用药剂量的0.7倍) 的剂量，可减少幼鼠的存活率。一个对大鼠为期2年的致癌性研究，在最高剂量时 (10mg/kg/日) ，在雄性和雌性大鼠中肝细胞腺瘤以及只在雌性大鼠中肠系膜淋巴结血管肉瘤的发生率有轻微增高，但具有统计学意义的升高。在另一个对小鼠为期2年的致癌性研究中也观察到了肝细胞腺瘤，显示了在剂量为50mg/kg/日时，雄性小鼠的发生率以及在最高剂量为90mg/kg/日时 (自第22周开始由125mg/kg/日减低至此剂量) ，雌性和雄性小鼠的发生率均有轻微升高。其中雌性小鼠的结果具有统计学显著性，雄性则无。尚不了解这些发现的临床相关性。
易瑞沙药监局批准完整处方信息
易瑞沙薄膜衣片[Iressa®]易瑞沙药监局批准的完整处方信息MIMS药理分类: 靶向治疗药物( Targeted Cancer Therapy )眼科：常见结膜炎和睑炎，主要为轻度(CTC1级) ；弱视。
少见可逆性角膜糜烂，有时伴睫毛生长异常。
极罕见角膜脱落；眼部缺血/出血。
血液和淋巴：常见出血，如鼻衄和血尿。
少见在服用华法林的一些患者中出现INR(International Normalised Ratio)升高及/或出血事件；出血性膀胱炎。
呼吸：常见呼吸困难。
少见间质性肺病，常较严重(CTC3-4级。
在全球进行的临床研究，扩大用药/同情用药，上市后使用中，约有158348名患者接受了本品治疗，在日本以外的地区，包括约92821名患者，间质性肺病总的发生率约为0.28％，在日本其发生率约为1.70％，包括约65527名患者，数据截至2004年6月2日)，已有致死性病例的报道。
药物相互作用对人肝微粒体进行的体外试验证实，吉非替尼主要通过肝细胞色素P-450系的CYP 3A4代谢。
所以吉非替尼可能会与诱导、抑制或为同一肝酶代谢的药物发生相互作用。
动物研究表明吉非替尼很少有酶诱导作用，体外研究显示吉非替尼可有限地抑制CYP 2D6。
以下列出了与吉非替尼产生或可能产生有临床意义地药物相互作用地药物或药物类别：影响吉非替尼的药物：已证明的相互作用- 抑制CYP3A4的药物：在健康志愿者中将吉非替尼与伊曲康唑(一种CYP 3A4抑制剂)合用，吉非替尼的平均AUC升高80％。
由于药物不良反应与剂量及暴露量相关，该升高可能有临床意义。
虽然未进行与其他CYP 3A4抑制剂相互作用的研究，但这一类药物如酮康唑，克霉唑，利托那韦同样可能抑制吉非替尼的代谢。
升高胃pH值的药物：在健康志愿者中进行临床研究，表明与能明显持续升高胃pH至≥5的药物合用，可使吉非替尼的平均AUC降低47％，这可能降低吉非替尼疗效。
GEFTINAT吉非替尼片剂说明书全文(中英对照翻译)
Renal Impairment: No clinical studies were conducted with Gefitinib in patients with severely compromised renal function (see PRECAUTIONS section). Gefitinib and its metabolites are not significantly excreted via the kidney(<4%).
肺癌一代靶向药吉非替尼片中文说明书
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。
易瑞沙产品介绍
LC-1012-IR-0085 有效期至2011年12月31日
内 容
产品概述
作用机制 药代动力学
处方信息
适应症 禁忌症
用法用量
包装
关键临床研究结果
易瑞沙的研发历程
1975年 1984年 1988年 1990年 1998年 2002年 阿斯利康科学家Harry Gregory分离出人体表皮生长因子 表皮生长因子受体(EGFR)结构被确认 阻断表皮生长因子酪氨酸激酶的可能分子被确定 发现了一组EGFR-TKI,其中包括易瑞沙 易瑞沙开始一期临床研究 易瑞沙在日本全球首度上市
荟萃分析是循证医学级别最高、最可信的证据
2009年ASCO/WCLC：首度报告全球首个EGFR-TKI 直接对照标准二线化疗的患者个体数据的荟萃分析， 包括全组和亚裔患者的结果
易瑞沙对照多西他赛治疗复治的 晚期NSCLC患者：来自四项临床研究的荟萃分析
Comparison of Gefitinib and Docetaxel in patients with pretreated advanced NSCLC: Meta-Analysis from four clinical trials
EGFR [表皮生长因子受体] 在多种恶性肿瘤中有表达，在肺癌 中的表达率为40%-84% EGFR的表达与肿瘤进展、低生存率、对治疗的低反应率以及细 胞毒性药物耐药性的产生相关 阻断EGFR可抑制肿瘤生长 易瑞沙可以通过抑制EGFR的酪氨酸激酶，阻断细胞信号的传导 ，带来抑制肿瘤生长、促进肿瘤细胞凋亡的作用。
观察到接受本品治疗的患者发生间质性肺病，可急性发作，有死亡病例报告。如 果患者呼吸道症状恶化，如呼吸困难，咳嗽，发热，应中断本品治疗，立即进行 检查。当证实有间质性肺病时，应停止使用本品，并对患者进行相应的治疗。
吉非替尼 Gefitinib说明书
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“250”，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(易瑞沙)用药手册
如果您的症状和疾病不好转或加重，请咨询您的医生。 严禁将您的药物分享给他人或服用他人的药物 建议将您在服用的所有药物（包括保健品）列一张清单，看病时给医生作参考 如果您要服用任何药品和保健品，请先咨询您的医生
说明：本文由康安途博士团队整理发布，仅供参考。
吉非替尼（易瑞沙）用药手册
商品名：易瑞沙 英文名：Geftinat
用药前需要告知医生：
您是否有对吉非替尼过敏，或者其他的药物过敏。如果有药物过敏，症状如何（皮疹， 风团，瘙痒，呼吸困难，咳嗽，眼睛或面部水肿，喉头水肿，休克等）
该药可能会与其他药物产生相互作用，请务必告知您的医生和康安途博士您在服用的所 有药物（处方药或非处方药，保健品，维生素等）和所有疾病史（高血压，糖尿病，心脏病 等）。医生要综合评估您是否适合服用该药物。任何情况下，绝对不能在未咨询医生的情况 下擅自开始服药、停止用药或更改药物剂量。
服用吉非替尼期间需要注意什么？
1、请在服药期间就诊时告知您的医生或护士您在服用吉非替尼 2、请遵医嘱定期复查血液指标，并咨询检查结果。 3、很少见的情况下，可能会出现消化道穿孔。 4、该药物可能会导致不孕，请咨询医生。 5、如果您怀孕，该药物可能会影响胎儿健康。 6、服药期间请采取避孕措施，直到停药 2 周后。 7、如果您怀孕或计划怀孕，请咨询医生有关怀孕期间注意事项。 8、如果您在母乳喂养，也请咨询医生相关风险。
这个药物有什么其他副作用？
所有的药物都可能有副作用，然而很多患者不会经历副作用或者只有轻微副作用。如果它们 引起您的顾忌或长时间不减轻，请咨询您的医生或就诊。 呕吐
腹泻 眼睛刺激 皮肤瘙痒 无饥饿感 指甲改变 粉刺 眼睛干涩 皮肤干燥
这个药物怎么服用？
1、坚持遵医嘱服药，勿私自改变剂量。 2、为保证最优药效，请勿漏服药物。 3、空腹或和食物一起服用皆可。 4、如果药片难以吞服，您可以将药物放入 120ml-240ml 水中，搅拌 15 分钟后喝药，再倒 120ml-240ml 水在同一个杯子中，将可能残余在杯壁的药物喝掉。 5、如果您在服用抑制胃酸的药物（西米替丁，埃索美拉唑，右兰索拉唑，法莫替丁，兰索 拉唑，尼扎替丁，奥美拉唑，泮托拉唑，雷贝拉唑，雷尼替丁），请咨询医生您该如何服用 吉非替尼。
吉非替尼片说明书
核准日期：吉非替尼片说明书请仔细阅读说明书并在医师指导下使用。
【药品名称】通用名称：吉非替尼片英文名称：Gefitinib Tablets汉语拼音：Jifeitini Pian【成份】本品主要成份为吉非替尼。
化学名称：N-(3-氯-4-氟苯基)-7-甲氧基-6-(3-吗啉丙氧基)喹唑啉-4-胺化学结构式：分子式：C22H24ClFN4O3分子量：446.90【性状】褐色薄膜衣片，除去包衣后显白色或类白色。
【适应症】本品单药适用于表皮生长因子受体(EGFR)基因具有敏感突变的局部晚期或转移性非小细胞肺癌(NSCLC)患者的一线治疗(见【注意事项】)。
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非小细胞肺癌(NSCLC)未显示出临床获益，所以不推荐此类联合方案作为一线治疗。
本品单药可试用于治疗既往接受过至少一次化学治疗失败的局部晚期或转移性非小细胞肺癌(NSCLC)。
不推荐本品用于EGFR野生型非小细胞肺癌患者。
【规格】0.25g。
【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。
如果漏服本品一次，应在患者记起后尽快服用。
如果距离下次服药时间不足12小时，则患者不应再服用漏服的药物。
患者不可为了弥补漏服的剂量而服用加倍的剂量(一次服用两倍剂量)。
当不能整个片剂给药时，例如患者只能吞咽液体，可将片剂分散于水中。
片剂应分散于半杯饮用水中(非碳酸饮料)无需压碎，搅拌至完全分散(约需15分钟)，即刻饮下药液。
以半杯水冲洗杯子，饮下洗液。
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。
易瑞沙简介中英文版
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，抑制肿瘤细胞的增殖，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，尤其对肺腺癌疗效确切，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。
Iressa ( gefitinib ) is a novel small molecular weight drugs for the treatment of cancer, its mechanism is mainly through the inhibition of EGFR phosphorylation and block the conduction, inhibit the proliferation of tumor cells, for targeted therapy. Clinical mainly for the treatment of previously received chemotherapy for locally advanced or metastatic non-small cell lung cancer, especially the effect of the exact curative effect on lung adenocarcinoma, squamous cell carcinoma than in adenocarcinoma and bronchioloalveolar carcinoma is low, but a large number of clinical data show that : the Yi Rui sand according to the actual situation of patients with lung cancer ( than gefitinib ) after treatment, there are still some lung squamous cell carcinoma and other non small cell lung cancer patients with obvious effect, and has good tolerance.。
药物说明书
易瑞莎（GEFTINAT）成分每片薄膜片剂含有：吉非替尼250毫克描述吉非替那（吉非替尼药片）含有250毫克吉非替，是一种红棕色薄膜药片，药片一面印有GEFITINAT，另一面印有250.，适用于每日口服。
吉非替尼的分子式为C22H24C1F4O3，相对分子质量为446.9，是一种白色药片。
吉非替尼是一个自由成分。
临床药理学行动机制：吉非替尼的临床抗肿瘤作用机制没有充分表征。
吉非替尼阻止大量酪氨酸激酶的细胞内磷酸化，这些酪氨酸激酶与跨膜细胞表面受体相联系，包含与表皮生长因子受体有关的酪氨酸激酶（EGFRTK）。
EGFR授体分布和对吉非替尼反应的关联性还未得到临床实验验证。
药代动力学：吉非替尼口服后消化很慢，生物利用率只有60%，最终将以粪便形式经新陈代谢（主要是CYP3A4）和分泌方式排出。
排除半衰期大约是48小时。
对于癌症病人来说，每日口服吉非替尼会造成单一剂量服用两倍的药物蓄积量，并在10日内形成稳态血药浓度。
吸收和分配：吉非替尼吸收很慢，最高血浆值将在剂量和口服平均生物利用率达到60%之后3-7小时出现。
生物利用率不会因食物而得到显著改善。
药剂进入静脉后，吉非替尼将以1400L的稳定分布量广泛分布到全身。
人类血浆蛋白（血清白蛋白和a1-酸糖蛋白）的结合反应是90%，而这与药物浓度无关。
新陈代谢和排泄：吉非替尼在人体中会经历广泛的肝脏新陈代谢，主要通过CYP3A4进行。
生物转化的3个部位已确定：N-丙氧基-吗啉代-群，甲氧基反甲基化-喹唑啉取代基和卤代苯基氧化脱氟群。
在人类血液中已发现5个代谢物。
只有去甲萘普生吉非替尼的显露可与吉非替尼相比。
在细胞分析实验中，尽管这个代谢物在独立的酵检验中和吉非替尼有相似的EGFK-TK活动，它只有吉非替尼能力的1/14。
吉非替尼主要由肝脏清除，以总血浆清除和半衰期清除量595ML/分和48小时的速度分别在静脉注射后进行。
分泌主要是通过粪便（86%）清除，同时还有药物的肾清除和新陈代谢清除不足4%的药物服用量。
Iressa(gefitinib) 使用说明书2015版
ADVERSE REACT IONS The most commonly reported adverse drug reactions (ADRs), reported in more than 20% of the patients and greater than placebo were skin reactions and diarrhea. (6.1) T o repo rt SUSPECT ED ADVERSE REACT IONS, co ntact AstraZeneca at 1-8 0 0 -236 -9 9 33 o r FDA at 1-8 0 0 -FDA10 8 8 o r /medwatch.
FULL PRESCRIBING INFORMAT ION: CONT ENT S* 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION
2.1 Patient Selection 2.2 Recommended Dose 2.3 Administration to Patients Who Have Difficulty Swallowing Solids 2.4 Dose Modification 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Interstitial Lung Disease (ILD) 5.2 Hepatotoxicity 5.3 Gastrointestinal Perforation 5.4 Severe or Persistent Diarrhea 5.5 Ocular Disorders including Keratitis 5.6 Bullous and Exfoliative Skin Disorders 5.7 Embryo-fetal Toxicity 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience 6.3 Postmarketing Experience 7 DRUG INTERACTIONS 7.1 Drugs Affecting Gefitinib Exposure 7.2 Hemorrhage in Patients taking Warfarin 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.2 Lactation 8.3 Females and Males of Reproductive Potential 8.4 Pediatric Use 8.5 Geriatric Use 8.6 Renal Impairment 8.7 Hepatic Impairment 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 14 CLINICAL STUDIES 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION
吉非替尼片说明书
吉非替尼片说明书通用名：吉非替尼片生产厂家: 齐鲁制药海南有限公司批准文号：国药准字H20213465药品规格：0.25g*10片药品价格：￥1680元【商品名称】伊瑞可吉非替尼片【通用名称】吉非替尼片【英文名】Gefitinib Tablets【汉语拼音】JiFeiTiNiPian【主要成分】吉非替尼。
【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】C22H24ClFN4O3【分子量】446.90【性状】本药为褐色圆形薄膜衣片;一面印有"IRESSA250"。
【适应症】本品单药适合用于表皮生长因子受体GEFR基因具有敏感突变的局部晚期或转移性非小细胞肺癌NSCLC患者的一线治疗以及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。
详见说明书。
【用法用量】本品的成人推荐剂量为250mg1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。
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。
【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。
临床研究两项大型的II期临床研究评估了本品单药治疗局部晚期或转移性非小细胞肺癌NSCLC的有效性和安全性。
各种靶向药--易瑞沙
吉非替尼吉非替尼，又名易瑞沙，是一种选择性表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，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）。
外文名Iressa中文别名易瑞沙中文名吉非替尼分子式C22H24ClFN4O3 适用症非小细胞肺癌英文别名GEFITINIB1 基本介绍编辑中文名称：吉非替尼中文别名：N-(3-氯-4-氟苯基)-7-甲氧基-6-(3-吗啉-4-丙氧基)喹唑啉-4-胺;易瑞沙(阿斯利康公司的抗肿瘤新药);吉非替尼(易瑞沙)英文名称：Iressa英文别名：GEFITINIB; AKOS 91371; n-(3-chloro-4-fluoro-phenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine;N-(3-Chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-4-quinazolinamine; ZD 1839; 4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-; Gefitinib(TINIBS); Gefitinib, Iressa, ZD1839; Gefitinib BaseCAS号：184475-35-2分子式：C22H24ClFN4O3分子量：446.90242 药物性状编辑褐色，圆形，双凸面，薄膜衣片；一面印有"IRESSA 250"，另一面光滑。
每瓶含吉非替尼250mg*30s。
3 用法用量编辑推荐剂量为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。
不需要因患者的年龄，体重，性别或肾功能状况以及对因肿瘤肝脏转移引起的中度或重度肝功能不全的患者进行剂量调整。
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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。
仿制药是指与商品名药在剂量、安全性和效力（不管如何服用）、质量、作用以及适应症上相同的一种仿制品。
目前中国厂商生产销售的西药有95%以上都属于仿制药，自行研发的专利药很少。
由于中国法律的保护，国内厂商短期内不会被批准仿制生产易瑞沙。
印度是世界著名的仿制药生产大国，印度法律未对阿斯利康易瑞沙实行专利保护，现在已经有不少于6家的印度药厂已经被政府批准仿制生产易瑞沙。
2005年,NACTO公司成为首家被政府批准生产易瑞沙仿制药的企业。
2007年Glenmark被印度政府批准生产易瑞沙。
Glenmark公司曾被评为世界最佳制药公司的殊荣，生产的易瑞沙（GEFTIB）以精良的包装和严谨的制药工艺受到赞誉。
NATCO生产的易瑞沙(GEFTINAT)最早被中国人熟知并让无数低薪家庭的患者受益。
但是2007年开始国内就出现大量模仿NACTO易瑞沙包装，私下采购工业原料药生产的假易瑞沙。
制假者在模仿包装上大下功夫，甚至将假药寄往印度再寄回，以获取患者信任。
中国法律是不允许印度易瑞沙进口的，所有在售印度产易瑞沙都是通过私下途径进入，不允许任何药店合法销售，NACTO公司在中国没有任何的所谓总代理、驻华机构。
【服用方法】本品的推荐剂量为250 mg(1片)，1日1次，口服，空腹或与食物同服。
如果漏服本品1次，应在患者记起后尽快服用。
如果距离下次服药时间不足12小时，则患者不应再服用漏服的药物。
患者不可为了弥补漏服的剂量而服用加倍的剂量(1次服用2倍剂量)。
当不能整个片剂给药时，例如患者只能吞咽液体，可将片剂分散于水中。
片剂应分散于半杯饮用水中(非碳酸饮料)无需压碎，搅拌至完全分散(约需15分钟)，即刻饮下药液。
以半杯水冲洗杯子，饮下洗液。
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。
如需加量服用，请咨询专业人士确定。
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。
【副作用】最常见（发生率20%以上）的药物不良反应为腹泻和皮肤反应（包括皮疹、痤疮、皮肤干燥和瘙痒），一般见于服药后的第1个月内（少数人可能服药数月后才会出现），通常是可逆性的。
大约10%的患者出现严重的药物不良反应（通用毒性评价标准(CTC)3或4级）。
因不良反应停止治疗的患者有约3%。
下面列出了相关不良反应发生频率的分类，这类数据来自III期临床试验ISEL、INTEREST和IPASS的汇总数据集（2462例吉非替尼治疗的患者）。
频率的分类没有考虑对照组报告的事件率，或研究者判断是否与试验药物相关。
与实验室检查异常相关的不良反应的发生率，是基于相关的化验指标与基线相比变化程度达到或超过2个CTC级别的患者。
各身体系统发生的不良事件按发生频率以降序排列（十分常见 ：≥10％ ；常见 ：≥1％且<10% ；偶见 ：≥0.1％且<1％ ；罕见 ：≥0.01％且<0.1％ ；极罕见 ：<0.01％）。
可能出现的不良反应归纳如下：很常见（＞10%）皮疹、脱发、手足皮肤反应、瘙痒腹泻、恶心、呕吐乏力、疼痛（包括口痛、腹痛、骨痛、头痛和癌痛）、红斑出血（包括为肠道出血、呼吸道出血及脑出血）、高血压、淋巴细胞减少淀粉酶升高、脂肪酶升高常见（＞1%～≤10%）皮肤干燥、剥脱性皮炎、痤疮、脱屑厌食、体重减轻、转氨酶短暂瞬间升高便秘、口腔炎（包括口干和舌痛）、消化不良、吞咽困难白细胞减少、中性粒细胞减少、贫血、血小板减少虚弱、发热、流行性感冒症状勃起机能障碍关节痛、肌痛、外周感觉神经病变声嘶、耳鸣 抑郁不常见（＞0.1%—≤1%）胃食管返流、胰腺炎、胃炎、胃肠穿孔鼻溢、高血压危象、心肌缺血和心肌梗死、充血性心力衰竭、低磷血症、低钠血症、脱水可逆性后脑部白质病甲状腺机能减退超敏反应（包括皮肤反应和荨麻疹）、毛囊炎、感染、湿疹、多形性红斑、角化棘皮瘤/皮肤鳞状上皮细胞癌碱性磷酸酶短暂性升高、胆红素升高和黄疸男性乳房发育【药理作用】吉非替尼由美国哈佛大学医学院最先研究，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。
表皮生长因子受体(EGFR)的活性或过度表达与一系列上皮来源的肿瘤有关。
EGFR活化可引起肿瘤形成中的细胞增殖/成熟、化疗/放疗抵抗、存活/(抗凋亡)、血管生成、肿瘤转移。
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，抑制EGFR酪氨酸激酶的活性可以抑制肿瘤生长，转移和血管生成，并加速肿瘤细胞的凋亡。
肿瘤EGFR突变情况是吉非替尼抗肿瘤活性的预测因素。
安全性吉非替尼的总体耐受性良好。
大部分不良事件为轻度，无需处理。
超过10%的受试者报告的不良事件为皮疹（44.0%）、皮肤瘙痒（15.7%）和腹泻（11.3%）。
所出现的不良事件严重程度及发生频率与在其他临床研究中观察到的相一致。
【注意事项】本品用于晚期或转移性NSCLC患者的一线治疗时，如果患者服用英国阿斯利康产的易瑞沙，推荐对患者的肿瘤组织进行EGFR突变检测。
在评价患者的突变状态时，需要选择经过良好验证的可靠的方法，以尽量减少假阴性或假阳性结果的可能。
基因检测并非必须，如果服用印度产易瑞沙，建议直接服用。
非吸烟、组织学类型为肺癌、女性或亚裔更可能从本品的治疗中获益。
这类临床特点和较高的肿瘤EGFR突变阳性率相关。
观察到接受本品治疗的患者发生间质性肺病，可急性发作，有死亡病例报告。
如果患者呼吸道症状恶化，如呼吸困难，咳嗽，发热，应中断本品治疗，立即进行检查。
当证实有间质性肺病时，应停止使用本品，并对患者进行相应的治疗。
一项在日本进行的流行病学病例对照研究中，对接受本品或化疗的3159名非小细胞肺癌患者进行为期12周的随访，确定了以下出现间质性肺病的高风险因素(不考虑患者接受的本品还是化疗) ：吸烟，较差的体力状态，在CT 扫描上正常肺组织覆盖范围≤50%，距离非小细胞肺癌诊断时间较短(<6个月)，原有间质性肺炎，年龄较大（≥55岁），伴有心脏疾病。
两个治疗组中发展为间质性肺病的患者，如具有以下危险因素则死亡率增加 ：吸烟、在CT 扫描上正常肺组织减少≤50%、原有间质性肺炎、年龄较大(≥65岁)，病灶与胸膜粘连(≥50%)。
已观察到肝功能检查异常(包括丙氨酸转氨酶升高，天冬氨酸转氨酶升高，胆红素升高)，偶见有表现为肝炎。
已有肝衰竭的个例报告，其中某些是致死性病例。
因此，建议定期检查肝功能。
肝转氨酶轻中度升高的患者应慎用本品。
如果肝转氨酶升高加重，应考虑停药。
在本品的临床试验中有脑血管事件的报告，但与本品的关系未确定。
诱导CYP 3A4活性增加的物质可增加本品的代谢，降低本品的血浆浓度。
因此当本品与CYP 3A4诱导剂(如苯妥英、卡马西平、利福平、巴比妥盐类或圣约翰草)联合使用时，可能降低本品疗效。
已报道在服用华法林的一些患者中出现INR（International Normalised Ratio，国际标准化比率）升高及/或出血事件。
服用华法林的患者应定期监测凝血酶原时间或INR的改变。
能显著而持续升高胃pH的药物，可能降低吉非替尼的平均血浆浓度从而可能降低吉非替尼疗效。
应告诫患者当以下情况加重时即刻就医 ：任何眼部症状 ；严重或持续的腹泻、恶心、呕吐或厌食。
这些症状应按临床需要进行处理。
随机对照试验证明，在晚期非小细胞肺癌患者中将本品和以铂类为基础的标准两药联合化疗方案合用，不会有额外的益处。
在一项对儿科患者进行本品和放疗治疗的I/II期临床研究中，45名入选患者(这些患者为新诊断出脑干神经胶质瘤或未完全切除的幕上恶性神经胶质瘤)中，发生4例(1例死亡)中枢神经系统出血。
在一项单用本品治疗的临床研究中，1位患有室管膜瘤的儿童也出现了中枢神经系统出血。
没有证据证明接受本品治疗的成年NSCLC患者的脑出血风险增高。
在II期临床研究中，将本品与长春瑞滨同时使用，显示本品可能会加剧长春瑞滨引起的中性粒细胞减少的作用。
有消化道穿孔的个例报道，涉及的患者本身包含相关风险因素(如，同时服用类固醇药物、非甾体类抗炎药；消化道基础疾病、溃疡、年龄、吸烟史、穿孔部位的肠道转移肿瘤)。
但是与吉非替尼的因果关系尚未建立。
对驾驶及操纵机器能力的影响 ：在本品治疗期间，可出现虚弱的症状，出现这些症状的患者在驾驶或操纵机器时应给予提醒。
附1：易瑞沙（吉非替尼）的临床试验结果一、易瑞沙延长肺癌患者生存期的国际多中心临床试验研究（ISEL）研究设计是Ⅲ期生存期研究，在以前接受过1～2个化疗方案失败或不能耐受的晚期非小细胞肺癌病人中，比较易瑞沙250毫克加最佳支持治疗与安慰剂加最佳支持治疗。