【正文】 r any other components of the product. EMEND，when administered orally，is a moderate cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitor. Because fosaprepitant is rapidly converted to aprepitant，neither drug should be used concurrently with pimozide，terfenadine，astemizole，or cisapride. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these drugs，potentially causing serious or lifethreatening reactions.,Contraindications,Align with local label,第一百零三頁，共一百一十三頁。,EMEND? (aprepitant)，a dosedependent inhibitor of CYP3A4，should be used with caution in patients receiving concomitant orally administered medicinal products (including chemotherapy agents) that are primarily metabolized through CYP3A4. Moderate inhibition of CYP3A4 by aprepitant，125 mg/80 mg regimen，could result in elevated plasma concentrations of these concomitant orally administered medicinal products. The effect of EMEND on the pharmacokinetics of orally administered CYP3A4 substrates is greater than the effect of EMEND on the pharmacokinetics of intravenously administered CYP3A4 substrates. Because fosaprepitant is rapidly converted to aprepitant，fosaprepitant should be used with caution in patients receiving concomitant orally administered medicinal products that are primarily metabolized through CYP3A4.,Selected Important Safety Information,Align with local label,第一百零四頁，共一百一十三頁。,Coadministration of EMEND? (aprepitant) with warfarin may result in a clinically significant decrease in international normalized ratio (INR) of prothrombin time. In patients on chronic warfarin therapy，the INR should be closely monitored in the 2week period，particularly at 7 to 10 days，following initiation of the 3day regimen of EMEND with each chemotherapy cycle. The efficacy of hormonal contraceptives may be reduced during coadministration with EMEND and for 28 days after the last dose of EMEND. Alternative or backup methods of contraception should be used during treatment with EMEND and for 1 month after the last dose of EMEND.,Selected Important Safety Information (continued),Align with local label,第一百零五頁，共一百一十三頁。,In clinical trials of EMEND? (aprepitant)，the most common adverse events reported at a frequency greater than with standard therapy in patients receiving highly emetogenic chemotherapy were hiccups (4.6%)，asthenia/fatigue (2.9%)，increased ALT (2.8%)，constipation (2.2%)，headache (2.2%)，and anorexia (2.0%). In clinical trials of EMEND，the most common adverse event reported at a frequency greater than with standard therapy in patients receiving moderately emetogenic chemotherapy was fatigue (1.4%). The most frequent drugrelated clinical adverse events reported in patients receiving IVEMEND? (fosaprepitant dimeglumine) were infusion site pain，headache，and infusion site induration.,Selected Important Safety Information (continued),Align with local label,第一百零六頁，共一百一十三頁。,EMEND? (aprepitant) should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4. Inhibition of CYP3A4 by EMEND could result in elevated plasma concentrations of these concomitant medications. Conversely，when EMEND is used concomitantly with another CYP3A4 inhibitor，aprepitant plasma concentrations could be elevated. In clinical studies，EMEND 125 mg/80 mg was administered commonly with etoposide，vinorelbine，docetaxel，or paclitaxel. The doses of these agents were not adjusted to account for potential drug interactions. In separate pharmacokinetic studies，EMEND 125 mg/80 mg did not influence the pharmacokinetics of docetaxel or vinorelbine.,Selected Important Safety Information (continued),Align with local label,第一百零七頁，共一百一十三頁。,There have been isolated reports of immediate hypersensitivity reactions including flushing，erythema，and dyspnea during infusion of fosaprepitant. These reactions have generally receded when the infusion was stopped and appropriate therapy was provided. It is not recommended to reinitiate the infusion in patients who have these reactions.,Selected Important Safety Information (continued),Align with local label,第一百零八頁，共一百一十三頁。,EMEND? (aprepitant) is given for 3 days as part of a regimen that includes a corticosteroid and a 5HT3 receptor antagonist. The recommended dosage includes EMEND (125 mg) on Day 1 followed by EMEND (80 mg) once daily on Days 2 and 3.,Dosage (continued),Align with local label,第一百零九頁，共一百一十三頁。,In clinical trials，EMEND? (aprepitant) increased the AUC of dexamethasone，a CYP3A4 substrate，by 2.2fold on Days 1 and 5。 therefore，the dexamethasone dose administered in the regimen with EMEND should be reduced by approximately 50% to achieve exposures of dexamethasone similar to those obtained without EMEND. See DRUG INTERACTIONS，Effect of aprepitant on the pharmacokinetics of other agents，Corticosteroids，in the Prescribing Information for additional information on dosage adjustment for methylprednisolone when coadministered with EMEND.,Dosage (continued),Align with local label,第一百一十頁，共一百一十三頁。,In clinical drug interaction studies，EMEND? (aprepitant) did not have clinically important effects on the pharmacokinetics of ondansetron，granisetron，or hydrodolasetron (the active metabolite of dolasetron). Caution: IVEMEND? (fosaprepitant dimeglumine) should not be mixed or reconstituted with solutions for which physical and chemical compatibility have not been established. IVEMEND is incompatible with any solutions containing divalent cations (eg，Ca2+，Mg2+)，including Lactated Ringer’s Solution and Hartmann’s Solution.,Dosage (continued),Align with local label,第一百一十一頁，共一百一十三頁。,處方EMEND? (阿瑞吡坦) 或 IVEMEND? (福沙吡坦二甲葡胺注射劑)之前，請(qǐng)查閱區(qū)域性產(chǎn)品說明書，而不是(b249。 shi)全球性產(chǎn)品指南。,Copyright 169。 2011 Merck Sharp amp。 Dohme Corp.，a subsidiary of Merck amp。 Co.，Inc.，Whitehouse Station，NJ，USA. All rights reserved. ONCO10065810000 08/11,與區(qū)域(qūy249。)說明書一致,第一百一十二頁，共一百一十三頁。,內(nèi)容(n232。ir243。ng)總結(jié),1。CINV的危險(xiǎn)因素:化療特異性因素。CINV: 不同時(shí)間不同神經(jīng)遞質(zhì)的參與1。與區(qū)域說明書一致。阿瑞吡坦治療組中報(bào)告惡心和嘔吐對(duì)日常生活影響極小(j237。 xiǎo)或無影響的患者比例高于活性對(duì)照組。a 由研究者評(píng)定為可能、很可能或肯定和研究藥物有關(guān)。在單組研究中，阿瑞吡坦+帕洛諾司瓊+地塞米松聯(lián)合療法對(duì)高和中致吐性化療均有效。不同病理生理機(jī)制產(chǎn)生不同的CINV階段。5HT3受體拮抗劑對(duì)急性嘔吐有效，對(duì)遲發(fā)性事件的療效不穩(wěn)定,第一百一十三頁，共一百一十三頁