齊多拉米雙夫定片說明書

FortheuseofaRegisteredMedicalPractitioneroraHospitaloraLaboratoryonly僅供注冊醫(yī)生、醫(yī)院、試驗(yàn)室使用Lamivudine,ZidovudineandNevirapineTabletsIP拉米夫定，齊多夫定和奈韋拉平片〔印度藥典級(jí)〕商品名〕Warning警告Duovir-Nisnotintendedforuseinpatientswhoarejustinitiatingtherapywithnevirapine.Duovir-NshouldbeadministeredonlytopatientswhohavereceivedZidovudine+Lamivudine(standarddoses)+Nevirapine(200mgOD)for2weeksandhavedemonstratedadequatetolerabilitytoNevirapine(seeIndications,DosageandAdministration).Duovir-N不適合那些剛開頭使用奈韋拉平治療的患者，Duovir-N只應(yīng)施用于那些已經(jīng)承受齊多夫定+拉米夫定〔標(biāo)準(zhǔn)劑量〕+奈韋拉平〔200毫克，每天一次〕2周，并證明對奈韋拉平具有足夠耐受性的患者〔見適應(yīng)癥、劑量和服用。ZidovudinehasbeenassociatedwithhaematologictoxicityincludingNeutropeniaandsevereanaemia.Particularlyinpatientswithadvanceddisease(seeWarningsandPrecautions).ProlongeduseofZidovudinehasbeenassociatedwithsymptomaticmyopathy.齊多夫定與血液學(xué)毒性相關(guān)，包括中性粒細(xì)胞削減和嚴(yán)峻貧血，特別是長期使用齊多夫定，始終伴隨病癥肌病的晚期患者〔見警告和留意事項(xiàng)。Severe,life-threateningskinreactions,includingfatalcases,haveoccurredinpatientstreatedwithNevirapine.ThesehaveincludedcasesofStevens-Johnsonsyndrome.Toxicepidermalnecrolysis,andhypersensitivityreactionscharacterisedbyrash,constitutionalfindingsandorgandysfunction.PatientsdevelopingsignsorsymptomsofsevereskinreactionsorhypersensitivityreactionsmustdiscontinueNevirapineassoonaspossible(seeWarningsandPrecautions).史蒂文斯-約翰遜綜合征(即：重癥多形性紅斑)病例、中毒性表皮壞死、和過敏性反響，,消滅嚴(yán)峻的皮膚反響、或過敏反響病癥或體征的患者，必需盡快停頓使用奈韋拉平〔見警告和留意事項(xiàng)。Severe, life-threatening, and in some cases fatal hepatotoxicity,including fulminant andcholestatichepatitis,hepaticnecrosisandhepaticfailurehasbeenreportedinpatientstreatedwithNevirapine.Insomecases,patientspresentedwithnon-specificprodromalsignsorsymptomsofhepatitisandprogressedtohepaticfailure.Theseeventsareoftenassociatedwithrash.WomenandpatientswithhigherCD4counts,areatincreasedriskofthesehepaticevents.WomenwithCD4counts>250cells/mm3,includingpregnantwomenreceivingchronictreatmentforHIVinfection,areatconsiderablyhigherriskoftheseevents.PatientswithsignsorsymptomsofhepatitismustdiscontinueNevirapineandseekmedicalevaluationimmediately(seeWarningsandPrecautions).已有報(bào)道，使用奈韋拉平治療的患者，消滅嚴(yán)峻、危及生命，而且在某些狀況下，呈現(xiàn)致命的肝毒性，包括：爆發(fā)性和膽汁淤積性肝炎、肝壞死和肝功能衰竭。在某些狀況下，患者伴有肝炎非特異性體征或病癥,并進(jìn)展為肝功能衰竭，這些病癥往往伴隨皮疹，女性和CD4CD4細(xì)胞計(jì)數(shù)>250cells〔細(xì)胞〕/mm3的女性，包括正在承受艾滋病毒感染〔HIV〕長期治療的孕婦，這些病癥有相當(dāng)高的風(fēng)險(xiǎn)，消滅肝炎病癥或體征的患者，必需停頓使用奈韋拉平，并馬上尋求醫(yī)療評估〔見警告和留意事項(xiàng)。Itisessentialthatpatientsbemonitoredintensivelyduringthefirst18weeksoftherapywithNevirapinetodetectpotentiallylife-threateninghepatotoxicityorskinreactions.Thegreatestriskofsevererashorhepaticevents(oftenassociatedwithrash)occursinthefirst6weeksoftherapy.However,theriskofanyhepaticevent,withorwithoutrash,continuespastthisperiodandmonitoringshouldcontinueatfrequentintervals.Insomecases,hepaticinjuryhasprogresseddespitediscontinuationoftreatment.Nevirapineshouldnotberestartedfollowingseverehepatic,skinorhypersensitivityreactions.Inaddition,the14-daylead-inperiodwithNevirapine200mgdailydosingmustbestrictlyfollowed(seeWarningsandPrecautions).18周期間，加強(qiáng)對患者進(jìn)展監(jiān)測，以檢測潛在的/肝衰竭(常伴隨皮疹)發(fā)生在治療的初始6周，然而，任何肝炎/肝衰竭的風(fēng)險(xiǎn)，伴有或不伴皮疹，在這段期間過去后，仍應(yīng)以繁頻的間隔，連續(xù)監(jiān)測，在某些狀況下，盡管治療停藥，肝臟損傷會(huì)有進(jìn)展，伴隨嚴(yán)峻200毫克/14天的導(dǎo)入期〔見警告和留意事項(xiàng)。Lacticacidosisandseverehepatomegalywithsteatosis,includingfatalcases,havebeenreportedwiththeuseofNucleosideanaloguesaloneorincombination,includingLamivudine,Zidovudineandotherantiretrovirals(seeWarningsandPrecautionssection).已有報(bào)道稱,由于單獨(dú)或聯(lián)合使用核苷類似物，包括：拉米夫定、齊多夫定和其他抗逆轉(zhuǎn)錄病毒藥物〔見“警告和留意事項(xiàng)”一節(jié)，消滅乳酸性酸中毒和嚴(yán)峻脂肪變性肝腫大，包括致命病例。Composition成分Duovir-NEachfilm-coatedtabletcontainsDuovir-N每一薄膜包衣片含：LamivudineIP拉米夫定〔印度藥典〕 150mg毫克ZidovudineIP齊多夫定〔印度藥典〕 300mg毫克NevirapineIP奈韋拉平〔印度藥典〕 200mg毫克Description說明Duovir-Nis a combination of 3 drugs commonly used in the management of HumanImmunodeficiencyVirus(HIV) infection.Both zidovudineand lamivudinebelong to thenucleosideanalogueclassofantiretroviraldrugs.BothdrugsactbyterminatingthegrowthoftheDNAchainandinhibitingthereversetranscriptase ofHIV.Nevirapineisanon-nucleosidereversetranscriptaseinhibitor.Itactsbydirectlyinhibitingreversetranscriptase.Duovir-N3種藥物的組合，常用于人類免疫缺陷病毒〔HIV即艾滋病毒〕感染的處糖核酸〔DNA〕鏈生長，并抑制艾滋病毒〔HIV〕逆轉(zhuǎn)錄酶，奈韋拉平是一種非核苷逆轉(zhuǎn)錄酶抑制劑，它的作用，直接抑制逆轉(zhuǎn)錄酶活性。EachtabletofDuovir-Ncontainshalfofthecommonlyprescribeddailydosesofzidovudine,lamivudineandnevirapine.Allthreedrugsaretobeadministeredtwicedaily,permittingafixed-dosecombinationtobeformulated.Withtheavailabilityofthiscombinationformulation,patientsmaybebetterabletoadheretotripledrugregimens,therebyenhancingcompliance.Duovir-N含規(guī)定的齊多夫定、拉米夫定和奈韋拉平的每日服用劑量的一半，全部三種藥物，每日服用兩次，允許制定一個(gè)固定劑量組合，由于該組合制劑的有效性，患者能更好地堅(jiān)持以三聯(lián)藥物療法，從而提高了遵從性。Indications適應(yīng)癥Duovir-NisindicatedforthetreatmentofHIVinfection,oncepatientshavebeenstabilizedonthemaintenanceregimenofnevirapine200mgbd,andhavedemonstratedadequatetolerabilitytonevirapine.Duovir-N用于治療艾滋病毒感染，一旦患者按奈韋拉平200毫克，每日兩次，已經(jīng)穩(wěn)定在維持狀況，充分證明對奈韋拉平的耐受性。DosageandAdministration劑量和用法Adult:1tablettwicedaily.成人：一次一片，每日兩次,。Duovir-Nshouldnotbeadministeredtopatientswhohavejustinitiatedtherapywithnevirapine.Thisisbecauseaninitiallead-indosingof200mgnevirapineoncedailyfor2weeksisrecommended.Followingthislead-indose,adoseescalation(maintenancedose)to200mgnevirapinebdmaybecarriedoutintheabsenceofanyhypersensitivityreactions(e.g.rash,liverfunctiontestabnormalities;seeWarningsandPrecautions).Duovir-N不應(yīng)當(dāng)用于那些剛開頭使用奈韋拉平治療的患者，這是由于推舉的奈韋拉平的初2002周時(shí)間，遵照該導(dǎo)入劑量，奈韋拉平劑量遞增〔維持劑量〕到200毫克，每日二次，服用可能沒有任何過敏反響〔如：皮疹，肝功能檢查特別;見警告和留意事項(xiàng)。Monitoringofpatients患者的監(jiān)測Intensiveclinicalandlaboratorymonitoring,includingliverfunctiontest,isessential,especiallyatbaseline,priortodoseescalationofnevirapine,andattwoweekspost doseescalation.Insomecases,hepaticinjuryhasprogresseddespitediscontinuationoftreatment(seeWarningsandPrecautions).〔見警告和留意事項(xiàng)。DosageAdjustment劑量調(diào)整Lamivudine:拉米夫定：Becauseitisafixed-dosecombination,Duovir-Nshouldnotbeprescribedforpatientsrequiringdosageadjustment,suchasthosewithlowbodyweight(<50kg).由于它是一個(gè)固定劑量組合，對劑量需要調(diào)整的患者，例如那些體重較輕患者<50公斤，Duovir-N的劑量。Zidovudine:齊多夫定：Becauseitisafixed-dosecombination,thisformulationshouldnotbeprescribedforpatientsrequiringdosageadjustmentsuchasthosewithreducedrenalfunction(creatinineclearance≤50ml/min)orthoseexperiencingdose-limitingadverseevents.腎功能較低的患者〔肌酐去除率≤50毫升/分〕或那些受到劑量限制不良反響的患者。Nevirapine:奈韋拉平：Duovir-Nshouldbediscontinuedifpatientsexperiencesevererashorarashaccompaniedbyconstitutionalfindings(SeeWarningsandPrecautions).Patientsexperiencingmildtomoderaterashduringthe14-daylead-inperiodof200mg/dayshouldnothavetheirnevirapinedoseincreasedorstarttherapywithDuovir-Nuntiltherashhasresolved(seeWarningsandPrecautions).假設(shè)患者患病嚴(yán)峻皮疹或伴隨原發(fā)性癥〔見警告和留意事項(xiàng)Duovir-N，14200毫克/天的導(dǎo)入期，患病輕度至中度皮疹的患者，不應(yīng)增加奈韋拉平劑量，或直Duovir-N的治療〔見警告和留意事項(xiàng)。Ifclinicalhepatitisoccurs,nevirapineshouldbepermanentlydiscontinuedandnotrestartedafterrecovery.假設(shè)發(fā)生臨床肝炎，奈韋拉平應(yīng)永久停用，而不要在恢復(fù)后重啟用。Patientswhointerruptnevirapinedosingformorethan7daysshouldrestarttherecommendeddosing,usingone200mgNevimunetabletdailyforthefirst14days(lead-in)incombinationwiththeotherantiretrovirals,followedby200mgtwicedailyusing Duovir-Nintheabsenceofanysignsofhypersensitivity.中斷奈韋拉平劑量，超過714天〔導(dǎo)入，每日服200毫克的通用奈韋拉平〔Nevimune〕片劑，結(jié)合其他抗逆轉(zhuǎn)錄病毒藥物200毫克，然后，在沒有任何過敏病癥的狀況下，每日兩次服用Duovir-N。)Pregnancy妊娠L(fēng)amivudine,zidovudineandnevirapineareallclassifiedundercategoryC.Therearenoadequateandwell-controlledstudiesinpregnantwomen.Duovir-Nshouldbeusedduringpregnancyonlyifthepotentialbenefitsoutweighthepotentialrisk.拉米夫定、齊多夫定和奈韋拉平，都?xì)w入C類，沒有對妊娠婦女進(jìn)展充分、嚴(yán)格的比照爭論，只有當(dāng)潛在的好處大于潛在的風(fēng)險(xiǎn)時(shí)，才可在懷孕期間使用Duovir-N。Lactation哺乳期ItisrecommendedthatHIV-infectedmothersdonotbreastfeedtheirinfantstoavoidriskingpostnataltransmissionofHIVinfection.Itisnotknownwhetherlamivudineisexcretedinhumanmilk.Nevirapineandzidovudinearepresentinbreastmilk.險(xiǎn)。不知道人是否分泌出拉米夫定，母存在奈韋拉平與齊多夫定。Paediatrics兒科Duovir-Nisnotintendedforuseinpaediatricpatients.Duovir-N是不供兒科患者使用。SideEffects副作用Zidovudineandlamivudine齊多夫定和拉米夫定ObservedduringClinicalPractice:Thefollowingeventshavebeenidentifiedduringpost-approvaluseoflamivudine,zidovudine,and/orlamivudine/zidovudine.Becausetheyarereportedvoluntarilyfromapopulationofunknownsize,estimatesoffrequencycannotbemade.Theseeventshavebeenchosenforinclusionduetoacombinationoftheirseriousness,frequencyofreporting,orpotentialcausalconnectiontolamivudine,zidovudine,and/orlamivudine/zidovudine.在臨床實(shí)踐中觀看到：在批準(zhǔn)使用拉米夫定、齊多夫定，和/或拉米夫定/齊多夫定后期間，狀況已列入選擇，由于報(bào)道綜合了它們的嚴(yán)峻性、頻率、或與拉米夫定、齊多夫定，和/或拉米夫定/齊多夫定的潛在的因果關(guān)系。BodyasaWhole:Redistribution/accumulationofbodyfat(seeWarningsandPrecautions:Fatredistribution)整體：體內(nèi)脂肪重分布積存〔見警告和留意事項(xiàng)：脂肪的重分布〕Cardiovascular:Cardiomyopathy.心血管：心肌病EndocrineandMotabolic:Gynecomastia,hyperglycemia.內(nèi)分泌和代謝：男性乳房發(fā)育癥，高血糖。Gastrointestinal:Oralmucosalpigmentation,stomatitis.胃腸道：口腔黏膜色素冷靜，口腔炎。General:Vasculitis,weakness綜合：脈管炎，四肢無力。HaemicandLymphatic:Aplasticanaemia,anaemia,lymphadenopathy,pureredcellaplasia,splenomegaly.血液和淋巴管：再生障礙性貧血、貧血、淋巴結(jié)腫大、純紅細(xì)胞再生障礙性貧血、脾腫大。HepaticandPancreatic:Lacticacidosisandhepaticsteatosis,pancreatitis,post-treatmentexacerbationofhepatitisB(seeWarningsandPrecautions).肝和胰腺：乳酸性酸中毒和脂肪肝、胰腺炎、乙型肝炎治療后發(fā)作〔見警告和留意事項(xiàng)。Hypersensitivity:Sensitizationreactions(includinganaphylaxis),urticaria.過敏癥：致敏反響〔包括過敏性反響、蕁麻疹。Musculoskeletal:Muscleweakness,CPKelevation,rhabdomyolysis.肌肉骨骼：肌肉無力、肌酸磷酸激酶(CPK)上升、橫紋肌溶解癥。Nervous:Paraesthesia,peripheralneuropathy,seizures.神經(jīng)系統(tǒng)：感覺特別、四周神經(jīng)病變、癲癇。Respiratory:Abnormalbreathsounds/wheezing.呼吸系統(tǒng)/哮喘。Skin:Alopecia,erythemamultiforme,Stevens-Johnsonsyndrome.皮膚：脫發(fā)、多形性紅斑、史蒂文斯—約翰遜綜合征。Nevirapine奈韋拉平Clinicalpracticehasshownthatthemostseriousadversereactionsassociatedwithnevirapineareclinicalhepatitis/hepaticfailure,Stevens-Johnsonsyndrome,toxicepidermalnecrolysis,andhypersensitivityreactions.Clinicalhepatitis/hepaticfailuremaybeisolatedorassociatedwithsignsofhypersensitivitywhichmayincludesevererashorrashaccompaniedbyfever,generalmalaise,fatigue,muscleorjointaches,blisters,orallesions,conjunctivitis,facial oedema,and/orhepatitis,eosinophilia,granulocytopenia,lymphadenopathy,andrenaldysfunction./—約翰遜〔Stevens–Johnson〕/肝衰竭可能是孤立的，或伴隨過敏癥兆，其中可能包括嚴(yán)峻皮疹或皮疹伴有發(fā)熱、全身不適、乏力、肌肉或關(guān)節(jié)苦痛、水泡、口腔潰瘍、結(jié)膜炎、面部水腫、和/或肝炎/嗜酸性細(xì)胞增多、粒細(xì)胞減少、淋巴結(jié)腫大和腎功能障礙。Severeandlife-threateninghepatotoxicity,andfatalfulminanthepatitishavebeenreportedinpatientstreatedwithnevirapine.Hepaticadverseeventshavebeenreportedtooccurmorefrequentlyduringthefirst18weeksoftreatment,butsucheventsmayoccuratanytimeduringtreatment.報(bào)道，肝不良反響更頻繁地發(fā)生在治療的初始18周，但治療期間，這樣的反響可能隨時(shí)發(fā)生。Incontrolledclinicaltrials,clinicalhepaticeventsregardlessofseverityoccurredin4.0%(range2.5%to11.0%)ofpatientswhoreceivednevirapineand1.2%ofpatientsincontrolgroups.Transaminaseelevations(ALTorAST＞5xULN)wereobservedin8.8%ofpatientsreceivingnevirapineand6.2%ofpatientsincontrolgroupsinclinicaltrials.Inaretrospectiveanalysisofcontrolledanduncontrolledclinicaltrials,patientswithhigherCD4countsatinitiationofnevirapinetherapy,particularlywomenwereatgreaterriskforacutesymptomatichepaticevents,includingdeath,especiallyinthefirstsixweeksoftherapy.PatientswithchronichepatitisBorCinfectionwereathigherriskforlaterhepaticevents.比照臨床試驗(yàn)中，承受奈韋拉平治療的患者，發(fā)生臨床肝炎病癥，不管嚴(yán)峻程度，在4.0％〔范圍在2.％—11.％1.,8.86.2％，轉(zhuǎn)氨酶上升〔谷丙轉(zhuǎn)氨酶[ALT]或谷草轉(zhuǎn)氨酶[AST]>5[ULNCD4計(jì)數(shù)更高的患者，在治療的初始6周時(shí)間，慢性乙型或丙型肝炎病毒感染的患者，后來的肝炎病癥風(fēng)險(xiǎn)較高。Themostcommonclinicaltoxicityofnavirapineisrash.Severeorlife-threateningrashoccurredinapproximately2%ofnevirapine-treatedpatients,mostfrequentlywithinthefirst6weeksoftherapy.Rashesareusuallymildtomoderate, maculopapularerythomatouscutaneouseruptions,withorwithoutpruritus,locatedonthetrunk,faceandextremities. Womentendtobeathigherriskfordevelopmentofnavirapineassociatedrash.奈韋拉平最常見的臨床毒性是皮疹，大約2％受奈韋拉平治療的患者，最常見是在治療的初始6相關(guān)的皮疹的高危人群。Withrespecttolaboratoryabnormalities,liverfunctiontestabnormalities(SGOT,SGPT)wereobservedmorefrequentlyinpatientsreceivingnovirapinethanincontrols.AsymptomaticelevationsinSGToccurfrequentlybutarenotacontraindicationtocontinuenevirapinetherapyintheabsenceofelevationsofotherliverfunctiontests.〔[SGOT[SGPT，常常發(fā)生梅毒絮狀沉淀試驗(yàn)SG治試驗(yàn)無病癥上升，但不是連續(xù)奈韋拉平治療的禁忌癥—在其他肝功能檢查數(shù)據(jù)沒有上升的狀況下。Becauseclinicalhepatitishasbeenreportedinnevirapine-treatedpatients,intensiveclinicalandlaboratorymonitoring,includingliverfunctiontests,isessentialatbaselineandduringthefirst18weeksoftreatment,Monitoringshouldcontinueatfrequentintervalsthereafter,dependingonthepatiensclinicalstatus.由于已有報(bào)道，承受奈韋拉平治療的患者發(fā)生臨床肝炎，在基線時(shí)和初始18周治療期間，頻繁的間隔，連續(xù)進(jìn)展監(jiān)測。Inadditiontotheadverseeventsindentifiedduringclinicaltrials,thefollowingeventshavebeenreportedwiththeuseofNevirapineinclinicalpractice.除了在臨床試驗(yàn)中被證明的不良反響，已有報(bào)道使用奈韋拉平的以下臨床反響：BodyasaWhole:fever,somnolence,drugwithdrawal全身：發(fā)熱、嗜睡、藥物戒斷。Gastrointestinal:vomiting胃腸道反響：嘔吐LiverandBiliary:jaundice,fulminantandcholestatichepatiltis,hepaticnecrosis,hepaticfailure肝和膽：黃疸、爆發(fā)型和淤膽性肝炎、肝壞死、肝功能衰竭。Haematology:anaemia,eosinophilia,neutropenia血液學(xué)：貧血，嗜曙紅細(xì)胞增多，嗜中性白血球削減癥。Musculoskeletal:arthralgia肌肉骨骼：關(guān)節(jié)痛Neurologic:paraesthesia神經(jīng)系統(tǒng)：感覺特別SkinandAppendages:allergicreactionsincludinganaphylaxis,angioedema,bullouseruptions,ulcerativestomatitisandurticariahaveallbeenreported.Inaddition,hypersensitivitysyndromeandhypersensitivityreactionswithrashassociatedwithconstitutionalfindingssuchasfever,blistering,orallesions,conjunctivitis,facialedema,muscleorjointaches,generalmalaise,fatigueorsignificanthepaticabnormalitiesplusoneormoreofthefollowing:hepatitis,eosinophilia,granulocytopenia,lymphadenopathyand/orrenaldysfunctionhavebeenreportedwiththeuseofnavirapine.皮膚及附件：過敏反響、包括過敏性休克、血管神經(jīng)性水腫、大皰爆發(fā)、潰瘍性口腔炎和蕁麻疹都有報(bào)道，此外，與原發(fā)性病癥相關(guān)的皮疹過敏綜合征和過敏反響，如：發(fā)熱、水泡、口腔潰瘍、結(jié)膜炎、面部水腫、肌肉或關(guān)節(jié)苦痛、全身不適、疲乏或明顯的肝功能特別，由于服用奈韋拉平，伴有一個(gè)或多個(gè)以下狀況：肝炎、嗜酸性粒細(xì)胞增多、粒細(xì)胞削減、淋巴結(jié)腫大、和/或腎功能失調(diào)，都有報(bào)道。Overdosage過劑量Lamivudine拉米夫定Thereisnoknownantidoteforlamivudine.Itisnotknownwhetherlamivudinecanberemovedbyperitonealdialysisorhemodialysis.Ifoverdoseoccurs,thepatientshouldbemonitored,andstandardsupportivetreatmentappliedasrequired.沒有的拉米夫定的解毒劑，不知是否可以通過腹膜透析或血液透析，來去除拉米夫定，假設(shè)發(fā)生過劑量時(shí)，應(yīng)監(jiān)測病人，依據(jù)需要，應(yīng)用標(biāo)準(zhǔn)的支持治療。Zidovudine齊多夫定Acuteoverdosesofzidovudinehavebeenreportedinpediatricpatientsandadults.Theseinvolvedexposuresupto50grams.Nospecificsymptomsorsignshavebeenidentifiedfollowingacuteoverdosagewithzidovudineapartfromthoselistedasadverseeventssuchasfatigue,headache,vomiting,andoccasionalreportsofhaematologicaldisturbances.Allpatientsrecoveredwithoutpermanentsequelae.Haemodialysisandperitonealdialysisappeartohaveanegligibleeffectontheremovalofzidovudinewhileeliminationofitsprimarymetabolite,GZDV,isenhanced.據(jù)報(bào)道，發(fā)生過小兒患者和成人齊多夫定服用急性過量，這些涉及暴露量高達(dá)50克的。沒有析，似乎對去除齊多夫定的作用微缺乏道，然而增加了消退其主要代謝產(chǎn)物—GZDV【3’-疊氮-3’-5’-O-〔β〕-D-glucopyranuronosylthymidineNevirapine奈韋拉平Thereisnoknownantidotefornevirapineoverdosage.沒有的奈韋拉平過量的解毒劑。Presentation贈(zèng)品Duovir-N containerof30tabletsDuovir-N 30片容器裝(第一頁左邊完)Contraindications禁忌癥Duovir-Niscontraindicatedinpatientswithclinicallysignificanthypersensitivitytoanyofthecomponentscontainedintheformulation.臨床上，對制劑中所含的任何成清楚顯過敏的患者，禁用Duovir-N。Duovir-Nisalsocontraindicatedforpatientswhoarejustinitiatingtherapywithnevirapine.Thesepatientsrequirealead-indoseofnevirapine200mgo.d.,whereasthisformulationcontainsthemaintenancedoseofnevirapine200mgb.d.(seeIndications).Duovir-200毫克的導(dǎo)入劑量，而這一制劑包含的奈韋拉平的維持劑量，為200〔見適應(yīng)癥。WarningsandPrecautions警告和留意事項(xiàng)DrugInteractions藥物交互作用Lamivudine拉米夫定Lamivudineispredominantlyeliminatedintheurinebyactiveorganiccationicsecretion.Thepossibilityofinteractionswithotherdrugsadministeredconcurrentlyshouldbeconsidered,particularlywhentheirmainrouteofeliminationisactiverenalsecretionviatheorganiccationictransportsystem(e.g.trimethoprim).〔芐氨啶〕的活潑腎臟分泌。Trimethoprim160mg/sulphamethoxazole800mgoncedailyhasbeenshowntoincreaselamivudineexposure(AUC).Nochangeindoseofeitherdrugisrecommended.ThereisnoinformationregardingtheeffectonlamivudinepharmacokineticsofhigherdosesofTMP/SMXsuchasthoseusedtotreatPneumocystiscariniipneumonia.Nodataareavailableregardinginteractionswithotherdrugsthathaverenalclearancemechanismssimilartothatoflamivudine.Lamivudineand zalcitabine mayinhibit the intracellular phosphorylationof one another.Therefore,useoflamivudineincombinationwithzalcitabineisnotrecommended.160毫克/800毫克，每天一次，已被證明能增加拉米夫定暴露量AU：藥時(shí)曲線下面積，不建議轉(zhuǎn)變兩種藥物的劑量，沒有關(guān)于拉米夫定藥代動(dòng)力學(xué)影響的資料—磺胺甲基異惡唑TMP/SMX，用于治療卡氏肺孢菌肺炎，無據(jù)可查類似拉米夫定與其他藥物的相互作用的腎臟去除機(jī)理，拉米夫定和扎西他賓〔zalcitabine抗艾滋病藥)，可能會(huì)相互抑制細(xì)胞內(nèi)磷酸化，因此，不推舉使用拉米夫定結(jié)合扎西他賓〔zalcitabine抗艾滋病藥)。Zidovudine齊多夫定Forpatientsexperiencingpronouncedanaemiaorotherseverezidovudine-associatedeventswhilereceivingchronicadministrationofzidovudineandsomeofthefollowingdrugs-atovaquone,fluconazole,methadone,nelfinavir,probenecid,rifampin,ritonavir,valproicacid-zidovudinedosereductionmaybeconsidered.SinceDuovir-Nisafixeddosecombination,itcannotbeusedforthispatientpopulation.對于患明顯貧血或其他嚴(yán)峻與齊多夫定相關(guān)反響的患者藥物：阿托喹酮(atovaquone抗瘧藥)、氟康唑、美沙酮、奈非那韋、丙磺舒、利福平、利托Duovir-N是一個(gè)固定劑量組合，它不能用于這個(gè)病患族群。Antiretroviralagents:Concomitantuseofzidovudinewithstavudineshouldbeavoidedsinceanantagonisticrelationshiphasbeendemonstratedinvitro.抗逆轉(zhuǎn)錄病毒藥物：應(yīng)避開齊多夫定與司他夫定〔stavudine〕相伴使用，由于已證明在體外的對立關(guān)系。SomenucleosideanaloguesaffectingDNAreplication,suchasribavirin,antagonizethe invitroantiviralactivityofzidovudineagainstHIV;concomitantuseofsuchdrugsshouldbeavoided.一些核苷(酸)類似物，影響脫氧核糖核酸〔DNA〕的復(fù)制，如：病毒唑，拮抗齊多夫定在體外對艾滋病毒的抗病毒活性，應(yīng)避開此類藥物的同時(shí)使用。Doxorubicin:Concomitantuseofzidovudinewithdoxorubicinshouldbeavoidedsinceanantagonisticrelationshiphasbeendemonstratedinvitro.。Phenytoin:Phenytoinplasmalevelshavebeenreportedtobelowinsomepatientsreceivingzidovudine，whilein1caseahighlevelwasdocumented.However,inapharmacokineticinteractionstudyinwhich12HIV-positivevolunteersreceivedasingle300-mgphenytoindosealoneandduringsteady-statezidovudineconditions(200mgevery4hours),nochangeinphenytoinkineticswasobserved.Althoughnotdesignedtooptimallyassesstheeffectofphenytoinonzidovudinekinetics,a30%decreaseinoralzidovudineclearancewasobservedwithphenytoin.例高水平病例記錄12獨(dú)承受單一的300毫克的苯妥英的劑量，在穩(wěn)態(tài)階段期間，齊多夫定的狀況〔4小時(shí)200毫克夫定動(dòng)力學(xué)的影響，但觀看到口服齊多夫定的去除削減30％。OverlappingToxicities:Co-administrationofganciclovir,interferon-alpha,andotherbonemarrowsuppressiveorcytotoxicagentsmayincreasethehaematologictoxicityofzidovudine.重疊毒性：更昔洛韋、α-干擾素、和其他骨髓抑制或細(xì)胞毒性藥物的聯(lián)合服用可能會(huì)增加齊多夫定的血液學(xué)毒性。Novirapine奈韋拉平NavirapineisprincipallymetabolizedbytheliverviathecytochromeP450isoenzymes,3A4and2B6.Nevireapineisknowntobeaninduceroftheseenzymes.Thus,ifapatienthasbeenstabilizedonadosageregimenforadrugmetabolizedbyCYP3A,andbeginstreatmentwithnevirapine,doseadjustmentsmaybenecessary.奈韋拉平主要通過細(xì)胞色素P450同功酶，3A4和2B6，由肝臟代謝，奈韋拉平是這些酶的誘導(dǎo)劑，因此，假設(shè)病人，始終穩(wěn)定在由CYP3A藥物代謝的給藥方案，并開頭用奈韋拉平治療，劑量的調(diào)整可能是必要的。Clinicalcommentsaboutpossibledosagemodificationsaregivenbelow:可能修改的臨床劑量意見，給出如下：EstablishedDrugInteractionswithnevirapine用奈韋拉平的藥物相互作用Ketoconazole:Nevirapineandketoconazoleshouldnotbeadministeredconcomitantly,becausedecreasesinketoconazoleplasmaconcentrationsmayreducetheefficacyofthedrug.的療效。Clarithromycin:Clarithromycinexposurewassignificantlydecreasedbynevirapine;however,14-OHmetaboliteconcentrationswereincreased.BecauseclarithromycinactivemetabolitehasreducedactivityagainstMycobacteriumavium-intracetlularecorlactivityagainstthispathogenmaybealtered.Alternativestoclarithromycin,suchasazithromycin,shouldbeconsidered.克拉克拉：克拉霉素暴露量被奈韋拉平明顯降低；然而，14-羥基代謝物濃度增加，由的整體活性，可能會(huì)轉(zhuǎn)變，應(yīng)考慮克拉霉素的替代物，如：阿奇霉素。Efavirenz:Efavirenzconcentrationsaredecreased.Appropriatedosesforthiscombinationarenotestablished.EthinylestradiolandNorethindrone:Concentrationsofbothdrugsaredecreased.Oralcontraceptivesandotherhormonalmethodsofbirthcontrolshouldnotbeusedasthesolemethodofcontraceptioninwomentakingnevirapine,sincenevirapinemaylowertheplasmalevelsofthesemedications.Analternativeofadditionalmethodofcontraceptionisrecommended.議選擇其他的避孕方法。Rifabutin:Concentrationsofrifabutinanditsmetaboliteweremoderatelyincreased.Duetohighintersubjectvariability,however,somepatientsmayexperiencelargeincreasesinrifabutinexposureandmaybeathigherriskforrifabutintoxicity.Therefore,cautionshouldbeusedinconcomitantadministration.利福布汀：利福布汀的濃度及其代謝產(chǎn)物，輕度增加，然而，由于個(gè)體之間的高度變異性，此，應(yīng)慎重同時(shí)服用。Rifampin:Nevirapineandrifampinshouldnotbeadministeredconcomitantlybecausedecreasesinnevirapineplasmaconcentrationsmay reducetheefficacyofthedrug.Physiciansneedingtotreatpatientsco-infectedwithtuberculosisandusinganevirapine-containingregimenmayuserifabutininstead.用利福布丁代替。Fluconazole:Becauseoftheriskofincreasedexposuretonevirapine,cautionshouldbeusedinconcomitantadministration,andpatientsshouldbemonitoredcloselyfornevirapine-associatedadverseevents.相關(guān)的不良大事監(jiān)測反響。Indinavir:Concentrationsofindinaviraredecreased.Appropriatedosesforthiscombinationarenotestablished,butanincreaseinthedosageofindinavirmayberequired.能是必需的。Lopinavir/Ritonavir:Adoseincreaseoflopinavir/ritonavirto533/133mgtwicedailywithfoodisrecommendedincombinationwithnevirapine洛匹那韋/利托那韋：建議在與奈韋拉平組合中，洛匹那韋/利托那韋的劑量增加到133/533毫克，每天兩次，結(jié)合食物。Nelfinavir:Theappropriatedosefornelfinavirincombinationwithnevirapine,withrespecttosafetyandefficacy,hasnotbeenestablished.奈非那韋：奈非那韋與奈韋拉平組合的適當(dāng)劑量，關(guān)于安全性和有效性方面，尚未確定。Saquinavir:Appropriatedosesforthiscombinationarenotestablished,butanincreaseinthedosageofsaquinavirmayberequired.沙奎那韋：這個(gè)組合的適當(dāng)劑量，尚未確定，但可能需要增加沙奎那韋的劑量。Methadone:Methadonelevelsmaybedecreased,increaseddosagesmayberequiredtopreventsymptomsofopiatewithdrawal.Methadone-maintainedpatientsbeginningnevirapinetherapyshouldbemonitoredforevidenceofwithdrawalandmethadonedoseshouldbeadjustedaccordingly.美沙酮：美沙酮水平可能會(huì)下降，可能需要增加劑量，以防止鴉片戒斷病癥，應(yīng)當(dāng)監(jiān)測開頭奈韋拉平治療的美沙酮替代維持患者的戒斷證據(jù)，并且美沙酮?jiǎng)┝?，?yīng)作相應(yīng)調(diào)整。Potentialdruginteractionsarelistedbelow:以下是潛在的藥物相互作用：Examplesofdrugsinwhichplasmaconcentrationsmaybedecreasedbyco-administrationwithnevirapine.與奈韋拉平聯(lián)合服用，藥物血漿濃度可能降低的例子：Antiarrhythmics: e.g. Amiodarone,disopyramide,lidocaine抗心律不齊藥：如:：胺碘酮、丙吡胺、利多卡因。Anticonvulsants: e.g. Carbamazepine,clonazepam,ethosuximide抗驚厥藥物：如：卡馬西平、氯硝西泮、乙琥胺。Antifungals: e.g.Itraconazole.抗真菌藥：如：伊曲康唑。Calciumchannelblockers:Diltiazem,nifedipine,verapamil鈣通道阻滯劑：恬爾心、硝苯地平、異博定。Cancerchemotherapy:Cyclophosphamide癌癥化療：環(huán)磷酰胺。Ergotalkaloids:Ergotamine麥角生物堿：麥角胺。Immunosuppressants:Cyclosporin,tacrolimus,sirolimus免疫抑制劑：環(huán)孢素、他克莫司、西羅莫司。Motilityagents:Cisapride蠕動(dòng)藥物：西沙必利。Opiateagonists:Fentanyl阿片受體感動(dòng)劑：芬太尼。Examplesofdrugsinwhichplasmaconcentrationsmaybeincreasedbyco-atiministrationwithnevirapine.與奈韋拉平聯(lián)合服用，藥物血漿濃度可能增加的例子：Anticoagulantse.g.warfarin.Potentialeffectonanticoagulation.Monitoringofanticoagulationlevelsisrecommended.抗凝血?jiǎng)?，如：華法林，潛在的抗凝血作用，建議監(jiān)測抗凝水平。Skinreactions:皮膚反響：Severe,life-threateningskinreactions,includingfatalcases,havebeenreportedwithnevirapinetreatment,occurringmostfrequentlyduringthefirst6weeksoftherapy.ThesehaveincludedcasesofStevens-Johnsonsyndrome,toxicepidermalnecrolysisandhypersensitivityreactionscharacterizedbyrash,constitutionalfindingsandorgandysfunction.Patientsdevelopingsignsorsymptomsofsevereskinreactionsorhypersensitivityreactions(including,butnotlimitedtosevererashorrashaccompaniedbyfever,generalmalaise,fatigue,muscleorjointaches,blisters,oral lesions,conjunctivitis,facialoedema,and/orhepatitis,eosinophilia,granulocytopenia,lymphadenopathy,andrenaldysfunction)mustpermanentlydiscontinuenevirapineandseekmedicalevaluationimmediately.Nevirapineshouldnotberestartedfollowingsevereskinrashorhypersensitivityreaction.Someoftheriskfactorsfordevelopingserious據(jù)報(bào)道，使用奈韋拉平治療，已發(fā)生過嚴(yán)峻、危及生命的皮膚反響，包括致命的病例，最常6周的治療時(shí)間，這些包括Stevens-Johnson綜合征〔史蒂文斯-約翰遜綜合征[即：重癥多形性紅斑])、中毒性表皮壞死松解癥和過敏反響，特征為：皮疹、原發(fā)性病癥和器〔包括但不限于嚴(yán)峻皮面或肝炎、嗜酸性粒細(xì)胞、粒細(xì)胞削減、淋巴結(jié)腫大和腎功能不全，必需盡快停頓反響，不應(yīng)重啟用奈韋拉平。一些危急因素進(jìn)展成嚴(yán)峻的〔轉(zhuǎn)下〕〔其次頁左邊完畢〕cutaneousreactionsincludefailuretofollowtheinitialdosingof200mgdailyduringthe14-daylead-inperiodanddelayinstoppingthenevirapinetreatmentaftertheonsetoftheinitialsymptoms.Ifpatientspresentwithasuspectednevirapine-associatedrash,liverfunctiontestsshouldbeperformed.Patientswithrash-associatedASTorALTelevationsshouldbepermanentlydiscontinuedfromnevirapine.〔接上14200mg和初期病癥期發(fā)作后，相關(guān)的谷丙轉(zhuǎn)案酶〔AST〕或谷丙轉(zhuǎn)氨酶〔ALT〕上升的病人，應(yīng)永久停用奈韋拉平。Therapywithnevirapinemustbeinitiatedwitha14-daylead-inperiodof200mg/day,whichhasbeenshowntoreducethefrequencyofrash.Ifrashisobservedduringthislead-inperiod,doseescalationshouldnotoccuruntiltherashhasresolved.(seeDosageandAdministration).Patientsshouldbemonitoredcloselyifisolatedrashofanyseverityoccurs.200毫克/14假設(shè)在此導(dǎo)入期，觀看到皮疹，不應(yīng)當(dāng)遞增劑量，直到皮疹已經(jīng)解決〔見用法用量。假設(shè)患者發(fā)生任何嚴(yán)峻孤立的皮疹，應(yīng)親熱監(jiān)測。Womenappeartobeathigherriskthanmanofdevelopingrashwithnevirapine.Theuseofprednisonetopreventnevirapineassociatedrashisnotrecommended.關(guān)的皮疹。Zidovudineandlamivudine齊多夫定和拉米夫定Lacticacidosis/severehepatomegalywithsteatosis,includingfatalcases,havebeenreportedwiththeuseofantiretroviralnucleosideanaloguesaloneorincombination.Amajorityofthesecaseshavebeeninwomen.Obesityandprolongednucleosideexposuremayberiskfactors.Cautionshould be exercised when administering zidovudine and lamivudine to any patient, a