齐多拉米双夫定片说明书

FortheuseofaRegisteredMedicalPractitioneroraHospitaloraLaboratoryonly仅供注册医生、医院、试验室使用Lamivudine,ZidovudineandNevirapineTabletsIP拉米夫定，齐多夫定和奈韦拉平片〔印度药典级〕商品名〕Warning警告Duovir-Nisnotintendedforuseinpatientswhoarejustinitiatingtherapywithnevirapine.Duovir-NshouldbeadministeredonlytopatientswhohavereceivedZidovudine+Lamivudine(standarddoses)+Nevirapine(200mgOD)for2weeksandhavedemonstratedadequatetolerabilitytoNevirapine(seeIndications,DosageandAdministration).Duovir-N不适合那些刚开头使用奈韦拉平治疗的患者，Duovir-N只应施用于那些已经承受齐多夫定+拉米夫定〔标准剂量〕+奈韦拉平〔200毫克，每天一次〕2周，并证明对奈韦拉平具有足够耐受性的患者〔见适应症、剂量和服用。ZidovudinehasbeenassociatedwithhaematologictoxicityincludingNeutropeniaandsevereanaemia.Particularlyinpatientswithadvanceddisease(seeWarningsandPrecautions).ProlongeduseofZidovudinehasbeenassociatedwithsymptomaticmyopathy.齐多夫定与血液学毒性相关，包括中性粒细胞削减和严峻贫血，特别是长期使用齐多夫定，始终伴随病症肌病的晚期患者〔见警告和留意事项。Severe,life-threateningskinreactions,includingfatalcases,haveoccurredinpatientstreatedwithNevirapine.ThesehaveincludedcasesofStevens-Johnsonsyndrome.Toxicepidermalnecrolysis,andhypersensitivityreactionscharacterisedbyrash,constitutionalfindingsandorgandysfunction.PatientsdevelopingsignsorsymptomsofsevereskinreactionsorhypersensitivityreactionsmustdiscontinueNevirapineassoonaspossible(seeWarningsandPrecautions).史蒂文斯-约翰逊综合征(即：重症多形性红斑)病例、中毒性表皮坏死、和过敏性反响，,消灭严峻的皮肤反响、或过敏反响病症或体征的患者，必需尽快停顿使用奈韦拉平〔见警告和留意事项。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).已有报道，使用奈韦拉平治疗的患者，消灭严峻、危及生命，而且在某些状况下，呈现致命的肝毒性，包括：爆发性和胆汁淤积性肝炎、肝坏死和肝功能衰竭。在某些状况下，患者伴有肝炎非特异性体征或病症,并进展为肝功能衰竭，这些病症往往伴随皮疹，女性和CD4CD4细胞计数>250cells〔细胞〕/mm3的女性，包括正在承受艾滋病毒感染〔HIV〕长期治疗的孕妇，这些病症有相当高的风险，消灭肝炎病症或体征的患者，必需停顿使用奈韦拉平，并马上寻求医疗评估〔见警告和留意事项。Itisessentialthatpatientsbemonitoredintensivelyduringthefirst18weeksoftherapywithNevirapinetodetectpotentiallylife-threateninghepatotoxicityorskinreactions.Thegreatestriskofsevererashorhepaticevents(oftenassociatedwithrash)occursinthefirst6weeksoftherapy.However,theriskofanyhepaticevent,withorwithoutrash,continuespastthisperiodandmonitoringshouldcontinueatfrequentintervals.Insomecases,hepaticinjuryhasprogresseddespitediscontinuationoftreatment.Nevirapineshouldnotberestartedfollowingseverehepatic,skinorhypersensitivityreactions.Inaddition,the14-daylead-inperiodwithNevirapine200mgdailydosingmustbestrictlyfollowed(seeWarningsandPrecautions).18周期间，加强对患者进展监测，以检测潜在的/肝衰竭(常伴随皮疹)发生在治疗的初始6周，然而，任何肝炎/肝衰竭的风险，伴有或不伴皮疹，在这段期间过去后，仍应以繁频的间隔，连续监测，在某些状况下，尽管治疗停药，肝脏损伤会有进展，伴随严峻200毫克/14天的导入期〔见警告和留意事项。Lacticacidosisandseverehepatomegalywithsteatosis,includingfatalcases,havebeenreportedwiththeuseofNucleosideanaloguesaloneorincombination,includingLamivudine,Zidovudineandotherantiretrovirals(seeWarningsandPrecautionssection).已有报道称,由于单独或联合使用核苷类似物，包括：拉米夫定、齐多夫定和其他抗逆转录病毒药物〔见“警告和留意事项”一节，消灭乳酸性酸中毒和严峻脂肪变性肝肿大，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〔印度药典〕 150mg毫克ZidovudineIP齐多夫定〔印度药典〕 300mg毫克NevirapineIP奈韦拉平〔印度药典〕 200mg毫克Description说明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种药物的组合，常用于人类免疫缺陷病毒〔HIV即艾滋病毒〕感染的处糖核酸〔DNA〕链生长，并抑制艾滋病毒〔HIV〕逆转录酶，奈韦拉平是一种非核苷逆转录酶抑制剂，它的作用，直接抑制逆转录酶活性。EachtabletofDuovir-Ncontainshalfofthecommonlyprescribeddailydosesofzidovudine,lamivudineandnevirapine.Allthreedrugsaretobeadministeredtwicedaily,permittingafixed-dosecombinationtobeformulated.Withtheavailabilityofthiscombinationformulation,patientsmaybebetterabletoadheretotripledrugregimens,therebyenhancingcompliance.Duovir-N含规定的齐多夫定、拉米夫定和奈韦拉平的每日服用剂量的一半，全部三种药物，每日服用两次，允许制定一个固定剂量组合，由于该组合制剂的有效性，患者能更好地坚持以三联药物疗法，从而提高了遵从性。Indications适应症Duovir-NisindicatedforthetreatmentofHIVinfection,oncepatientshavebeenstabilizedonthemaintenanceregimenofnevirapine200mgbd,andhavedemonstratedadequatetolerabilitytonevirapine.Duovir-N用于治疗艾滋病毒感染，一旦患者按奈韦拉平200毫克，每日两次，已经稳定在维持状况，充分证明对奈韦拉平的耐受性。DosageandAdministration剂量和用法Adult:1tablettwicedaily.成人：一次一片，每日两次,。Duovir-Nshouldnotbeadministeredtopatientswhohavejustinitiatedtherapywithnevirapine.Thisisbecauseaninitiallead-indosingof200mgnevirapineoncedailyfor2weeksisrecommended.Followingthislead-indose,adoseescalation(maintenancedose)to200mgnevirapinebdmaybecarriedoutintheabsenceofanyhypersensitivityreactions(e.g.rash,liverfunctiontestabnormalities;seeWarningsandPrecautions).Duovir-N不应当用于那些刚开头使用奈韦拉平治疗的患者，这是由于推举的奈韦拉平的初2002周时间，遵照该导入剂量，奈韦拉平剂量递增〔维持剂量〕到200毫克，每日二次，服用可能没有任何过敏反响〔如：皮疹，肝功能检查特别;见警告和留意事项。Monitoringofpatients患者的监测Intensiveclinicalandlaboratorymonitoring,includingliverfunctiontest,isessential,especiallyatbaseline,priortodoseescalationofnevirapine,andattwoweekspost doseescalation.Insomecases,hepaticinjuryhasprogresseddespitediscontinuationoftreatment(seeWarningsandPrecautions).〔见警告和留意事项。DosageAdjustment剂量调整Lamivudine:拉米夫定：Becauseitisafixed-dosecombination,Duovir-Nshouldnotbeprescribedforpatientsrequiringdosageadjustment,suchasthosewithlowbodyweight(<50kg).由于它是一个固定剂量组合，对剂量需要调整的患者，例如那些体重较轻患者<50公斤，Duovir-N的剂量。Zidovudine:齐多夫定：Becauseitisafixed-dosecombination,thisformulationshouldnotbeprescribedforpatientsrequiringdosageadjustmentsuchasthosewithreducedrenalfunction(creatinineclearance≤50ml/min)orthoseexperiencingdose-limitingadverseevents.肾功能较低的患者〔肌酐去除率≤50毫升/分〕或那些受到剂量限制不良反响的患者。Nevirapine:奈韦拉平：Duovir-Nshouldbediscontinuedifpatientsexperiencesevererashorarashaccompaniedbyconstitutionalfindings(SeeWarningsandPrecautions).Patientsexperiencingmildtomoderaterashduringthe14-daylead-inperiodof200mg/dayshouldnothavetheirnevirapinedoseincreasedorstarttherapywithDuovir-Nuntiltherashhasresolved(seeWarningsandPrecautions).假设患者患病严峻皮疹或伴随原发性症〔见警告和留意事项Duovir-N，14200毫克/天的导入期，患病轻度至中度皮疹的患者，不应增加奈韦拉平剂量，或直Duovir-N的治疗〔见警告和留意事项。Ifclinicalhepatitisoccurs,nevirapineshouldbepermanentlydiscontinuedandnotrestartedafterrecovery.假设发生临床肝炎，奈韦拉平应永久停用，而不要在恢复后重启用。Patientswhointerruptnevirapinedosingformorethan7daysshouldrestarttherecommendeddosing,usingone200mgNevimunetabletdailyforthefirst14days(lead-in)incombinationwiththeotherantiretrovirals,followedby200mgtwicedailyusing Duovir-Nintheabsenceofanysignsofhypersensitivity.中断奈韦拉平剂量，超过714天〔导入，每日服200毫克的通用奈韦拉平〔Nevimune〕片剂，结合其他抗逆转录病毒药物200毫克，然后，在没有任何过敏病症的状况下，每日两次服用Duovir-N。)Pregnancy妊娠Lamivudine,zidovudineandnevirapineareallclassifiedundercategoryC.Therearenoadequateandwell-controlledstudiesinpregnantwomen.Duovir-Nshouldbeusedduringpregnancyonlyifthepotentialbenefitsoutweighthepotentialrisk.拉米夫定、齐多夫定和奈韦拉平，都归入C类，没有对妊娠妇女进展充分、严格的比照争论，只有当潜在的好处大于潜在的风险时，才可在怀孕期间使用Duovir-N。Lactation哺乳期ItisrecommendedthatHIV-infectedmothersdonotbreastfeedtheirinfantstoavoidriskingpostnataltransmissionofHIVinfection.Itisnotknownwhetherlamivudineisexcretedinhumanmilk.Nevirapineandzidovudinearepresentinbreastmilk.险。不知道人是否分泌出拉米夫定，母存在奈韦拉平与齐多夫定。Paediatrics儿科Duovir-Nisnotintendedforuseinpaediatricpatients.Duovir-N是不供儿科患者使用。SideEffects副作用Zidovudineandlamivudine齐多夫定和拉米夫定ObservedduringClinicalPractice:Thefollowingeventshavebeenidentifiedduringpost-approvaluseoflamivudine,zidovudine,and/orlamivudine/zidovudine.Becausetheyarereportedvoluntarilyfromapopulationofunknownsize,estimatesoffrequencycannotbemade.Theseeventshavebeenchosenforinclusionduetoacombinationoftheirseriousness,frequencyofreporting,orpotentialcausalconnectiontolamivudine,zidovudine,and/orlamivudine/zidovudine.在临床实践中观看到：在批准使用拉米夫定、齐多夫定，和/或拉米夫定/齐多夫定后期间，状况已列入选择，由于报道综合了它们的严峻性、频率、或与拉米夫定、齐多夫定，和/或拉米夫定/齐多夫定的潜在的因果关系。BodyasaWhole:Redistribution/accumulationofbodyfat(seeWarningsandPrecautions:Fatredistribution)整体：体内脂肪重分布积存〔见警告和留意事项：脂肪的重分布〕Cardiovascular:Cardiomyopathy.心血管：心肌病EndocrineandMotabolic:Gynecomastia,hyperglycemia.内分泌和代谢：男性乳房发育症，高血糖。Gastrointestinal:Oralmucosalpigmentation,stomatitis.胃肠道：口腔黏膜色素冷静，口腔炎。General:Vasculitis,weakness综合：脉管炎，四肢无力。HaemicandLymphatic:Aplasticanaemia,anaemia,lymphadenopathy,pureredcellaplasia,splenomegaly.血液和淋巴管：再生障碍性贫血、贫血、淋巴结肿大、纯红细胞再生障碍性贫血、脾肿大。HepaticandPancreatic:Lacticacidosisandhepaticsteatosis,pancreatitis,post-treatmentexacerbationofhepatitisB(seeWarningsandPrecautions).肝和胰腺：乳酸性酸中毒和脂肪肝、胰腺炎、乙型肝炎治疗后发作〔见警告和留意事项。Hypersensitivity:Sensitizationreactions(includinganaphylaxis),urticaria.过敏症：致敏反响〔包括过敏性反响、荨麻疹。Musculoskeletal:Muscleweakness,CPKelevation,rhabdomyolysis.肌肉骨骼：肌肉无力、肌酸磷酸激酶(CPK)上升、横纹肌溶解症。Nervous:Paraesthesia,peripheralneuropathy,seizures.神经系统：感觉特别、四周神经病变、癫痫。Respiratory:Abnormalbreathsounds/wheezing.呼吸系统/哮喘。Skin:Alopecia,erythemamultiforme,Stevens-Johnsonsyndrome.皮肤：脱发、多形性红斑、史蒂文斯—约翰逊综合征。Nevirapine奈韦拉平Clinicalpracticehasshownthatthemostseriousadversereactionsassociatedwithnevirapineareclinicalhepatitis/hepaticfailure,Stevens-Johnsonsyndrome,toxicepidermalnecrolysis,andhypersensitivityreactions.Clinicalhepatitis/hepaticfailuremaybeisolatedorassociatedwithsignsofhypersensitivitywhichmayincludesevererashorrashaccompaniedbyfever,generalmalaise,fatigue,muscleorjointaches,blisters,orallesions,conjunctivitis,facial oedema,and/orhepatitis,eosinophilia,granulocytopenia,lymphadenopathy,andrenaldysfunction./—约翰逊〔Stevens–Johnson〕/肝衰竭可能是孤立的，或伴随过敏症兆，其中可能包括严峻皮疹或皮疹伴有发热、全身不适、乏力、肌肉或关节苦痛、水泡、口腔溃疡、结膜炎、面部水肿、和/或肝炎/嗜酸性细胞增多、粒细胞减少、淋巴结肿大和肾功能障碍。Severeandlife-threateninghepatotoxicity,andfatalfulminanthepatitishavebeenreportedinpatientstreatedwithnevirapine.Hepaticadverseeventshavebeenreportedtooccurmorefrequentlyduringthefirst18weeksoftreatment,butsucheventsmayoccuratanytimeduringtreatment.报道，肝不良反响更频繁地发生在治疗的初始18周，但治疗期间，这样的反响可能随时发生。Incontrolledclinicaltrials,clinicalhepaticeventsregardlessofseverityoccurredin4.0%(range2.5%to11.0%)ofpatientswhoreceivednevirapineand1.2%ofpatientsincontrolgroups.Transaminaseelevations(ALTorAST＞5xULN)wereobservedin8.8%ofpatientsreceivingnevirapineand6.2%ofpatientsincontrolgroupsinclinicaltrials.Inaretrospectiveanalysisofcontrolledanduncontrolledclinicaltrials,patientswithhigherCD4countsatinitiationofnevirapinetherapy,particularlywomenwereatgreaterriskforacutesymptomatichepaticevents,includingdeath,especiallyinthefirstsixweeksoftherapy.PatientswithchronichepatitisBorCinfectionwereathigherriskforlaterhepaticevents.比照临床试验中，承受奈韦拉平治疗的患者，发生临床肝炎病症，不管严峻程度，在4.0％〔范围在2.％—11.％1.,8.86.2％，转氨酶上升〔谷丙转氨酶[ALT]或谷草转氨酶[AST]>5[ULNCD4计数更高的患者，在治疗的初始6周时间，慢性乙型或丙型肝炎病毒感染的患者，后来的肝炎病症风险较高。Themostcommonclinicaltoxicityofnavirapineisrash.Severeorlife-threateningrashoccurredinapproximately2%ofnevirapine-treatedpatients,mostfrequentlywithinthefirst6weeksoftherapy.Rashesareusuallymildtomoderate, maculopapularerythomatouscutaneouseruptions,withorwithoutpruritus,locatedonthetrunk,faceandextremities. Womentendtobeathigherriskfordevelopmentofnavirapineassociatedrash.奈韦拉平最常见的临床毒性是皮疹，大约2％受奈韦拉平治疗的患者，最常见是在治疗的初始6相关的皮疹的高危人群。Withrespecttolaboratoryabnormalities,liverfunctiontestabnormalities(SGOT,SGPT)wereobservedmorefrequentlyinpatientsreceivingnovirapinethanincontrols.AsymptomaticelevationsinSGToccurfrequentlybutarenotacontraindicationtocontinuenevirapinetherapyintheabsenceofelevationsofotherliverfunctiontests.〔[SGOT[SGPT，常常发生梅毒絮状沉淀试验SG治试验无病症上升，但不是连续奈韦拉平治疗的禁忌症—在其他肝功能检查数据没有上升的状况下。Becauseclinicalhepatitishasbeenreportedinnevirapine-treatedpatients,intensiveclinicalandlaboratorymonitoring,includingliverfunctiontests,isessentialatbaselineandduringthefirst18weeksoftreatment,Monitoringshouldcontinueatfrequentintervalsthereafter,dependingonthepatiensclinicalstatus.由于已有报道，承受奈韦拉平治疗的患者发生临床肝炎，在基线时和初始18周治疗期间，频繁的间隔，连续进展监测。Inadditiontotheadverseeventsindentifiedduringclinicaltrials,thefollowingeventshavebeenreportedwiththeuseofNevirapineinclinicalpractice.除了在临床试验中被证明的不良反响，已有报道使用奈韦拉平的以下临床反响：BodyasaWhole:fever,somnolence,drugwithdrawal全身：发热、嗜睡、药物戒断。Gastrointestinal:vomiting胃肠道反响：呕吐LiverandBiliary:jaundice,fulminantandcholestatichepatiltis,hepaticnecrosis,hepaticfailure肝和胆：黄疸、爆发型和淤胆性肝炎、肝坏死、肝功能衰竭。Haematology:anaemia,eosinophilia,neutropenia血液学：贫血，嗜曙红细胞增多，嗜中性白血球削减症。Musculoskeletal:arthralgia肌肉骨骼：关节痛Neurologic:paraesthesia神经系统：感觉特别SkinandAppendages:allergicreactionsincludinganaphylaxis,angioedema,bullouseruptions,ulcerativestomatitisandurticariahaveallbeenreported.Inaddition,hypersensitivitysyndromeandhypersensitivityreactionswithrashassociatedwithconstitutionalfindingssuchasfever,blistering,orallesions,conjunctivitis,facialedema,muscleorjointaches,generalmalaise,fatigueorsignificanthepaticabnormalitiesplusoneormoreofthefollowing:hepatitis,eosinophilia,granulocytopenia,lymphadenopathyand/orrenaldysfunctionhavebeenreportedwiththeuseofnavirapine.皮肤及附件：过敏反响、包括过敏性休克、血管神经性水肿、大疱爆发、溃疡性口腔炎和荨麻疹都有报道，此外，与原发性病症相关的皮疹过敏综合征和过敏反响，如：发热、水泡、口腔溃疡、结膜炎、面部水肿、肌肉或关节苦痛、全身不适、疲乏或明显的肝功能特别，由于服用奈韦拉平，伴有一个或多个以下状况：肝炎、嗜酸性粒细胞增多、粒细胞削减、淋巴结肿大、和/或肾功能失调，都有报道。Overdosage过剂量Lamivudine拉米夫定Thereisnoknownantidoteforlamivudine.Itisnotknownwhetherlamivudinecanberemovedbyperitonealdialysisorhemodialysis.Ifoverdoseoccurs,thepatientshouldbemonitored,andstandardsupportivetreatmentappliedasrequired.没有的拉米夫定的解毒剂，不知是否可以通过腹膜透析或血液透析，来去除拉米夫定，假设发生过剂量时，应监测病人，依据需要，应用标准的支持治疗。Zidovudine齐多夫定Acuteoverdosesofzidovudinehavebeenreportedinpediatricpatientsandadults.Theseinvolvedexposuresupto50grams.Nospecificsymptomsorsignshavebeenidentifiedfollowingacuteoverdosagewithzidovudineapartfromthoselistedasadverseeventssuchasfatigue,headache,vomiting,andoccasionalreportsofhaematologicaldisturbances.Allpatientsrecoveredwithoutpermanentsequelae.Haemodialysisandperitonealdialysisappeartohaveanegligibleeffectontheremovalofzidovudinewhileeliminationofitsprimarymetabolite,GZDV,isenhanced.据报道，发生过小儿患者和成人齐多夫定服用急性过量，这些涉及暴露量高达50克的。没有析，似乎对去除齐多夫定的作用微缺乏道，然而增加了消退其主要代谢产物—GZDV【3’-叠氮-3’-5’-O-〔β〕-D-glucopyranuronosylthymidineNevirapine奈韦拉平Thereisnoknownantidotefornevirapineoverdosage.没有的奈韦拉平过量的解毒剂。Presentation赠品Duovir-N containerof30tabletsDuovir-N 30片容器装(第一页左边完)Contraindications禁忌症Duovir-Niscontraindicatedinpatientswithclinicallysignificanthypersensitivitytoanyofthecomponentscontainedintheformulation.临床上，对制剂中所含的任何成清楚显过敏的患者，禁用Duovir-N。Duovir-Nisalsocontraindicatedforpatientswhoarejustinitiatingtherapywithnevirapine.Thesepatientsrequirealead-indoseofnevirapine200mgo.d.,whereasthisformulationcontainsthemaintenancedoseofnevirapine200mgb.d.(seeIndications).Duovir-200毫克的导入剂量，而这一制剂包含的奈韦拉平的维持剂量，为200〔见适应症。WarningsandPrecautions警告和留意事项DrugInteractions药物交互作用Lamivudine拉米夫定Lamivudineispredominantlyeliminatedintheurinebyactiveorganiccationicsecretion.Thepossibilityofinteractionswithotherdrugsadministeredconcurrentlyshouldbeconsidered,particularlywhentheirmainrouteofeliminationisactiverenalsecretionviatheorganiccationictransportsystem(e.g.trimethoprim).〔苄氨啶〕的活泼肾脏分泌。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，已被证明能增加拉米夫定暴露量AU：药时曲线下面积，不建议转变两种药物的剂量，没有关于拉米夫定药代动力学影响的资料—磺胺甲基异恶唑TMP/SMX，用于治疗卡氏肺孢菌肺炎，无据可查类似拉米夫定与其他药物的相互作用的肾脏去除机理，拉米夫定和扎西他宾〔zalcitabine抗艾滋病药)，可能会相互抑制细胞内磷酸化，因此，不推举使用拉米夫定结合扎西他宾〔zalcitabine抗艾滋病药)。Zidovudine齐多夫定Forpatientsexperiencingpronouncedanaemiaorotherseverezidovudine-associatedeventswhilereceivingchronicadministrationofzidovudineandsomeofthefollowingdrugs-atovaquone,fluconazole,methadone,nelfinavir,probenecid,rifampin,ritonavir,valproicacid-zidovudinedosereductionmaybeconsidered.SinceDuovir-Nisafixeddosecombination,itcannotbeusedforthispatientpopulation.对于患明显贫血或其他严峻与齐多夫定相关反响的患者药物：阿托喹酮(atovaquone抗疟药)、氟康唑、美沙酮、奈非那韦、丙磺舒、利福平、利托Duovir-N是一个固定剂量组合，它不能用于这个病患族群。Antiretroviralagents:Concomitantuseofzidovudinewithstavudineshouldbeavoidedsinceanantagonisticrelationshiphasbeendemonstratedinvitro.抗逆转录病毒药物：应避开齐多夫定与司他夫定〔stavudine〕相伴使用，由于已证明在体外的对立关系。SomenucleosideanaloguesaffectingDNAreplication,suchasribavirin,antagonizethe invitroantiviralactivityofzidovudineagainstHIV;concomitantuseofsuchdrugsshouldbeavoided.一些核苷(酸)类似物，影响脱氧核糖核酸〔DNA〕的复制，如：病毒唑，拮抗齐多夫定在体外对艾滋病毒的抗病毒活性，应避开此类药物的同时使用。Doxorubicin:Concomitantuseofzidovudinewithdoxorubicinshouldbeavoidedsinceanantagonisticrelationshiphasbeendemonstratedinvitro.。Phenytoin:Phenytoinplasmalevelshavebeenreportedtobelowinsomepatientsreceivingzidovudine，whilein1caseahighlevelwasdocumented.However,inapharmacokineticinteractionstudyinwhich12HIV-positivevolunteersreceivedasingle300-mgphenytoindosealoneandduringsteady-statezidovudineconditions(200mgevery4hours),nochangeinphenytoinkineticswasobserved.Althoughnotdesignedtooptimallyassesstheeffectofphenytoinonzidovudinekinetics,a30%decreaseinoralzidovudineclearancewasobservedwithphenytoin.例高水平病例记录12独承受单一的300毫克的苯妥英的剂量，在稳态阶段期间，齐多夫定的状况〔4小时200毫克夫定动力学的影响，但观看到口服齐多夫定的去除削减30％。OverlappingToxicities:Co-administrationofganciclovir,interferon-alpha,andotherbonemarrowsuppressiveorcytotoxicagentsmayincreasethehaematologictoxicityofzidovudine.重叠毒性：更昔洛韦、α-干扰素、和其他骨髓抑制或细胞毒性药物的联合服用可能会增加齐多夫定的血液学毒性。Novirapine奈韦拉平NavirapineisprincipallymetabolizedbytheliverviathecytochromeP450isoenzymes,3A4and2B6.Nevireapineisknowntobeaninduceroftheseenzymes.Thus,ifapatienthasbeenstabilizedonadosageregimenforadrugmetabolizedbyCYP3A,andbeginstreatmentwithnevirapine,doseadjustmentsmaybenecessary.奈韦拉平主要通过细胞色素P450同功酶，3A4和2B6，由肝脏代谢，奈韦拉平是这些酶的诱导剂，因此，假设病人，始终稳定在由CYP3A药物代谢的给药方案，并开头用奈韦拉平治疗，剂量的调整可能是必要的。Clinicalcommentsaboutpossibledosagemodificationsaregivenbelow:可能修改的临床剂量意见，给出如下：EstablishedDrugInteractionswithnevirapine用奈韦拉平的药物相互作用Ketoconazole:Nevirapineandketoconazoleshouldnotbeadministeredconcomitantly,becausedecreasesinketoconazoleplasmaconcentrationsmayreducetheefficacyofthedrug.的疗效。Clarithromycin:Clarithromycinexposurewassignificantlydecreasedbynevirapine;however,14-OHmetaboliteconcentrationswereincreased.BecauseclarithromycinactivemetabolitehasreducedactivityagainstMycobacteriumavium-intracetlularecorlactivityagainstthispathogenmaybealtered.Alternativestoclarithromycin,suchasazithromycin,shouldbeconsidered.克拉克拉：克拉霉素暴露量被奈韦拉平明显降低；然而，14-羟基代谢物浓度增加，由的整体活性，可能会转变，应考虑克拉霉素的替代物，如：阿奇霉素。Efavirenz:Efavirenzconcentrationsaredecreased.Appropriatedosesforthiscombinationarenotestablished.EthinylestradiolandNorethindrone:Concentrationsofbothdrugsaredecreased.Oralcontraceptivesandotherhormonalmethodsofbirthcontrolshouldnotbeusedasthesolemethodofcontraceptioninwomentakingnevirapine,sincenevirapinemaylowertheplasmalevelsofthesemedications.Analternativeofadditionalmethodofcontraceptionisrecommended.议选择其他的避孕方法。Rifabutin:Concentrationsofrifabutinanditsmetaboliteweremoderatelyincreased.Duetohighintersubjectvariability,however,somepatientsmayexperiencelargeincreasesinrifabutinexposureandmaybeathigherriskforrifabutintoxicity.Therefore,cautionshouldbeusedinconcomitantadministration.利福布汀：利福布汀的浓度及其代谢产物，轻度增加，然而，由于个体之间的高度变异性，此，应慎重同时服用。Rifampin:Nevirapineandrifampinshouldnotbeadministeredconcomitantlybecausedecreasesinnevirapineplasmaconcentrationsmay reducetheefficacyofthedrug.Physiciansneedingtotreatpatientsco-infectedwithtuberculosisandusinganevirapine-containingregimenmayuserifabutininstead.用利福布丁代替。Fluconazole:Becauseoftheriskofincreasedexposuretonevirapine,cautionshouldbeusedinconcomitantadministration,andpatientsshouldbemonitoredcloselyfornevirapine-associatedadverseevents.相关的不良大事监测反响。Indinavir:Concentrationsofindinaviraredecreased.Appropriatedosesforthiscombinationarenotestablished,butanincreaseinthedosageofindinavirmayberequired.能是必需的。Lopinavir/Ritonavir:Adoseincreaseoflopinavir/ritonavirto533/133mgtwicedailywithfoodisrecommendedincombinationwithnevirapine洛匹那韦/利托那韦：建议在与奈韦拉平组合中，洛匹那韦/利托那韦的剂量增加到133/533毫克，每天两次，结合食物。Nelfinavir:Theappropriatedosefornelfinavirincombinationwithnevirapine,withrespecttosafetyandefficacy,hasnotbeenestablished.奈非那韦：奈非那韦与奈韦拉平组合的适当剂量，关于安全性和有效性方面，尚未确定。Saquinavir:Appropriatedosesforthiscombinationarenotestablished,butanincreaseinthedosageofsaquinavirmayberequired.沙奎那韦：这个组合的适当剂量，尚未确定，但可能需要增加沙奎那韦的剂量。Methadone:Methadonelevelsmaybedecreased,increaseddosagesmayberequiredtopreventsymptomsofopiatewithdrawal.Methadone-maintainedpatientsbeginningnevirapinetherapyshouldbemonitoredforevidenceofwithdrawalandmethadonedoseshouldbeadjustedaccordingly.美沙酮：美沙酮水平可能会下降，可能需要增加剂量，以防止鸦片戒断病症，应当监测开头奈韦拉平治疗的美沙酮替代维持患者的戒断证据，并且美沙酮剂量，应作相应调整。Potentialdruginteractionsarelistedbelow:以下是潜在的药物相互作用：Examplesofdrugsinwhichplasmaconcentrationsmaybedecreasedbyco-administrationwithnevirapine.与奈韦拉平联合服用，药物血浆浓度可能降低的例子：Antiarrhythmics: e.g. Amiodarone,disopyramide,lidocaine抗心律不齐药：如:：胺碘酮、丙吡胺、利多卡因。Anticonvulsants: e.g. Carbamazepine,clonazepam,ethosuximide抗惊厥药物：如：卡马西平、氯硝西泮、乙琥胺。Antifungals: e.g.Itraconazole.抗真菌药：如：伊曲康唑。Calciumchannelblockers:Diltiazem,nifedipine,verapamil钙通道阻滞剂：恬尔心、硝苯地平、异博定。Cancerchemotherapy:Cyclophosphamide癌症化疗：环磷酰胺。Ergotalkaloids:Ergotamine麦角生物碱：麦角胺。Immunosuppressants:Cyclosporin,tacrolimus,sirolimus免疫抑制剂：环孢素、他克莫司、西罗莫司。Motilityagents:Cisapride蠕动药物：西沙必利。Opiateagonists:Fentanyl阿片受体感动剂：芬太尼。Examplesofdrugsinwhichplasmaconcentrationsmaybeincreasedbyco-atiministrationwithnevirapine.与奈韦拉平联合服用，药物血浆浓度可能增加的例子：Anticoagulantse.g.warfarin.Potentialeffectonanticoagulation.Monitoringofanticoagulationlevelsisrecommended.抗凝血剂，如：华法林，潜在的抗凝血作用，建议监测抗凝水平。Skinreactions:皮肤反响：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据报道，使用奈韦拉平治疗，已发生过严峻、危及生命的皮肤反响，包括致命的病例，最常6周的治疗时间，这些包括Stevens-Johnson综合征〔史蒂文斯-约翰逊综合征[即：重症多形性红斑])、中毒性表皮坏死松解症和过敏反响，特征为：皮疹、原发性病症和器〔包括但不限于严峻皮面或肝炎、嗜酸性粒细胞、粒细胞削减、淋巴结肿大和肾功能不全，必需尽快停顿反响，不应重启用奈韦拉平。一些危急因素进展成严峻的〔转下〕〔其次页左边完毕〕cutaneousreactionsincludefailuretofollowtheinitialdosingof200mgdailyduringthe14-daylead-inperiodanddelayinstoppingthenevirapinetreatmentaftertheonsetoftheinitialsymptoms.Ifpatientspresentwithasuspectednevirapine-associatedrash,liverfunctiontestsshouldbeperformed.Patientswithrash-associatedASTorALTelevationsshouldbepermanentlydiscontinuedfromnevirapine.〔接上14200mg和初期病症期发作后，相关的谷丙转案酶〔AST〕或谷丙转氨酶〔ALT〕上升的病人，应永久停用奈韦拉平。Therapywithnevirapinemustbeinitiatedwitha14-daylead-inperiodof200mg/day,whichhasbeenshowntoreducethefrequencyofrash.Ifrashisobservedduringthislead-inperiod,doseescalationshouldnotoccuruntiltherashhasresolved.(seeDosageandAdministration).Patientsshouldbemonitoredcloselyifisolatedrashofanyseverityoccurs.200毫克/14假设在此导入期，观看到皮疹，不应当递增剂量，直到皮疹已经解决〔见用法用量。假设患者发生任何严峻孤立的皮疹，应亲热监测。Womenappeartobeathigherriskthanmanofdevelopingrashwithnevirapine.Theuseofprednisonetopreventnevirapineassociatedrashisnotrecommended.关的皮疹。Zidovudineandlamivudine齐多夫定和拉米夫定Lacticacidosis/severehepatomegalywithsteatosis,includingfatalcases,havebeenreportedwiththeuseofantiretroviralnucleosideanaloguesaloneorincombination.Amajorityofthesecaseshavebeeninwomen.Obesityandprolongednucleosideexposuremayberiskfactors.Cautionshould be exercised when administering zidovudine and lamivudine to any patient, a