Ativan (Lorazepam): Uses, Dosage, Side Effects, Interactions ...

Ativan is a prescription medicine used to treat the symptoms of anxiety disorders. Ativan may be used alone or with other medications. Ativan belongs to a class ... Ativan GenericName:lorazepamBrandName:Ativan DrugClass:HowDoBenzodiazepineAnxiolyticsWork?,,Anticonvulsants,Benzodiazepine LastupdatedonRxList:3/1/2021 home drugsa-zlist sideeffectsdrugcenterativan(lorazepam)drug SideEffectsCenter RelatedDrugs Alsuma Amerge Aptiom Belsomra Buspar Byfavo DexedrineSpansule DiazepamInjection Dilantin125 Dilaudid Doral Fintepla Flexeril ImitrexInjection Klonopin Librax Librium Lortab2.5 Maxalt Niravam Onfi Oxazepam OxtellarXR Phenobarbital Prosom Savella Seizalam Trileptal Valium Vimpat Xanax XanaxXR Xeomin Zonegran HealthResources Anxiety Seizure(Epilepsy) SeizuresSymptomsandTypes Stress StressManagementTechniques RelatedSupplements Kava Melatonin N-AcetylCysteine DrugComparison Ataraxvs.Ativan Ativanvs.Baclofen Ativanvs.Klonopin Ativanvs.Lexapro Ativanvs.Librium Ativanvs.Nortriptyline Ativanvs.Valium Ativanvs.Xanax BuSparvs.Ativan Haldolvs.Ativan Midazolamvs.Ativan Restorilvs.Ativan Vistarilvs.Ativan AtivanUserReviews DrugDescription Indications&Dosage SideEffects DrugInteractions Warnings Precautions Overdose&Contraindications ClinicalPharmacology MedicationGuide DrugDescription FindLowestPriceson WhatisAtivanandhowisitused?Ativanisaprescriptionmedicineusedtotreatthesymptomsofanxietydisorders.Ativanmaybeusedaloneorwithothermedications.AtivanbelongstoaclassofdrugscalledAntianxietyAgents,Anxiolytics,Benzodiazepines,Anticonvulsants,Benzodiazepine.WhatarethepossiblesideeffectsofAtivan?Ativanmaycauseserioussideeffectsincluding:severedrowsiness,thoughtsofsuicideorhurtingyourself,unusualchangesinmoodorbehavior,confusion,aggression,hallucinations,worsenedsleepproblems,suddenrestlessfeelingorexcitement,muscleweakness,droopingeyelids,troubleswallowing,visionchanges,upperstomachpain,darkurine,andyellowingoftheskinoreyes(jaundice)Getmedicalhelprightaway,ifyouhaveanyofthesymptomslistedabove.ThemostcommonsideeffectsofAtivaninclude:dizziness,drowsiness,weakness,slurredspeech,lackofbalanceorcoordination,memoryproblems,andfeelingunsteadyTellthedoctorifyouhaveanysideeffectthatbothersyouorthatdoesnotgoaway.ThesearenotallthepossiblesideeffectsofAtivan.Formoreinformation,askyourdoctororpharmacist.Callyourdoctorformedicaladviceaboutsideeffects.YoumayreportsideeffectstoFDAat1-800-FDA-1088.DESCRIPTIONAtivan(lorazepam),anantianxietyagent,hasthechemicalformula,7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one:C15H10Cl2N2O2    MW:321.16Itisanearlywhitepowderalmostinsolubleinwater.EachAtivan(lorazepam)tablet,tobetakenorally,contains0.5mg,1mg,or2mgoflorazepam.Theinactiveingredientspresentarelactosemonohydrate,magnesiumstearate,microcrystallinecellulose,andpolacrilinpotassium. Indications&Dosage INDICATIONSAtivan(lorazepam)isindicatedforthemanagementofanxietydisordersorfortheshort-termreliefofthesymptomsofanxietyoranxietyassociatedwithdepressivesymptoms.Anxietyortensionassociatedwiththestressofeverydaylifeusuallydoesnotrequiretreatmentwithananxiolytic.TheeffectivenessofAtivan(lorazepam)inlong-termuse,thatis,morethan4months,hasnotbeenassessedbysystematicclinicalstudies.Thephysicianshouldperiodicallyreassesstheusefulnessofthedrugfortheindividualpatient.DOSAGEANDADMINISTRATIONAtivan(lorazepam)isadministeredorally.Foroptimalresults,dose,frequencyofadministration,anddurationoftherapyshouldbeindividualizedaccordingtopatientresponse.Tofacilitatethis,0.5mg,1mg,and2mgtabletsareavailable.Theusualrangeis2to6mg/daygivenindivideddoses,thelargestdosebeingtakenbeforebedtime,butthedailydosagemayvaryfrom1to10mg/day.Foranxiety,mostpatientsrequireaninitialdoseof2to3mg/daygiventwotimesadayorthreetimesaday.Forinsomniaduetoanxietyortransientsituationalstress,asingledailydoseof2to4mgmaybegiven,usuallyatbedtime.Forelderlyordebilitatedpatients,aninitialdosageof1to2mg/dayindivideddosesisrecommended,tobeadjustedasneededandtolerated.ThedosageofAtivan(lorazepam)shouldbeincreasedgraduallywhenneededtohelpavoidadverseeffects.Whenhigherdosageisindicated,theeveningdoseshouldbeincreasedbeforethedaytimedoses.DiscontinuationOrDosageReductionOfAtivanToreducetheriskofwithdrawalreactions,useagradualtapertodiscontinueAtivanorreducethedosage.Ifapatientdevelopswithdrawalreactions,considerpausingthetaperorincreasingthedosagetotheprevioustapereddosagelevel.Subsequentlydecreasethedosagemoreslowly(seeWARNINGS:DependenceAndWithdrawalReactionsandDrugAbuseAndDependence:Dependence).HOWSUPPLIEDAtivan®(lorazepam)Tabletsareavailableinthefollowingdosagestrengths:0.5mg,white,five-sided(shieldshape)tabletwitharaised"A"ononesideand"BPI"and"63"impressedonreverseside.NDC0187-0063-01-Bottlesof100tablets.1mg,white,five-sided(shieldshape)tabletwitharaised"A"ononesideand"BPI"and"64"impressedonscoredreverseside.NDC0187-0064-01-Bottlesof100tablets.NDC0187-0064-10-Bottlesof1,000tablets.2mg,white,five-sided(regularpentagon)tabletwitharaised"A"andimpressed"2"ononesideand"BPI"and"65"impressedonscoredreverseside.NDC0187-0065-01-Bottlesof100tablets.Keepbottlestightlyclosed.Keepoutofreachofchildren.Storeat25°C(77°F);excursionspermittedto15°to30°C(59°to86°F)[seeUSPControlledRoomTemperature].Dispenseinatightcontainer.Manufacturedby:BauschHealthCompaniesInc.Steinbach,MBR5G1Z7,Canada.Revised:Feb2021 SLIDESHOW AnxietyDisorderPictures:Symptoms,PanicAttacks,andMorewithPictures SeeSlideshow SideEffects SIDEEFFECTSMostadversereactionstobenzodiazepines,includingCNSeffectsandrespiratorydepression,aredosedependent,withmoresevereeffectsoccurringwithhighdoses.Inasampleofabout3500patientstreatedforanxiety,themostfrequentadversereactiontoAtivan(lorazepam)wassedation(15.9%),followedbydizziness(6.9%),weakness(4.2%),andunsteadiness(3.4%).Theincidenceofsedationandunsteadinessincreasedwithage.Otheradversereactionstobenzodiazepines,includinglorazepamarefatigue,drowsiness,amnesia,memoryimpairment,confusion,disorientation,depression,unmaskingofdepression,disinhibition,euphoria,suicidalideation/attempt,ataxia,asthenia,extrapyramidalsymptoms,convulsions/seizures,tremor,vertigo,eyefunction/visualdisturbance(includingdiplopiaandblurredvision),dysarthria/slurredspeech,changeinlibido,impotence,decreasedorgasm;headache,coma;respiratorydepression,apnea,worseningofsleepapnea,worseningofobstructivepulmonarydisease;gastrointestinalsymptomsincludingnausea,changeinappetite,constipation,jaundice,increaseinbilirubin,increaseinlivertransaminases,increaseinalkalinephosphatase;hypersensitivityreactions,anaphylactoidreactions;dermatologicalsymptoms,allergicskinreactions,alopecia;syndromeofinappropriateantidiuretichormone(SIADH),hyponatremia;thrombocytopenia,agranulocytosis,pancytopenia;hypothermia;andautonomicmanifestations.Paradoxicalreactions,includinganxiety,excitation,agitation,hostility,aggression,rage,sleepdisturbances/insomnia,sexualarousal,andhallucinationsmayoccur.Smalldecreasesinbloodpressureandhypotensionmayoccurbutareusuallynotclinicallysignificant,probablybeingrelatedtothereliefofanxietyproducedbyAtivan(lorazepam).ToreportSUSPECTEDADVERSEREACTIONS,contactBauschHealthUS,LLCat1-800-3214576orFDAat1-800-FDA-1088orwww.fda.gov/medwatch. DrugInteractions DRUGINTERACTIONSTheconcomitantuseofbenzodiazepinesandopioidsincreasestheriskofrespiratorydepressionbecauseofactionsatdifferentreceptorsitesintheCNSthatcontrolrespiration.BenzodiazepinesinteractatGABAAsitesandopioidsinteractprimarilyatmureceptors.Whenbenzodiazepinesandopioidsarecombined,thepotentialforbenzodiazepinestosignificantlyworsenopioid-relatedrespiratorydepressionexists.Limitdosageanddurationofconcomitantuseofbenzodiazepinesandopioids,andmonitorpatientscloselyforrespiratorydepressionandsedation.Thebenzodiazepines,includingAtivan(lorazepam),produceincreasedCNS-depressanteffectswhenadministeredwithotherCNSdepressantssuchasalcohol,barbiturates,antipsychotics,sedative/hypnotics,anxiolytics,antidepressants,narcoticanalgesics,sedativeantihistamines,anticonvulsants,andanesthetics.Concomitantuseofclozapineandlorazepammayproducemarkedsedation,excessivesalivation,hypotension,ataxia,delirium,andrespiratoryarrest.Concurrentadministrationoflorazepamwithvalproateresultsinincreasedplasmaconcentrationsandreducedclearanceoflorazepam.Lorazepamdosageshouldbereducedtoapproximately50%whencoadministeredwithvalproate.Concurrentadministrationoflorazepamwithprobenecidmayresultinamorerapidonsetorprolongedeffectoflorazepamduetoincreasedhalf-lifeanddecreasedtotalclearance.Lorazepamdosageneedstobereducedbyapproximately50%whencoadministeredwithprobenecid.Theeffectsofprobenecidandvalproateonlorazepammaybeduetoinhibitionofglucuronidation.Administrationoftheophyllineoraminophyllinemayreducethesedativeeffectsofbenzodiazepines,includinglorazepam.DrugAbuseAndDependenceControlledSubstanceAtivancontainslorazepam,aScheduleIVcontrolledsubstance.AbuseAtivanisabenzodiazepineandaCNSdepressantwithapotentialforabuseandaddiction.Abuseistheintentional,non-therapeuticuseofadrug,evenonce,foritsdesirablepsychologicalorphysiologicaleffects.Misuseistheintentionaluse,fortherapeuticpurposes,ofadrugbyanindividualinawayotherthanprescribedbyahealthcareproviderorforwhomitwasnotprescribed.Drugaddictionisaclusterofbehavioral,cognitive,andphysiologicalphenomenathatmayincludeastrongdesiretotakethedrug,difficultiesincontrollingdruguse(e.g.,continuingdrugusedespiteharmfulconsequences,givingahigherprioritytodrugusethanotheractivitiesandobligations),andpossibletoleranceorphysicaldependence.Eventakingbenzodiazepinesasprescribedmayputpatientsatriskforabuseandmisuseoftheirmedication.Abuseandmisuseofbenzodiazepinesmayleadtoaddiction.Abuseandmisuseofbenzodiazepinesoften(butnotalways)involvetheuseofdosesgreaterthanthemaximumrecommendeddosageandcommonlyinvolveconcomitantuseofothermedications,alcohol,and/orillicitsubstances,whichisassociatedwithanincreasedfrequencyofseriousadverseoutcomes,includingrespiratorydepression,overdose,ordeath.Benzodiazepinesareoftensoughtbyindividualswhoabusedrugsandothersubstances,andbyindividualswithaddictivedisorders(seeWARNINGS:Abuse,Misuse,AndAddiction).Thefollowingadversereactionshaveoccurredwithbenzodiazepineabuseand/ormisuse:abdominalpain,amnesia,anorexia,anxiety,aggression,ataxia,blurredvision,confusion,depression,disinhibition,disorientation,dizziness,euphoria,impairedconcentrationandmemory,indigestion,irritability,musclepain,slurredspeech,tremors,andvertigo.Thefollowingsevereadversereactionshaveoccurredwithbenzodiazepineabuseand/ormisuse:delirium,paranoia,suicidalideationandbehavior,seizures,coma,breathingdifficulty,anddeath.Deathismoreoftenassociatedwithpolysubstanceuse(especiallybenzodiazepineswithotherCNSdepressantssuchasopioidsandalcohol).DependencePhysicalDependenceAtivanmayproducephysicaldependencefromcontinuedtherapy.Physicaldependenceisastatethatdevelopsasaresultofphysiologicaladaptationinresponsetorepeateddruguse,manifestedbywithdrawalsignsandsymptomsafterabruptdiscontinuationorasignificantdosereductionofadrug.Abruptdiscontinuationorrapiddosagereductionofbenzodiazepinesoradministrationofflumazenil,abenzodiazepineantagonist,mayprecipitateacutewithdrawalreactions,includingseizures,whichcanbelife-threatening.Patientsatanincreasedriskofwithdrawaladversereactionsafterbenzodiazepinediscontinuationorrapiddosagereductionincludethosewhotakehigherdosages(i.e.,higherand/ormorefrequentdoses)andthosewhohavehadlongerdurationsofuse(seeWARNINGS:DependenceAndWithdrawalReactions).Toreducetheriskofwithdrawalreactions,useagradualtapertodiscontinueAtivanorreducethedosage(seeDOSAGEANDADMINISTRATION:DiscontinuationOrDosageReductionOfAtivanandWARNINGS).AcuteWithdrawalSignsandSymptomsAcutewithdrawalsignsandsymptomsassociatedwithbenzodiazepineshaveincludedabnormalinvoluntarymovements,anxiety,blurredvision,depersonalization,depression,derealization,dizziness,fatigue,gastrointestinaladversereactions(e.g.,nausea,vomiting,diarrhea,weightloss,decreasedappetite),headache,hyperacusis,hypertension,irritability,insomnia,memoryimpairment,musclepainandstiffness,panicattacks,photophobia,restlessness,tachycardia,andtremor.Moresevereacutewithdrawalsignsandsymptoms,includinglife-threateningreactions,haveincludedcatatonia,convulsions,deliriumtremens,depression,hallucinations,mania,psychosis,seizuresandsuicidality.ProtractedWithdrawalSyndromeProtractedwithdrawalsyndromeassociatedwithbenzodiazepinesischaracterizedbyanxiety,cognitiveimpairment,depression,insomnia,formication,motorsymptoms(e.g.,weakness,tremor,muscletwitches),paresthesia,andtinnitusthatpersistsbeyond4to6weeksafterinitialbenzodiazepinewithdrawal.Protractedwithdrawalsymptomsmaylastweekstomorethan12months.Asaresult,theremaybedifficultyindifferentiatingwithdrawalsymptomsfrompotentialreemergenceorcontinuationofsymptomsforwhichthebenzodiazepinewasbeingused.ToleranceTolerancetoAtivanmaydevelopfromcontinuedtherapy.Toleranceisaphysiologicalstatecharacterizedbyareducedresponsetoadrugafterrepeatedadministration(i.e.,ahigherdoseofadrugisrequiredtoproducethesameeffectthatwasonceobtainedatalowerdose).TolerancetothetherapeuticeffectofAtivanmaydevelop;however,littletolerancedevelopstotheamnesticreactionsandothercognitiveimpairmentscausedbybenzodiazepines. Warnings WARNINGSRisksFromConcomitantUseWithOpioidsConcomitantuseofbenzodiazepines,includingAtivan,andopioidsmayresultinprofoundsedation,respiratorydepression,coma,anddeath.Becauseoftheserisks,reserveconcomitantprescribingofthesedrugsinpatientsforwhomalternativetreatmentoptionsareinadequate.Observationalstudieshavedemonstratedthatconcomitantuseofopioidanalgesicsandbenzodiazepinesincreasestheriskofdrug-relatedmortalitycomparedtouseofopioidsalone.IfadecisionismadetoprescribeAtivanconcomitantlywithopioids,prescribethelowesteffectivedosagesandminimumdurationsofconcomitantuse,andfollowpatientscloselyforsignsandsymptomsofrespiratorydepressionandsedation.Inpatientsalreadyreceivinganopioidanalgesic,prescribealowerinitialdoseofAtivanthanindicatedintheabsenceofanopioidandtitratebasedonclinicalresponse.IfanopioidisinitiatedinapatientalreadytakingAtivan,prescribealowerinitialdoseoftheopioidandtitratebaseduponclinicalresponse.AdvisebothpatientsandcaregiversabouttherisksofrespiratorydepressionandsedationwhenAtivanisusedwithopioids.Advisepatientsnottodriveoroperateheavymachineryuntiltheeffectsofconcomitantusewiththeopioidhavebeendetermined(seeDRUGINTERACTIONS).Abuse,Misuse,AndAddictionTheuseofbenzodiazepines,includingAtivan,exposesuserstotherisksofabuse,misuse,andaddiction,whichcanleadtooverdoseordeath.Abuseandmisuseofbenzodiazepinesoften(butnotalways)involvetheuseofdosesgreaterthanthemaximumrecommendeddosageandcommonlyinvolveconcomitantuseofothermedications,alcohol,and/orillicitsubstances,whichisassociatedwithanincreasedfrequencyofseriousadverseoutcomes,includingrespiratorydepression,overdose,ordeath(seeDrugAbuseAndDependence:Abuse).BeforeprescribingAtivanandthroughouttreatment,assesseachpatient’sriskforabuse,misuse,andaddiction(e.g.,usingastandardizedscreeningtool).UseofAtivan,particularlyinpatientsatelevatedrisk,necessitatescounselingabouttherisksandproperuseofAtivanalongwithmonitoringforsignsandsymptomsofabuse,misuse,andaddiction.Prescribethelowesteffectivedosage;avoidorminimizeconcomitantuseofCNSdepressantsandothersubstancesassociatedwithabuse,misuse,andaddiction(e.g.,opioidanalgesics,stimulants);andadvisepatientsontheproperdisposalofunuseddrug.Ifasubstanceusedisorderissuspected,evaluatethepatientandinstitute(orreferthemfor)earlytreatment,asappropriate.DependenceAndWithdrawalReactionsToreducetheriskofwithdrawalreactions,useagradualtapertodiscontinueAtivanorreducethedosage(apatient-specificplanshouldbeusedtotaperthedose)(seeDOSAGEANDADMINSTRATION:DiscontinuationOrDosageReductionOfAtivan).Patientsatanincreasedriskofwithdrawaladversereactionsafterbenzodiazepinediscontinuationorrapiddosagereductionincludethosewhotakehigherdosages,andthosewhohavehadlongerdurationsofuse.AcuteWithdrawalReactionsThecontinueduseofbenzodiazepines,includingAtivan,mayleadtoclinicallysignificantphysicaldependence.AbruptdiscontinuationorrapiddosagereductionofAtivanaftercontinueduse,oradministrationofflumazenil(abenzodiazepineantagonist)mayprecipitateacutewithdrawalreactions,whichcanbelife-threatening(e.g.,seizures)(seeDrugAbuseAndDependence:Dependence).ProtractedWithdrawalSyndromeInsomecases,benzodiazepineusershavedevelopedaprotractedwithdrawalsyndromewithwithdrawalsymptomslastingweekstomorethan12months(seeDrugAbuseAndDependence:Dependence).Pre-existingdepressionmayemergeorworsenduringuseofbenzodiazepinesincludinglorazepam.Ativan(lorazepam)isnotrecommendedforuseinpatientswithaprimarydepressivedisorderorpsychosis.Useofbenzodiazepines,includinglorazepam,bothusedaloneandincombinationwithotherCNSdepressants,mayleadtopotentiallyfatalrespiratorydepression(seeDRUGINTERACTIONS).AswithallpatientsonCNS-depressantdrugs,patientsreceivinglorazepamshouldbewarnednottooperatedangerousmachineryormotorvehiclesandthattheirtoleranceforalcoholandotherCNSdepressantswillbediminished. Precautions PRECAUTIONSInpatientswithdepression,apossibilityforsuicideshouldbeborneinmind;benzodiazepinesshouldnotbeusedinsuchpatientswithoutadequateantidepressanttherapy.Lorazepamshouldbeusedwithcautioninpatientswithcompromisedrespiratoryfunction(e.g.,COPD,sleepapneasyndrome).Elderlyordebilitatedpatientsmaybemoresusceptibletothesedativeeffectsoflorazepam.Therefore,thesepatientsshouldbemonitoredfrequentlyandhavetheirdosageadjustedcarefullyaccordingtopatientresponse;theinitialdosageshouldnotexceed2mg.Paradoxicalreactionshavebeenoccasionallyreportedduringbenzodiazepineuse.Suchreactionsmaybemorelikelytooccurinchildrenandtheelderly.Shouldtheseoccur,useofthedrugshouldbediscontinued.Theusualprecautionsfortreatingpatientswithimpairedrenalorhepaticfunctionshouldbeobserved.Aswithallbenzodiazepines,theuseoflorazepammayworsenhepaticencephalopathy;therefore,lorazepamshouldbeusedwithcautioninpatientswithseverehepaticinsufficiencyand/orencephalopathy.Dosageforpatientswithseverehepaticinsufficiencyshouldbeadjustedcarefullyaccordingtopatientresponse;lowerdosesmaybesufficientinsuchpatients.Inpatientswheregastrointestinalorcardiovasculardisorderscoexistwithanxiety,itshouldbenotedthatlorazepamhasnotbeenshowntobeofsignificantbenefitintreatingthegastrointestinalorcardiovascularcomponent.Esophagealdilationoccurredinratstreatedwithlorazepamformorethan1yearat6mg/kg/day.Theno-effectdosewas1.25mg/kg/day(approximately6timesthemaximumhumantherapeuticdoseof10mg/day).Theeffectwasreversibleonlywhenthetreatmentwaswithdrawnwithin2monthsoffirstobservationofthephenomenon.Theclinicalsignificanceofthisisunknown.However,useoflorazepamforprolongedperiodsandingeriatricpatientsrequirescaution,andthereshouldbefrequentmonitoringforsymptomsofupperGIdisease.SafetyandeffectivenessofAtivan(lorazepam)inchildrenoflessthan12yearshavenotbeenestablished.InformationForPatientsAdvisethepatienttoreadtheFDA-approvedpatientlabeling(MedicationGuide).RisksFromConcomitantUseWithOpioidsAdvisebothpatientsandcaregiversabouttherisksofpotentiallyfatalrespiratorydepressionandsedationwhenAtivanisusedwithopioidsandnottousesuchdrugsconcomitantlyunlesssupervisedbyahealthcareprovider.Advisepatientsnottodriveoroperateheavymachineryuntiltheeffectsofconcomitantusewiththeopioidhavebeendetermined(seeWARNINGS:RisksFromConcomitantUseOfOpioidsandDRUGINTERACTIONS).Abuse,Misuse,andAddictionInformpatientsthattheuseofAtivanevenatrecommendeddoses,exposesuserstorisksofabuse,misuse,andaddiction,whichcanleadtooverdoseanddeath,especiallywhenusedincombinationwithothermedications(e.g.,opioidanalgesics),alcohol,and/orillicitsubstances.Informpatientsaboutthesignsandsymptomsofbenzodiazepineabuse,misuse,andaddiction;toseekmedicalhelpiftheydevelopthesesignsand/orsymptoms;andontheproperdisposalofunuseddrug(seeWARNINGS:AbuseMisuse,AndAddictionandDrugAbuseAndDependence).WithdrawalReactionsInformpatientsthatthecontinueduseofAtivanmayleadtoclinicallysignificantphysicaldependenceandthatabruptdiscontinuationorrapiddosagereductionofAtivanmayprecipitateacutewithdrawalreactions,whichcanbelife-threatening.Informpatientsthatinsomecases,patientstakingbenzodiazepineshavedevelopedaprotractedwithdrawalsyndromewithwithdrawalsymptomslastingweekstomorethan12months.InstructpatientsthatdiscontinuationordosagereductionofAtivanmayrequireaslowtaper(seeWARNINGS:DependenceAndWithdrawalReactionsandDrugAbuseAndDependence).EssentialLaboratoryTestsSomepatientsonAtivan(lorazepam)havedevelopedleukopenia,andsomehavehadelevationsofLDH.Aswithotherbenzodiazepines,periodicbloodcountsandliverfunctiontestsarerecommendedforpatientsonlong-termtherapy.CarcinogenesisAndMutagenesisNoevidenceofcarcinogenicpotentialemergedinratsduringan18-monthstudywithAtivan(lorazepam).Nostudiesregardingmutagenesishavebeenperformed.PregnancyReproductivestudiesinanimalswereperformedinmice,rats,andtwostrainsofrabbits.Occasionalanomalies(reductionoftarsals,tibia,metatarsals,malrotatedlimbs,gastroschisis,malformedskull,andmicrophthalmia)wereseenindrug-treatedrabbitswithoutrelationshiptodosage.Althoughalloftheseanomalieswerenotpresentintheconcurrentcontrolgroup,theyhavebeenreportedtooccurrandomlyinhistoricalcontrols.Atdosesof40mg/kgandhigher,therewasevidenceoffetalresorptionandincreasedfetallossinrabbitswhichwasnotseenatlowerdoses.Theclinicalsignificanceoftheabovefindingsisnotknown.However,anincreasedriskofcongenitalmalformationsassociatedwiththeuseofminortranquilizers(chlordiazepoxide,diazepam,andmeprobamate)duringthefirsttrimesterofpregnancyhasbeensuggestedinseveralstudies.Becausetheuseofthesedrugsisrarelyamatterofurgency,theuseoflorazepamduringthisperiodshouldbeavoided.Thepossibilitythatawomanofchildbearingpotentialmaybepregnantatthetimeofinstitutionoftherapyshouldbeconsidered.Patientsshouldbeadvisedthatiftheybecomepregnant,theyshouldcommunicatewiththeirphysicianaboutthedesirabilityofdiscontinuingthedrug.Inhumans,bloodlevelsobtainedfromumbilicalcordbloodindicateplacentaltransferoflorazepamandlorazepamglucuronide.Infantsofmotherswhoingestedbenzodiazepinesforseveralweeksormoreprecedingdeliveryhavebeenreportedtohavewithdrawalsymptomsduringthepostnatalperiod.Symptomssuchashypoactivity,hypotonia,hypothermia,respiratorydepression,apnea,feedingproblems,andimpairedmetabolicresponsetocoldstresshavebeenreportedinneonatesbornofmotherswhohavereceivedbenzodiazepinesduringthelatephaseofpregnancyoratdelivery.NursingMothersLorazepamhasbeendetectedinhumanbreastmilk;therefore,itshouldnotbeadministeredtobreastfeedingwomen,unlesstheexpectedbenefittothewomanoutweighsthepotentialrisktotheinfant.Sedationandinabilitytosucklehaveoccurredinneonatesoflactatingmotherstakingbenzodiazepines.Infantsoflactatingmothersshouldbeobservedforpharmacologicaleffects(includingsedationandirritability).GeriatricUseClinicalstudiesofAtivangenerallywerenotadequatetodeterminewhethersubjectsaged65andoverresponddifferentlythanyoungersubjects;however,theincidenceofsedationandunsteadinesswasobservedtoincreasewithage(seeADVERSEREACTIONS).Agedoesnotappeartohaveasignificanteffectonlorazepamkinetics(seeCLINICALPHARMACOLOGY).Clinicalcircumstances,someofwhichmaybemorecommonintheelderly,suchashepaticorrenalimpairment,shouldbeconsidered.Greatersensitivity(e.g.,sedation)ofsomeolderindividualscannotberuledout.Ingeneral,doseselectionforanelderlypatientshouldbecautious,andlowerdosesmaybesufficientinthesepatients(seeDOSAGEANDADMINISTRATION). Overdose&Contraindications OVERDOSEInpostmarketingexperience,overdosewithlorazepamhasoccurredpredominantlyincombinationwithalcoholand/orotherdrugs.Therefore,inthemanagementofoverdosage,itshouldbeborneinmindthatmultipleagentsmayhavebeentaken.SymptomsOverdosageofbenzodiazepinesisusuallymanifestedbyvaryingdegreesofCNSdepressionrangingfromdrowsinesstocoma.Inmildcases,symptomsincludedrowsiness,mentalconfusion,paradoxicalreactions,dysarthria,andlethargy.Inmoreseriouscases,andespeciallywhenotherdrugsoralcoholwereingested,symptomsmayincludeataxia,hypotonia,hypotension,cardiovasculardepression,respiratorydepression,hypnoticstate,coma,anddeath.ManagementGeneralsupportiveandsymptomaticmeasuresarerecommended;vitalsignsmustbemonitoredandthepatientcloselyobserved.Whenthereisariskofaspiration,inductionofemesisisnotrecommended.Gastriclavagemaybeindicatedifperformedsoonafteringestionorinsymptomaticpatients.Administrationofactivatedcharcoalmayalsolimitdrugabsorption.Hypotension,thoughunlikely,usuallymaybecontrolledwithnorepinephrinebitartrateinjection.Lorazepamispoorlydialyzable.Lorazepamglucuronide,theinactivemetabolite,maybehighlydialyzable.Thebenzodiazepineantagonistflumazenilmaybeusedinhospitalizedpatientsasanadjunctto,notasasubstitutefor,propermanagementofbenzodiazepineoverdose.Theprescribershouldbeawareofariskofseizureinassociationwithflumazeniltreatment,particularlyinlong-termbenzodiazepineusersandincyclicantidepressantoverdose.ThecompleteflumazenilpackageinsertincludingCONTRAINDICATIONS,WARNINGS,andPRECAUTIONSsectionsshouldbeconsultedpriortouse.CONTRAINDICATIONSAtivan(lorazepam)iscontraindicatedinpatientswith:hypersensitivitytobenzodiazepinesortoanycomponentsoftheformulationacutenarrow-angleglaucoma. ClinicalPharmacology CLINICALPHARMACOLOGYStudiesinhealthyvolunteersshowthatinsinglehighdosesAtivan(lorazepam)hasatranquilizingactiononthecentralnervoussystemwithnoappreciableeffectontherespiratoryorcardiovascularsystems.Ativan(lorazepam)isreadilyabsorbedwithanabsolutebioavailabilityof90%.Peakconcentrationsinplasmaoccurapproximately2hoursfollowingadministration.Thepeakplasmaleveloflorazepamfroma2mgdoseisapproximately20ng/mL.Themeanhalf-lifeofunconjugatedlorazepaminhumanplasmaisabout12hoursandforitsmajormetabolite,lorazepamglucuronide,about18hours.Atclinicallyrelevantconcentrations,lorazepamisapproximately85%boundtoplasmaproteins.Ativan(lorazepam)israpidlyconjugatedatits3-hydroxygroupintolorazepamglucuronidewhichisthenexcretedintheurine.Lorazepamglucuronidehasnodemonstrablecentralnervoussystem(CNS)activityinanimals.Theplasmalevelsoflorazepamareproportionaltothedosegiven.Thereisnoevidenceofaccumulationoflorazepamonadministrationupto6months.Studiescomparingyoungandelderlysubjectshaveshownthatadvancingagedoesnothaveasignificanteffectonthepharmacokineticsoflorazepam.However,inonestudyinvolvingsingleintravenousdosesof1.5to3mgofAtivanInjection,meantotalbodyclearanceoflorazepamdecreasedby20%in15elderlysubjectsof60to84yearsofagecomparedtothatin15youngersubjectsof19to38yearsofage. MedicationGuide PATIENTINFORMATIONATIVAN(AT-ivan)(lorazepam)TabletsWhatisthemostimportantinformationIshouldknowaboutATIVAN?DonotdriveoroperateheavymachineryuntilyouknowhowtakingATIVANwithopioidsaffectsyou.ATIVANisabenzodiazepinemedicine.Takingbenzodiazepineswithopioidmedicines,alcohol,orothercentralnervoussystemdepressants(includingstreetdrugs)cancauseseveredrowsiness,breathingproblems(respiratorydepression),comaanddeath.Getemergencyhelprightawayifanyofthefollowinghappens:shalloworslowedbreathingbreathingstops(whichmayleadtotheheartstopping)excessivesleepiness(sedation)Riskofabuse,misuse,andaddiction.Thereisariskofabuse,misuse,andaddictionwithbenzodiazepinesincludingATIVANwhichcanleadtooverdoseandserioussideeffectsincludingcomaanddeath.Serioussideeffectsincludingcomaanddeathhavehappenedinpeoplewhohaveabusedormisusedbenzodiazepines,includingATIVAN.Theseserioussideeffectsmayalsoincludedelirium,paranoia,suicidalthoughtsoractions,seizures,anddifficultybreathing.Callyourhealthcareproviderorgotothenearesthospitalemergencyroomrightawayifyougetanyoftheseserioussideeffects.YoucandevelopanaddictionevenifyoutakeATIVANexactlyasprescribedbyyourhealthcareprovider.TakeATIVANexactlyasyourhealthcareproviderprescribed.DonotshareyourATIVANwithotherpeople.KeepATIVANinasafeplaceandawayfromchildren.Physicaldependenceandwithdrawalreactions.ATIVANcancausephysicaldependenceandwithdrawalreactions.DonotsuddenlystoptakingATIVAN.StoppingATIVANsuddenlycancauseseriousandlife-threateningsideeffects,including,unusualmovements,responsesorexpressions,seizures,suddenandseverementalornervoussystemchanges,depression,seeingorhearingthingsthatothersdonotseeorhear,anextremeincreaseinactivityortalking,losingtouchwithreality,andsuicidalthoughtsoractions.Callyourhealthcareproviderorgotothenearesthospitalemergencyroomrightawayifyougetanyofthesesymptoms.Somepeoplewhosuddenlystopbenzodiazepineshavesymptomsthatcanlastforseveralweekstomorethan12months,includinganxiety,troubleremembering,learning,orconcentrating,depression,problemssleeping,feelinglikeinsectsarecrawlingunderyourskin,weakness,shaking,muscletwitching,burningorpricklingfeelinginyourhands,arms,legsorfeet,andringinginyourears.Physicaldependenceisnotthesameasdrugaddiction.Yourhealthcareprovidercantellyoumoreaboutthedifferencesbetweenphysicaldependenceanddrugaddiction.DonottakemoreATIVANthanprescribedortakeATIVANforlongerthanprescribed.WhatisATIVAN?ATIVANisaprescriptionmedicineused:totreatanxietydisordersfortheshort-termreliefofthesymptomsofanxietyoranxietythatcanhappenwithsymptomsofdepressionATIVANisafederalcontrolledsubstance(CIV)becauseitcontainslorazepamthatcanbeabusedorleadtodependence.KeepATIVANinasafeplacetopreventmisuseandabuse.SellingorgivingawayATIVANmayharmothers,andisagainstthelaw.Tellyourhealthcareproviderifyouhaveabusedorbeendependentonalcohol,prescriptionmedicinesorstreetdrugs.ItisnotknownifATIVANissafeandeffectiveforuseinchildrenlessthan12yearsofage.ItisnotknownifATIVANissafeandeffectiveforuseforlongerthan4months.DonottakeATIVANifyou:areallergictolorazepam,otherbenzodiazepines,oranyoftheingredientsinATIVAN.SeetheendofthisMedicationGuideforacompletelistofingredientsinATIVAN.BeforeyoutakeATIVAN,tellyourhealthcareprovideraboutallofyourmedicalconditions,includingifyou:haveorhavehaddepression,moodproblems,orsuicidalthoughtsorbehaviorhaveahistoryofdrugoralcoholabuseoraddictionhavelungdiseaseorbreathingproblems(suchasCOPD,sleepapneasyndrome)haveliverorkidneyproblemshaveorhavehadseizuresarepregnantorplantobecomepregnant.ATIVANmayharmyourunbornbaby.YouandyourhealthcareprovidershoulddecideifyoushouldtakeATIVANwhileyouarepregnant.arebreastfeedingorplantobreastfeed.ATIVANpassesintoyourbreastmilkandmayharmyourbaby.TalktoyourhealthcareprovideraboutthebestwaytofeedyourbabyifyoutakeATIVAN.YoushouldnotbreastfeedwhiletakingATIVAN.Tellyourhealthcareprovideraboutallthemedicinesyoutake,includingprescriptionandoverthe-countermedicines,vitamins,andherbalsupplements.TakingATIVANwithcertainothermedicinescancausesideeffectsoraffecthowwellATIVANortheothermedicineswork.Donotstartorstopothermedicineswithouttalkingtoyourhealthcareprovider.HowshouldItakeATIVAN?TakeATIVANexactlyasyourhealthcareprovidertellsyoutotakeit.YourhealthcareproviderwilltellyouhowmuchATIVANtotakeandwhentotakeit.IfyoutaketoomuchATIVAN,callyourhealthcareproviderorgotothenearesthospitalemergencyroomrightaway.WhatarethepossiblesideeffectsofATIVAN?ATIVANmaycauseserioussideeffects,including:See“WhatisthemostimportantinformationIshouldknowaboutATIVAN?”ATIVANcanmakeyousleepyordizzyandcanslowyourthinkingandmotorskills.Donotdrive,operateheavymachinery,ordootherdangerousactivitiesuntilyouknowhowATIVANaffectsyou.DonotdrinkalcoholortakeotherdrugsthatmaymakeyousleepyordizzywhiletakingATIVANwithoutfirsttalkingtoyourhealthcareprovider.Whentakenwithalcoholordrugsthatcausesleepinessordizziness,ATIVANmaymakeyoursleepinessordizzinessmuchworse.Depression.Pre-existingdepressionmayemergeorworsenduringuseofbenzodiazepinesincludingATIVAN.ThemostcommonsideeffectsofATIVANinclude:sedationweaknessdizzinessunsteadinessThesearenotallthepossiblesideeffectsofATIVAN.Callyourdoctorformedicaladviceaboutsideeffects.YoumayreportsideeffectstoFDAat1-800-FDA-1088.HowshouldIstoreATIVAN?StoreATIVANinatightlyclosedcontaineratroomtemperaturebetween68°Fto77°F(20°Cto25°C).KeepATIVANandallmedicinesoutofthereachofchildren.GeneralinformationaboutthesafeandeffectiveuseofATIVANMedicinesaresometimesprescribedforpurposesotherthanthoselistedinaMedicationGuide.DonotuseATIVANforaconditionforwhichitwasnotprescribed.DonotgiveATIVANtootherpeople,eveniftheyhavethesamesymptomsthatyouhave.Itmayharmthem.YoucanaskyourpharmacistorhealthcareproviderforinformationaboutATIVANthatiswrittenforhealthprofessionals.WhataretheingredientsinATIVAN?Activeingredient:lorazepamInactiveingredients:lactosemonohydrate,magnesiumstearate,microcrystallinecellulose,andpolacrilinpotassium.ThisMedicationGuidehasbeenapprovedbytheU.S.FoodandDrugAdministration. 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LifewithCancer PillIdentifierToolQuick,Easy,PillIdentification DrugInteractionToolCheckPotentialDrugInteractions PharmacyLocatorToolIncluding24Hour,Pharmacies AtivanInjectionDrugImprint 003782321_PB round,white,imprintedwithM,321 003782457_PB round,white,imprintedwithMYLAN457 003782777_PB round,white,imprintedwithMYLAN777 005910240_PB round,white,imprintedwith2400.5,WATSON 005910241_PB round,white,imprintedwith2411,WATSON 005910242_PB round,white,imprintedwith2422,WATSON 009046009_PB round,white,imprintedwithEP906,2 633040772_PB round,white,imprintedwithRX7 633040773_PB round,white,imprintedwithRx773 633040774_PB round,white,imprintedwithRX774 637390499_PB round,white,imprintedwithWATSON,2400.5 637390500_PB round,white,imprintedwith2411,WATSON 637390501_PB round,white,imprintedwithWATSON,2422 641250904_PB round,white,imprintedwithEP90-4 641250905_PB round,white,imprintedwithEP905,1 Ativan0.5mg pentagonal,white,imprintedwithA,WYETH81 Ativan1mg pentagonal,white,imprintedwithA,64WYETH Ativan2mg pentagonal,white,imprintedwithA,65WYETH Lorazepam0.5mg-AMN round,white,imprintedwithIP15 Lorazepam0.5mg-GG round,white,imprintedwith91,GG Lorazepam0.5mg-MYL round,white,imprintedwithM,321 Lorazepam0.5mg-TEV round,white,imprintedwithI,L Lorazepam0.5mg-WAT round,white,imprintedwithWATSON,2400.5 Lorazepam1mg-AMN round,white,imprintedwithIP16 Lorazepam1mg-MUT round,white,imprintedwithMP39 Lorazepam1mg-MYL round,white,imprintedwithMYLAN457 Lorazepam1mg-PP round,white,imprintedwith59,R Lorazepam1mg-TEV round,white,imprintedwithI1,4821 Lorazepam1mg-WAT round,white,imprintedwith2411,WATSON Lorazepam2mg-AMN round,white,imprintedwithIP17 Lorazepam2mg-GG round,white,imprintedwithGG93 Lorazepam2mg-MUT round,white,imprintedwithMP96 Lorazepam2mg-MYL round,white,imprintedwithMYLAN777 Lorazepam2mg-TEV round,white,imprintedwithI2,4822 Lorazepam2mg-WAT round,white,imprintedwith2422,WATSON