FDA Safety Announcement - Sleeping Pills [1-10-2013]

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  • 7/30/2019 FDA Safety Announcement - Sleeping Pills [1-10-2013]

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    Risk

    of

    next

    morning

    impairment

    after

    use

    of

    insomnia

    drugs;

    FDA

    requireslowerrecommendeddosesforcertaindrugscontainingzolpidem

    (Ambien,AmbienCR,Edluar,andZolpimist)

    SafetyAnnouncement

    [1102013]TheU.S.FoodandDrugAdministration(FDA)isnotifyingthepublicofnew

    informationaboutzolpidem,awidelyprescribedinsomniadrug.FDArecommendsthat

    thebedtimedosebeloweredbecausenewdatashowthatbloodlevelsinsomepatients

    maybehighenoughthemorningafterusetoimpairactivitiesthatrequirealertness,

    includingdriving.Todaysannouncementfocusesonzolpidemproductsapprovedforbedtimeuse,whicharemarketedasgenericsandunderthebrandnamesAmbien,

    AmbienCR,Edluar,andZolpimist.

    FDAisalsoremindingthepublicthatalldrugstakenforinsomniacanimpairdrivingand

    activitiesthatrequirealertnessthemorningafteruse.Drowsinessisalreadylistedasa

    commonsideeffectinthedruglabelsofallinsomniadrugs,alongwithwarningsthat

    patientsmaystillfeeldrowsythedayaftertakingtheseproducts.Patientswhotake

    insomniadrugscanexperienceimpairmentofmentalalertnessthemorningafteruse,

    eveniftheyfeelfullyawake.

    FDAurgeshealthcareprofessionalstocautionallpatients(menandwomen)whouse

    thesezolpidemproductsabouttherisksofnextmorningimpairmentforactivitiesthat

    requirecompletementalalertness,includingdriving.Forzolpidemproducts,datashow

    theriskfornextmorningimpairmentishighestforpatientstakingtheextendedrelease

    formsofthesedrugs(AmbienCRandgenerics).Womenappeartobemoresusceptible

    tothisriskbecausetheyeliminatezolpidemfromtheirbodiesmoreslowlythanmen

    (seeDataSummarybelow).

    Becauseuseoflowerdosesofzolpidemwillresultinlowerbloodlevelsinthemorning,

    FDAisrequiringthemanufacturersofAmbien,AmbienCR,Edluar,andZolpimistto

    lowertherecommendeddose.FDAhasinformedthemanufacturersthattherecommendeddoseofzolpidemforwomenshouldbeloweredfrom10mgto5mgfor

    immediatereleaseproducts(Ambien,Edluar,andZolpimist)andfrom12.5mgto6.25

    mgforextendedreleaseproducts(AmbienCR).FDAalsoinformedthemanufacturers

    that,formen,thelabelingshouldrecommendthathealthcareprofessionalsconsider

    prescribingthelowerdoses5mgforimmediatereleaseproductsand6.25mgfor

    extendedreleaseproducts(seeZolpidemDosingRecommendationsforAdults).

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    TherecommendeddosesofIntermezzo,alowerdosezolpidemproductapprovedfor

    middleofthenightawakenings,arenotchanging.AtthetimeofIntermezzosapproval

    inNovember2011,thelabelalreadyrecommendedalowerdosageforwomenthanfor

    men.

    FDAiscontinuingtoevaluatetheriskofimpairedmentalalertnesswithotherinsomnia

    drugs,includingoverthecounter(OTC)drugsavailablewithoutaprescription.

    Todecreasethepotentialriskofimpairmentwithallinsomniadrugs,healthcare

    professionalsshouldprescribe,andpatientsshouldtake,thelowestdosecapableof

    treatingthepatientsinsomnia.Patientswhodriveorwhoseactivitiesrequirefull

    alertnessthemorningafteruseofaninsomniadrugshoulddiscusstheappropriateness

    oftheirmedicinewiththeirhealthcareprofessional(seeInsomniaMedicinesbelow).

    FDAhaspreparedalistofquestionsandanswerstoprovideanadditionaloverviewof

    thissafetyissue.

    FactsaboutZolpidem

    Asedativehypnotic(sleep)medicineusedinadultsforthetreatmentofinsomnia MarketedasgenericsandunderthebrandnamesAmbien,AmbienCR,Edluar,Zolpimist,andIntermezzo

    In2011,about39millionprescriptionsforzolpidemproductsweredispensed,andabout9millionpatientsreceivedzolpidemproductsfromU.S.outpatientretail

    pharmacies,ofwhich63%ofthepatientswerefemale.Extendedreleasezolpidem

    products(AmbienCRandgenerics)accountedfor11%(4.4millionprescriptions)of

    thezolpidemmarket,immediatereleaseproductsaccountedfor89%(35million

    prescriptions)ofthemarketinY2011.1

    AdditionalInformationforPatients

    Patientswhotakeinsomniamedicinescanexperiencedecreasedmentalalertnessthemorningafteruse,eveniftheyfeelfullyawake.

    Zolpidemextendedrelease(AmbienCRandgenerics)productsmaynotbetherightmedicationchoiceforpatients(menorwomen)withinsomniawhoneedto

    driveorperformactivitiesthatrequirefullalertnessthenextmorning. Forwomen,FDAisrequiringthemanufacturersofzolpidemcontainingproductstolowertherecommendeddosesofAmbienandAmbienCR,Edluar,and

    Zolpimistintheprofessionaldruglabelsthataccompanythemedications.FDAis

    alsorequiringmanufacturerstorecommendthathealthcareprofessionals

    considerprescribingthelowerdoseofthesedrugsinmen(seeZolpidemDosing

    RecommendationsforAdults).

    http://www.fda.gov/drugs/drugsafety/ucm334041.htmhttp://www.fda.gov/drugs/drugsafety/ucm334041.htmhttp://www.fda.gov/drugs/drugsafety/ucm334041.htmhttp://www.fda.gov/drugs/drugsafety/ucm334041.htmhttp://www.fda.gov/drugs/drugsafety/ucm334041.htmhttp://www.fda.gov/drugs/drugsafety/ucm334041.htm
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    Ifyouarecurrentlytakingthe10mgor12.5mgdoseofazolpidemcontaininginsomniamedicine,continuetakingyourprescribeddoseasdirecteduntilyou

    havecontactedyourhealthcareprofessionaltoaskforinstructionsonhowto

    safelycontinuetotakeyourmedicine.Eachpatientandsituationisunique,and

    theappropriatedoseshouldbediscussedwithyourhealthcareprofessional.

    Thelowerzolpidemdosewillbeeffectiveinmostwomenandmanymen. ReadtheMedicationGuidethatcomesalongwithyourzolpidemprescriptionforadditionalinformation.

    Forotherinsomniamedicines,talktoyourhealthcareprofessionalaboutwaystotakethelowestdosethattreatsyoursymptoms.

    Takeyourinsomniamedicineexactlyasprescribed. Overthecounter(OTC)insomniamedicinesthatareavailablewithoutaprescriptionshouldnotbeconsideredsaferthanprescriptioninsomnia

    medicinesfornextmorningalertnessanddriving.

    Contactyourhealthcareprofessionalifyouhaveanyquestionsorconcernsaboutzolpidemorotherinsomniamedicines.

    ReportsideeffectsfromtheuseofzolpidemorotherinsomniamedicinestoFDAsMedWatchprogram,usingtheinformationinthe"ContactFDA"boxatthe

    bottomofthispage.

    AdditionalInformationforHealthCareProfessionals

    Immediatereleaseproducts:FDAisrequiringthemanufacturersofcertainimmediatereleasezolpidemproducts(Ambien,Edluar,andZolpimist)tolower

    therecommendeddose.FDAhasinformedmanufacturersthat:

    o Therecommendedinitialdoseforwomenshouldbeloweredfrom10mgto5mg,immediatelybeforebedtime.

    o Thedruglabelingshouldrecommendthathealthcareprofessionalsconsiderprescribingalowerdoseof5mgformen.Inmanymen,the5

    mgdoseprovidessufficientefficacy.

    o Thedruglabelingshouldincludeastatementthat,forbothmenandwomen,the5mgdosecouldbeincreasedto10mgifneeded,butthe

    higherdoseismorelikelytoimpairnextmorningdrivingandother

    activitiesthatrequirefullalertness.

    Extendedreleaseproducts:FDAisalsorequiringthemanufacturerofextendedreleasezolpidem(AmbienCR)tolowertherecommendeddose.FDAhas

    informedthemanufacturerthat:

    o Therecommendedinitialdoseforwomenshouldbeloweredfrom12.5mgto6.25mg,immediatelybeforebedtime.

    o Thedruglabelingshouldrecommendthathealthcareprofessionalsconsiderprescribingalowerdoseof6.25mginmen.Inmanymen,the

    6.25mgdoseprovidessufficientefficacy.

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    o Thedruglabelingshouldincludeastatementthat,forbothmenandwomen,the6.25mgdosecanbeincreasedto12.5mgifneeded,butthe

    higherdoseismorelikelytoimpairnextmorningdrivingandother

    activitiesthatrequirefullalertness.

    FDAhasinformedthemanufacturersthattherecommendedzolpidemdosesforwomenandmenshouldbedifferentbecausewomeneliminatezolpidemfromtheirbodiesataslowerratethanmen.

    Forzolpidemandotherinsomniadrugs,prescribethelowestdosethattreatsthepatientssymptoms.

    FDAurgeshealthcareprofessionalstocautionallpatients(menandwomen)whousetheseproductsabouttherisksofnextmorningimpairmentforactivities

    thatrequirecompletementalalertness,includingdriving.

    Informpatientsthatimpairmentfromsleepdrugscanbepresentdespitefeelingfullyawake.

    EncouragepatientstoreadtheMedicationGuidewhentheyreceivetheirzolpidemprescription.

    ReportadverseeventsinvolvingzolpidemorotherinsomniadrugstoFDAsMedWatchprogram,usingtheinformationinthe"ContactFDA"boxatthe

    bottomofthispage.

    DataSummary

    DrivingsimulationandlaboratorystudiesrecentlysubmittedtoFDAindicatethat

    zolpidembloodlevelsaboveapproximately50ng/mLappearcapableofimpairing

    drivingtoadegreethatincreasestheriskofamotorvehicleaccident.In

    pharmacokinetictrialsof10mgAmbien(orbioequivalentzolpidemproducts)that

    includedapproximately250menand250women,about15%ofwomenand3%ofmen

    hadzolpidemconcentrationsthatexceeded50ng/mLapproximately8hourspost

    dosing.Threemeasurementsinwomenandoneinmenwere 90ng/mLatabout8

    hoursafteruse.

    Ahigherpercentageofbothmenandwomenexperiencepotentiallyimpairingmorning

    zolpidemlevelsafteruseofextendedreleasezolpidemproducts(AmbienCRorgeneric

    equivalents).Inpharmacokinetictrialsofzolpidemextendedrelease12.5mg,

    approximately33%ofwomenand25%ofmenhadzolpidembloodconcentrations

    exceeding50ng/mLapproximately8hourspostdosing.About5%ofpatientshadblood

    levels 100ng/mL.

    Instudiesofzolpidemextendedrelease6.25mg,at8hoursafterdosing,about15%of

    adultwomenand5%ofadultmenhadazolpidemlevelof50ng/mL,whereasforboth

    elderlymenandwomen,about10%hadsuchazolpidemlevel.

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    FDAiscontinuingtoevaluatetheriskofnextmorningimpairmentwithotherinsomnia

    drugs.

    ZolpidemDosingRecommendationsforAdults(NonElderly)

    Dosingrecommendations

    in

    currentdruglabelfor

    zolpidem

    FDAsproposed

    new

    dosing

    recommendationsfor

    zolpidem

    Ambien,Edluar,

    Zolpimist

    MenandWomen:

    10mgoncedaily,immediately

    beforebedtime

    Women:

    5mgoncedaily,immediately

    beforebedtime

    Men:

    5or10mgoncedaily,

    immediatelybeforebedtime

    Ambien

    CR

    Men

    and

    Women:

    12.5mgoncedaily,

    immediatelybeforebedtime

    Women:

    6.25mgoncedaily,

    immediatelybeforebedtime

    Men:

    6.25or12.5mgoncedaily,

    immediatelybeforebedtime

    InsomniaMedicines

    PrescriptionInsomniaMedicines

    Genericname

    Found

    in

    brand

    name(s)

    zolpidemtartrate Ambien,AmbienCR,Edluar,Zolpimist,

    Intermezzo

    butabarbitalsodium Butisolsodium

    pentobarbitaland

    carbromal

    Carbrital

    flurazepamhydrochloride Dalmane

    quazepam Doral

    triazolam Halcion

    eszopiclone Lunesta

    ethchlorvynol Placidyl

    estazolam Prosom

    temazepam Restoril

    ramelteon Rozerem

    secobarbitalsodium Seconal

    doxepinhydrochloride Silenor

    zaleplon Sonata

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    Overthecounter(OTC)InsomniaMedicines

    Genericname Commonbrandname(s)

    diphenhydramine Benadryl

    Alsoinmanycoldandheadachecombinationproducts*

    doxylamine Unisom

    Alsoinmanycoldandheadache

    combinationproducts*

    *BesuretoalwaysreadtheDrugFactsboxonOTCmedicines.

    Reference

    1. IMS,VectorOne:National(VONA)andTotalPatientTracker(TPT).Year2011.Extracted

    June

    2012.

    ContactFDA

    18003321088

    1800FDA0178Fax

    ReportaSeriousProblem

    MedWatchOnline

    RegularMail:UsepostagepaidFDAForm3500

    Mailto:MedWatch5600FishersLane

    Rockville,MD20857

    RelatedInformation

    FDADrugSafetyCommunication:Riskofnextmorningimpairmentafteruseofinsomniadrugs;FDArequireslowerrecommendeddosesforcertaindrugs

    containingzolpidem(Ambien,AmbienCR,Edluar,andZolpimist) QuestionsandAnswers

    https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htmhttps://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htmhttps://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htmhttp://www.fda.gov/downloads/Safety/MedWatch/DownloadForms/UCM082725.pdfhttp://www.fda.gov/downloads/Safety/MedWatch/DownloadForms/UCM082725.pdfhttp://www.fda.gov/downloads/Safety/MedWatch/DownloadForms/UCM082725.pdfhttp://www.fda.gov/downloads/Safety/MedWatch/DownloadForms/UCM082725.pdfhttp://www.fda.gov/downloads/Safety/MedWatch/DownloadForms/UCM082725.pdfhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334041.htmhttp://www.fda.gov/drugs/drugsafety/ucm334041.htmhttp://www.fda.gov/drugs/drugsafety/ucm334041.htmhttp://www.fda.gov/drugs/drugsafety/ucm334041.htmhttp://www.fda.gov/drugs/drugsafety/ucm334041.htmhttp://www.fda.gov/drugs/drugsafety/ucm334041.htmhttp://www.fda.gov/drugs/drugsafety/ucm334041.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/drugs/drugsafety/ucm334033.htmhttp://www.fda.gov/downloads/Safety/MedWatch/DownloadForms/UCM082725.pdfhttps://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm