Upload
lisabrenner
View
214
Download
0
Embed Size (px)
Citation preview
7/30/2019 FDA Safety Announcement - Sleeping Pills [1-10-2013]
1/6
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).
7/30/2019 FDA Safety Announcement - Sleeping Pills [1-10-2013]
2/6
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.htm7/30/2019 FDA Safety Announcement - Sleeping Pills [1-10-2013]
3/6
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.
7/30/2019 FDA Safety Announcement - Sleeping Pills [1-10-2013]
4/6
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.
7/30/2019 FDA Safety Announcement - Sleeping Pills [1-10-2013]
5/6
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
7/30/2019 FDA Safety Announcement - Sleeping Pills [1-10-2013]
6/6
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