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com

PioglitazoneHydrochloride
Class:Thiazolidinediones
ATCClass:A10BG03
VAClass:HS502
ChemicalName:()5[p[2(5Ethyl2pyridyl)ethoxy]benzyl]2,4thiazolidinedionemonohydrochloride
MolecularFormula:C19H20N2O3SClH
CASNumber:112529154
Brands:Actos

Warning(s)

CHF
Thiazolidinediones,includingpioglitazone,causeorexacerbateCHFinsomepatients. 1 27 28Monitorforsignsand
symptomsofCHF(e.g.,dyspnea,rapidandexcessiveweightgain,edema)afterinitiationoftherapyanddosage
titration. 1 27 28IfCHFdevelops,manageaccordingtocurrentstandardsofcareconsiderdiscontinuanceorreductionin
dosageofpioglitazone. 1 27 28
Notrecommendedinpatientswithsymptomaticheartfailure. 1 27 28
InitiationofpioglitazonecontraindicatedinpatientswithNYHAclassIIIorIVheartfailure. 1 27 28(SeeCHFunder
Cautions.)

Introduction
Antidiabeticagentthiazolidinedione(glitazone).18912

UsesforPioglitazoneHydrochloride
DiabetesMellitus
Usedaloneorincombinationwithasulfonylurea,metformin,orinsulinasanadjuncttodietandexerciseto
improveglycemiccontrolinpatientswithtype2(noninsulindependent)diabetesmellitus(NIDDM).12142728
Shouldbeaddedto,notsubstitutedfor,otherantidiabeticagentsinpatientswhoseNIDDMisnotadequately
controlledbytheseagents.13

Maybeaddedtoglyburide/metforminfixedcombinationtherapyifhyperglycemiaisnotadequatelycontrolled
withthefixedcombination.14Maybeusedincombinationwithrepaglinideifhyperglycemiaisnotadequately
controlledwithdiet,exercise,andmonotherapywithanotheroralantidiabeticagent.17

Noteffectiveassoletherapyfortype1diabetesmellitusordiabeticketoacidosis.1

PioglitazoneHydrochlorideDosageandAdministration
Administration

OralAdministration
Administerpioglitazoneoncedailywithoutregardtomeals.1

Administerfixedcombinationofpioglitazoneandimmediatereleasemetforminhydrochloride(ActoPlusMet)
onceortwicedailywithmealstoreducetheGIeffectsofmetformincomponent.27

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Administerfixedcombinationofpioglitazoneandextendedreleasemetforminhydrochloride(ActoPlusMetXR)
oncedailywiththeeveningmealtoreduceGIeffectsofmetformincomponent.27

Administerfixedcombinationofpioglitazoneandglimepiride(Duetact)oncedailywiththefirstmainmeal.28

Dosage
Availableaspioglitazonehydrochloridedosageexpressedintermsofpioglitazone.1

InitiationordiscontinuanceofaCYP2C8inducerduringpioglitazonetherapymaynecessitatechangesin
antidiabetictherapy.1(SeeInteractions.)

IfapotentCYP2C8inhibitorisusedconcomitantly,reductionofthemaximumdailypioglitazonedosageis
recommended.1(SeeInteractions.)

Adults

DiabetesMellitus

Monotherapy
Oral
Initially,15or30mgoncedaily.1Ifresponseinadequate,increasedosagegraduallyuptomaximumof45mg
daily.1

Allowsufficienttime(812weeks)toevaluateadequacyofresponseasdeterminedbyHbA1cunlessglycemic
controlbasedonfastingplasmaglucosedeteriorates.27

Pioglitazone/ImmediatereleaseMetforminHydrochlorideFixedcombinationTherapy(ActoPlusMet)
Oral
Baseinitialdosageoffixedcombinationonpatient'scurrentdosageofpioglitazoneand/orimmediaterelease
metforminhydrochlorideandonusualinitialdosagesofthesedrugs.27

Initially,15mgofpioglitazoneand500or850mgofimmediatereleasemetforminhydrochlorideonceortwice
daily.27

Graduallytitratedosagebasedonadequacyoftherapeuticresponse.27Allowsufficienttime(812weeks)to
evaluateadequacyofresponseasdeterminedbyHbA1cunlessglycemiccontrolbasedonfastingplasma
glucosedeteriorates.27

Pioglitazone/ExtendedreleaseMetforminHydrochlorideFixedcombinationTherapy(ActoPlusMetXR)
Oral
Baseinitialdosageoffixedcombinationonpatient'scurrentdosageofpioglitazoneand/orextendedrelease
metforminhydrochlorideandonusualinitialdosagesofthesedrugs.27

Initially,15or30mgofpioglitazoneand1gofextendedreleasemetforminhydrochlorideoncedaily.1

Graduallytitratedosagebasedonadequacyoftherapeuticresponse.27Allowsufficienttime(812weeks)to
evaluateadequacyofresponseasdeterminedbyHbA1cunlessglycemiccontrolbasedonfastingplasma
glucosedeteriorates.27

Pioglitazone/GlimepirideFixedcombinationTherapy(Duetact)
Oral
Baseinitialdosageoffixedcombinationonpatient'scurrentdosageofpioglitazoneand/orsulfonylurea(e.g.,
glimepiride).28

Patientscurrentlyreceivingglimepiridemonotherapy:Initially,30mgofpioglitazoneand2or4mgofglimepiride
oncedaily.28

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Patientscurrentlyreceivingpioglitazonemonotherapy:Initially,30mgofpioglitazoneand2mgofglimepiride
oncedaily.28

Patientsswitchingfromcombinedtherapywithseparatepioglitazoneandglimepiridepreparations:Usualinitial
dosageofthefixedcombinationisthesameasthepatient'sexistingdosageoftheindividualdrugs.28When
switchingtothefixedcombination,carefullymonitorpatientswithinadequateglycemiccontrolonpioglitazone15
mgdailyincombinationwithglimepiride.28

Patientsswitchingfrommonotherapywithasulfonylureaotherthanglimepiride(e.g.,glyburide,glipizide,
chlorpropamide,tolbutamide,acetohexamide)orfromcombinedtherapywithpioglitazoneplusasulfonylurea
otherthanglimepiride:Initially,30mgofpioglitazoneand2mgofglimepirideoncedailynoexactdosage
relationshipexistsbetweenglimepirideandothersulfonylureas.28

Graduallytitratedosagebasedonadequacyoftherapeuticresponse.28Allowsufficienttime(812weeks)to
evaluateadequacyofresponseasdeterminedbyHbA1cunlessglycemiccontrolbasedonfastingplasma
glucosedeteriorates.28

PrescribingLimits

Adults
Maximum45mgdaily(asmonotherapyorincombinationwithasulfonylurea,metformin,orinsulin).12728

SpecialPopulations

HepaticImpairment

Monotherapy
Nodosageadjustmentnecessary.1

Pioglitazone/ImmediateorExtendedreleaseMetforminHydrochlorideFixedcombinationTherapy
Donotinitiateinpatientswithclinicalevidenceofactiveliverdiseaseorelevatedserumaminotransferase
concentrations(ALT>2.5timesULN).27

Pioglitazone/GlimepirideFixedcombinationTherapy
Initially,glimepiride1mgdailyasmonotherapy,followedbyconservativeinitialandmaintenancedosagesofthe
fixedcombinationindividualswithhepaticimpairmentmaybeparticularlysensitivetothehypoglycemiceffectsof
glimepiride.28

Donotinitiateinpatientswithclinicalevidenceofactiveliverdiseaseorelevatedserumaminotransferase
concentrations(ALT>2.5timesULN).28

RenalImpairment

Monotherapy
Nodosageadjustmentnecessary.1

Pioglitazone/ImmediateorExtendedreleaseMetforminHydrochlorideFixedcombinationTherapy
Donotuseinpatientswithrenalimpairment.27

Pioglitazone/GlimepirideFixedcombinationTherapy
Initially,glimepiride1mgdailyasmonotherapy,followedbyconservativeinitialandmaintenancedosagesofthe
fixedcombinationindividualswithrenalimpairmentmaybeparticularlysensitivetothehypoglycemiceffectsof
glimepiride.28

GeriatricPatients

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Monotherapy
Nodosageadjustmentnecessary.1

Pioglitazone/ImmediateorExtendedreleaseMetforminHydrochlorideFixedcombinationTherapy
Conservativeinitialandmaintenancedosagesrecommendedgeriatricindividualsareparticularlysensitiveto
hypoglycemiceffects.27Generally,donottitratetomaximumrecommendeddosage.27

Pioglitazone/GlimepirideFixedcombinationTherapy
Initially,glimepiride1mgdailyasmonotherapy,followedbyconservativeinitialandmaintenancedosagesofthe
fixedcombinationgeriatricindividualsmaybeparticularlysensitivetothehypoglycemiceffectsofglimepiride.28

PatientswithCHF
NYHAclassIIIorIVheartfailure:Usecontraindicated.12728

Monotherapy
NYHAclassIorIIheartfailure:Initially,15mgoncedaily.1Increasedosagegradually,ifneeded,uptomaximum
of45mgdailybasedonHbA1cconcentrations.1Monitorcarefullyforweightgain,edema,orothermanifestations
ofCHFexacerbationfollowinginitiationanddosageincrease.1

Pioglitazone/GlimepirideFixedcombinationTherapy
Systolicdysfunction:Initially,pioglitazone15mgoncedailyasmonotherapysafelytitratedosageto30mgonce
dailyasmonotherapybeforeinitiatingthefixedcombinationofglimepiride2mgandpioglitazone30mg.28If
subsequentdosageadjustmentisnecessarywiththefixedcombinationpreparation,monitorcloselyforweight
gain,edema,orothermanifestationsofCHFexacerbation.28

DebilitatedorMalnourishedPatients

Pioglitazone/ImmediateorExtendedreleaseMetforminHydrochlorideFixedcombinationTherapy
Generally,donottitratetomaximumrecommendeddosagetheseindividualsareparticularlysusceptibleto
hypoglycemiceffects.27

Pioglitazone/GlimepirideFixedcombinationTherapy
Initially,glimepiride1mgdailyasmonotherapy,followedbyconservativeinitialandmaintenancedosagesofthe
fixedcombinationtheseindividualsareparticularlysusceptibletohypoglycemiceffects.28

PatientswithAdrenalorPituitaryInsufficiency

Pioglitazone/GlimepirideFixedcombinationTherapy
Initially,glimepiride1mgdailyasmonotherapy,followedbyconservativeinitialandmaintenancedosagesofthe
fixedcombinationtheseindividualsareparticularlysusceptibletohypoglycemiceffects.28

CautionsforPioglitazoneHydrochloride
Contraindications
InitiationoftherapyinpatientswithNYHAclassIIIorIVheartfailure.12728(SeeBoxedWarning.)
Knownserious1hypersensitivitytopioglitazoneoranyingredientintheformulation.12728

Warnings/Precautions

Warnings

CHF

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Fluidretentionassociatedwithuseofpioglitazone,aloneorincombinationwithotherantidiabeticagents,may
leadtoorexacerbateCHF.1192728303137384041(SeeBoxedWarning.)Useincombinationwithinsulinorin
patientswithNYHAclassIorIIheartfailuremayincreasetherisk.1

MonitorforsignsandsymptomsofCHF(e.g.,dyspnea,rapidweightgain,edema,unexplainedcoughor
fatigue),especiallyduringinitiationoftherapyanddosagetitration.11927283740

IfCHFdevelops,manageaccordingtocurrentstandardsofcare.11927283740Considerdosagereductionor
discontinuanceofpioglitazone.11927283740

Donotinitiatethiazolidinedionetherapyinhospitalizedpatientswithdiabetesmellitusbecauseofdelayedonset
ofactionandpotentialforincreasedvascularvolumeandCHF.34

Edema
FluidretentionreportedmayleadtoorexacerbateCHF.113

UsewithcautioninpatientswithedemaandinthoseatriskforCHF.127ObserveformanifestationsofCHF(e.g.,
dyspnea,rapidweightgain,edema).1(SeeCHFunderCautions.)

WeightGain
Reportedmayinvolvefluidretentionandfataccumulation.1(SeeBoxedWarning.)

OtherWarnings/Precautions

HepaticEffects
Noevidenceofhepatotoxicityinclinicalstudiestodate.11213However,hepatitis,elevationsinhepaticenzymes,
mixedhepatocellularcholestaticliverinjury,15and,veryrarely,hepaticfailureassociatedwithfatalitiesreported
duringpostmarketingexperience.1

Monitorliverfunctiontestspriortoinitiationoftherapy,thenperiodicallythereafteraccordingtoclinician
judgment.112Monitormorefrequentlyifusedinpatientswithmildhepaticimpairment(ALT12.5timestheupper
limitofnormal[ULN]).1(SeeHepaticImpairmentunderCautions.)

RecheckliverfunctionifALTincreasesto>3timestheULNorifmanifestationssuggestiveofhepaticdysfunction
(e.g.,unexplainednausea,vomiting,abdominalpain,fatigue,anorexia,darkurine)occur.1Discontinuetherapyif
ALTremainselevatedat>3timestheULNorifjaundicedevelops.1

MusculoskeletalEffects
Riskofbonelossandfracturesinwomen,andpossiblyinmen,receivingthiazolidinedionetherapy.1293536394750

Fracturesreportedmorefrequentlyinwomenreceivingpioglitazone(5.1%)thaninwomenreceivingplacebo
(2.5%)inlongtermstudy(mean34.5monthsfollowup).12728303233Effectsnotedafterfirstyearoftreatment
andpersistedthroughouttreatment.12728303233Mostfractureswerenonvertebral,occurringinadistallimb
(forearm,hand,wrist,foot,ankle,fibula,tibia).1272829

Inanobservationalstudy,useofpioglitazoneorrosiglitazoneforapproximately1218monthsassociatedwith
twofoldtothreefoldincreaseinfractures,particularlyofhipandwrist.50Overallriskoffracturesimilaramongmen
andwomen.50

Considerriskoffracture,particularlyinfemalepatients.12935Assessandmaintainbonehealthaccordingto
currentstandardsofcare.1282930323335

RiskofBladderCancer
Increasedriskofbladdercancer.12728Donotuseinpatientswithactivebladdercancerusewithcautionin
patientswithhistoryofbladdercancer,weighingbenefitsofglycemiccontrolagainstunknownrisksofcancer
recurrence.1272880

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Hypoglycemia
Concomitantuseofinsulinorotherantidiabeticdrugs(e.g.,insulinsecretagogues)increasesriskfor
hypoglycemia.12728Mayneedtoreducedosageofconcomitantantidiabeticagenttodecreaseriskof
hypoglycemia.12728(SeeDosageunderDosageandAdministration.)

OcularEffects
Newonsetorworsening(diabetic)macularedemawithdecreasedvisualacuityreportedrarelyconcurrent
peripheraledemareportedfrequently.127283233Symptomsimprovedinsomepatientsfollowingdiscontinuance
ofpioglitazone.127283233

Regulareyeexaminationsbyophthalmologistadvised.12728323334Promptlyreferpatientsreportingvisual
symptomstoophthalmologist,regardlessofotherconcurrenttherapyorphysicalfindings.127283233

OvulatoryEffects
Maycauseovulationinpremenopausalanovulatorywomenriskofpregnancyunlessadequatecontraceptive
measuresinitiated.1

MacrovascularOutcomes
Evidenceofmacrovascularriskreductionwithpioglitazoneoranyotherantidiabeticagenthasnotbeen
conclusivelydemonstratedincontrolledclinicaltrials.1

LaboratoryAbnormalities
Possibledoserelateddecreasesinhemoglobinandhematocritusuallyevidentwithin412weeksoftherapy.1
Mayberelatedtoplasmavolumeexpansion.1Rarelyassociatedwithclinicallyimportanthematologic
manifestations.1

IsolatedelevationsinserumCK>10timesULNnotedrarelyduringclinicaltrials.1Resolvedinmostpatients
withoutapparentsequelaedespitecontinuedtherapywiththedruganyrelationshiptopioglitazonetherapy
unknown.1

UseofFixedCombinations
Whenusedinfixedcombinationwithmetforminhydrochlorideorglimepiride,considerthecautions,precautions,
andcontraindicationsassociatedwiththeconcomitantagent.2728

SpecificPopulations

Pregnancy
CategoryC.1Mostcliniciansrecommendthatinsulinbeusedduringpregnancyinwomenwithdiabetesmellitus.1

Lactation
Distributedintomilkinratsnotknownwhetherdistributedintohumanmilk.1Usenotrecommended.1

PediatricUse
Safetyandefficacynotestablishedinpediatricpatients<18yearsofageusenotrecommended.113

GeriatricUse
Nosubstantialdifferencesinsafetyandefficacyrelativetoyoungeradults.1

HepaticImpairment
Usewithcautioninpatientswithmildhepaticimpairment(ALT12.5timestheULN).112Usenotrecommended
inpatientswithactivehepaticdisease,ALT>2.5timestheULN,ortroglitazoneassociatedjaundice(troglitazone
nolongercommerciallyavailableinUS).112

CommonAdverseEffects
Upperrespiratorytractinfection,headache,sinusitis,myalgia,pharyngitis,edema.1

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InteractionsforPioglitazoneHydrochloride
MetabolizedprincipallybyCYP2C8and,toalesserextent,byCYP3A4andotherisoenzymes(e.g.,CYP1A1).1
WeakinducerofCYP3A4.1

DrugsAffectingHepaticMicrosomalEnzymes
PotentCYP2C8inhibitors:IncreasedpioglitazoneAUCandhalflifedonotexceedmaximumpioglitazone
dosageof15mgoncedaily.1

CYP2C8inducers:DecreasedpioglitazoneAUC.1InitiationordiscontinuanceofaCYP2C8inducerduring
pioglitazonetherapymaynecessitatechangesinantidiabetictherapyhowever,donotexceedmaximum
recommendedpioglitazonedosageof45mgdaily.1

SpecificDrugs

Drug Interaction Comments

Antidiabeticagents Additiveeffectspossible Mayneedtoreducedosageofotherantidiabeticagents1

hypoglycemia1

Atorvastatin Decreasedplasma
concentrationsandAUC
foratorvastatinand
pioglitazone1

Digoxin Pharmacokinetic
interactionunlikely1

Fexofenadine Pharmacokinetic
interactionunlikely1

Gemfibrozil Increasedpioglitazone Donotexceedmaximumpioglitazonedosageof15mg

AUCandhalflife127 oncedaily

Ketoconazole Increasedserum
concentrationsandAUC
forpioglitazone11327

Midazolam Decreasedmidazolam
AUCandpeakplasma
concentrations1

Nifedipine,extended Decreasedpeakplasma Clinicalimportanceunknown1

release nifedipineconcentrations
andAUC1

Oralcontraceptives, Smalldecreasesinpeak Clinicalimportanceunknown1

hormonal(ethinyl plasmaethinylestradiol

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estradiol/norethindrone) concentrationsand
AUC1

Ranitidine Pharmacokinetic
interactionunlikely1

Rifampin Decreasedpioglitazone Mayrequirechangeinantidiabetictherapyifrifampin

AUC127 initiatedordiscontinuedduringpioglitazonetherapy,but
donotexceedmaximumpioglitazonedosageof45mg
daily127

Theophylline Pharmacokinetic
interactionunlikely1

Warfarin Pharmacokineticor
pharmacologic
interaction(e.g.,effect
onPT)unlikely1

PioglitazoneHydrochloridePharmacokinetics
Absorption

Bioavailability
Peakserumconcentrationsattainedwithin2hours.1

Absolutebioavailabilityis83%.81

Food
Fooddelaystimetopeakserumconcentrationto34hoursbutdoesnotaffectextentofabsorption.1

SpecialPopulations
Inpatientswithhepaticimpairment(ChildPughclassBorC),peakpioglitazoneconcentrationisdecreasedby
45%.1

Ingeriatricpatients,AUCofpioglitazoneisincreasednotclinicallyrelevant.1

Infemales,peakserumconcentrationandAUCareincreasedby2060%.1

Distribution

Extent
Distributedintomilkinrats.1Notknownwhetherthedrugdistributesintohumanmilk.1

PlasmaProteinBinding
>99%(mainlyalbumin).1

Elimination

Metabolism

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Extensivelymetabolized,principallybyCYP2C8and,toalesserextent,byCYP3A4andotherisoenzymes(e.g.,
CYP1A1).1

EliminationRoute
Excretedinurine(1530%)andinfeces,primarilyasmetabolites.1

Halflife
37hours(forpioglitazone)or1624hours(forpioglitazoneandmetabolites).1

SpecialPopulations
Ingeriatricpatients,terminalhalflifeisprolongednotclinicallyrelevant.1

Stability
Storage

Oral

Tablets
Tightcontainersat25C(maybeexposedto1530C).1Protectfrommoistureandhumidity.1

Actions
Structurallyandpharmacologicallyrelatedtorosiglitazoneandtroglitazone(nolongercommerciallyavailable
intheUS)189112unrelatedtootherantidiabeticagents(e.g.,sulfonylureas,biguanides,glucosidase
inhibitors).112
Aperoxisomeproliferatoractivatedreceptor(PPAR)agonistincreasestranscriptionofinsulinresponsive
genes.1
Increasesinsulinsensitivityintargettissuesanddecreaseshepaticgluconeogenesis.1Amelioratesinsulin
resistanceassociatedwithtype2diabetesmellituswithoutincreasinginsulinsecretionfrompancreatic
cells.1Doesnotlowerglucoseconcentrationsbeloweuglycemia.1
Ineffectiveinabsenceofinsulin.1

AdvicetoPatients
Importanceofreadingmedicationguideprovidedbymanufacturerbeforestartingpioglitazoneandeachtime
prescriptionisrefilled.1
Importanceofinformingpatientsofpotentialrisksandadvantagesoftherapyandofalternativetherapies.28
Discusspotentialforalterationsindosagerequirementsduringperiodsofstress(e.g.,fever,trauma,infection,
surgery)importanceofcontactingaclinicianpromptly.127
Importanceofinformingpatientsthatpioglitazonemustnotbeusedinpatientswithsevereheartfailure
(NYHAclassIIIorIV).1ImportanceofimmediatelyinformingclinicianifpotentialmanifestationsofCHF(e.g.,
rapidweightgain,edema,unusualfatigue,troublebreathing,shortnessofbreath)occur.12728
Importanceofinformingpatientsthatliverfunctiontestswillbeperformedpriortoinitiationoftherapyand
periodicallythereafter.1(SeeHepaticEffectsunderCautions.)Advisepatientstoinformclinicianifpotential
manifestationsofhepaticdysfunction(e.g.,unexplainednausea,vomiting,abdominalpain,fatigue,anorexia,
darkurine,yellowingofskinorwhitesofeyes)occur.12728
Increasedriskofbladdercancer.12728Importanceofpatientnottakingpioglitazoneifreceivingtreatmentfor
bladdercancer.12728Importanceofpatientreportinganysignofmacroscopichematuriaorsymptomssuchas
dysuriaorurinaryurgencythatdeveloporincreaseduringpioglitazonetreatment.12728
Importanceoftakingexactlyasprescribed.12728Ifadoseismissedononeday,takethenextdoseas
prescribedunlessotherwiseinstructedbycliniciandonotdoublethedosetomakeupforthemisseddose.127
28 27 28
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28Importanceofchangingdosagewithcautionandonlyundermedicalsupervision.2728Importanceof
immediatelycontactingaclinicianorgoingtothenearesthospitalemergencydepartmentifaccidental
overdosageoccurs.1
Importanceofadvisingpatientnottochew,cut,orcrushthecombinationpreparationcontainingpioglitazone
andextendedreleasemetforminhydrochloride(ActoPlusMetXR)mustswallowthisdosageformwhole.27
Advisepatientsthatbiologicallyinertcomponentsoftheextendedreleasecombinationtabletmayoccasionally
beeliminatedinfecesasasoftmassthatmayresembleoriginaltablet.27
Riskofhypoglycemiainpatientsreceivingconcomitantinsulinorotherantidiabetictherapy.1Provide
instructionsregardingmanagementofhypoglycemia,includingrecognitionofsymptoms,predisposing
conditions,andtreatment.1
Riskofpregnancyinpremenopausalanovulatorywomen.12728Advisepatientstoutilizeeffective
contraceptionduringtherapy.12728
Importanceofadheringtodietandexerciseregimen.1Importanceofregularmonitoring(preferablyself
monitoring)ofbloodglucoseandofHbA1c.127

Riskoffractures(e.g.,hand,upperarm,foot)inwomen.150
Importanceofregulareyeexaminations.1Importanceofreportingchangesinvision.1
Importanceofinformingcliniciansofexistingorcontemplatedconcomitanttherapy,includingprescriptionand
OTCdrugs,aswellasanyconcomitantillnesses.127
Importanceofwomeninformingtheirclinicianiftheyareorplantobecomepregnantorplantobreastfeed.127
28

Importanceofinformingpatientsofotherimportantprecautionaryinformation.127(SeeCautions.)

Preparations
Excipientsincommerciallyavailabledrugpreparationsmayhaveclinicallyimportanteffectsinsomeindividuals
consultspecificproductlabelingfordetails.

PleaserefertotheASHPDrugShortagesResourceCenterforinformationonshortagesofoneormoreof
thesepreparations.

PioglitazoneHydrochloride
Routes DosageForms Strengths BrandNames Manufacturer

Oral Tablets,filmcoated 15mg(ofpioglitazone) Actos Takeda

30mg(ofpioglitazone) Actos Takeda

45mg(ofpioglitazone) Actos Takeda

PioglitazoneHydrochlorideCombinations
Routes DosageForms Strengths Brand Manufacturer
Names

Oral Tablets 15mg(ofpioglitazone)with Actoplus Takeda

MetforminHydrochloride500mg Met

Takeda

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15mg(ofpioglitazone)with Actoplus
MetforminHydrochloride850mg Met

30mg(ofpioglitazone)with Duetact Takeda

Glimepiride2mg

30mg(ofpioglitazone)with Duetact Takeda

Glimepiride4mg

Oral Tablets,extendedrelease 15mg(ofpioglitazone)with Actoplus Takeda

(metforminhydrochloridecore) MetforminHydrochloride1g MetXR

30mg(ofpioglitazone)with Actoplus Takeda

MetforminHydrochloride1g MetXR

AHFSDIEssentials.Copyright,2016,AmericanSocietyofHealthSystemPharmacists,Inc.,7272WisconsinAvenue,Bethesda,Maryland20814.
Datemodified:February08,2016
Lastreviewed:February09,2015
Datepublished:May01,2004

References
1.TakedaPharmaceuticalsAmerica.Actos(pioglitazonehydrochloride)tabletsprescribinginformation.Deerfield,IL2012Jan.
2.KawamoriR,MatsuhisaM,KinoshitaJetal.Pioglitazoneenhancessplanchnicglucoseuptakeaswellasperipheralglucoseuptakeinnoninsulindep
endentdiabetesmellitus.AD4833ClampOGLStudyGroup.DiabetesResClinPract.1998Jul41(1):3543.
3.BergerJ,BaileyP,BiswasCetal.Thiazolidinedionesproduceaconformationalchangeinperoxisomalproliferatoractivatedreceptor:bindinganda
ctivationcorrelatewithantidiabeticactionsindb/dbmice.Endocrinology.1996137:418995.[PubMed8828476]
8.YoungPW,BuckleDR,CantelloBCetal.Identificationofhighaffinitybindingsitesfortheinsulinsensitizerrosiglitazone(BRL49653)inrodentandh
umanadipocytesusingaradioiodinatedligandforperoxisomalproliferatoractivatedreceptorgamma.JPharmacolExpTher.1998284:7519.[PubMe
d9454824]
9.ArakawaK,InamasuM,MatsumotoMetal.Novelbenzoxazol2,4thiazolidinedionesaspotenthypoglycemicagents.ChemPharmBull.199745:198
493.[PubMed9433768]
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