orlistat label.pdf
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XENICAL - orlistat capsule
RochePharmaceuticals
XENICAL®
(orlistat)
CAPSULES
DESCRIPTION
XENICAL(orlistat)isalipaseinhibitorforobesitymanagementthatactsbyinhibitingtheabsorptionofdietaryfats.
Orlistatis(S)-2-formylamino-4-methyl-pentanoicacid(S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]-dodecylester.Itsempirica
formulaisC29H53NO5,anditsmolecularweightis495.7.Itisasinglediastereomericmoleculethatcontainsfourchiralcenters,with
anegativeopticalrotationinethanolat529nm.Thestructureis:
Orlistatisawhitetooff-whitecrystallinepowder.Orlistatispracticallyinsolubleinwater,freelysolubleinchloroform,andvery
solubleinmethanolandethanol.OrlistathasnopK awithinthephysiologicalpHrange.
XENICALisavailablefororaladministrationindark-blue,hard-gelatincapsules,withlight-blueimprinting.Eachcapsulecontains120mgoftheactiveingredient,orlistat.Thecapsulesalsocontaintheinactiveingredientsmicrocrystallinecellulose,sodiumstarch
glycolate,sodiumlaurylsulfate,povidone,andtalc.Eachcapsuleshellcontainsgelatin,titaniumdioxide,andFD&CBlueNo.1,with
printingofpharmaceuticalglazeNF,titaniumdioxide,andFD&CBlueNo.1aluminumlake.
CLINICAL PHARMACOLOGY
Mechanism of Action
Orlistatisareversibleinhibitoroflipases.Itexertsitstherapeuticactivityinthelumenofthestomachandsmallintestinebyforming
acovalentbondwiththeactiveserineresiduesiteofgastricandpancreaticlipases.Theinactivatedenzymesarethusunavailableto
hydrolyzedietaryfatintheformoftriglyceridesintoabsorbablefreefattyacidsandmonoglycerides.Asundigestedtriglyceridesare
notabsorbed,theresultingcaloricdeficitmayhaveapositiveeffectonweightcontrol.Systemicabsorptionofthedrugistherefore
notneededforactivity.Attherecommendedtherapeuticdoseof120mgthreetimesaday,orlistatinhibitsdietaryfatabsorptionby
approximately30%.
Pharmacokinetics
Absorption
Systemicexposuretoorlistatisminimal.Followingoraldosingwith360mg14C-orlistat,plasmaradioactivitypeakedat
approximately8hours;plasmaconcentrationsofintactorlistatwerenearthelimitsofdetection(
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life(approximately3hours)whereasthesecondarymetaboliteM3disappearedataslowerrate(half-lifeapproximately13.5hours).In
obesepatients,steady-stateplasmalevelsofM1,butnotM3,increasedinproportiontoorlistatdoses.
Elimination
Followingasingleoraldoseof360mg14C-orlistatinbothnormalweightandobesesubjects,fecalexcretionoftheunabsorbed
drugwasfoundtobethemajorrouteofelimination.OrlistatanditsM1andM3metaboliteswerealsosubjecttobiliaryexcretion.
Approximately97%oftheadministeredradioactivitywasexcretedinfeces;83%ofthatwasfoundtobeunchangedorlistat.The
cumulativerenalexcretionoftotalradioactivitywas
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DiastolicBloodPressure,mmHg -1.19 +0.46
Anthropometric:
WaistCircumference,cm -6.45 -4.04
HipCircumference,cm -5.31 -2.96
*TreatmentdesignatesXENICAL120mgthreetimesadayplusdietorplaceboplusdiet
†Intent-to-treatpopulationatweek52,observeddatabasedonpooleddatafrom5studies
Population With Abnormal Risk Factors at Randomization
Thechangesfromrandomizationfollowing1-yeartreatmentinthepopulationwithabnormallipidlevels(LDL≥ 130mg/dL,LDL/HDL≥ 3.5,HDL
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*TreatmentdesignatesXENICAL120mgthreetimesadayplusdietorplaceboplusdiet
†Lastobservationcarriedforward
‡Allstudies,withtheexceptionof14161wereconductedatcentersspecializingintreatingobesityorcomplicationsofobesity.Study
14161wasconductedwithprimarycarephysicians.
Therelativechangesinriskfactorsassociatedwithobesityfollowing2yearsoftherapywerealsoassessedinthepopulationasa
wholeandthepopulationwithabnormalriskfactorsatrandomization.
Population as a Whole
TherelativedifferencesinriskfactorsbetweentreatmentwithXENICALandplaceboweresimilartotheresultsfollowing1yearof
therapyfortotalcholesterol,LDL-cholesterol,LDL/HDLratio,triglycerides,fastingglucose,fastinginsulin,diastolicbloodpressure,
waistcircumference,andhipcircumference.TherelativedifferencesbetweentreatmentgroupsforHDLcholesterolandsystolicblood
pressurewerelessthanthatobservedintheyearoneresults.
Population With Abnormal Risk Factors at Randomization
TherelativedifferencesinriskfactorsbetweentreatmentwithXENICALandplaceboweresimilartotheresultsfollowing1yearof
therapyforLDL- andHDL-cholesterol,triglycerides,fastinginsulin,diastolicbloodpressure,andwaistcircumference.Therelative
differencesbetweentreatmentgroupsforLDL/HDLratioandisolatedsystolicbloodpressurewerelessthanthatobservedintheyear
oneresults.
Four-year Results: Long-term Weight Control and Risk Factors
Inthe4-yeardouble-blind,placebo-controlledXENDOSstudy,theeffectsoforlistatindelayingtheonsetoftype2diabetesand
onbodyweightwerecomparedtoplaceboin3304obesepatientswhohadeithernormalorimpairedglucosetoleranceatbaseline.
Thirty-fourpercentofthe1655patientswhowererandomizedtotheplacebogroupand52%ofthe1649patientswhowere
randomizedtotheorlistatgroupcompletedthe4-yearstudy.
Attheendofthestudy,themeanpercentweightlossintheplacebogroupwas-2.75%comparedwith-5.17%intheorlistatgroup
(p
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patientswhohadimpairedglucosetoleranceatbaseline(Table6andFigure2).Orlistatdidnotreducetheriskforthedevelopmentof
diabetesinpatientswithnormalglucosetoleranceatbaseline.
TheeffectofXENICALtodelaytheonsetoftype2diabetesinobesepatientswithIGTispresumablyduetoweightloss,andnotto
anyindependenteffectsofthedrugonglucoseorinsulinmetabolism.Theeffectoforlistatonweightlossisadjunctivetodietand
exercise.
Table6IncidenceRateofDiabetesatYear4byOGTTStatusatBaseline*
OGTT at baseline Normal Impaired All
Treatment Placebo Orlistat Placebo Orlistat Placebo Orlistat
Numberofpatients* 1148 1235 324 337 1472 1572
#ptsdevelopingdiabetes 16 21 62 48 78 69
Lifetablerate† 2.1% 1.7% 27.2% 18.7% 8.3% 5.5%
Observedpercent 1.4% 1.7% 19.1% 14.2% 5.3% 4.4%
Absoluteriskreduction
Lifetable 0.4% 8.5% 2.8%
Observed -0.3% 4.9% 0.9%
Relativeriskreduction‡ 8% 42% 34%
p-value 0.79
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*TreatmentdesignatesXENICAL120mgthreetimesadayplusdietorplaceboplusdiet
†Lastobservationcarriedforward
INDICATIONS AND USAGE
XENICALisindicatedforobesitymanagementincludingweightlossandweightmaintenancewhenusedinconjunctionwith
areduced-caloriediet.XENICALisalsoindicatedtoreducetheriskforweightregainafterpriorweightloss.XENICALis
indicatedforobesepatientswithaninitialbodymassindex(BMI)≥ 30kg/m2or≥ 27kg/m2inthepresenceofotherriskfactors(eg,
hypertension,diabetes,dyslipidemia).
Table8illustratesbodymassindex(BMI)accordingtoavarietyofweightsandheights.TheBMIiscalculatedbydividingweightin
kilogramsbyheightinmeterssquared.Forexample,apersonwhoweighs180lbsandis5'5"wouldhaveaBMIof30.
Table8BodyMassIndex(BMI),kg/m2*
WEIGHT (lb)
120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 310 320
4'10" 25 27 29 31 34 36 38 40 42 44 46 48 50 52 54 57 59 61 63 65 67
4'11" 24 26 28 30 32 34 36 38 40 43 45 47 49 51 53 55 57 59 61 63 65
5'0" 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 61 63
5'1" 23 25 27 28 30 32 34 36 38 40 42 44 45 47 49 51 53 55 57 59 61
5'2" 22 24 26 27 29 31 33 35 37 38 40 42 44 46 48 49 51 53 55 57 59
5'3" 21 23 25 27 28 30 32 34 36 37 39 41 43 44 46 48 50 51 53 55 57
5'4" 21 22 24 26 28 29 31 33 34 36 38 40 41 43 45 46 48 50 52 53 55
5'5" 20 22 23 25 27 28 30 32 33 35 37 38 40 42 43 45 47 48 50 52 53
5'6" 19 21 23 24 26 27 29 31 32 34 36 37 39 40 42 44 45 47 49 50 52
5'7" 19 20 22 24 25 27 28 30 31 33 35 36 38 39 41 42 44 46 47 49 50
5'8" 18 20 21 23 24 26 27 29 30 32 34 35 37 38 40 41 43 44 46 47 49
5'9" 18 19 21 22 24 25 27 28 30 31 33 34 36 37 38 40 41 43 44 46 47
5'10" 17 19 20 22 23 24 26 27 29 30 32 33 35 36 37 39 40 42 43 45 46
5'11" 17 18 20 21 22 24 25 27 28 29 31 32 34 35 36 38 39 41 42 43 45
6'0" 16 18 19 20 22 23 24 26 27 29 30 31 33 34 35 37 38 39 41 42 43
6'1" 16 17 19 20 21 22 24 25 26 28 29 30 32 33 34 36 37 38 40 41 42
6'2" 15 17 18 19 21 22 23 24 26 27 28 30 31 32 33 35 36 37 39 40 41
HEIGHT
(ft/in)
*ConversionFactors:
Weightinlbs÷2.2=weightinkilograms(kg)
Heightininches×0.0254=heightinmeters(m)
1foot=12inches
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CONTRAINDICATIONS
XENICALiscontraindicatedinpatientswithchronicmalabsorptionsyndromeorcholestasis,andinpatientswithknown
hypersensitivitytoXENICALortoanycomponentofthisproduct.
WARNINGS
Miscellaneous
Organiccausesofobesity(eg,hypothyroidism)shouldbeexcludedbeforeprescribingXENICAL.
PreliminarydatafromaXENICALandcyclosporinedruginteractionstudyindicateareductionincyclosporineplasmalevelswhen
XENICALwascoadministeredwithcyclosporine.Therefore,XENICALandcyclosporineshouldnotbecoadministered.Toreduce
thechanceofadrug-druginteraction,cyclosporineshouldbetakenatleast2hoursbeforeorafterXENICALinpatientstakingboth
drugs.Inaddition,inthosepatientswhosecyclosporinelevelsarebeingmeasured,morefrequentmonitoringshouldbeconsidered.
PRECAUTIONS
General
Patientsshouldbeadvisedtoadheretodietaryguidelines(seeDOSAGEANDADMINISTRATION).Gastrointestinalevents
(seeADVERSEREACTIONS)mayincreasewhenXENICAListakenwithadiethighinfat(>30%totaldailycaloriesfromfat).
Thedailyintakeoffatshouldbedistributedoverthreemainmeals.IfXENICAListakenwithanyonemealveryhighinfat,the
possibilityofgastrointestinaleffectsincreases.
Patientsshouldbestronglyencouragedtotakeamultivitaminsupplementthatcontainsfat-solublevitaminstoensureadequate
nutritionbecauseXENICALhasbeenshowntoreducetheabsorptionofsomefat-solublevitaminsandbeta-carotene(seeDOSAGE
ANDADMINISTRATION).Inaddition,thelevelsofvitaminDandbeta-carotenemaybelowinobesepatientscomparedwithnon-
obesesubjects.Thesupplementshouldbetakenonceadayatleast2hoursbeforeoraftertheadministrationofXENICAL,suchasat
bedtime.
Table9illustratesthepercentageofadultpatientsonXENICALandplacebowhodevelopedalowvitaminlevelontwoormore
consecutivevisitsduring1and2yearsoftherapyinstudiesinwhichpatientswerenotpreviouslyreceivingvitaminsupplementation.
Table9IncidenceofLowVitaminValuesonTwoorMoreConsecutiveVisits(NonsupplementedAdultPatientsWithNormal
BaselineValues- FirstandSecondYear)
Placebo* XENICAL*
VitaminA 1.0% 2.2%
VitaminD 6.6% 12.0%
VitaminE 1.0% 5.8%
Beta-carotene 1.7% 6.1%*TreatmentdesignatesplaceboplusdietorXENICALplusdiet
Table10illustratesthepercentageofadolescentpatientsonXENICALandplacebowhodevelopedalowvitaminlevelontwoor
moreconsecutivevisitsduringthe1-yearstudy.
Table10IncidenceofLowVitaminValuesonTwoorMoreConsecutiveVisits(PediatricPatientsWithNormalBaselineValues*)
Placebo†
XENICAL†
VitaminA 0.0% 0.0%
VitaminD 0.7% 1.4%
VitaminE 0.0% 0.0%
Beta-carotene 0.8% 1.5%
*Allpatientsweretreatedwithvitaminsupplementationthroughoutthecourseofthestudy
†TreatmentdesignatesplaceboplusdietorXENICALplusdiet
SomepatientsmaydevelopincreasedlevelsofurinaryoxalatefollowingtreatmentwithXENICAL.Cautionshouldbeexercised
whenprescribingXENICALtopatientswithahistoryofhyperoxaluriaorcalciumoxalatenephrolithiasis.
Weight-lossinductionbyXENICALmaybeaccompaniedbyimprovedmetaboliccontrolindiabetics,whichmightrequirea
reductionindoseoforalhypoglycemicmedication(eg,sulfonylureas,metformin)orinsulin(seeCLINICALSTUDIES).
Substantialweightlosscanincreasetheriskofcholelithiasis.InaclinicaltrialofXENICALforthepreventionoftype2diabetes,
theratesofcholelithiasisasanadverseeventwere2.9%(47/1649)forpatientsrandomizedtoXENICALand1.8%(30/1655)for
patientsrandomizedtoplacebo.Inthistrial,theincidenceofcholelithiasiswassimilarforXENICALandplaceboatsimilaramounts
ofweightloss.AnincreaseincholelithiasiswithXENICALwasnotseenintrialsthatwerenotevaluatingthepreventionoftype2
diabetes.
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Misuse Potential
Aswithanyweight-lossagent,thepotentialexistsformisuseofXENICALininappropriatepatientpopulations(eg,patientswith
anorexianervosaorbulimia).SeeINDICATIONSANDUSAGEforrecommendedprescribingguidelines.
Information for Patients
PatientsshouldreadthePatientInformationbeforestartingtreatmentwithXENICALandeachtimetheirprescriptionisrenewed.
Drug Interactions
Alcohol
Inamultiple-dosestudyin30normal-weightsubjects,coadministrationofXENICALand40gramsofalcohol(eg,approximately3 glassesofwine)didnotresultinalterationofalcoholpharmacokinetics,orlistatpharmacodynamics(fecalfatexcretion),orsystemic
exposuretoorlistat.
Cyclosporine
PreliminarydatafromaXENICALandcyclosporinedruginteractionstudyindicateareductionincyclosporineplasmalevelswhen
XENICALwascoadministeredwithcyclosporine(seeWARNINGS).
Digoxin
In12normal-weightsubjectsreceivingXENICAL120mgthreetimesadayfor6days,XENICALdidnotalterthepharmacokinetics
ofasingledoseofdigoxin.
Fat-solubleVitaminSupplementsandAnalogues
Apharmacokineticinteractionstudyshoweda30%reductioninbeta-carotenesupplementabsorptionwhenconcomitantly administeredwithXENICAL.XENICALinhibitedabsorptionofavitaminEacetatesupplementbyapproximately60%.Theeffectof
orlistatontheabsorptionofsupplementalvitaminD,vitaminA,andnutritionally-derivedvitaminKisnotknownatthistime.
Glyburide
In12normal-weightsubjectsreceivingorlistat80mgthreetimesadayfor5days,orlistatdidnotalterthepharmacokineticsor
pharmacodynamics(bloodglucose-lowering)ofglyburide.
Levothyroxine
Hypothyroidismhasbeenreportedinpatientstreatedconcomitantlywithorlistatandlevothyroxinepostmarketing(seeADVERSE
REACTIONS: Other Clinical Studies or Postmarketing Surveillance).Patientstreatedconcomitantlywithorlistatand
levothyroxineshouldbemonitoredforchangesinthyroidfunction.Administerlevothyroxineandorlistatatleast4hoursapart.
Nifedipine(extended-releasetablets) In17normal-weightsubjectsreceivingXENICAL120mgthreetimesadayfor6days,XENICALdidnotalterthebioavailabilityof
nifedipine(extended-releasetablets).
OralContraceptives
In20normal-weightfemalesubjects,thetreatmentofXENICAL120mgthreetimesadayfor23daysresultedinnochangesinthe
ovulation-suppressingactionoforalcontraceptives.
Phenytoin
In12normal-weightsubjectsreceivingXENICAL120mgthreetimesadayfor7days,XENICALdidnotalterthepharmacokinetics
ofasingle300-mgdoseofphenytoin.
Pravastatin
Ina2-waycrossoverstudyof24normal-weight,mildlyhypercholesterolemicpatientsreceivingXENICAL120mgthreetimesaday
for6days,XENICALdidnotaffectthepharmacokineticsofpravastatin.
Warfarin
In12normal-weightsubjects,administrationofXENICAL120mgthreetimesadayfor16daysdidnotresultinanychangeineither
warfarinpharmacokinetics(bothR- andS-enantiomers)orpharmacodynamics(prothrombintimeandserumFactorVII).Although
undercarboxylatedosteocalcin,amarkerofvitaminKnutritionalstatus,wasunalteredwithXENICALadministration,vitaminK
levelstendedtodeclineinsubjectstakingXENICAL.Therefore,asvitaminKabsorptionmaybedecreasedwithXENICAL,patients
onchronicstabledosesofwarfarinwhoareprescribedXENICALshouldbemonitoredcloselyforchangesincoagulationparameters.
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FlatuswithDischarge 23.9 1.4 2.1 0.2
FecalUrgency 22.1 6.7 2.8 1.7
Fatty/OilyStool 20.0 2.9 5.5 0.6
OilyEvacuation 11.9 0.8 2.3 0.2
IncreasedDefecation 10.8 4.1 2.6 0.8
FecalIncontinence 7.7 0.9 1.8 0.2
*TreatmentdesignatesXENICALthreetimesadayplusdietorplaceboplusdiet
Theseandothercommonlyobservedadversereactionsweregenerallymildandtransient,andtheydecreasedduringthesecondyearoftreatment.Ingeneral,thefirstoccurrenceoftheseeventswaswithin3monthsofstartingtherapy.Overall,approximately50%of
allepisodesofGIadverseeventsassociatedwithorlistattreatmentlastedforlessthan1week,andamajoritylastedfornomorethan
4weeks.However,GIadverseeventsmayoccurinsomeindividualsoveraperiodof6monthsorlonger.
Discontinuation of Treatment
Incontrolledclinicaltrials,8.8%ofpatientstreatedwithXENICALdiscontinuedtreatmentduetoadverseevents,comparedwith
5.0%ofplacebo-treatedpatients.ForXENICAL,themostcommonadverseeventsresultingindiscontinuationoftreatmentwere
gastrointestinal.
Incidence in Controlled Clinical Trials
Thefollowingtablelistsothertreatment-emergentadverseeventsfromsevenmulticenter,double-blind,placebo-controlledclinical
trialsthatoccurredatafrequencyof≥ 2%amongpatientstreatedwithXENICAL120mgthreetimesadayandwithanincidencetha
wasgreaterthanplaceboduringyear1andyear2,regardlessofrelationshiptostudymedication.
Table12OtherTreatment-EmergentAdverseEventsFromSevenPlacebo-ControlledClinicalTrials
Body System/Adverse Event
Year 1 Year 2
XENICAL*
% Patients
(N=1913)
Placebo*
% Patients
(N=1466)
XENICAL*
% Patients
(N=613)
Placebo*
% Patients
(N=524)
Gastrointestinal System
AbdominalPain/Discomfort 25.5 21.4 – –
Nausea 8.1 7.3 3.6 2.7
InfectiousDiarrhea 5.3 4.4 – –
RectalPain/Discomfort 5.2 4.0 3.3 1.9ToothDisorder 4.3 3.1 2.9 2.3
GingivalDisorder 4.1 2.9 2.0 1.5
Vomiting 3.8 3.5 – –
Respiratory System
Influenza 39.7 36.2 – –
UpperRespiratoryInfection 38.1 32.8 26.1 25.8
LowerRespiratoryInfection 7.8 6.6 – –
Ear,Nose&ThroatSymptoms 2.0 1.6 – –
Musculoskeletal System
BackPain 13.9 12.1 – –
PainLowerExtremities – – 10.8 10.3
Arthritis 5.4 4.8 – –
Myalgia 4.2 3.3 – –
JointDisorder 2.3 2.2 – –
Tendonitis – – 2.0 1.9
Central Nervous System
Headache
Dizziness
30.6
5.2
27.6
5.0
–
–
–
–
Body as a Whole
Fatigue 7.2 6.4 3.1 1.7
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SleepDisorder 3.9 3.3 – –
Skin & Appendages
Rash
DrySkin
4.3
2.1
4.0
1.4
–
–
–
–
Reproductive, Female
MenstrualIrregularity
Vaginitis
9.8
3.8
7.5
3.6
–
2.6
–
1.9
Urinary System
UrinaryTractInfection 7.5 7.3 5.9 4.8
Psychiatric Disorder
PsychiatricAnxiety
Depression
4.7
–
2.9
–
2.8
3.4
2.1
2.5
Hearing & Vestibular Disorders
Otitis 4.3 3.4 2.9 2.5
Cardiovascular Disorders
PedalEdema – – 2.8 1.9
–Nonereportedatafrequency≥ 2%andgreaterthanplacebo
*TreatmentdesignatesXENICAL120mgthreetimesadayplusdietorplaceboplusdiet
Inthe4-yearXENDOSstudy,thegeneralpatternofadverseeventswassimilartothatreportedforthe1- and2-yearstudieswiththe
totalincidenceofgastrointestinal-relatedadverseeventsoccurringinyear1decreasingeachyearoverthe4-yearperiod.
Other Clinical Studies or Postmarketing Surveillance
RarecasesofhypersensitivityhavebeenreportedwiththeuseofXENICAL.Signsandsymptomshaveincludedpruritus,rash,
urticaria,angioedema,bronchospasmandanaphylaxis.Veryrarecasesofbullouseruption,increaseintransaminasesandinalkaline
phosphatase,andexceptionalcasesofhepatitisthatmaybeserioushavebeenreported.Nocausalrelationshiporphysiopathological
mechanismbetweenhepatitisandorlistattherapyhasbeenestablished.Reportsofdecreasedprothrombin,increasedINRand
unbalancedanticoagulanttreatmentresultinginchangeofhemostaticparametershavebeenreportedinpatientstreatedconcomitantly
withorlistatandanticoagulants.Hypothyroidismhasbeenreportedinpatientstreatedconcomitantlywithorlistatandlevothyroxine.
PancreatitishasbeenreportedwiththeuseofXENICALinpostmarketingsurveillance.Nocausalrelationshiporphysiopathological
mechanismbetweenpancreatitisandobesitytherapyhasbeendefinitivelyestablished.
Inclinicaltrialsinobesediabeticpatients,hypoglycemiaandabdominaldistensionwerealsoobserved.
PreliminarydatafromaXENICALandcyclosporinedruginteractionstudyindicateareductionincyclosporineplasmalevelswhen
XENICALwascoadministeredwithcyclosporine(seeWARNINGS).
Pediatric Patients
InclinicaltrialswithXENICALinadolescentpatientsages12to16years,theprofileofadversereactionswasgenerallysimilarto
thatobservedinadults.
OVERDOSAGE
Singledosesof800mgXENICALandmultipledosesofupto400mgthreetimesadayfor15dayshavebeenstudiedinnormal
weightandobesesubjectswithoutsignificantadversefindings.
ShouldasignificantoverdoseofXENICALoccur,itisrecommendedthatthepatientbeobservedfor24hours.Basedonhumanand
animalstudies,systemiceffectsattributabletothelipase-inhibitingpropertiesoforlistatshouldberapidlyreversible.
DOSAGE AND ADMINISTRATIONTherecommendeddoseofXENICALisone120-mgcapsulethreetimesadaywitheachmainmealcontainingfat(duringorupto1
hourafterthemeal).
Thepatientshouldbeonanutritionallybalanced,reduced-caloriedietthatcontainsapproximately30%ofcaloriesfromfat.Thedaily
intakeoffat,carbohydrate,andproteinshouldbedistributedoverthreemainmeals.Ifamealisoccasionallymissedorcontainsno
fat,thedoseofXENICALcanbeomitted.
BecauseXENICALhasbeenshowntoreducetheabsorptionofsomefat-solublevitaminsandbeta-carotene,patientsshouldbe
counseledtotakeamultivitamincontainingfat-solublevitaminstoensureadequatenutrition(seePRECAUTIONS:General).The
supplementshouldbetakenatleast2hoursbeforeoraftertheadministrationofXENICAL,suchasatbedtime.
Forpatientsreceivingbothorlistatandlevothyroxinetherapy,administerlevothyroxineandorlistatatleast4hoursapart.
Dosesabove120mgthreetimesadayhavenotbeenshowntoprovideadditionalbenefit.
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Basedonfecalfatmeasurements,theeffectofXENICALisseenassoonas24to48hoursafterdosing.Upondiscontinuationof
therapy,fecalfatcontentusuallyreturnstopretreatmentlevelswithin48to72hours.
ThesafetyandeffectivenessofXENICALbeyond4yearshavenotbeendeterminedatthistime.
HOW SUPPLIED
XENICALisadark-blue,hard-gelatincapsulecontainingpelletsofpowder.
XENICAL120mgCapsules:Dark-blue,two-piece,No.1opaquehard-gelatincapsuleimprintedwithRocheandXENICAL120in
light-blueink—bottleof90(NDC0004-0256-52).
Storage Conditions
Storeat25°C(77°F);excursionspermittedto15°to30°C(59°to86°F)[seeUSPControlledRoomTemperature].Keepbottletightly
closed.
XENICALshouldnotbeusedafterthegivenexpirationdate.
PIRevised:July2008
IMPORTANT PATIENT INFORMATION
Patient Information about XENICAL® (orlistat) Capsules
XENICAL (zen' i-cal)
Generic Name: orlistat
PleasereadthisinformationbeforeyoustarttakingXENICALandeachtimeyourenewyourprescription.Thisimportantinformation
mayhelpyousuccessfullyloseweightandmaintainyourweightlosswhiletakingXENICAL.Thispatientinformationisasummary
andisnotintendedtotaketheplaceofdiscussionswithyourdoctor.ItdoesnotlistallbenefitsandrisksofXENICAL.The
medicationdescribedherecanonlybeprescribedanddispensedbyalicensedhealthcareprofessional,whohasinformationabout
yourmedicalconditionandmoreinformationaboutthedrug,includinghowtotakeit,whattoexpect,andpotentialsideeffects.Ifyou
haveanyquestionsaboutXENICAL,talkwithyourdoctor.
What is XENICAL?
XENICALisanoralprescriptionweightlossmedicationusedtohelpobesepeopleloseweightandkeepthisweightoff.XENICAL
worksinyourintestines,whereitblockssomeofthefatyoueatfrombeingabsorbed.Thisundigestedfatistheneliminatedinyour
bowelmovements.XENICALshouldbeusedtogetherwithareduced-caloriedietthatyourdoctorwillrecommend.
Excessweighthasbeenproventocontributetoanincreasedriskofdevelopingmanymedicalproblems,includinghighblood
pressure,highcholesterol,heartdisease,anddiabetes.Theconsumptionofexcessfattyfoodandcaloriesplaysasignificantrolein
thedevelopmentofexcessweight.Whilefatisanimportantcomponentofabalanceddiet,theconsumptionofexcessfatcontributes
toexcessbodyweight,sincefatprovidestwicethenumberofcaloriespergramofweightascarbohydratesandprotein.Reductionof
dietaryfatintakeisonepotentialwayoflosingweight.
How does XENICAL work?
Ifyoueatanexcessamountoffatorcalories,theexcessisstoredasfatbythebodyresultinginweightgain.Whenyoueatfat,yourbodybreaksitdownintoitssimplestcomponentssothatitcanbeabsorbed.Enzymesinyourintestinaltract,calledlipases,help
digest(orbreakdown)fat.WhenyoutakeXENICALwithmeals,XENICALattachestothelipasesandblocksthemfrombreaking
downsomeofthefatyouhaveeaten.Theundigestedfatcannotbeabsorbedandiseliminatedinyourbowelmovements.Byworking
thisway,XENICALhelpsblockabout30%ofthefateateninfoodfrombeingabsorbedbyyourbody.
Information for adult obese patients
Followingoneyearoftreatment,XENICALincombinationwithdietwasshowntobemoreeffectiveinreducingweightthandiet
alone.Inmostcases,weightlosswasgradual.PatientstreatedwithXENICALandareduced-caloriedietforoneyearlostanaverage
of13.4poundswhilethoseonareduced-caloriedietalonelost5.8pounds.
Information for adolescent obese patients
Followingoneyearoftreatment,XENICALincombinationwithdietwasshowntobemoreeffectiveinreducingBodyMassIndex
(BMI)thandietalone.AreductioninBodyMassIndexisabetterindicatorofweightlossinchildrenbecauseittakesintoaccount
changesinweightrelatedtogrowingchildren.
Who should use XENICAL?Aweightlossprogramthatincludesareduced-caloriedietandappropriatephysicalactivitymaybeadequateinsomepatients.You
shoulddiscusswithyourdoctororotherhealthcareproviderwhetherXENICALshouldbeaddedtosuchaprogram.
XENICALmayberightforyouifyouareconsiderablyoverweight(atleast30%aboveidealweightorabodymassindexof30or
greater).XENICALmayalsoberightforyouifyouareoverweight(atleast20%aboveidealweightorabodymassindexof27or
greater)andalsohaveotherriskfactorssuchashighbloodpressure,highcholesterol,heartdisease,ordiabetes.
Howtodetermineyourbodymassindex(BMI):
ThechartbelowillustratesBMIaccordingtoavarietyofweightsandheights.TheBMIiscalculatedbydividingyourweightin
kilogramsbyyourheightinmeterssquared.Tousethischart:
• Findtheheightclosesttoyourheightintheleft-handcolumn.
• Thenmoveacrossthetoprowtofindtheweightclosesttoyourweight.
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1600 53
1800 60
2000 67
Should I take a multivitamin with XENICAL?
XENICALinterfereswithyourbody’sabsorptionofsomefat-solublevitamins.Therefore,whenyouuseXENICAL,itishighly
recommendedthatyoutakeadailymultivitaminsupplementcontainingvitaminsD,E,K,andbeta-carotene.Takeyourmultivitamin
onceadayatleast2hoursbeforeoraftertakingXENICAL,suchasatbedtime.
Can I take XENICAL while taking other medications?
Besuretodiscusswithyourdoctorallmedications(includingherbalproducts)youarecurrentlytaking,includingmedicinesyou
cangetwithoutaprescription(over-the-counter),todetermineifXENICALcanbetakeninadditiontothesemedications.Ifyou
aretakingcyclosporine,XENICALandcyclosporineshouldbetakenatleast2hoursapart.Ifyourcyclosporinelevelsarebeing
measured,morefrequentmonitoringmaybenecessary.Ifyouaretakinglevothyroxine,XENICALandlevothyroxineshouldbetaken
atleast4hoursapart.
How long should I use XENICAL?
TheuseofXENICALformorethan4yearshasnotbeenstudied.Youandyourdoctorshoulddiscusshowlongyoushoulduse
XENICAL.
What are the most common side effects of XENICAL?
BecauseXENICALworksbyblockingtheabsorptionofdietaryfat,itislikelythatyouwillexperiencesomechangesinbowelhabits
Thesegenerallyoccurduringthefirstweeksoftreatment;however,theymaycontinuethroughoutyouruseofXENICAL.These
changesmayincludeoilyspotting,gaswithdischarge,urgentneedtogotothebathroom,oilyorfattystools,anoilydischarge, increasednumberofbowelmovements,andinabilitytocontrolbowelmovements.Duetothepresenceofundigestedfat,theoilseen
inabowelmovementmaybeclearorhaveacolorationsuchasorangeorbrown.
ThesebowelchangesareanaturaleffectofblockingthefatfrombeingabsorbedandindicatethatXENICALisworking.They
generallyoccurearlyintreatment,particularlyaftermealscontaininghigheramountsoffatthanarerecommended.Thesesymptoms
areoftentemporaryandmaylessenordisappearasyoucontinuetreatmentandkeeptoyourrecommendeddietofmealscontainingno
morethanabout30%fat.However,thesesideeffectsmayoccurinsomeindividualsoveraperiodof6monthsorlonger.
InobeseadolescentpatientstreatedwithXENICAL,thesideeffectsreportedweresimilartothoseobservedinadults.
If you are concerned about these or any other side effects you experience while taking XENICAL, talk to your doctor or
pharmacist.
What lifestyle changes should I consider when taking XENICAL?
You must use XENICAL with a recommended mildly reduced-calorie diet. Youshouldalsofollowaprogramofregularphysical
activity,suchaswalking.However, before you undertake any activity or exercise program, be sure to speak with your doctor or
health care professional.How can I reduce dietary fat?
Tohelpyougetstartedonreducingthefatinyourdiettoaround30%,readthelabelsonallthefoodsyoubuy.Youshouldavoid
foodsthatcontainmorethan30%fatwhileyouaretakingXENICAL.
• Wheneatingmeat,poultryorfish,limityourportionto2or3ounces(roughlythesizeofadeckofcards).Chooseleancutsof
meatandremovetheskinfrompoultry.Fillupyourmealplatebyincludingmoregrains,fruits,andvegetables.
• Replacewhole-milkproductswithnonfator1%milkandnonfat,reduced-fat,orlow-fatdairyitems.
• Cookwithlessfat.Usevegetableoilspraywhencooking.Saladdressings,manybakeditems,andprepackaged,processed,and
fastfoodsareusuallyhighinfat.Usethelow- ornon-fatversionsand/orcutbackonservingsizes.
• Whendiningout,askhowfoodsarepreparedandrequestthattheybepreparedwithlittleornoaddedfat.
Please visit www.xenical.com to help you succeed with your weight loss goals.
PPIRevised:January2009
Distributedby:
RocheLaboratories,Inc.
340KingslandStreet
Nutley,NJ07110–1199
27899513
27899661
Copyright©1999-2009byRocheLaboratoriesInc.Allrightsreserved.
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