FLIXOTIDE EVOHALER 250 MICROGRAMS, PRESSURISED INH

Main information

  • Trade name:
  • FLIXOTIDE EVOHALER 250 MICROGRAMS, PRESSURISED INH
  • Dosage:
  • 250 Microgram
  • Pharmaceutical form:
  • Pressurised Inhalation Suspension
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FLIXOTIDE EVOHALER 250 MICROGRAMS, PRESSURISED INH
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/073/002A
  • Authorization date:
  • 07-09-2001
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

FlixotideEvohaler250micrograms,PressurisedInhalation,Suspension.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachmetereddosecontains250microgramsoffluticasonepropionate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

PressurisedInhalation,Suspension.

ProductimportedfromGreece,theNetherlandsandtheUK:

PressurisedinhalationSuspensionsuppliedinanaluminiumcanwithmeteringvalveandanactuator.

4CLINICALPARTICULARS

4.1TherapeuticIndications

FlixotideEvohalerisindicatedforthetreatmentandpreventionofasthmaandCOPD.

4.2Posologyandmethodofadministration

FlixotideEvohalerisforinhalationbyoralinhalationonly.

Patientsshouldbemadeawareoftheprophylacticnatureoftherapywithinhaledfluticasonepropionateandthatit

shouldbetakenregularlyevenwhentheyareasymptomatic.Theonsetoftherapeuticeffectis4to7days,although

somebenefitmaybeapparentassoonas24hoursforpatientswhohavenotpreviouslyreceivedinhaledsteroids.

Thedosageoffluticasonepropionateshouldbeadjustedaccordingtotheindividualresponse.

Ifpatientsfindthatreliefwithshort-actingbronchodilatortreatmentbecomeslesseffectiveortheyneedmore

inhalationsthanusual,medicalattentionmustbesought.

Itisintendedthateachprescribeddosebegivenbyaminimumof2inhalations.

Inpatientswhofindco-ordinationofapressurisedmetered-doseinhalerdifficultaVolumatic TM

spacermaybeused

withFlixotideEvohaler.

Asthma:-

Adultsandadolescentsover16yearsofage:100to1000microgramstwicedaily.

Patientsshouldbegivenastartingdoseofinhaledfluticasonepropionatewhichisappropriatefortheseverityoftheir

disease:-

Mildasthma:upto250microgramstwicedaily.

Moderateasthma:250to500microgramstwicedaily.

Severeasthma:500to1000microgramstwicedaily.

Thedosemaythenbeadjusteduntilcontrolisachievedorreducedtotheminimumeffectivedose,accordingtothe

individualresponse.

Alternatively,thestartingdoseoffluticasonepropionatemaybegaugedathalfthetotaldailydoseofbeclomethasone

dipropionateorequivalentasadministeredbymetered-doseinhaler.

Childrenover4yearsofage:-

50-100microgramstwicedaily.

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disease.

Thedosemaythenbeadjusteduntilcontrolisachieved,orreducedtotheminimumeffectivedose,accordingto

individualresponse.

Specialpatientgroups:Thereisnoneedtoadjustthedoseinelderlypatientsorinthosewithhepaticorrenal

impairment.

Chronicobstructivepulmonarydisease(COPD):-

AdultDose:500microgramstwicedaily.

4.3Contraindications

Hypersensitivitytoanyingredientofthepreparation.

4.4Specialwarningsandprecautionsforuse

Themanagementofasthmashouldfollowastepwiseprogramme,andpatientresponseshouldbemonitoredclinically

andbylungfunctiontests.

Increasinguseofshort-actinginhaledbeta-2-agoniststocontrolsymptomsindicatesdeteriorationofasthmacontrol.

Undertheseconditions,thepatient'stherapyplanshouldbereassessed.

Suddenandprogressivedeteriorationinasthmacontrolispotentiallylife-threateningandconsiderationshouldbegiven

toincreasingcorticosteroiddosage.Inpatientsconsideredatrisk,dailypeakflowmonitoringmaybeinstituted.

FlixotideEvohalerisnotforuseinacuteattacks,butforroutinelong-termmanagement.Patientswillrequireafast-

andshort-acting inhaledbronchodilatortorelieveacuteasthmaticsymptoms. Lackofresponseorsevere

exacerbationsofasthmashouldbetreatedbyincreasingthedoseofinhaledfluticasonepropionateand,ifnecessary,by

givingasystemicsteroidand/oranantibioticitthereisaninfection.

Patients'inhalertechniqueshouldbecheckedtomakesurethatinhaleractuationissynchronisedwithinspirationto

ensureoptimumdeliveryofthedrugtothelungs.

Adrenocorticalfunction:Somedepressionofplasmacortisolmayoccurinasmallnumberofadultpatientsonhigher

doses(forexample>1mg/day).However,adrenalfunctionandadrenalreserveusuallyremainwithinnormalrangeon

inhaledfluticasonepropionatetherapy.Patientstransferredfromotherinhaledsteroidsororalsteroidsremainatriskof

impairedadrenalreserveforaconsiderabletimeaftertransferringtoinhaledfluticasonepropionate.Withthese

patientsadrenocorticoidfunctionmustbemonitoredregularly.

Patientsinamedicalorsurgicalemergency,whointhepasthaverequiredhighdosesofotherinhaledsteroidsand/or

intermittenttreatmentwithoralsteroids,remainatriskofimpairedadrenalreserveforaconsiderabletimeafter

transferringtoinhaledfluticasonepropionate.Theextentoftheadrenalimpairmentmayrequirespecialistadvice

beforeelectiveprocedures.Thepossibilityofresidualimpairedadrenalresponseshouldalwaysbeborneinmindin

emergencyandelectivesituationslikelytoproducestressandappropriatecorticosteroidtreatmentmustbeconsidered.

Inchildrentakingrecommendeddosesofinhaledfluticasonepropionateadrenalfunctionandadrenalreserveusually

remainwithinthenormalrange.Nosystemicsideeffectsand,inparticularnostuntingofgrowthhasbeenobservedin

childrenoninhaledfluticasonepropionate.However,thepossibleeffectsofpreviousorintermittenttreatmentwith

oralsteroidsshouldnotbediscounted.Nevertheless,thebenefitsofinhaledfluticasonepropionateshouldminimise

theneedfororalsteroids.

Forthetransferofpatientsbeingtreatedwithoralcorticosteroids:

Thetransferoforalsteroid-dependentpatientstoFlixotideEvohalerandtheirsubsequentmanagementneeds

specialcareasrecoveryfromimpairedadrenocorticalfunction,causedbyprolongedsystemicsteroidtherapy,

maytakeaconsiderabletime.

Patientswhohavebeentreatedwithsystemicsteroidsforlongperiodsoftimeoratahighdosemayhave

adrenocorticalsuppression.Withthesepatientsadrenocorticalfunctionshouldbemonitoredregularlyandtheir

doseofsystemicsteroidreducedcautiously.

Afterapproximatelyaweek,gradualwithdrawalofthesystemicsteroidiscommenced.Decrementsindosages

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intervals.Formaintenancedosesofprednisolone(orequivalent)of10mgdailyorless,thedecrementsindoseshould

notbegreaterthan1mgperday,atnotlessthanweeklyintervals.Formaintenancedosesofprednisolonein

excessof10mgdaily,itmaybeappropriatetoemploycautiously,largerdecrementsindoseatweeklyintervals.

Somepatientsfeelunwellinanon-specificwayduringthewithdrawalphasedespitemaintenanceoreven

improvementoftherespiratory

Function.Theyshouldbeencouragedtoperseverewithinhaledfluticasonepropionateandtocontinue

withdrawalofsystemicsteroid,unlessthereareobjectivesignsofadrenalinsufficiency.

Patientsweanedofforalsteroidswhoseadrenocorticalfunctionisstillimpairedshouldcanasteroidwarning

cardindicatingthattheyneedsupplementarysystemicsteroidduringperiodsofstress,e.g.worseningasthma

attacks,chestinfections,majorintercurrentillness,surgery,trauma,etc.

Replacementofsystemicsteroidtreatmentwithinhaledtherapysometimesunmasksallergiessuchasallergicrhinitis

oreczemapreviouslycontrolledbythesystemicdrug.Theseallergiesshouldbesymptomaticallytreatedwith

antihistamineand/ortopicalpreparations,includingtopicalsteroids.

TreatmentwithFlixotideEvohalershouldnotbestoppedabruptly.

Aswithallinhaledcorticosteroids,specialcareisnecessaryinpatientswithactiveorquiescentpulmonary

tuberculosis.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Duetotheverylowplasmaconcentrationsachievedafterinhaleddosingclinicallysignificantdruginteractionsare

unlikely.However,careshouldbetakenwhenco-administeringknownCYP3A4inhibitors,e.g.ritonavirand

ketoconazoleasthereispotentialforincreasedsystemicexposuretofluticasonepropionate.Thisshouldbetakeninto

accountduringlongtermconcomitanttreatment.

4.6Fertility,pregnancyandlactation

Topicalandsystemiccorticosteroidshavebeenshowntobeteratogenicinanimals.However,theseeffectswere

demonstratedatdosesinexcessofequivalenthumandosage.Noexperienceofuseduringpregnancyorlactationis

availableinhumanbeings.

Theproductshouldonlybeusedduringpregnancyorbreast-feedingifconsideredessentialbythephysician.

4.7Effectsonabilitytodriveandusemachines

Fluticasonepropionateisunlikelytoproduceaneffect.

4.8Undesirableeffects

Candidiasisofthemouthandthroat(thrush)occursinsomepatients.Suchpatientsmayfindithelpfultorinseouttheir

mouthwithwaterafterusingtheinhaler.Symptomaticcandidiasiscanbetreatedwithtopicalanti-fungaltherapy

whilststillcontinuingwithFlixotideEvohaler.

Insomepatientsinhaledfluticasonepropionatemaycausehoarseness.Itmaybehelpfultorinseoutthemouthwith

waterimmediatelyafterinhalation.

Aswithotherinhalationtherapy,paradoxicalbronchospasmmayoccurwithanimmediateincreaseinwheezingafter

dosing.Thisshouldbetreatedimmediatelywithafast-actinginhaledbronchodilator.FlixotideEvohalershouldbe

discontinuedimmediately,thepatientassessed,andifnecessaryalternativetherapyinstituted.

Cutaneoushypersensitivityreactionshavebeenreported.

Rarecasesoffacialandoropharyngealoedemahavebeenreported.

4.9Overdose

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function.Thisdoesnotnecessitateemergencyactionbeingtaken.Inthesepatientstreatmentwithfluticasone

propionatebyinhalationshouldbecontinuedatadosesufficienttocontrolasthma;adrenalfunctionrecoversinafew

daysandcanbeverifiedbymeasuringplasmacortisol.

Chronic-Useofinhaledfluticasonepropionateindailydosesinexcessof2milligramsoverprolongedperiodsmay

leadtosomedegreeofadrenalsuppression.Monitoringofadrenalreservemaybeindicated.Treatmentwithinhaled

fluticasonepropionateshouldbecontinuedatadosesufficienttocontrolasthma.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Fluticasonepropionategivenbyinhalationatrecommendeddoseshasapotentglucocorticoidanti-inflammatoryaction

withinthelungs.Thisresultsinreducedsymptomsandexacerbationsofasthmaandimprovementinlungfunctionand

reductionofsymptomsinCOPD.Theseareachievedwithoutadverseeffectsobservedwhencorticosteroidsare

administeredsystemically.

Severeasthmarequiresregularmedicalassessmentasdeathmayoccur.Patientswithsevereasthmahaveconstant

symptomsandfrequentexacerbations,withlimitedphysicalcapacity,andPEFvaluesbelow60%predictedatbaseline

withgreaterthan30%variability,usuallynotreturningentirelytonormalafterabronchodilator.Thesepatientswill

requirehighdoseinhaled(seedosageinstructions)ororalcorticosteroidtherapy.

Suddenworseningofsymptomsmayrequireincreasedcorticosteroiddosagewhichshouldbeadministeredunder

urgentmedicalsupervision.

Adults:-

Prophylacticmanagementin:-

Mildasthma(PEFvaluesgreaterthan80%predictedatbaselinewithlessthan20%variability): Patients

requiringintermittentsymptomaticbronchodilatorasthmamedicationonmorethananoccasionalbasis.

Moderateasthma(PEFvalues60-80%predictedatbaselinewith20-30%variability):Patientsrequiringregular

asthmamedicationandpatientswithunstableorworseningasthmaoncurrentlyavailableprophylactictherapyor

bronchodilatoralone.

Severeasthma(PEFvalueslessthan60%predictedatbaselinewithgreaterthan30%variability):Patientswith

severechronicasthma.Onintroductionofinhaledfluticasonepropionatemanypatientswhoaredependenton

systemiccorticosteroidsforadequatecontrolofsymptomsmaybeabletoreducesignificantlyortoeliminate

theirrequirementfororalcorticosteroids.

5.2Pharmacokineticproperties

Followingintravenousadministrationthepharmacokineticsoffluticasonepropionateareproportionaltothedose,and

canbedescribedbythreeexponentials.

Fluticasonepropionateisextensivelydistributedwithinthebody(Vssisapproximately300litres)andhasaveryhigh

clearance(estimatedtoCl1.1litres/min)indicatingextensivehepaticextraction.Peakplasmaconcentrationsare

reducedbyapproximately98%within3-4hours,andonlylowplasmaconcentrationsareassociatedwiththeterminal

half-life,whichisapproximately8hours.Followingoraladministrationof fluticasonepropionate,87-100%ofthe

doseisexcretedinthefaeces.Followingdosesofeither1or16mg,upto20%and75%respectively,isexcretedinthe

faecesasparentcompound.Absoluteoralbioavailabilityisnegligible(<1%)duetoacombinationofincomplete

absorptionfromthegastro-intestinaltractandextensivefirstpassmetabolism.

Followinginhaleddosing,systemicabsolutebioavailabilityofluticasonepropionateisestimatedas12-26%,dependent

onpresentation.Systemicabsorptionoffluticasonepropionateoccursmainlythroughthelungs,andisinitiallyrapid,

thenprolonged.

Plasmaproteinbindingis91%.

FluticasonepropionateisextensivelymetabolisedbyCYP3A4enzymetoaninactivecarboxylicacidderivative.

Asfluticasonepropionateisgivenatverylowdoses,anyeffectonco-administereddrugsisunlikely.

Inclinicalprogrammes,therewerenoreportsofsuspecteddruginteractionswhilstpatientswereoninhaledfluticasone

propionatetherapy.

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Adrenocorticalfunction:Dailyoutputofadrenocorticalhormonesusuallyremainswithinthenormalrangeduring

chronictreatmentwithinhaledfluticasonepropionate,evenatthehighestrecommendeddosesinchildrenandadults.

Aftertransferfromotherinhaledsteroidstoinhaledfluticasonepropionate,thedailyoutputgraduallyimprovesdespite

pastandpresentintermittentuseoforalsteroids,thusdemonstratingreturnofnormaladrenalfunctiononinhaled

fluticasonepropionate.Theadrenalreservealsoremainsnormalduringchronictreatmentwithinhaledfluticasone

propionate,asmeasuredbyanormalincrementonastimulationtest.However,anyresidualimpairmentofadrenal

reservefromprevioustreatmentsmaypersistforaconsiderabletimeandshouldbeborneinmind(seeSpecial

warningsandspecialprecautionsforuse).

5.3Preclinicalsafetydata

Toxicologyhasshownonlythoseclasseffectsofpotentcorticosteroids,andtheseonlyatdoesgreatlyinexcessofthat

proposedfortherapeuticuse.Nonoveleffectswereidentifiedinrepeatdosetoxicitytests,reproductivestudiesor

teratologystudies.Fluticasonepropionateisdevoidofmutagenicactivityin-vitroandin-vivoandshowedno

tumorigenicpotentialinrodents.Itisbothnon-irritantandnon-sensitisinginanimalmodels.

Thenon-CFCpropellant,HFA134a,hasbeenshowntohavenotoxiceffectatveryhighvapourconcentrations,farin

excessofthoselikelytobeexperiencedbypatients,inawiderangeofanimalspeciesexposeddailyforperiodsoftwo

years.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Norflurane(1,1,1,2-Tetrafluoroethane(HFA134a))

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

Donotrefrigerateorfreeze.

Thecanistercontainsapressurizedliquid.

Donotexposetotemperatureshigherthan50°C.

Donotpiercethecontainerevenwhenapparentlyempty.

6.5Natureandcontentsofcontainer

Thesuspensioniscontainedinanaluminiumcanwithameteringvalve.Thecanisfittedintoaplasticactuator

incorporatinganatomizingorificeandfittedwithadustcap.Packsizes120metereddosesperinhaler.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

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PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA0465/073/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:07September2001

Dateoflastrenewal:07September2006

10DATEOFREVISIONOFTHETEXT

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