FLIXOTIDE EVOHALER

Main information

  • Trade name:
  • FLIXOTIDE EVOHALER
  • Dosage:
  • 125 Microgram
  • Pharmaceutical form:
  • Pressurised Inhalation Suspension
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FLIXOTIDE EVOHALER
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1447/031/001
  • Authorization date:
  • 06-03-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

FlixotideEvohaler125micrograms,PressurisedInhalationSuspension

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachmetereddosecontains125microgramsofFluticasonepropionate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Pressurisedinhalation,suspension.

ProductasimportedfromItaly:

Pressurisedinhalationsuspensionsuppliedinanaluminiumcanwithmeteringvalveandared(120dose)actuator.

4CLINICALPARTICULARS

4.1TherapeuticIndications

FlixotideEvohalermicrogramsisindicatedforthetreatmentandpreventionofasthmaandCOPD.

4.2Posologyandmethodofadministration

Thedosemaythenbeadjusteduntilcontrolisachievedorreducedtotheminimumeffectivedose,accordingtothe

individualresponse.Alternatively,thestartingdoseoffluticasonepropionatemaybegaugedathalfthetotaldailydose

FlixotideEvohalerisforinhalationbyoralinhalationonly.

Patientsshouldbemadeawareoftheprophylacticnatureoftherapywithinhaledfluticasone

propionateandthatitshouldbetakenregularlyevenwhentheyareasymptomatic.Theonset

oftherapeuticeffectis4to7days,althoughsomebenefitmaybeapparentassoonas24

hoursforpatientswhohavenotpreviouslyreceivedinhaledsteroids.

Thedosageoffluticasonepropionateshouldbeadjustedaccordingtotheindividual

response.

Ifpatientsfindthatreliefwithshort-actingbronchodilatortreatmentbecomeslesseffective

ortheyneedmoreinhalationsthanusual,medicalattentionmustbesought.

Itisintendedthateachprescribeddoseisgivenbyaminimumof2inhalations.

Inpatientswhofindco-ordinationofapressurisedmetered-doseinhalerdifficultaspacer

maybeusedwithFlixotideEvohalerorinhaler.

Asthma:-

Adultsandadolescentsover16yearsofage:-

−100to1000microgramstwicedaily.

Patientsshouldbegivenastartingdoseofinhaledfluticasonepropionatewhichis

appropriatefortheseverityoftheirdisease:-

Mildasthma: upto250microgramstwicedaily.

Moderateasthma:250to500microgramstwicedaily.

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Specialpatientgroups:-

Thereisnoneedtoadjustthedoseinelderlypatientsorinthosewithhepaticorrenalimpairment.

Chronicobstructivepulmonarydisease(COPD):-

FlixotideEvohaler50micrograms,PressurisedInhalationSuspension:

Ahigherstrengthoffluticasonepropionateinhalere.g250mcgEvohalerordrypowderinhalerswouldbemore

appropriateformsforthisindication.

FlixotideEvohaler125&250micrograms,PressurisedInhalationSuspension:

AdultDose:

−500microgramstwicedaily.

Testingyourinhaler

Beforeusingforthefirsttimeremovethemouthpiececoverbygentlysqueezingthesidesofthecover,shakethe

inhalerwell,andreleasetwopuffsintotheairtomakesurethatitworks.Ifithasnotbeenusedforseveraldaysshake

itwellandreleaseonepuffintotheairtomakesurethatitworks.

Usingyourinhaler

1.Removethemouthpiececoverbygentlysqueezingthesidesofthecover.

2.Checkinsideandoutsideoftheinhalerincludingthemouthpieceforthepresenceoflooseobjects.

3.Shaketheinhalerwelltoensurethatanylooseobjectsareremovedandthatthecontentsoftheinhalerareevenly

mixed.

4.Holdtheinhaleruprightbetweenfingersandthumbwithyourthumbonthebase,belowthemouthpiece.

5.Breatheoutasfarasiscomfortableandthenplacethemouthpieceinyourmouthbetweenyourteethandcloseyour

lipsarounditbutdonotbiteit.

6.Justafterstartingtobreatheinthroughyourmouthpressdownonthetopoftheinhalertoreleasefluticasone

propionatewhilestillbreathinginsteadilyanddeeply.

7.Whileholdingyourbreath,taketheinhalerfromyourmouthandtakeyourfingerfromthetopoftheinhaler.

Continueholdingyourbreathforaslongasiscomfortable.

8.Ifyouaretotakefurtherpuffskeeptheinhaleruprightandwaitabouthalfaminutebeforerepeatingstages3to7.

9.Replacethemouthpiececoverbyfirmlypushingandsnappingthecapintoposition.

IMPORTANT

DonotrushStages5,6and7.Itisimportantthatyoustarttobreatheinasslowlyaspossiblejustbeforeoperatingyour

inhaler.

Practiseinfrontofamirrorforthefirstfewtimes.Ifyousee'mist'comingfromthetopoftheinhalerorthesidesof

yourmouthyoushouldstartagainfromstage2.

Ifyourdoctorhasgivenyoudifferentinstructionsforusingyourinhaler,pleasefollowthemcarefully.Tellyourdoctor

ifyouhaveanydifficulties.

Cleaning

Yourinhalershouldbecleanedatleastonceaweek.

1.Removethemetalcanisterfromtheplasticcasingoftheinhalerandremovethemouthpiececover.

2.Rinsetheactuatorthoroughlyunderwarmrunningwater.

3.DrytheactuatorTHOROUGHLYinsideandout.

4.Replacethemetalcanisterandmouthpiececover.

DONOTPUTTHEMETALCANISTERINTOWATER.

4.3Contraindications

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4.4Specialwarningsandprecautionsforuse

Themanagementofasthmashouldfollowastepwiseprogrammeandpatientresponseshouldbemonitoredclinically

andbylungfunctiontests.

Increasinguseofshort-actinginhaled

-agoniststocontrolasthmasymptomsindicatesdeteriorationofasthma

control.Undertheseconditions,thepatient'stherapyplanshouldbereassessed.

Suddenandprogressivedeteriorationinasthmacontrolispotentiallylife-threateningandconsiderationshouldbegiven

toincreasingcorticosteroiddosage.Inpatientsconsideredatrisk,dailypeakflowmonitoringmaybeinstituted.

FlixotideEvohalerisnotforuseinacuteattacks,butforroutinelong-termmanagement.Patientswillrequireafast-

andshort-actinginhaledbronchodilatortorelieveacuteasthmaticsymptoms.

Lackofresponseorsevereexacerbationsofasthmashouldbetreatedbyincreasingthedoseofinhaledfluticasone

propionateand,ifnecessary,bygivingasystemicsteroidand/oranantibioticifthereisaninfection.

TherewasanincreasedreportingofpneumoniainstudiesofpatientswithCOPDreceivingFP500micrograms(see

Section4.8).PhysiciansshouldremainvigilantforthepossibledevelopmentofpneumoniainpatientswithCOPDas

theclinicalfeaturesofpneumoniaandexacerbationfrequentlyoverlap.

Patients'inhalertechniqueshouldbecheckedtomakesurethatinhaleractuationissynchronisedwithinspirationto

ensureoptimumdeliveryofthedrugtothelungs.

Becauseofthepossibilityofimpairedadrenalresponse,patientstransferringfromoralsteroidtherapytoinhaled

fluticasonepropionatetherapyshouldbetreatedwithspecialcare,andadrenocorticalfunctionregularlymonitored.

Followingintroductionofinhaledfluticasonepropionate,withdrawalofsystemictherapyshouldbegradualand

patientsareencouragedtocarryasteroidwarningcardsindicatingthepossibleneedforadditionaltherapyintimesof

stress.

Systemiceffectsmayoccurwithanyinhaledcorticosteroid,particularlyathighdosesprescribedforlongperiods.

Theseeffectsaremuchlesslikelytooccurthanwithoralcorticosteroids.Possiblesystemiceffectsincludeadrenal

suppression,growthretardationinchildrenandadolescents,decreaseinbonemineraldensity,cataractandglaucoma

andmorerarely,arangeofpsychologicalorbehaviouraleffectsincludingpsychomotorhyperactivity,sleepdisorders,

anxiety,depressionoraggression(particularlyinchildren).Itisimportant,therefore,thatthepatientisreviewed

regularlyandthedoseofinhaledcorticosteroidisreducedtothelowestdoseatwhicheffectivecontrolofasthmais

maintained.

Itisrecommendedthattheheightofchildrenreceivingprolongedtreatmentwithinhaledcorticosteroidisregularly

monitored.

Certainindividualscanshowgreatersusceptibilitytotheeffectsofinhaledcorticosteroidthandomostpatients.

Prolongedtreatmentofpatientswithhighdosesofinhaledcorticosteroidsmayresultinadrenalsuppressionandacute

adrenalcrisis.Childrenandadolescents<16yearstakinghighdosesoffluticasonepropionate(typically1000mcg/day)

maybeatparticularrisk.Veryrarecasesofadrenalsuppressionandacuteadrenalcrisishavebeendescribedwith

dosesoffluticasonebetween500mcgandlessthan1000mcg.Situations,whichcouldpotentiallytriggeracuteadrenal

crisisincludetrauma,surgery,infectionoranyrapidreductionindosage.Presentingsymptomsaretypicallyvagueand

mayincludeanorexia,abdominalpain,weightloss,tiredness,headache,nausea,vomiting,decreasedlevelof

consciousness,hypoglycemiaandseizures.Additionalsystemiccorticosteroidcovershouldbeconsideredduring

periodsofstressorelectivesurgery.

Thebenefitsofinhaledfluticasonepropionatetherapyshouldminimisetheneedfororalsteroids,butpatients

transferringfromoralsteroidsmayremainatriskofimpairedadrenalreserveforaconsiderabletime.Patientswhohave

requiredhighdoseemergencycorticosteroidtherapyinthepastmayalsobeatrisk.Thispossibilityofresidual

impairmentshouldalwaysbeborneinmindinemergencyandelectivesituationslikelytoproducestress,and

appropriatecorticosteroidtreatmentmustbeconsidered.Theextentoftheadrenalimpairmentmayrequirespecialist

advicebeforeelectiveprocedures.

Similarlyreplacementofsystemicsteroidtreatmentwithinhaledtherapymayunmaskallergiessuchasallergicrhinitis

oreczemapreviouslycontrolledbythesystemicdrug.Theseallergiesshouldbesymptomaticallytreatedwith

antihistamineand/ortopicalpreparations,includingtopicalsteroids.

TreatmentwithFlixotideEvohalershouldnotbestoppedabruptly.

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tuberculosis.

Ritonavircangreatlyincreasetheconcentrationoffluticasonepropionateinplasma.Therefore,concomitantuseshould

beavoided,unlessthepotentialbenefittothepatientoutweighstheriskofsystemiccorticosteroidside-effects.Thereis

alsoanincreasedriskofsystemicsideeffectswhencombiningfluticasonepropionatewithotherpotentCYP3A

inhibitors(see4.5InteractionwithOtherMedicinalProductsandOtherFormsofInteraction).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Undernormalcircumstances,lowplasmaconcentrationsoffluticasonepropionateareachievedafterinhaleddosing,

duetoextensivefirstpassmetabolismandhighsystemicclearancemediatedbycytochromeP4503A4inthegutand

liver.Hence,clinicallysignificantdruginteractionsmediatedbyfluticasonepropionateareunlikely.

Inaninteractionstudyinhealthysubjectswithintranasalfluticasonepropionate,ritonavir(ahighlypotentcytochrome

P4503A4inhibitor)100mgb.i.d.increasedthefluticasonepropionateplasmaconcentrationsseveralhundredfold,

resultinginmarkedlyreducedserumcortisolconcentrations.Informationaboutthisinteractionislackingforinhaled

fluticasonepropionate,butamarkedincreaseinfluticasonepropionateplasmalevelsisexpected.CasesofCushing's

syndromeandadrenalsuppressionhavebeenreported.Thecombinationshouldbeavoidedunlessthebenefit

outweighstheincreasedriskofsystemicglucocorticoidsideeffects.

Inasmallstudyinhealthyvolunteers,theslightlylesspotentCYP3Ainhibitorketoconazoleincreasedtheexposureof

fluticasonepropionateafterasingleinhalationby150%.Thisresultedinagreaterreductionofplasmacortisolas

comparedwithfluticasonepropionatealone.Co-treatmentwithotherpotentCYP3Ainhibitors,suchasitraconazole,is

alsoexpectedtoincreasethesystemicfluticasonepropionateexposureandtheriskofsystemicside-effects.Cautionis

recommendedandlong-termtreatmentwithsuchdrugsshouldifpossiblebeavoided.

4.6Fertility,pregnancyandlactation

Thereareinsufficientdataontheuseoffluticasonepropionateduringpregnancyandlactationinmantoassessthe

possibleharmfuleffects.Inanimalstudiesfoetalabnormalitiesoccurafteradministrationofglucocorticosteroids(see

5.3PreclinicalSafetyData).

Administrationoffluticasonepropionatetopregnantwomenshouldonlybeconsiderediftheexpectedbenefittothe

motherisgreaterthananypossiblerisktothefoetus.

Thelowesteffectivedoseoffluticasonepropionateneededtomaintainadequateasthmacontrolshouldbeusedinthe

treatmentofpregnantwomen.

Therearenodataavailableforhumanbreastmilk.Fluticasonepropionateisexcretedintobreastmilkinrats.

Administrationoffluticasonepropionatetowomenwhoarebreast-feedingshouldonlybeconsiderediftheexpected

benefittothemotherisgreaterthananypossiblerisktothechild.

4.7Effectsonabilitytodriveandusemachines

Fluticasonepropionateisunlikelytoproduceaneffect.

4.8Undesirableeffects

Adverseeventsarelistedbelowbysystemorganclassandfrequency.Frequenciesare

definedas:verycommon(1/10),common(1/100and<1/10),uncommon(1/1000and

<1/100),rare(1/10,000and<1/1000)andveryrare(<1/10,000)includingisolatedreports.

Verycommon,commonanduncommoneventsweregenerallydeterminedfromclinicaltrial

data.Rareandveryrareeventsweregenerallydeterminedfromspontaneousdata.

InfectionsandInfestations

Verycommon:Candidiasisofmouthandthroat.

Candidiasis(thrush)ofthemouthandthroatoccursinsomepatients.Theincidenceof

candidiasismayberelievedbygarglingwithwaterusingtheEvohaler.Symptomatic

candidiasiscanbetreatedwithtopicalanti-fungaltherapywhilststillcontinuingwiththe

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PsychiatricDisorders

Unknown: Psychomotorhyperactivity,sleepdisorders,anxiety,depression,aggression,behaviouralchanges

(predominantlyinchildren)

4.9Overdose

Acute:Acuteinhalationoffluticasonepropionatedosesinexcessofthoserecommendedmayleadtotemporary

suppressionofadrenalfunction.Thisdoesnotneedemergencyactionasadrenalfunctionisrecoveredinafewdays,as

verifiedbyplasmacortisolmeasurements.Chronicoverdoseofinhaledoffluticasonepropionate:Refertosection4.4:

riskofadrenalsuppression.Monitoringofadrenalreservemaybenecessary.Incasesoffluticasonepropionate

overdosetherapymaystillbecontinuedatasuitabledosageforsymptomcontrol.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Fluticasonepropionategivenbyinhalationatrecommendeddoseshasaglucocorticoidanti-inflammatoryactionwithin

thelungs.Thisresultsinreducedsymptomsandexacerbationsofasthmaandimprovementinlungfunctionand

reductioninCOPD.Theseareachievedwithoutadverseeffectsobservedwhencorticosteroidsareadministered

systemically.

Severasthmarequiresregularmedicalassessmentasdeathmayoccur.Patientswithsevereasthmahaveconstant

symptomsandfrequentexacerbations,withlimitedphysicalcapacity,andPEFvaluesbelow60%predicatedat

baselinewithgreaterthan30%variability,usuallynotreturningentirelytonormalafterabronchodilator.These

patientswillrequirehighdoseinhaled(seedosageinstructions)ororalcorticosteroidtherapy.Suddenworseningof

symptomsmayrequireincreasedcorticosteroidsdosagewhichshouldbeadministeredunderurgentmedical

Common:Pneumonia(inCOPDpatients).

ImmuneSystemDisorders

Hypersensitivityreactionswiththefollowingmanifestationshavebeenreported:

Uncommon: Cutaneoushypersensitivityreactions.

Veryrare: Angioedema(mainlyfacialandoropharyngealoedema),respiratory

symptoms(dyspnoeaand/orbronchospasm)andanaphylacticreactions.

EndocrineDisorders

Possiblesystemiceffects(see4.4SpecialWarningsandSpecialPrecautionsforUse)

include:

Veryrare: Adrenalsuppression,growthretardationinchildrenandadolescents,

decreasedbonemineraldensity,cataract,glaucoma.

Respiratory,ThoracicandMediastinalDisorders

Common: Hoarseness.

Hoarsenesscanoccurinsomepatients.Hoarsenessmayberelievedbygarglingwithwater

afterusingtheproduct.

Veryrare: Paradoxicalbronchospasm.

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Adults:-

-Mildasthma(PEFvalues60-80%predicatedatbaselinewithlessthan20%variability):Patientsrequiring

intermittentsymptomaticbronchodilatorasthmamedicationonmorethananoccasionalbasis.

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

asthmamedicationandpatientswithunstableorworseningasthmaoncurrentlyavailableprophylactictherapyor

bronchodilatoralone.

5.2Pharmacokineticproperties

Theabsolutebioavailabilityofinhaledfluticasonepropionateinhealthysubjectsvariesbetweenapproximately10-30%

ofthenominaldosedependingontheinhalationdeviceused.InpatientswithasthmaorCOPDalesserdegreeof

systemicexposuretoinhaledfluticasonepropionatehasbeenobserved.

Systemicabsorptionoccursmainlythroughthelungsandisinitiallyrapidthenprolonged.Theremainderoftheinhaled

dosemaybeswallowedbutcontributesminimallytosystemicexposureduetothelowaqueoussolubilityandpre-

systemicmetabolism,resultinginoralavailabilityoflessthan1%.Thereisalinearincreaseinsystemicexposurewith

increasinginhaleddose.

Thedispositionoffluticasonepropionateischaracterisedbyhighplasmaclearance(1150ml/min),alargevolumeof

distributionatsteady-state(approximately300l)andaterminalhalf-lifeofapproximately8hours.

Plasmaproteinbindingis(91%).

Fluticasonepropionateisclearedveryrapidlyfromthesystemiccirculation.Themainpathwayismetabolismtoan

inactivecarboxylicacidmetabolite,bythecytochromeP450enzymeCYP3A4.Otherunidentifiedmetabolitesarealso

foundinthefaeces.

Therenalclearanceoffluticasonepropionateisnegligible.Lessthan5%ofthedoseisexcretedinurine,mainlyas

metabolites.Themainpartofthedoseisexcretedinfaecesasmetabolitesandunchangeddrug.

5.3Preclinicalsafetydata

Toxicologyhasshownonlythoseclasseffectstypicalofpotentcorticosteroids,andtheseonlyatdosesgreatlyin

excessofthatproposedfortherapeuticuse.Nonoveleffectswereidentifiedinrepeatdosetoxicitytests,reproductive

studiesorteratologystudies.Fluticasonepropionateisdevoidofmutagenicactivityin-vitroandin-vivoandshowedno

tumorigenicpotentialinrodents.Itisbothnon-irritantandnon-sensitisinginanimalmodels.Thenon-CFCpropellant,

HFA134a,hasbeenshowntohavenotoxiceffectatveryhighvapourconcentrations,farinexcessofthoselikelytobe

experiencedbypatients,inawiderangeofanimalspeciesexposeddailyforperiodsoftwoyears.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Norflurane(Hydrofluroalkane(HFA)134a)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Theshelflifeexpirydateofthisproductisthedateshownontheoutercartonandthecanisterlabeloftheproductas

marketedinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

Donotrefrigerateorfreeze.

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Thecanistercontainsapressurisedliquid.Donotexposetotemperaturesabove50°C.Donotpierceorburnthe

canister,evenwhenapparentlyempty.

6.5Natureandcontentsofcontainer

Thesuspensioniscontainedinametalcanistersealedwithameteringvalve.Thecanistersarefittedintoplastic

actuatorsincorporatinganatomisingorificeandfittedwithdustcaps.FlixotideEvohaler125mcgPressurised

InhalationSuspensionisavailableinapackof120metereddosesperinhaler.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Patientsshouldbecarefullyinstructedinthecorrectuseoftheinhaler.

7PARALLELPRODUCTAUTHORISATIONHOLDER

G&AlicensingLimited

Ballymurray,

Co.Roscommon

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1447/31/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:6thMarch2009

10DATEOFREVISIONOFTHETEXT

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