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:
  • PPA0465/073/001A
  • Authorization date:
  • 07-09-2001
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

FlixotideEvohaler125microgramsPressurisedInhalation,Suspension.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachmetereddosecontains125microgramsoffluticasonepropionate.

Forfulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Pressurisedinhalation,suspension.

ProductimportedfromGreece,theNetherlands,andtheUK:

Pressurisedinhalationsuspensionsuppliedinanaluminiumcanwithmeteringvalveandactuator.

4CLINICALPARTICULARS

4.1TherapeuticIndications

FlixotideEvohalerisindicatedforthetreatmentandpreventionofasthmaandCOPD.

4.2Posologyandmethodofadministration

FlixotideEvohalerisforinhalationbyoralinhalationonly.

Patientsshouldbecarefullyinstructedinthecorrectuseoftheinhaler.

Patientsshouldbemadeawareoftheprophylacticnatureoftherapywithinhaledfluticasonepropionateandthatit

shouldbetakenregularlyevenwhentheyareasymptomatic.Theonsetoftherapeuticeffectis4to7days,although

somebenefitmaybeapparentassoonas24hoursforpatientswhohavenotpreviouslyreceivedinhaledsteroids.

Thedosageoffluticasonepropionateshouldbeadjustedaccordingtotheindividualresponse.

Ifpatientsfindthatreliefwithshort-actingbronchodilatortreatmentbecomeslesseffectiveortheyneedmore

inhalationsthanusual,medicalattentionmustbesought.

Itisintendedthateachprescribeddosebegivenbyaminimumof2inhalations.

Inpatientswhofindco-ordinationofapressurisedmetered-doseinhalerdifficultaVolumatic TM

spacermaybeused

withFlixotideEvohaler.

Asthma:

Adultsandadolescentsover16yearsofage:

250to1000microgramstwicedaily/

Patientsshouldbegivenastartingdoseofinhaledfluticasonepropionatewhichisappropriatefortheseverityoftheir

disease:

Mildasthma:upto250microgramstwicedaily.

Moderateasthma:250to500microgramstwicedaily.

Severeasthma:500to1000microgramstwicedaily.

Thedosemaythenbeadjusteduntilcontrolisachievedorreducedtotheminimumeffectivedose,accordingtothe

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Alternatively,thestartingdoseoffluticasonepropionatemaybegaugedathalfthetotaldailydoseofbeclomethasone

dipropionateorequivalentasadministeredbymetered-doseinhaler.

Specialpatientgroups:

Thereisnoneedtoadjustthedoseinelderlypatientsorinthosewithhepaticorrenalimpairment.

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-actinginhaledbronchodilatortorelieveacuteasthmaticsymptoms.

Lackofresponseorsevereexacerbationsofasthmashouldbetreatedbyincreasingthedoseofinhaledfluticasone

propionateand,ifnecessary,bygivingasystemicsteroidand/oranantibioticitthereisaninfection.

Patients'inhalertechniqueshouldbecheckedtomakesurethatinhaleractuationissynchronisedwithinspirationto

ensureoptimumdeliveryofthedrugtothelungs.

Becauseofthepossibilityofimpairedadrenalresponse,patientstransferringfromoralsteroidtherapytoinhaled

fluticasonepropionatetherapyshouldbetreatedwithspecialcare,andadrenocorticalfunctionregularlymonitored.

Followingintroductionofinhaledfluticasonepropionate,withdrawalofsystemictherapyshouldbegradualand

patientsareencouragedtocarryasteroidwarningcardindicatingthepossibleneedforadditionaltherapyintimesof

stress.

Systemiceffectsmayoccurwithanyinhaledcorticosteroidparticularlyathighdosesprescribedforlongperiods.These

effectsaremuchlesslikelytooccurthanwithoralcorticosteroids.Possiblesystemiceffectsincludeadrenal

suppression,growthretardationinchildrenandadolescents,decreaseinbonemineraldensity,cataractandglaucoma.

Itisimportant,therefore,thatthepatientisreviewedregularlyandthedoseofinhaledcorticosteroidisreducedtothe

lowestdoseatwhicheffectivecontrolofasthmaismaintained.

Itisrecommendedthattheheightofchildrenreceivingprolongedtreatmentwithinhaledcorticosteroidberegularly

monitored.

Certainindividualscanshowgreatersusceptibilitytotheeffectsofinhaledcorticosteroidthandomostpatients.

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adrenalcrisis.Childrenandadolescents<16yearstakinghighdosesoffluticasonepropionate(typically ≥

1000mcg/day)maybeatparticularrisk.Veryrarecasesofadrenalsuppressionandacuteadrenalcrisishavebeen

describedwithdosesoffluticasonebetween500mcgandlessthan1000mcg.Situations,whichcouldpotentiallytrigger

acuteadrenalcrisisincludetrauma,surgery,infectionoranyrapidreductionindosage.Presentingsymptomsare

typicallyvagueandmayincludeanorexia,abdominalpain,weightloss,tiredness,headache,nausea,vomiting,

decreasedlevelofconsciousness,hypoglycemia,andseizures.Additionalsystemiccorticosteroidcovershouldbe

consideredduringperiodsofstressorelectivesurgery.

Thebenefitsofinhaledfluticasonepropionatetherapyshouldminimisetheneedfororalsteroids,butpatients

transferringfromoralsteroidsmayremainatriskofimpairedadrenalreserveforaconsiderabletime.Patientswhohave

requiredhighdoseemergencycorticosteroidtherapyinthepastmayalsobeatarisk.Thispossibilityofresidual

impairmentshouldalwaysbeborneinmindinemergencyandelectivesituationslikelytoproducestress,and

appropriatecorticosteroidtreatmentmustbeconsidered.Theextentoftheadrenalimpairmentmayrequirespecialist

advicebeforeelectiveprocedures.

Similarlyreplacementofsystemicsteroidtreatmentwithinhaledtherapymayunmaskallergiessuchasallergicrhinitis

oreczemapreviouslycontrolledbythesystemicdrug.Theseallergiesshouldbesymptomaticallytreatedwith

antihistamineand/ortopicalpreparations,includingtopicalsteroids.

TreatmentwithFlixotideEvohalershouldnotbestoppedabruptly.

Aswithallinhaledcorticosteroids,specialcareisnecessaryinpatientswithactiveorquiescentpulmonary

tuberculosis.

Ritonavircangreatlyincreasetheconcentrationoffluticasonepropionateinplasma.Therefore,concomitantuseshould

beavoided,unlessthepotentialbenefittothepatientoutweighstheriskofsystemiccorticosteroidsideeffect.Thereis

alsoanincreasedriskofsystemicsideeffectswhencombiningfluticasonepropionatewithotherCYP3Ainhibitors

(see4.5InteractionwithOtherMedicinalProductsandOtherFormsofInteraction).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Undernormalcircumstances,lowplasmaconcentrationoffluticasonepropionateareachievedafterinhaleddosing,due

totheextensivefirstpassmetabolismandhighsystemicclearancemediatedbycytochromeP4503A4inthegutand

liver.Hence,clinicallysignificantdruginteractionsmediatedbyfluticasonepropionateareunlikely.

Inaninteractionstudyinhealthysubjectswithintrnasalfluticasonepropionate,ritonavir(ahighlypotentcytochrome

P4503A4inhibitor)100mgb.i.dincreasedthefluticasonepropionateplasmaconcentrationsseveralhundredfold,

resultinginmarkedlyreducedserumcortisolconcentrations.Informationaboutthisinformationislackingforinhaled

fluticasonepropionate,butamarkedincreaseinfluticasonepropionateplasmalevelsisexpected.CasesofCushing’s

syndromeandadrenalsuppressionhavebeenreported.Thecombinationshouldbeavoidedunlessthebenefit

outweighstheincreasedriskofsystemicglucocorticoidsideeffects.

Inasmallstudyinhealthyvolunteers,theslightlylesspotentCYP3Ainhibitorketoconazoleincreasedtheexposureof

fluticasonepropionateafterasingleinhalationby150%.Thisresultedinagreaterreductionofplasmacortisolas

comparedwithfluticasonepropionatealone.Co-treatmentwithotherpotentCYP3Ainhibitors,suchasitraconazole,is

alsoexpectedtoincreasethesystemicfluticasonepropionateexposureandtheriskofsystemicside-effects.Cautionis

recommendedandlong-termtreatmentwithsuchdrugsifpossiblebeavoided.

4.6Fertility,pregnancyandlactation

Thereareinsufficientdataontheuseoffluticasonepropionateduringpregnancyandlactationinmantoassessthe

possibleharmfuleffects.Inanimalstudiesfoetalabnormalitiesoccurafteradministrationofglucocorticosteroids(see

5.3PreclinicalSafetyData).

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motherisgreaterthananypossiblerisktothefoetus.

Thelowesteffectivedoseoffluticasonepropionateneededtomaintainadequateasthmacontrolshouldbeusedinthe

treatmentofpregnantwomen.

Therearenodataavailableforhumanbreastmilk.Fluticasonepropionateisexcretedintobreastmilkinrats.

Administrationoffluticasonepropionatetowomenwhoarebreast-feedingshouldonlybeconsiderediftheexpected

benefittothemotherisgreaterthananypossiblerisktothechild.

4.7Effectsonabilitytodriveandusemachines

Fluticasonepropionateisunlikelytoproduceaneffect.

4.8Undesirableeffects

Adverseeventsarelistedbelowbysystemorganclassandfrequency.Frequenciesaredefinedas:verycommon( ≥

1/10),common( ≥1/100and<1/10),uncommon(≥1/1000and<1/100),rare(≥1/10,000and<1/1000)andveryrare

(<1/10000)includingisolatedreports.Verycommon,commonanduncommoneventsweregenerallydeterminedfrom

clinicaltrialdata.Rareandveryrareeventsweregenerallydeterminedfromspontaneousdata.

InfectionsandInfestations

Verycommon:Candidiasisofmouthandthroat.

Candidiasis(thrush)ofthemouthandthroatoccursinsomepatients.Theincidenceofcandidiasismayberelievedby

garglingwithwaterusingtheEvohaler.Symptomaticcandidiasiscanbetreatedwithtopicalanti-fungaltherapywhilst

stillcontinuingwithFlixotideEvohaler.

ImmuneSystemDisorders

Hypersensitivityreactionswiththefollowingmanifestationshavebeenreported:

Uncommon:Cutaneoushypersensitivityreactions.

Veryrare:Angioedema(mainlyfacialandoropharyngaeloedema),respiratorysymptoms(dyspnoeaand/or

bronchospasm)andanaphylacticreaction

EndocrineDisorders

Possiblesystemiceffects(see4.5SpecialWarningsandSpecialPrecautionsforUse)include:

Veryrare:Adrenalsuppression,growthretardationinchildrenandadolescents,decreasedbonemineraldensity,

cataract,glaucoma.

Respiratory,ThoracicandMediastinalDisorsers

Common:Hoarseness

Hoarsenesscanoccurinsomepatients.Hoarsenessmayberelievedbygarglingwithwaterafterusingthisproduct.

Veryrare:Paradoxicalbronchospasm.

Aswithotherinhalationtherapy,paradoxicalbronchospasmmayoccur.

4.9Overdose

Acute-Inhalationofthedrugindosesinexcessofthoserecommendedmayleadtotemporarysuppressionofadrenal

function.Thisdoesnotnecessitateemergencyactionbeingtakenasadrenalfunctionisrecoveredinafewdays,as

verifiedbyplasmacortisolmeasurements.

Chronic-Chronicoverdoseofinhaledfluticasonepropionate:Refertosection4.4:riskofadrenalsuppression.

Monitoringofadrenalreservemaybenecessary.Incasesoffluticasonepropionateoverdosetherapymaystillbe

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Fluticasonepropionategivenbyinhalationatrecommendeddoseshasapotentglucocorticoidanti-inflammatoryaction

withinthelungs.Thisresultsinreducedsymptomsandexacerbationsofasthmaandimprovementinlungfunctionand

reductionofsymptomsinCOPD.Theseareachievedwithoutadverseeffectsobservedwhencorticosteroidsare

administeredsystemically.

Severeasthmarequiresregularmedicalassessmentasdeathmayoccur.Patientswithsevereasthmahaveconstant

symptomsandfrequentexacerbations,withlimitedphysicalcapacity,andPEFvaluesbelow60%predictedatbaseline

withgreaterthan30%variability,usuallynotreturningentirelytonormalafterabronchodilator.Thesepatientswill

requirehighdoseinhaled(seedosageinstructions)ororalcorticosteroidtherapy.Suddenworseningofsymptomsmay

requireincreasedcorticosteroiddosagewhichshouldbeadministeredunderurgentmedicalsupervision.

Adults:-

Prophylacticmanagementin:-

Mildasthma(PEFvaluesgreaterthan80%predictedatbaselinewithlessthan20%variability):Patients

requiringintermittentsymptomaticbronchodilatorasthmamedicationonmorethananoccasionalbasis.

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

asthmamedicationandpatientswithunstableorworseningasthmaoncurrentlyavailableprophylactictherapyor

bronchodilatoralone.

5.2Pharmacokineticproperties

Theabsolutebioavailabilityofinhaledfluticasonepropionateinhealthysubjectsvariesbetweenapproximately

10-30%ofthenormaldosedependingontheinhalationdeviceused.InpatientswithasthmaorCOPDalesser

degreeofsystemicexposuretoinhaledfluticasonepropionatehasbeenobserved.Systemicabsorptionoccurs

mainlythroughthelungsandisinitiallyrapidthenprolonged.Theremainderoftheinhaleddosemaybe

swallowedbutcontributesminimallytosystemicexposureduetothelowaqueoussolubilityandpre-systemic

metabolism,resultinginoralavailabilityoflessthan1%.Thereisalinearincreaseinsystemicexposurewith

increasinginhaleddose.

Thedispositionoffluticasonepropionateischaracterizedbyhighplasmaclearance(1150ml/mon),alarge

volumeofdistributionatsteady-state(approximately3001)andaterminalhalf-lifeofapproximately8hours.

Plasmaproteinbindingis(91%).

Fluticasonepropionateisclearedveryrapidlyfromthesystemiccirculation.Themainpathwayismetabolismto

aninactivecarboxylicacidmetabolite,bythecytochromeP450enzymeCYP3A4.Otherunidentifiedmetabolites

arealsofoundinthefaeces.

Therenalclearanceoffluticasonepropionateisnegligible.Lessthan5%ofthedoseisexcretedinurine,mainlyas

metabolites.Themainpartofthedoseisexcretedinfaecesasmetabolitesandunchangeddrug.

5.3Preclinicalsafetydata

Toxicologyhasshownonlythoseclasseffectsofpotentcorticosteroids,andtheseonlyatdoesgreatlyinexcessofthat

proposedfortherapeuticuse.Nonoveleffectswereidentifiedinrepeatdosetoxicitytests,reproductivestudiesor

teratologystudies.Fluticasonepropionateisdevoidofmutagenicactivityin-vitroandin-vivoandshowedno

tumorigenicpotentialinrodents.Itisbothnon-irritantandnon-sensitisinginanimalmodels.

Thenon-CFCpropellant,HFA134a,hasbeenshowntohavenotoxiceffectatveryhighvapourconcentrations,farin

excessofthoselikelytobeexperiencedbypatients,inawiderangeofanimalspeciesexposeddailyforperiodsoftwo

years.

6PHARMACEUTICALPARTICULARS

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Norflurane(Hydrofluroalkane(HFA)134a)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

Donotrefrigerateorfreeze.

Thecanistercontainsapressurisedliquid.

Donotexposetotemperatureshigherthan50°C.

Donotpiercethecontainerevenwhenapparentlyempty.

6.5Natureandcontentsofcontainer

Thesuspensioniscontainedinanaluminiumpressurisedcanwithameteringvalve.Thecanisfittedintoaplastic

actuatorincorporatinganatomisingorificeandfittedwithadustcap.Packsize:120metereddosesperinhaler.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Patientsshouldbecarefullyinstructedinthecorrectuseoftheinhaler.

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA0465/073/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:07July2001

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10DATEOFREVISIONOFTHETEXT

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