COMBIVENT UDVS

Main information

  • Trade name:
  • COMBIVENT UDVS
  • Dosage:
  • 0.5/2.5 Base Milligrams
  • Pharmaceutical form:
  • Nebuliser Solution
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • COMBIVENT UDVS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1328/123/001
  • Authorization date:
  • 08-01-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PPA1328/123/001

CaseNo:2072302

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

B&SHealthcare

Unit4,BradfieldRoad,Ruislip,Middlesex,HA40NU,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

CombiventUDVs500micrograms/2.5mgper2.5mlNebuliserSolution

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom08/01/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CombiventUDVs500micrograms/2.5mgper2.5mlNebuliserSolution

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Each2.5mlsingledoseunitcontains500microgramsipratropiumbromide(asthemonohydrate)and2.5mg

salbutamol(asthesulphate).

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

ProductimportedfromUK

Nebulisersolution.

Clear,colourlessoralmostcolourlesssolution.

4CLINICALPARTICULARS

4.1TherapeuticIndications

CombiventUDVsareindicatedforthemanagementofbronchospasminpatientssufferingfromchronicobstructive

pulmonarydiseasewhorequireregulartreatmentwithbothipratropiumandsalbutamol.

4.2Posologyandmethodofadministration

Therecommendeddoseis:

Adults(includingelderlypatientsandchildrenover12years):

1vialthreeorfourtimesdaily.

Children:

ThereisnoexperienceoftheuseofCombiventUDVsinchildrenunder12years.

COMBIVENTUDVsareintendedforinhalationonlyandmaybeadministeredfromasuitablenebuliseroran

intermittentpositivepressureventilator.Thesingledoseunitsshouldnotbetakenorallyoradministeredparenterally.

Thedoseofnebulisersolutionmayneedtobedilutedinordertoobtainafinalvolumesuitablefortheparticular

nebuliserbeingused;ifdilutionisnecessaryuseonlysterilesodiumchloride0.9%solution.

Administration

Preparethenebuliserbyfollowingthemanufacturer'sinstructionsandtheadviceofyourdoctor.

ii)Carefullyseparateanewvialfromthestrip.NEVERuseonethathasbeenopenedalready.

iii)Openthevialbysimplytwistingoffthetop,alwaystakingcaretoholditinanuprightposition.

iv)Unlessotherwiseinstructedbyyourdoctorsqueezeallthecontentsoftheplasticvialintothenebuliserchamber.

v)Assemblethenebuliseranduseitasdirectedbyyourdoctor.

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Sincethesingledoseunitscontainnopreservatives,itisimportantthatthecontentsareusedimmediatelyafteropening

andthatafreshvialisusedforeachadministrationtoavoidmicrobialcontamination.Partlyused,openedordamaged

singledoseunitsshouldbediscarded.

ItisstronglyrecommendednottomixCOMBIVENTUDVswithotherdrugsinthesamenebuliser.

4.3Contraindications

CombiventUDVsarecontraindicatedinpatientswithhypertrophicobstructivecardiomyopathyortachyarrhythmia.

CcombiventUDVsarealsocontraindicatedinpatientswithahistoryofhypersensitivitytoipratropiumbromide,

salbutamolsulphateortoatropineoritsderivatives.

4.4Specialwarningsandprecautionsforuse

ImmediatehypersensitivityreactionsmayoccurafteradministrationofCombiventUDVs,asdemonstratedbyrare

casesofurticaria,angioedema,rash,bronchospasmandoropharyngealoedema.

Therehavebeenrarereportsofocularcomplications(i.e.mydriasis,blurringofvision,narrow-angleglaucomaandeye

pain)whenthecontentsofmeteredaerosolscontainingipratropiumbromidehavebeensprayedinadvertentlyintothe

eye.

PatientsmustbeinstructedinthecorrectuseofCombiventUDVsandwarnednottoallowthesolutionormisttoenter

theeyes.Thisisparticularlyimportantinpatientswhomaybepre-disposedtoglaucoma.Suchpatientsshouldbe

warnedspecificallytoprotecttheireyes.Eyepainordiscomfort,blurredvision,visualhalosorcolouredimages,in

associationwithredeyesfromconjunctivalcongestionandcornealoedemamaybesignsofacutenarrow-angle

glaucoma.Shouldanycombinationofthesesymptomsdevelop,treatmentwithmioticdropsshouldbeinitiatedand

specialistadvicesoughtimmediately.

InthefollowingconditionsCombiventUDVsshouldonlybeusedaftercarefulrisk/benefitassessment:

Inadequatelycontrolleddiabetesmellitus,recentmyocardialinfarctionand/orsevereorganicheartorvascular

disorders,hyperthyroidism,pheochromocytoma,riskofnarrow-angleglaucoma,prostatichypertrophyorbladder-neck

obstruction.

Thepatientshouldbeinstructedtoconsultadoctorimmediatelyintheeventofacute,rapidlyworseningdyspnoea.In

addition,thepatientshouldbewarnedtoseekmedicaladviceshouldareducedresponsebecomeapparent.

Potentiallyserioushypokalaemiamayresultfrombeta

-agonisttherapy.Particularcautionisadvisedinsevereairway

obstruction,asthiseffectmaybepotentiatedbyconcomitanttreatmentwithxanthinederivatives,steroidsanddiuretics.

Additionally,hypoxiamayaggravatetheeffectsofhypokalaemiaoncardiacrhythm(especiallyinpatientsreceiving

digoxin).Itisrecommendedthatserumpotassiumlevelsaremonitoredinsuchsituations.

Patientswithcysticfibrosismaybemorepronetogastro-intestinalmotilitydisturbances.

Cardiovasculareffectsmaybeseenwithsympathomimeticdrugs,includingsalbutamol.Thereissomeevidencefrom

post-marketingdataandpublishedliteratureofmyocardialischaemiaassociatedwithsalbutamol.Patientswith

underlyingsevereheartdisease(e.g.ischaemicheartdisease,arrhythmiaorsevereheartfailure)whoarereceiving

salbutamolshouldbewarnedtoseekmedicaladviceiftheyexperiencechestpainorothersymptomsofworsening

heartdisease.Attentionshouldbepaidtoassessmentofsymptomssuchasdyspnoeaandchestpainastheymaybeof

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Theuseofadditionalbeta-agonists,xanthinederivativesandcorticosteroidsmayenhancetheeffectofCombivent

UDVs.Theconcurrentadministrationofotherbeta-mimetics,systemicallyabsorbedanticholinergicsandxanthine

derivativesmayincreasetheseverityofsideeffects.Apotentiallyseriousreductionineffectmayoccurduring

concurrentadministrationofbeta-blockers.

Beta-adrenergicagonistsshouldbeadministeredwithcautiontopatientsbeingtreatedwithmonoamineoxidase

inhibitorsortricyclicantidepressants,sincetheactionofbeta-adrenergicagonistsmaybeenhanced.

Inhalationofhalogenatedhydrocarbonanaestheticssuchashalothane,trichloroethyleneandenfluranemayincreasethe

susceptibilitytothecardiovasculareffectsofbeta-agonists.

4.6Pregnancyandlactation

Ipratropiumbromidehasbeeningeneraluseforseveralyearsandthereisnodefiniteevidenceofill-consequence

duringpregnancy;animalstudieshaveshownnohazard.

Salbutamolhasbeeninwidespreaduseformanyyearswithoutapparentill-consequenceduringpregnancy.Thereis

inadequatepublishedevidenceofsafetyintheearlystagesofhumanpregnancybutinanimalstudiestherehasbeen

evidenceofsomeharmfuleffectsonthefoetusatveryhighdoselevels.

Aswithallmedicines,CombiventUDVsshouldnotbeusedinpregnancy,especiallythefirsttrimester,unlessthe

expectedbenefitisthoughttooutweighanypossiblerisktothefoetus.

Similarly,CombiventUDVsshouldnotbeadministeredtobreast-feedingmothersunlesstheexpectedbenefitis

thoughttooutweighanypossiblerisktotheneonate.

4.7Effectsonabilitytodriveandusemachines

Nonestated.

4.8Undesirableeffects

Thefollowingsideeffectshavebeenreportedbasedonclinicaltrialsinvolving821patients.

Frequencies

Verycommon1/10

Common1/100<1/10

Uncommon1/1,000<1/100

Rare1/10,000<1,000

Veryrare <1/10,000

Notknown cannotbeestimatedfromtheavailabledata

Immunesystemdisorders:

Notknown:Anaphylacticreaction

Notknown:Hypersensitivity

Metabolismandnutritiondisorders:

Notknown:Hypokalaemia

Psychiatricdisorders:

Notknown:Mentaldisorder

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Nervoussystemdisorders:

Uncommon:Dizziness

Uncommon:Headache

Uncommon:Tremor

Eyedisorders:

Notknown:Angleclosureglaucoma

Notknown:Eyepain

Notknown:Intraocularpressureincreased

Notknown:Mydriasis

Notknown:Visionblurred

Therehavebeenisolatedreportsofocularcomplicationswithsymptomsmentionedabovewhenaerosolised

ipratropiumbromideeitheraloneorincombinationwithanadrenergicbeta

-agonist,hasescapedintotheeyes

Cardiacdisorders:

Veryrare:Arrhythmia

Veryrare:Atrialfibrillation

Veryrare:Myocardialischaemia

Uncommon:Palpitations

Uncommon:Tachycardia

Notknown:Bloodpressurediastolicdecreased

Notknown:Bloodpressuresystolicincreased

Respiratory,thoracicandmediastinaldisorders:

Notknown:Bronchospasm

Notknown:Laryngospasm

Notknown:Pharyngealoedema

Uncommon:Cough

Uncommon:Dysphonia

Notknown:Throatirritation

Gastrointestinaldisorders:

Notknown:Oedemamouth

Common:Drymouth

Notknown:Gastrointestinalmotilitydisorder

Uncommon:Nausea

Notknown:Vomiting

Skinandsubcutaneoustissuedisorders:

Notknown:Angioedema

Notknown:Hyperhidrosis

Notknown:Rash

Notknown:Skinreaction

Notknown:Urticaria

Musculoskeletalandconnectivetissuedisorders:

Notknown:Musclespasms

Notknown:Muscularweakness

Notknown:Myalgia

Renalandurinarydisorders:

Uncommon:Urinaryretention

Generaldisordersandadministrationsiteconditions:

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4.9Overdose

Acuteeffectsofoverdosagewithipratropiumbromideareunlikelyduetoitspoorsystemicabsorptionaftereither

inhalationororaladministration.Anyeffectsofoverdosagearethereforelikelytoberelatedtothesalbutamol

component.

Manifestationsofoverdosagewithsalbutamolmayincludeanginalpain,hypertension,hypokalaemiaandtachycardia.

Thepreferredantidoteforoverdosagewithsalbutamolisacardioselectivebeta-blockingagentbutcautionshouldbe

usedinadministeringthesedrugsinpatientswithahistoryofbronchospasm.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Ipratropiumbromideisananticholinergicagentwhichinhibitsvagally-mediatedreflexesbyantagonisingtheactionof

acetylcholine,thetransmitteragentreleasedfromthevagusnerve.Thebronchodilationfollowinginhalationof

ipratropiumbromideisprimarilylocalandsitespecifictothelungandnotsystemicinnature.

Salbutamolisabeta-adrenergicagentwhichactsonairwaysmoothmuscleresultinginrelaxation.Salbutamolrelaxes

allsmoothmusclefromthetracheatotheterminalbronchiolesandprotectsagainstbronchoconstrictorchallenges.

CombiventUDVsprovidethesimultaneousdeliveryofipratropiumbromideandsalbutamolsulphateallowingeffects

onbothmuscarinicandbeta-adrenergicreceptorsinthelungleadingtoincreasedbronchodilationoverthatprovided

byeachagentsingly.

5.2Pharmacokineticproperties

Ipratropiumbromideisquicklyabsorbedafteroralinhalation.Thesystemicbioavailabilityafterinhalationisestimated

tobelessthan10%ofthedose.Renalexcretionofipratropiumbromideisgivenas46%ofthedoseafterintravenous

administration.Thehalf-lifeoftheterminaleliminationphaseisabout1.6hoursasdeterminedafterintravenous

administration.Thehalf-lifeforeliminationofdrugandmetabolitesis3.6hours,asdeterminedafterradio-labelling.

Ipratropiumbromidedoesnotcrosstheblood-brainbarrier.

Salbutamolisrapidlyandcompletelyabsorbedfollowingoraladministrationeitherbytheinhaledorthegastricroute.

Peakplasmasalbutamolconcentrationsareseenwithinthreehoursofadministrationandthedrugisexcreted

unchangedintheurineafter24hours.Theeliminationhalf-lifeis4hours.Salbutamolwillcrossthebloodbrainbarrier

reachingconcentrationsamountingtoaboutfivepercentoftheplasmaconcentrations.

Ithasbeenshownthatco-nebulisationofipratropiumbromideandsalbutamolsulphatedoesnotpotentiatethesystemic

absorptionofeithercomponentandthatthereforetheadditiveactivityofCombiventUDVsisduetothecombined

localeffectonthelungfollowinginhalation.

5.3Preclinicalsafetydata

Theindividualactiveingredients,ipratropiumbromideandsalbutamolsulphate,havebeenextensivelyinvestigatedin

animalmodelsandtherearenoclinicallyrelevantsafetyissueswhenCombiventUDVsareusedattherecommended

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiumchloride

Hydrochloricacid

Purifiedwater

6.2Incompatibilities

Intheabsenceofcompatibilitystudies,itisstronglyrecommendednottomixCOMBIVENTUDVswithotherdrugs

inthesamenebuliser.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Storebelow25°C.Donotfreeze.Keepvialsintheoutercartoninordertoprotectfromlight.

6.5Natureandcontentsofcontainer

Lowdensitypolyethylene(LDPE)vialscontaining2.5mlofsolution,formedintostripsof10andpackedintocartons

containing60vials.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Sincethesingledoseunitscontainnopreservatives,itisimportantthatthecontentsareusedimmediatelyafteropening

andthatafreshvialisusedforeachadministrationtoavoidmicrobialcontamination.Partlyused,openedordamaged

singledoseunitsshouldbediscarded.Donotuseifsolutionisdiscoloured.

7ParallelProductAuthorisationHolder

B&SHealthcare

Unit4BradfieldRoad

Ruislip

MiddlesexHA40NU

UnitedKingdom

8ParallelProductAuthorisationNumber

PPA1328/123/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:8thJanuary2010

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