COMBIVENT UDVS 500 MICROGRAMS/2.5MG PER 2.5ML NEBU

Main information

  • Trade name:
  • COMBIVENT UDVS 500 MICROGRAMS/2.5MG PER 2.5ML NEBU
  • Dosage:
  • 0.5/2.5 Base mg/unit
  • Pharmaceutical form:
  • Nebuliser Solution
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • COMBIVENT UDVS 500 MICROGRAMS/2.5MG PER 2.5ML NEBU
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/105/002A
  • Authorization date:
  • 05-03-2004
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CombiventUDVs500micrograms/2.5mgper2.5mlNebuliserSolution

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Each2.5mlsingledoseunitcontains:

500microgramsipratropiumbromide(asthemonohydrate)and2.5mgsalbutamol(asthesulphate)

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Nebulisersolution.

Aclear,colourlesssolution

4CLINICALPARTICULARS

4.1TherapeuticIndications

CombiventUDVsareindicatedforthemanagementofbronchospasminpatientssufferingfromchronicobstructive

pulmonarydiseasewhorequireregulartreatmentwithbothipratropiumandsalbutamol

4.2Posologyandmethodofadministration

Therecommendeddoseis:

Adults(includingelderlypatientsandchildrenover12years):

1vialthreeorfourtimesdaily.

Children:

ThereisnoexperienceoftheuseofCOMBIVENTUDVsinchildrenunder12years.

COMBIVENTUDVsareintendedforinhalationonlyandmaybeadministeredfromasuitablenebuliseroran

intermittentpositivepressureventilator.Thesingledoseunitsshouldnotbetakenorallyoradministeredparenterally.

Thedoseofnebulisersolutionmayneedtobedilutedinordertoobtainafinalvolumesuitablefortheparticular

nebuliserbeingused;ifdilutionisnecessaryuseonlysterilesodiumchloride0.9%solution.

InstructionsforUse:

1.Preparethenebuliserbyfollowingthemanufacturer'sinstructionsandtheadviceofyourdoctor.

2.Carefullyseparateanewvialfromthestrip.NEVERuseonethathasbeenopenedalready.

3.Openthevialbysimplytwistingoffthetop,alwaystakingcaretoholditinanuprightposition.

4.Unlessotherwiseinstructedbyyourdoctorsqueezeallthecontentsoftheplasticvialintothenebuliser

chamber.

5.Assemblethenebuliseranduseitasdirectedbyyourdoctor.

6.Afternebulisationcleanthenebuliseraccordingtothemanufacturer'sinstructions.

Sincethesingledoseunitscontainnopreservatives,itisimportantthatthecontentsareusedimmediatelyafteropening

andthatafreshvialisusedforeachadministrationtoavoidmicrobialcontamination.Partlyused,openedordamaged

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ItisstronglyrecommendednottomixCOMBIVENTwithotherdrugsinthesamenebuliser.

4.3Contraindications

COMBIVENTUDVsarecontraindicatedinpatientswithhypertrophicobstructivecardiomyopathyortachyarrhythmia.

COMBIVENTUDVsarealsocontraindicatedinpatientswithahistoryofhypersensitivitytoipratropiumbromide,

salbutamolsulphateortoatropineoritsderivatives.

4.4Specialwarningsandprecautionsforuse

ImmediatehypersensitivityreactionsmayoccurafteradministrationofCOMBIVENTUDVs,asdemonstratedbyrare

casesofurticaria,angioedema,rash,bronchospasmandoropharyngealoedema.

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

pain)whenthecontentsofmeteredaerosolscontainingipratropiumbromidehavebeensprayedinadvertentlyintothe

eye.

PatientsmustbeinstructedinthecorrectuseofCOMBIVENTUDVsandwarnednottoallowthesolutionormistto

entertheeyes.Thisisparticularlyimportantinpatientswhomaybepre-disposedtoglaucoma.Suchpatientsshouldbe

warnedspecificallytoprotecttheireyes.Eyepainordiscomfort,blurredvision,visualhalosorcolouredimages,in

associationwithredeyesfromconjunctivalcongestionandcornealoedemamaybesignsofacutenarrow-angle

glaucoma.Shouldanycombinationofthesesymptomsdevelop,treatmentwithmioticdropsshouldbeinitiatedand

specialistadvicesoughtimmediately.

InthefollowingconditionsCOMBIVENTUDVsshouldonlybeusedaftercarefulrisk/benefitassessment:

inadequatelycontrolleddiabetesmellitus,recentmyocardialinfarctionand/orsevereorganicheartorvascular

disorders,hyperthyroidism,phaeochromocytoma,prostatichypertrophy,riskofnarrow-angleglaucomaorbladder-

neckobstruction.

Thepatientshouldbeinstructedtoconsultadoctorimmediatelyintheeventofacute,rapidlyworseningdyspnoea.In

addition,thepatientshouldbewarnedtoseekmedicaladviceshouldareducedresponsebecomeapparent.

Potentiallyserioushypokalaemiamayresultfrombeta2-agonisttherapy.Particularcautionisadvisedinsevereairway

obstructionasthiseffectmaybepotentiatedbyconcomitanttreatmentwithxanthinederivatives,steroidsanddiuretics.

Additionally,hypoxiamayaggravatetheeffectsofhypokalaemiaoncardiacrhythm(especiallyinpatientsreceiving

digoxin).Itisrecommendedthatserumpotassiumlevelsaremonitoredinsuchsituations.

Patientswithcysticfibrosismaybemorepronetogastro-intestinalmotilitydisturbances.

Cardiovasculareffectsmaybeseenwithsympathomimeticdrugs,includingsalbutamol.Thereissomeevidencefrom

post-marketingdataandpublishedliteratureofrareoccurrencesofmyocardialischaemiaassociatedwithsalbutamol.

Patientswithunderlyingsevereheartdisease(e.g.ischaemicheartdisease,tachyarrhythmiaorsevereheartfailure)who

arereceivingsalbutamolforrespiratorydisease,shouldbewarnedtoseekmedicaladviceiftheyexperiencechestpain

orothersymptomsofworseningheartdisease.Attentionshouldbepaidtoassessmentofsymptomssuchasdyspnoea

andchestpain,astheymaybeofeitherrespiratoryorcardiacorigin.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Theuseofadditionalbeta-agonists,xanthinederivativesandcorticosteroidsmayenhancetheeffectofCOMBIVENT

UDVs.Theconcurrentadministrationofotherbeta-mimetics,systemicallyabsorbedanticholinergicsandxanthine

derivativesmayincreasetheseverityofsideeffects.

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Beta-adrenergicagonistsshouldbeadministeredwithcautiontopatientsbeingtreatedwithmonoamineoxidase

inhibitorsortricyclicantidepressants,sincetheactionofbeta-adrenergicagonistsmaybeenhanced.

Inhalationofhalogenatedhydrocarbonanaestheticssuchashalothane,trichloroethyleneandenfluranemayincreasethe

susceptibilitytothecardiovasculareffectsofbeta-agonists.

4.6Fertility,pregnancyandlactation

Ipratropiumbromidehasbeeningeneraluseforseveralyearsandthereisnodefiniteevidenceofill-consequence

duringpregnancy;animalstudieshaveshownnohazard.

Salbutamolhasbeeninwidespreaduseformanyyearswithoutapparentill-consequenceduringpregnancy.Thereis

inadequatepublishedevidenceofsafetyintheearlystagesofhumanpregnancybutinanimalstudiestherehasbeen

evidenceofsomeharmfuleffectsonthefoetusatveryhighdoselevels.

Aswithallmedicines,COMBIVENTshouldnotbeusedinpregnancy,especiallythefirsttrimester,unlessthe

expectedbenefitisthoughttooutweighanypossiblerisktothefoetus.Similarly,COMBIVENTshouldnotbe

administeredtobreast-feedingmothersunlesstheexpectedbenefitisthoughttooutweighanypossiblerisktothe

neonate.

4.7Effectsonabilitytodriveandusemachines

Nonestated.

4.8Undesirableeffects

Thefollowingsideeffectshavebeenreportedbasedonclinicaltrialsinvolving821patients.

Frequencies

Verycommon1/10

Common1/100<1/10

Uncommon1/1,000<1/100

Rare1/10,000<1/1,000

VeryRare<1/10,000

Notknowncannotbeestimatedfromtheavailabledata

Immunesystemdisorders:

Notknown:Anaphylacticreaction

Notknown:Hypersensitivity

Metabolismandnutritiondisorders:

Notknown:Hypokalaemia

Psychiatricdisorders:

Notknown:Mentaldisorder

Uncommon:Nervousness

Nervoussystemdisorders:

Uncommon:Dizziness

Uncommon:Headache

Uncommon:Tremor

Eyedisorders:

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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

Ipratropiumbromideisananticholinergicagentwhichinhibitsvagallymediatedreflexesbyantagonisingtheactionof

acetylcholine,thetransmitteragentreleasedfromthevagusnerve.Thebronchodilationfollowinginhalationof

ipratropiumbromideisprimarilylocalandsitespecifictothelungandnotsystemicinnature.

Salbutamolisabeta

-adrenergicagentwhichactsonairwaysmoothmuscleresultinginrelaxation.Salbutamolrelaxes

allsmoothmusclefromthetracheatotheterminalbronchiolesandprotectsagainstallbronchoconstrictorchallenges.

COMBIVENTUDVsprovidethesimultaneousdeliveryofipratropiumbromideandsalbutamolsulphateallowing

effectsonbothmuscarinicandbeta2-adrenergicreceptorsinthelungleadingtoincreasedbronchodilationoverthat

providedbyeachagentsingly.

5.2Pharmacokineticproperties

Ipratropiumbromideisquicklyabsorbedafteroralinhalation.Thesystemicbioavailabilityafterinhalationisestimated

tobelessthan10%ofthedose.Renalexcretionofipratropiumbromideisgivenas46%ofthedoseafterintravenous

administration.Thehalflifeoftheterminaleliminationphaseisabout1.6hoursasdeterminedafterintravenous

administration.Thehalflifeforeliminationofdrugandmetabolitesis3.6hours,asdeterminedafterradiolabelling.

Ipratropiumbromidedoesnotcrosstheblood-brainbarrier.

Salbutamolisrapidlyandcompletelyabsorbedfollowingoraladministrationeitherbytheinhaledorgastricroute.Peak

plasmasalbutamolconcentrationsareseenwithinthreehoursofadministrationandthedrugisexcretedunchangedin

theurineafter24hours.Theeliminationhalf-lifeis4hours.Salbutamolwillcrossthebloodbrainbarrierreaching

concentrationsamountingtoaboutfivepercentoftheplasmaconcentrations.

Ithasbeenshownthatco-nebulisationofipratropiumbromideandsalbutamolsulphatedoesnotpotentiatethesystemic

absorptionofeithercomponentandthatthereforetheadditiveactivityofCOMBIVENTUDVsisduetothecombined

localeffectonthelungfollowinginhalation.

5.3Preclinicalsafetydata

Theindividualactiveingredients,ipratropiumbromideandsalbutamolsulphate,havebeenextensivelyinvestigatedin

animalmodelsandtherearenoclinicallyrelevantsafetyissueswhenCOMBIVENTUDVsareusedatthe

recommendeddosesbypatients.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiumchloride

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Purifiedwater

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductisthedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryoforigin.

Astheproductcontainsnopreservative,afreshvialshouldbeusedforeachadministrationandthevialshouldbe

openedimmediatelybeforeuse.Anysolutionleftinthevialshouldbediscarded.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

Storeintheoriginalpackage.

Donotfreeze.

6.5Natureandcontentsofcontainer

Lowdensitypolyethylenevialscontaining2.5mlsolution,formedintostripsof10andpackedintocartonscontaining

20or60vials.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Forinstructionsforuse,pleaserefertosection4.2

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA465/105/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:5 th

March2004

Dateoflastrenewal:5 th

March2010

10DATEOFREVISIONOFTHETEXT

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