ALUPENT EXPECTORANT

Main information

  • Trade name:
  • ALUPENT EXPECTORANT
  • Dosage:
  • 10/ 4 mg / 5m MG/ 5ml
  • Pharmaceutical form:
  • Oral Suspension
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ALUPENT EXPECTORANT
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0007/015/002
  • Authorization date:
  • 01-04-1979
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0007/015/002

CaseNo:2053944

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

BoehringerIngelheimLimited

EllesfieldAvenue,Bracknell,BerkshireRG128YS,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

AlupentExpectorantMixture

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom11/08/2008until31/03/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 12/08/2008 CRN 2053944 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AlupentExpectorantMixture

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Each5mlcontainsorciprenalinesulphate10mgandbromhexinehydrochloride4mg.

Forexcipients,see6.1.

3PHARMACEUTICALFORM

Syrup

Clear,colourlesssyrupwithanodourofcocoa.

4CLINICALPARTICULARS

4.1TherapeuticIndications

AlupentExpectorantMixtureisindicatedforconditionsinwhichbothbronchospasmandsputumarepresent,e.g.in

asthmaorbronchitis.Duringinfectiveepisodesasuitableantibioticshouldalsobegiven.

4.2Posologyandmethodofadministration

Dosageandadministrationorally:

Diluent:AlupentExpectorantmaybedilutedwithSyrupBPorSorbitolBP.

4.3Contraindications

Hypertrophicobstructivecardiomyopathyandtachyarrhythmia.Knownhypersensitivitytoorciprenaline,bromhexine

oranyotherexcipientinthisproduct.

Incasesofrarehereditaryconditionsthatmaybeincompatiblewithanexcipientoftheproduct(pleasereferto'Special

warningsandprecautions')theuseoftheproductiscontraindicated.

4.4Specialwarningsandprecautionsforuse

Patientsrequiringlong-termmanagementwithbronchodilatorsshouldbekeptunderregularsurveillance.

OthersympathomimeticbronchodilatorsshouldonlybeusedwithAlupentExpectorantMixtureunderstrictmedical

Adults Children

(5-10years) Children

(2-5years)

2x5ml

fourtimes

daily 1x5ml

threeorfour

timesdaily 1x5ml

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InthefollowingconditionsAlupentExpectorantMixtureshouldbeusedaftercarefulrisk/benefitassessment,

especiallywhendoseshigherthanrecommendedareused:

insufficientlycontrolleddiabetesmellitus,recentmyocardialinfarctionand/orsevereorganicheartorvascular

disorders,hyperthyroidism,pheochromocytoma,andinpatientswhoareunusuallyresponsivetosympathomimetic

amines.

Patientsmustbewarnednottoexceedtheprescribeddose.Inthecaseofacute,rapidlyworseningdyspnoea,adoctor

shouldbeconsultedimmediately.

Ifbronchialobstructiondeteriorates,itisinappropriateandpossiblyhazardoustosimplyincreasetheuseofbeta-

agonistsbeyondtherecommendeddoseoverextendedperiodsoftime.Theuseofhighamountsofbeta-agonistslike

orciprenalineonaregularbasistocontrolsymptomsofbronchialobstructionmaysuggestdecliningdiseasecontrol.In

thissituation,thepatient'stherapyplan,andinparticulartheadequacyofanti-inflammatorytherapyshouldbe

reviewedtopreventpotentiallylife-threateningdeteriorationofdiseasecontrol.

Potentiallyserioushypokalaemiamayresultfrombeta

-agonisttherapy.Particularlycautionisadvisedinsevere

asthma,asthiseffectmaybepotentiatedbyconcomitanttreatmentwithxanthinederivatives,steroidsanddiuretics.

Additionally,hypoxiamayaggravatetheeffectsofhypokalaemiaoncardiacrhythm.Itisrecommendedthatserum

potassiumlevelsaremonitoredinsuchsituations.

Bromhexineshouldbeusedwithcautioninpatientswithahistoryof,orexisting,pepticulceration.

TherehavebeenveryrarereportsofsevereskinlesionssuchasStevensJohnsonsyndromeandLyell'ssyndromein

temporalassociationwiththeadministrationofmucolyticsubstancessuchasbromhexine.Mostlythesecouldbe

explainedbytheseverityoftheunderlyingdiseaseorconcomitantmedication.Ifnewskinormucosallesionsoccur,

medicaladviceshouldbesoughtimmediatelyandtreatmentwithbromhexinediscontinuedasaprecaution.

Ondemandtreatment(symptomorientated)maybepreferabletoregularuseinpatientsonlong-termtreatment.In

addition,thesepatientsshouldbere-evaluatedfortheadditionortheincreaseofanti-inflammatorytherapy(e.g.

inhaledcorticosteroids)tocontrolairwayinflammation,andtopreventlong-termdamage.

Astheproductcontainssorbitol,patientswithrarehereditaryproblemsoffructoseintoleranceshouldnottakethis

medicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Inviewofthepossibleinteractionbetweenbeta-adrenergicsandmonoamineoxidaseinhibitorsortricyclicanti-

depressants,careshouldbeexercisedifitisproposedtoadministerthesecompoundsconcurrentlywithAlupent

ExpectorantMixture.Beta-adrenergics,anticholinergicsandxanthinederivatives(suchastheophylline)mayenhance

thebronchodilatoryeffectoforciprenaline.

Theconcurrentadministrationofotherbeta-adrenergics,systemicallyabsorbedanticholinergicsandxanthine

derivatives(e.g.theophylline)mayincreasethefrequencyandseverityofunwantedeffects.

Beta

-receptorblockerscounteracttheactionoforciprenaline.Potentiallyseriousbronchospasmmayoccurduring

concurrentadministrationofbeta-blockerstopatientswithreversibleairwaysobstruction.

Inhalationofhalogenatedhydrocarbonanaestheticssuchashalothane,trichloroethyleneandenfluranemayincreasethe

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4.6Pregnancyandlactation

Insomepre-clinicalstudiesathighdoses,orciprenalinehasshownthepotentialtocausefoetalabnormalities.The

significancetohumansisnotknown.Therearenoadequateandwellcontrolledstudiesinpregnantwomen.Alupent

ExpectorantMixtureshouldonlybeusedduringpregnancy,especiallythefirsttrimester,ifthepotentialbenefit

outweighsthepotentialrisktothefoetus.Theinhibitoryeffectoforciprenalineonuterinecontractionshouldbetaken

intoaccount.

Safetyduringlactationhasnotyetbeenestablishedalthoughasbromhexineisexpectedtoenterbreastmilktheproduct

shouldbeavoidedduringlactation.

4.7Effectsonabilitytodriveandusemachines

Nonestated.

4.8Undesirableeffects

Themostfrequentlyreportedundesirableeffectsobservedwithorciprenalinearetremorandnervousness,headache,

dizziness,tachycardia,palpitations,gastro-intestinaldiscomfort,nauseaandvomiting.Somepatientshaveexperienced

afeelingoftightnessinthechest.

Inrarecases,localirritation,skinreactionsorallergicreactionshavebeenreported.Therehavebeenisolatedcasesof

anaphylacticoranaphylactoidreactions.Inindividualcasespsychologicalalterationshavebeenreportedunder

inhalationaltherapywithbetamimetics.

Potentiallyserioushypokalemiamayresultfrombeta

-agonisttherapy.

Aswithotherbeta-mimetics,sweating,weaknessandmyalgia/musclecrampsmayoccur.Inrarecasesdecreasein

diastolicbloodpressure,increaseinsystolicbloodpressure,arrhythmias,particularlyafterhigherdosesmayoccur.

Diarrhoea,nausea,vomitingandothermildgastro-intestinalsideeffectshavebeenreportedwithbromhexine

hydrochloride.Allergicreactionsincludingskinrashes,urticaria,bronchospasm,angio-oedemaandanaphylaxishave

beenreportedrarely.

Inaveryfewpatientsatransitoryriseinserumtransaminaselevelsmaybeseenduringtreatmentwithbromhexine

hydrochloride.Withcontinuationofthedrug,transaminasesreturntopre-treatmentlevels,eveninthosepatientsin

whomtherewaspre-existingimpairmentofhepaticfunction.

4.9Overdose

Symptoms:Theexpectedsymptomsofoverdosagewithorciprenalinearethoseofexcessivebeta-stimulationsuchas

flushing,tremor,nausea,restlessness,tachycardia,palpitation,dizziness,headache,hypotension,hypertension,a

feelingofpressureinthechest,excitation,angina,increasedpulsepressureandarrhythmia.Hypokalemiamayoccur

followingoverdosewithorciprenaline.Serumpotassiumlevelsshouldbemonitored.

Toxiceffectsfollowingoverdosagewithbromhexinehydrochloridehavenotbeenreported,butanimalstudiessuggest

thatthesemayincludelistlessness,anorexia,ataxia,cyanosis,pulmonaryrales,hypothermia,diuresis,respiratory

failure,convulsionsorcoma.

Therapy:Treatmentconsistsofdiscontinuationoftheproducttogetherwithappropriatesymptomatictherapy.Should

theadministrationofabeta-adrenergicblockingagentbenecessarytocounteracttheeffectsofoverdosage,itsuseina

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

AlupentExpectorantMixtureprovidesthedualactionofthebronchodilatororciprenalinesulphateandthemucolytic

agentbromhexinehydrochloride.Orciprenalinesulphateisasympathomimeticaminewithbronchodilatorproperties.

Bromhexineisasyntheticderivativeoftheherbalactiveingredientvasicine.Preclinically,ithasbeenshownto

increasetheproportionofserousbronchialsecretion.Bromhexineenhancesmucustransportbyreducingmucus

viscosityandbyactivatingtheciliatedepithelium(mucociliaryclearance.)

Inclinicalstudies,bromhexineshowedasecretolyticandsecretomotoreffectinthebronchialtractarea,which

facilitatesexpectorationandeasescough.

Followingtheadministrationofbromhexineantibioticconcentrations(amoxicillin,erythromycin,oxytetracycline)in

thesputumandbronchopulmonarysecretionsareincreased.

5.2Pharmacokineticproperties

FollowingoraladministrationorciprenalineisabsorbedfromtheGItractandundergoesextensivefirstpass

metabolism;about40%ofanoraldoseisreportedtoreachthecirculationunchanged.Itisexcretedintheurine

primarilyasglucuronideconjugates.

Bromhexineshowsdoseproportionalpharmacokinetics.Itisrapidlyandcompletelyabsorbedfromthegastrointestinal

tract.Afteradministrationofradiolabelledbromhexineabout97.4+1.9%ofthedosewererecoveredasradioactivity

inurine,withlessthan1%asparentcompound.Bromhexineisahighclearancedrug(CL~843-1073mL/min)

resultinginhighinter-andintraindividualvariability(CV >

30%).

Afteroraladministrationsolidandliquidformulationsshowsimilarbioavailability.Theabsolutebioavailabilityof

bromhexinehydrochloridewasabout22.2+8.5%upto26.8+13.1%forBISOLVON tabletsandsolution,

respectively.

Intravenousadministrationsshowedameanvolumeofdistribution(Vss)ofupto1209+206L.Thedistributionin

lungtissue(bronchialandparenchymal)wasinvestigatedafteri.v.(8mg,16mg)andoral(32mg,64mg)

administration.Bromhexinetissueconcentrationstwohourspostdosewerethreetofourtimeshigherinlungtissue

comparedtoplasma.Parenchymaltissueseemedtoshowahigherenrichmentofbromhexinethanbronchialtissue

especiallyafteroralabsorption.

Unchangedbromhexineisboundtoplasmaproteinsby95%(non-restrictivebinding).

Bromhexineisalmostcompletelymetabolisedtoavarietyofhydroxylatedmetabolitesandtodibromanthranilicacid.

AllmetabolitesandbromhexineitselfareconjugatedmostprobablyinformofN-glucuronidesandO-glucuronides.A

minorpartofbromhexineismetabolisedtodibromanthranilicacidmostprobablyviacytochromeP4503A4.Thereare

nosubstantialhintsforachangeofthemetabolicpatternbyasulphonamideoroxytetracyclin.Thereisainsufficient

pharmacokineticdatatoevaluateapossibledrug-druginteractionbetweenbromhexineanderythromycin.

Bromhexineplasmaconcentrationsshowedamultiexponentialdecline.Therelevanthalf-lifetopredictthemultiple

dosepharmacokineticsisabout1hour,thusnoaccumulationwasseenaftermultipledosing(accumulationfactor1.05).

Therearenodataforbromhexinepharmacokineticsintheelderlyorinpatientswithrenalorliverinsufficiency.

Concomitantfoodleadstoanincreaseofbromhexineplasmaconcentrations.

Bromhexinepharmacokineticsisnotrelevantlyaffectedbyco-administrationofampicillinoroxytetracycline.

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5.3Preclinicalsafetydata

Nonestated.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Ethylenediaminetetraacetatedisodiumsalt

Methylparahydroxybenzoate(E218)

Propylparahydroxybenzoate(E216)

Hydroxyethylcellulose

Sorbitolsolution70%(E420)

Artificialcocoaaroma

Hydrochloricacid25%

PurifiedWater

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

5years.

6.4Specialprecautionsforstorage

Storebelow25°C.

Storeintheoriginalcontainer.

6.5Natureandcontentsofcontainer

250ml,300mland2Lamberglassbottleswithtamper-evident,child-resistantpolypropylenecapswithexpanded

polyethyleneliners.Thecurrentmarketedpackis300ml.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

BoehringerIngelheimLimited

EllesfieldAvenue

Bracknell

Berkshire

RG128YS

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

Irish Medicines Board

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:01April1979

Dateoflastrenewal:01April2004

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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