BREVIBLOC

Main information

  • Trade name:
  • BREVIBLOC Solution for Injection 10
  • Dosage:
  • 10
  • Pharmaceutical form:
  • Solution for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BREVIBLOC Solution for Injection 10
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0167/099/001
  • Authorization date:
  • 09-09-1994
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Brevibloc100mg/10mlSolutionforInjection.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Each10mlvialcontains100mgesmololhydrochloride(10mg/ml).

Excipients:Containsapproximately28mgsodiumperdose.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

SolutionforInjection.

Clear,colourlesstoslightstrawcolouredsolution.

ThesolutionhasapHof5andosmolarityof312mOsmol/l.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Supraventriculartachyarrhythmias,includingatrialfibrillation,atrialflutterandsinustachycardiaorother

circumstanceswhereshort-termcontrolofventricularratewithashortactingagentisdesirable

Perioperativetachycardiaandhypertensionincludingthemanagementoftachycardiaandhypertension

associatedwithsurgicalprocedures,suchasendotrachealintubation,inductionofanaesthesia,skinincision,

sternotomyandaorticdissection

4.2Posologyandmethodofadministration

IntravenousInjection

Brevibloc100mgisaready-to-usepreparationinvialsataconcentrationof10mg/ml.

SupraventricularTachyarrhythmia

TheeffectivedoseofBreviblocfortreatmentofsupraventriculartachyarrhythmiais50to200mcg/kg/min,although

dosesashighas300mcg/kg/minhavebeenused.Inafewpatientsadosageof25mcg/kg/minhasbeenadequate.

Breviblocdosageinsupraventriculartachyarrhythmiamustbeindividualisedbytitrationinwhicheach stepconsists

ofaloadingdosagefollowedbyamaintenancedose.

FlowChartforInitiationandMaintenanceofTreatment

Loadingdosageinfusionof500mcg/kg/minfor1minuteTHENmaintenanceinfusionof50mcg/kg/minfor4minutes*

*Asthedesiredheartratesafetyend-point(egloweredbloodpressure)isapproached,OMITtheloadinginfusionand

reducetheincrementaldoseinthemaintenanceinfusionfrom50mcg/kg/minto25mcg/kg/minorlower.Ifnecessary,

theintervalbetweenthetitrationstepsmaybeincreasedfrom5to10minutes.

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safetyofdosesabove300mcg/kg/minhasnotbeenstudied.

Afterachievinganadequatecontroloftheheartrateandastableclinicalstatusinpatientswithsupraventricular

tachyarrhythmia,transitiontoalternativeantiarrhythmicagentssuchasverapamil,propranololormetoprolol,digoxin

orquinidinemaybeaccomplished.Arecommendedguidelineforsuchatransitionisgivenbelowbut thephysician

shouldcarefullyconsiderthelabellinginstructionsforthealternativeagentselected:

Alternativeagent Dosage

Propranololhydrochloride 10-20mg4-6hourly(po)

Digoxin 0.125-0.5mg6hourly(pooriv)

Verapamil 80mg6hourlypo

Quinidine 200mg2hourlypo

ThedosageofBreviblocshouldbereducedasfollows:

Withinthefirsthourafterthefirstdoseofthealternativeagent,reducetheBreviblocinfusionratebyone-half

(50%).

Followingtheseconddoseofthealternativeagent,monitorthepatient'sresponseandifsatisfactorycontrolis

maintainedforthefirsthour,discontinuetheBreviblocinfusion.

TheuseofBreviblocinfusionsforlongerthan24hourshasnotbeenthoroughlyevaluated.Infusiondurationsgreater

than24hoursshouldonlybeusedwithcaution.

Perioperativetachycardiaandhypertension

Inanticipationofasurgicalevent:

Breviblocshouldbeinfusedasaloadingdoseof500mcg/kg/minfor4minutesfollowedbyamaintenance

doseof300mcg/kg/min2-5minutespriortotheanticipatedevent

Whentreatingtachycardiaand/orhypertensionintheperioperativesetting,thefollowingdoseregimensmay

beused.

Fortheintraoperativetreatment-duringanaesthesiawhenimmediatecontrolisrequired,givean80mgloading

bolusover15-30secondsfollowedbya150mcg/kg/mininfusion.Titratetheinfusionrateasrequiredupto

300mcg/kg/min.

Uponawakeningfromanaesthesia,administeraninfusionof500mcg/kg/minforfourminutesfollowedbya

300mcg/kg/mininfusion.

Forpostoperativesituationswhentimefortitrationisavailablegivethe500mcg/kg/minloadingdoseoverone

minutebeforeeachtitrationsteptoproducearapidonsetofaction.Usetitrationstepsof50,100,150,200,250

and300mcg/kg/mingivenoverfourminutes,stoppingatthedesiredtherapeuticeffect.

Additionaldosinginformation:asthedesiredtherapeuticeffectorasafetyendpoint(egloweredbloodpressure)is

approached,omittheloadingdoseandreducetheincrementalinfusionto12.5-25mcg/kg/min.Also,ifdesired,

increasetheintervalbetweentitrationstepsfromfivetotenminutes.

Breviblocshouldbediscontinuedwhenheartrateorbloodpressurerapidlyapproachorexceedasafetylimit,andthen

restartedwithoutaloadinginfusionatalowerdoseaftertheheartrateorbloodpressurehasreturnedtoanacceptable

level

Useinchildren:ThesafetyandeffectivenessofBreviblocinchildrenhavenotbeenestablished.

Useintheelderly:Specialstudiesintheelderlyhavenotbeenconducted.However,analysisofdatafrom252

patientsover65yearsofageindicatedthatnovariationsinpharmacodynamiceffectsoccurredascomparedwithdata

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4.3Contraindications

heartblockgreaterthanfirstdegree

severebradycardia

overtheartfailure

cardiogenicshock

4.4Specialwarningsandprecautionsforuse

Patientswithbronchospasticdiseaseshould,ingeneral,notreceivebetablockers.Becauseofitsrelativebeta

selectivityandtitratability,Breviblocshouldbeusedwithcautioninpatientswithbronchospasticdiseases.However,

sincebeta

selectivityisnotabsolute,Breviblocshouldbecarefullytitratedtoobtainthelowestpossibleeffective

dose.Intheeventofbronchospasm,theinfusionshouldbeterminatedimmediatelyandabeta

agonistshouldbe

administeredifnecessary.

Inpatientswithsupraventriculartachyarrhythmia,Breviblochasbeenshowntoproduceadecreaseinsystolicblood

pressure.Accordinglypatientswithlowpre-treatmentsystolicpressuresshouldbecarefullyobservedduringtitration

andmaintenanceinfusionswithBrevibloc.

Continueddepressionofthemyocardiumwithbeta-blockingagentsoveraperiodoftimecan,insomecases,leadto

cardiacfailure.Atthefirstsignorsymptomofimpendingcardiacfailure,thedosageshouldbereducedorBrevibloc

shouldbewithdrawnandspecifictreatmentshouldalsobeconsidered.

Breviblocshouldbeadministeredwithcautiontopatientswithimpairedrenalfunctionbecausetheacidmetaboliteof

Breviblocisprimarilyexcretedunchangedbythekidney.

Breviblocshouldbeusedwithcautionindiabeticpatients.

TheuseofBreviblocinfusionsforlongerthan24hourshasnotbeenthoroughlyevaluated.Infusiondurationsgreater

than24hoursshouldonlybeusedwithcaution.

Infusionconcentrationsof20mg/mlhavebeenassociatedwithsignificantvenousirritationandthrombophlebitisin

animalsandman,thereforeconcentrationsgreaterthan10mg/mlshouldbeavoided.

AbruptdiscontinuationofBreviblocinpatientshasnotbeenreportedtoproducethewithdrawalofbeta-blockers

followingchronicuseincoronaryarterydisease(CAD)patients.However,cautionshouldstillbeusedindiscontinuing

BreviblocinfusionsabruptlyinCADpatients.

Ifalocalinfusionsitereactiondevelops,analternativeinfusionsiteshouldbeused.

Thismedicinalproductcontainsapproximately28mgsodiumperdose.Tobetakenintoconsiderationbypatientsona

controlledsodiumdiet.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Catecholamine-depletingagentsegreserpine,mayhaveanadditiveeffectwhengivenwithbeta-blockingagents.

PatientstreatedconcurrentlywithBreviblocandacatecholaminedepletorshouldthereforebecloselyobservedfor

evidenceofhypotensionormarkedbradycardia,whichmayresultinvertigo,syncopeorposturalhypotension.

DatafromaninteractionstudybetweenBreviblocandwarfarinshowedthatconcomitantadministrationofBrevibloc

andwarfarindoesnotalterwarfarinplasmalevels.Breviblocconcentrations,however,wereequivocallyhigherwhen

givenwithwarfarin.

WhendigoxinandBreviblocwereconcomitantlyadministeredintravenouslytonormalvolunteers,therewasa10-20%

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WhenintravenousmorphineandBreviblocinteractionwasstudiedinnormalsubjects,noeffectonmorphineblood

levelswasseen.TheBreviblocsteady-statebloodlevelswereincreasedby46%inthepresenceofmorphine,butno

otherpharmacokineticparameterswerechanged.

TheeffectofBrevibloconthedurationofsuccincylcholine-inducedneuromuscularblockadehasbeenstudiedin

patientsundergoingsurgery.TheonsetofneuromuscularblockadebysuccinylcholinewasunaffectedbyBrevibloc,but

thedurationofneuromuscularblockadewasprolongedfrom5minutesto8minutes.

Althoughtheinteractionsobservedinthesestudiesarenotofmajorclinicalimportance,Breviblocshouldbetitrated

withcautioninpatientsbeingtreatedconcurrentlywithdigoxin,morphine,succinylcholineorwarfarin.

ThehypotensiveeffectsofinhalationanaestheticagentsmaybeincreasedinthepresenceofBrevibloc.Thedosageof

eitheragentmaybemodifiedasneededtomaintainthedesiredhaemodynamics.

Thereexistnodataontheinteractionsofesmololwithcalciumchannelblockers;however,incommonwithotherbeta-

adrenoceptorantagonistsitisrecommended thatesmololbeusedwithcautionincombinationwithverapamilin

patientswithimpairedventricularfunction.Thecombinationshouldnotbegiventopatientswithconduction

abnormalitiesandesmololshouldnotbeadministeredwithin48hoursofdiscontinuingverapamil.

4.6Pregnancyandlactation

Noteratogeniceffectshavebeenobservedinanimalstudies.However,therearenohumandataavailableand

Breviblocshouldonlybeusedinpregnancyifthepotentialbenefitoutweighsthepotentialrisktothefoetus.

ItisnotknownwhetherBreviblocisexcretedinhumanmilk,thereforecautionshouldbeexercisedwhenBreviblocis

administeredtonursingmothers.

4.7Effectsonabilitytodriveandusemachines

Notrelevant.

4.8Undesirableeffects

Themostfrequentlyobservedsideeffecthasbeenhypotension.Lessfrequentlyobservedweresweating,nausea,

peripheralischaemia,confusion,somnolence,dizziness,fatigue,agitation,headache,vomiting,inflammation,

indurationorinfiltrationattheinfusionsite.

Rarelyseenareoedema,wheezing,dyspnoea,anxiety,anorexia,constipation,urinaryretention,speechdisorder,

abnormalvision,rigorandfever.

4.9Overdose

OverdosesofBrevibloc(esmololhydrochloride)cancausecardiacarrest.Inaddition,overdosescanproduce

bradycardia,hypotension,electromechanicaldissociationandlossofconsciousness.Casesofmassiveaccidental

overdosesofBreviblochaveoccurredduetodilutionerrors.Someoftheseoverdoseshavebeenfatalwhileothers

resultedinpermanentdisability.Bolusdosesintherangeof625mgto2.5g(12.5-50mg/kg)havebeenfatal.Patients

haverecoveredcompletelyfromoverdosesashighas1.75ggivenoveroneminuteordosesof7.5ggivenoverone

hourforcardiovascularsurgery.Thepatientswhosurvivedappeartobethosewhosecirculationcouldbesupported

untiltheeffectsofBreviblocresolved.

Becauseofitsapproximately9-minuteeliminationhalf-life,thefirststepintheeventoftoxicityshouldbeto

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Brevibloc(esmololhydrochloride)isabeta-selective(cardioselective)adrenergicreceptorblockingagentwitharapid

onset,averyshortdurationofactionandnosignificantintrinsicsympathomimeticormembranestabilisingactivityat

therapeuticdoses.

5.2Pharmacokineticproperties

Brevibloc(esmololhydrochloride)israpidlymetabolisedbyhydrolysisoftheesterlinkagebyesterasesinthered

bloodcells.Thedistributionhalf-lifeafterintravenousinfusionis2minutesandtheeliminationhalf-life9minutes.

MetabolismofBreviblocresultsintheformationofthecorrespondingfreeacidASL-8123andmethanol.Theacid

metaboliteASL-8123hasweak(lessthan0.1%ofesmolol)beat-blockingactivity.

Consistentwiththehighblood-basedmetabolismofBrevibloc,lessthan2%ofthedrugisexcretedunchangedinthe

urine.

Theacidmetabolitehasaneliminationhalf-lifeofabout3.7hoursandisexcretedintheurine.

Breviblochasbeenshowntobe55%boundtohumanplasmaproteincomparedwithonly10%fortheacidmetabolite.

5.3Preclinicalsafetydata

Notapplicable.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiumacetate

Glacialaceticacid

SodiumChloride

Sodiumhydroxideorhydrochlorideacid(forpHadjustment)

Waterforinjections

6.2Incompatibilities

BreviblocisnotcompatiblewithSodiumbicarbonate.

6.3ShelfLife

Unopened:2years.

Theproductshouldbeusedimmediatelyafteropening.

6.4Specialprecautionsforstorage

Storebelow25°C.

6.5Natureandcontentsofcontainer

TypeIPh.Eur.,amberglassvialwithrubberstopper,10ml.Packsizes3,5,10and20.

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Forsingleuseonly.

Discardanyunusedcontents.

7MARKETINGAUTHORISATIONHOLDER

BaxterHealthcareLimited

CaxtonWay

Thetford

NorfolkIP243SE

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA0167/099/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 08September1994

Dateoflastrenewal: 23March2008

10DATEOFREVISIONOFTHETEXT

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