BETA-ADALAT

Main information

  • Trade name:
  • BETA-ADALAT Capsule 20mg/50 mg Milligram
  • Dosage:
  • 20mg/50 mg Milligram
  • Pharmaceutical form:
  • Capsule
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BETA-ADALAT Capsule 20mg/50 mg Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1410/026/001
  • Authorization date:
  • 04-01-2007
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Beta–Adalat20mg/50mgCapsules

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachhardcapsulecontains20mgnifedipineand50mgatenolol.

Excipient:contains10.0mgoflactosemonohydratepercapsule

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Capsule,hard.(capsule)

Brown–reddish,opaquegelatincapsulesoverprintedwith“BETA–ADALAT”andtheBayercross,containingwhite

granulesandapinkfilm-coated,round,biconvextablet.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Managementofhypertensionandofchronicstableanginapectoriswheretherapywitheitheracalciumchannelblocker

orabeta-blockerproveinadequate.

4.2Posologyandmethodofadministration

Adults:

Hypertension:Onecapsuledailyswallowedwithwater.Ifnecessary,thedosagemaybeincreasedtoonecapsuledosed

every12hours.Patientscanbetransferredtothecombinationfromotherantihypertensivetreatmentswiththeexception

ofclonidine(seeSection4.4).

Angina:Onecapsuleevery12hoursswallowedwithwater.Whereadditionalefficacyisnecessary,prophylacticnitrate

therapyoradditionalnifedipinemaybeofbenefit.

Elderly:

Dosageshouldnotexceedonecapsuledailyinhypertensionoronecapsuletwicedailyinangina.

Thepharmacokineticsofnifedipinearealteredintheelderlysothatlowermaintenancedosesofnifedipinemaybe

requiredcomparedtoyoungerpatients.

Children:

ThereisnopaediatricexperiencewithBeta-Adalatandthereforethispreparationshouldnotbeusedinchildren.

General:

PatientswithrenalorhepaticinsufficiencymayrequirelowerdosagesofBeta-Adalat,(seeSection4.4).

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4.3Contraindications

Beta-Adalatshouldnotbeadministeredtopatientswithknownhypersensitivitytoatenolol,nifedipineorother

dihydropyridinesbecauseofthetheoreticalriskofcross-reactivity.

Beta-Adalatshouldnotbeadministeredtopatientswithahistoryofwheezingorasthmaoratendencyto

bronchospasm(obstructiverespiratorydisease/bronchialasthma).(Labelwarning:Donotuseifyouhaveahistoryof

wheezingorasthma.)

Beta-Adalatmustnotbeadministeredtowomencapableofchild-bearingortonursingmothers.

Beta-Adalatmustnotbeusedinthepresenceofsecondorthirddegreeheartblock,sicksinussyndrome,sino-atrial

block,inpatientswithevidenceofovertheartfailureorinadequatelytreatedheartfailureordecompensatedheart

failure,NYHAgradesIIIandIV.

Beta-Adalatshouldnotbeusedincardiogenicshock,clinicallysignificantaorticstenosis,unstableanginapectoris,or

duringorwithinonemonthofamyocardialinfarction.

Beta-Adalatshouldnotbeusedforthetreatmentofacuteattacksofangina.

ThesafetyofBeta-Adalatinmalignanthypertensionhasnotbeenestablished.

Beta-Adalatshouldnotbeusedforsecondarypreventionofmyocardialinfarction.

Beta-Adalatmustnotbeusedinconjunctionwithotherdrugswithacardio-depressantaction,e.g.verapamil,as

conductiondisturbancesmayensue.

Beta-Adalatshouldnotbeadministeredconcomitantlywithrifampicinsinceeffectiveplasmalevelsofnifedipinemay

notbeachievedowingtoenzymeinduction(seeSection4.5).

Beta-Adalatshouldnotbeusedinpronouncedbradycardia(restingheartratebeforetreatmentlessthan50beats/min),

hypotensionwithsystolicpressurelessthan90mmHg,orinthelatestagesofcirculatorydisturbancesinthehandsand

legsorinsevereperipheralarterialcirculatorydisturbances.

Beta-AdalatshouldnotbeusedinpatientswithadeclineinthepHoftheblood(acidosis).

Inpatientswithphaeochromocytoma,Beta-Adalatmustbeadministeredonlyafterpriortherapywithalpha-blockers.

Beta-Adalatmustnotbegivenwithsimultaneousadministrationofmonoamineoxidaseinhibitors(MAOinhibitors).

Beta-Adalatmustnotbeusedinpatientswithmarkedrenalimpairment(i.e.creatineclearancebelow

15ml/min/1.73m 2

,serumcreatinegreaterthan600micromol/litre).

4.4Specialwarningsandprecautionsforuse

Cardiac

Particularcareshouldbetakenwithpatientswithconductiondefectsorwhosecardiacreserveispoor.However,in

patientsalreadytreatedwithabeta-adrenoceptorantagonist,and/orwheresignsofcardiacfailurehavebeencontrolled,

Beta-Adalatmaybesubstitutedwithcareifnecessary.

Beta-Adalatshouldonlybeusedwithcautioninpatientswithcontrolledcongestiveheartfailure.Evidenceof

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Beta-Adalatmaybeusedincombinationwithbeta-blockingdrugsandotherantihypertensiveagentsbutthepossibilityof

anadditiveeffectresultinginposturalhypotensionshouldbeborneinmind.Beta-Adalatwillnotpreventpossiblerebound

effectsaftercessationofotherantihypertensivetherapy,(seeSection4.5).

Inpatientswithperipheralcirculatorydisorders(Raynaud’sdiseaseorsyndrome,intermittentclaudication),beta-

blockersshouldbeusedwithcautionasaggravationofthesedisordersmayoccur.

Careshouldbetakeninprescribingabeta-adrenoceptorblockingdrugwithClassIanti-dysrhythmicagentssuchas

disopyramide.

Oneofthepharmacologicalactionsofbeta-adrenoceptorblockingdrugsistoreduceheartrate.Intherareinstances

wheresymptomsmaybeattributabletotheslowheartrateatadoseofonecapsuledaily,thedrugshouldbediscontinued.

Ischaemicpainhasbeenreportedinasmallproportionofpatientswithinonetofourhoursoftheintroductionof

nifedipinetherapy.Althougha"steal"effecthasnotbeendemonstrated,patientsexperiencingthiseffectshould

discontinueBeta-Adalat.

Cessationoftherapywithabeta-adrenoceptorblockingdruginpatientswithischaemicheartdiseaseshouldbegradual,if

necessaryinitiatingreplacementtherapyatthesametime,topreventexacerbationofanginapectoris.

Cautionshouldbeexercisedwhentransferringpatientsfromclonidinetobeta-adrenoceptorblockingdrugs.Ifbeta-

adrenoceptorblockingdrugsaregivenconcurrently,clonidineshouldnotbediscontinueduntilseveraldaysafter

withdrawalofthebeta-adrenoceptorblockingdrug.

Cautionshouldbeexercisedinpatientswithseverehypotension(systolicpressure<90mmHg)incasesofmanifestheart

failureandinsevereaorticstenosis.

Cautionshouldbeexercisedincasesoffirstdegreeheartblockormildheartfailure,NYHAgradeII.

Beta-blockersmayincreasethenumberanddurationofanginalattacksinpatientswithPrinzmetal’sanginadueto

unopposedalpha-receptormediatedcoronaryarteryvasoconstriction.Therefore,beta

selectiveblockerssuchasatenolol

shouldbeusedwithcare.

Obstructiveairwaysdisease

Althoughcardioselective(beta

)beta-blockersmayhavelesseffectonlungfunctionthannon-selectivebeta-blockers,as

withallbeta-blockers,theseshouldnotbeadministeredtopatientswithreversibleobstructiveairwaysdisease.

Renalimpairment

Dosageshouldnotexceedonecapsuledailyinpatientswithrenaldysfunction.Theuseofthecombinationiscontra-

indicatedinpatientswithmarkedrenalimpairment,(seeSection4.3).

Indialysispatientswithmalignanthypertensionandhypovolaemia,amarkeddecreaseinbloodpressurecanoccur.

Hepaticimpairment

Careshouldbetakeninpatientswithmarkedhepaticimpairment.Althoughnodosageadjustmentissuggestedfromthe

systemicavailabilityofthemonocomponentsinpatientswithcirrhosis,hypertensivepatientswithclinicallysignificant

liverdiseasehavenotbeenstudied.Nifedipineismetabolisedprimarilybytheliverandthereforepatientswithliver

dysfunctionshouldbecarefullymonitored.

Anaesthesia

Itisnotadvisabletowithdrawbeta-adrenoceptorblockingdrugspriortosurgeryinthemajorityofpatients.However,

careshouldbetakenwhenusinganaestheticagentssuchasether,cyclopropaneandtrichloroethylene.Vagaldominance,

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Diabetes

Theuseofnifedipineindiabeticpatientsmayrequireadjustmentoftheircontrol.

Atenololmaymasksomeofthesymptomsofthyrotoxicosisofhypoglycaemiabyinhibitionofsympatheticnerve

function.Theeffectofhypoglycaemicagentsmaybeincreased,particularlybynon-cardioselectivebeta-blockers.The

tachycardiaofhypoglycaemiamaybemodified.

General

Thebenefitsandrisksmustbecarefullyconsideredbeforedrugscontainingbeta-receptorblockers(suchasBeta-

Adalat)areusedin:patientswithahistoryorfamilyhistoryofpsoriasis;patientswithahistoryofsevere

hypersensitivityreactionsandpatientsondesensitisationtherapy(decreasedadrenergiccounter-regulation).

Whilstnifedipineiscontra-indicatedinpregnancy,particularcaremustbeexercisedwhenadministeringnifedipinein

combinationwithi.v.magnesiumsulphatetopregnantwomen.

Co-administrationofnifedipinewitherythromycin,ketoconazole,itraconazole,fluconazole,fluoxetine,indinavir,

nelfinavir,ritonavir,amprenavirandsaquinavirmaytheoreticallyresultinanincreaseinnifedipineplasma

concentrations.Uponco-administrationwithanyofthesecytochromeP4503A4inhibitors,bloodpressureshouldbe

monitoredand,ifnecessary,areductioninthenifedipinedoseconsidered(seeSection4.5).

Beta-Adalatshouldnotbeadministeredtopatientswithrarehereditaryproblemsofgalactoseintolerance,theLapp

lactasedeficiencyorglucose-galactosemalabsorption.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

KnownInteractions

Aswithotherdihydropyridines,nifedipineshouldnotbetakenwithgrapefruitjuiceaselevatedplasmaconcentrations

occur,duetoadecreasedfirstpassmetabolism.Asaconsequence,thebloodpressureloweringeffectofnifedipinemay

beincreased.Afterregularintakeofgrapefruitjuice,thiseffectmaylastforatleastthreedaysafterthelastingestionof

grapefruitjuice(seeSection4.2).

Theantihypertensiveeffectofnifedipinecanbepotentiatedbysimultaneousadministrationofcimetidine.

Whenusedincombinationwithnifedipine,serumquinidinelevelsmaybesuppressedregardlessofdosageofquinidine.

Therefore,monitoringofquinidineplasmalevelsandifnecessaryadjustmentofthequinidinedosagearerecommended.

Thepharmacokineticsofnifedipinemayalsobealteredwhenusedincombinationwithquinidine.Itistherefore

recommendedtomonitorbloodpressure,andifnecessaryreducethenifedipinedosage.

PhenytoininducesthecytochromeP4503A4system.Uponco-administrationwithphenytoin,thebioavailabilityof

nifedipineisreducedandthusitsefficacyweakened.Whenbothdrugsareconcomitantlyadministered,theclinical

responsetonifedipineshouldbemonitoredand,ifnecessary,anincreaseofthenifedipinedoseconsidered.Ifthedoseof

nifedipineisincreasedduringco-administrationofbothdrugs,areductionofthenifedipinedoseshouldbeconsidered

whenthetreatmentwithphenytoinisdiscontinued.

Beta-Adalatshouldnotbeadministeredconcomitantlywithrifampicinsinceeffectiveplasmalevelsofnifedipinemaynot

beachievedowingtoenzymeinduction(seeSection4.3).

Concomitantuseofprostaglandinsyntheaseinhibitingdrugs(e.g.ibuprofen,indomethacin)maydecreasethehypotensive

effectsofbeta-blockers.WhenBeta-Adalatisadministeredsimultaneouslywithreserpine,alpha-methyldopa,clonidine,

guanethidine,guanfacine,orcardiacglycosides,theheartratemaydeclinemoremarkedly,andstimulusconductionmay

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Beta-Adalatcanincreasetheplasmalevelsofdigoxinandtheophylline.Monitoringisthereforerecommended,andin

somecasesareductionofthedosemaybenecessary.

Beta-Adalatshouldbeusedwithgreatcautioninpatientswhoarereceivingconcomitantmyocardialdepressantssuchas

chloroform,lignocaine,procainamide,beta-adrenoceptorstimulantssuchasisoprenaline,oralpha-adrenoceptor

stimulantssuchasnoradrenaline.

IfBeta-Adalatisadministeredsimultaneouslywithanotherbeta-blocker,inadditiontoamoremarkeddecreaseinthe

bloodpressure,heartfailuremaydevelop.Simultaneousadministrationofintravenousbeta-receptorblockersmust

thereforebeavoided.

InpatientswithahypoglycaemicmetabolicdisordersimultaneouslytreatedwithBeta-Adalatandinsulinororal

antidiabetics,normalisationoftheconditionmaybedelayed,andthesymptomofhypoglycaemia,tachycardia,be

masked.Regularmonitoringofthebloodglucoseisthereforenecessary.

WhenBeta-Adalatisadministeredsimultaneouslywithcalciumantagonistsoftheverapamilordiltiazemtypeor

antiarrhythmics,theremaybeamoremarkeddecreaseinthebloodpressure,adeclineintheheartrate,anddisturbances

ofheartrhythm.CarefulmonitoringofthebloodpressureandECGisthereforenecessary.Concomitantintravenous

administrationofcalciumantagonistsmustbeavoidedduringtreatmentwithBeta-Adalat.

Asdiltiazemdecreasestheclearanceofnifedipine,thecombinationofbothdrugsshouldbeadministeredwithcaution.

SimultaneoustherapywithnoradrenalineoradrenalineaswellastheadministrationofMAO-inhibitorscanleadtoan

excessiveincreaseinbloodpressure.

Sincesimultaneoustherapywithnarcoticsorantiarrhythmicsadverselyaffectscardiacoutput,theanaesthetistshouldbe

informedthatthepatientisbeingtreatedwithBeta-Adalat.Ifpossible,Beta-Adalatshouldnotbediscontinuedbeforethe

operation.However,itmustbeborneinmindthatinthecourseofinteractionofatenololwithnarcoticsor

antiarrhythmics,cardiacoutputmaybereducedmoremarkedly,sincethecardiacdepressanteffects(negativeinotropism)

ofatenololwithnarcoticsorantiarrhythmicsmaybeadditive.

Neuromuscularblockadebytubocurarinesmaybepotentiatedbybeta-receptorinhibition.

Nifedipinemayincreasethespectrophotometricvaluesofurinaryvanillylmandelicacidfalsely.However,HPLC

measurementsareunaffected.

Simultaneousadministrationofcisaprideandnifedipineorquinupristin/dalfopristinandnifedipinemayleadto

increasedplasmaconcentrationsofnifedipine.Consequently,thebloodpressureshouldbemonitoredand,if

necessary,thenifedipinedosereduced.

Potentiationofthebloodpressure-loweringactionmustbeanticipatedwhenBeta-Adalatisusedincombinationwith

otherantihypertensivesorwithdiuretics,vasodilators,nitrates,narcotics,tricyclicantidepressants,barbituratesor

phenothiazines,(seeSection4.4).

TheoreticalInteractions

NifedipineismetabolisedviathecytochromeP4503A4systemand,therefore,therearetheoreticalinteractionsfor

drugs,whichareknowntoinhibitthisenzymesystem(e.g.erythromycin,ketoconazole,itraconazole,fluconazole,

fluoxetine,indinavir,nelfinavir,ritonavir,amprenavirandsaquinavir).Althoughnoformalinvivointeractionstudies

havebeenperformedwiththesedrugs,co-administrationcanbeexpectedtoleadtoanincreaseinplasma

concentrationsofnifedipine.Bloodpressureshouldthereforebemonitoredand,ifnecessary,areductioninthe

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TacrolimushasbeenshowntobemetabolisedviathecytochromeP4503A4system.Uponco-administrationofboth

drugs,thetacrolimusplasmaconcentrationsshouldbemonitoredand,ifnecessary,areductioninthetacrolimusdose

considered.

Aclinicalstudyinvestigatingthepotentialofadruginteractionbetweennifedipineandnefazodonehasnotyetbeen

performed.NefazodoneisknowntoinhibitthecytochromeP4503A4mediatedmetabolismofotherdrugs.Therefore

anincreaseinnifedipineplasmaconcentrationsuponco-administrationofbothdrugscannotbeexcluded.When

nefazodoneisgiventogetherwithnifedipine,thebloodpressureshouldbemonitoredand,ifnecessary,areductionin

thenifedipinedoseconsidered.

Althoughnoformalinteractionstudieshavebeenperformedbetweennifedipineandcarbamazipine,phenobarbitoneor

valproicacid,thesedrugshavebeenshowntoaltertheplasmaconcentrationsofacalciumchannelblockerstructurally

similartonifedipine.Achangeinnifedipineplasmaconcentrationsandhenceanalterationinefficacycannotbe

excluded.

4.6Fertility,pregnancyandlactation

Beta-Adalatiscontra-indicatedinwomencapableofchild-bearing.

Thesafetyofnifedipineforuseinhumanpregnancyhasnotbeenestablished.Evaluationofexperimentalanimalstudies

hasshownreproductivetoxicityconsistingofembryotoxicityandteratogeniceffectsatmaternallytoxicdoses.

Beta-Adalatiscontra-indicatedinnursingmothers,asnifedipineandatenololmaybepresentinbreastmilk.

Insinglecasesofinvitrofertilisationcalciumantagonistslikenifedipinehavebeenassociatedwithreversible

biochemicalchangesinthespermatozoa’sheadsectionthatmayresultinimpairedspermfunction.Inthosemenwho

arerepeatedlyunsuccessfulinfatheringachildbyinvitrofertilisation,andwherenootherexplanationcanbefound,

calciumantagonistslikenifedipineshouldbeconsideredaspossiblecauses.

Theoretically,beta-blockerssuchasatenololcauseadecreaseinplacentalbloodflow,whichcanresultinintrauterine

foetal death,andimmatureandprematuredeliveries.Inaddition,adverseeffects(especiallyhypoglycaemiaand

bradycardia)mayoccurinfoetusandneonates.Thereisanincreasedriskofcardiacandpulmonarycomplicationsin

theneonateinthepostnatalperiod.

4.7Effectsonabilitytodriveandusemachines

Reactionstothedrug,whichvaryinintensityfromindividualtoindividual,mayimpairtheabilitytodriveorto

operatemachinery.Thisappliesparticularlyatthestartoftreatment,onchangingthemedicationandincombination

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4.8Undesirableeffects

Beta-Adalatiswell-tolerated.Sideeffectsoccurpredominantlyatthebeginningoftreatmentorathighdoses,andare

generallymildandtransient.Inclinicalstudies,theundesiredeventsreportedareusuallyattributedtothe

pharmacologicalactionsofitscomponents.Thefollowingundesiredevents,listedbybodysystem,havebeen

reported:

Beta-Adalat

Cardiovascular: flushing;oedema

CNS: headache;dizziness

Digestivesystem: gastrointestinaldisturbance

Others: fatigue

Atenololmonotherapy

Cardiovascular: disturbancesofAVconduction;bradycardia;heartfailuredeterioration;posturalhypotension

whichmaybeassociatedwithsyncope;coldandcyanoticextremities;insusceptiblepatients:

precipitationofheartblock,intermittentclaudication,Raynaud’sphenomenon(coldextremities)

CNS: confusion;moodchanges;nightmares;psychosisandhallucinations;sleepdisturbancesofthe

typenotedwithotherbeta-blockers

Digestivesystem: drymouth

Metabolic: hyperglycaemiawhichmaycauselatentdiabetesmellitustobecomemanifest,orleadto

deteriorationinpre-existingdiabetes;shouldahypoglycaemicmetabolicdisorderdevelopina

patientwithdiabetes,itmustbeborneinmindthat,undertreatmentwithBeta-Adalat,

normalisationoftheconditionmaybedelayedandthesymptomofhypoglycaemia,tachycardia,

bemasked

Haematological: purpura;thrombocytopenia

Skin: alopecia;psoriasiformskinreactions;exacerbationofpsoriasis;skinrashes

Musculo-skeletal: jointreactions(lupuserythematosus-likesyndrome)

Neurological: paraesthesia;myasthenia

Respiratory: bronchospasmmayoccurinpatientswithbronchialasthmaorahistoryofasthmaticcomplaints

Specialsenses: visualdisturbances;dryeyes

Urogenital: impotence

Others: anincreasein(ANA)antinuclearantibodieshasbeenobserved,howevertheclinicalrelevanceof

thisisnotclear

Nifedipinemonotherapy

Mostside-effectsareconsequencesofthevasodilatoryeffectsofnifedipineandusuallyregressonwithdrawalof

therapy.Side-effectsofnifedipinesuchasflushingandheadachemayoccuratthebeginningofthetreatment.Theyare,

however,mostlyslightanddiminishwithcontinuoususe.

Otherundesirableeffectsreportedwere:

Cardiovascular: palpitations;tachycardia;syncopalepisodeswithinitialdoseduetobloodpressuredecrease;

gravitationaloedema;vasodilatation(flush,sensationofwarmth,erythromelalgia);hypotension

CNS: headache;dizziness;asthenia;lethargy;vertigo

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Digestivesystem: alteredbowelhabit;nausea;feelingofrepletion;gingivalhyperplasiawhichusuallyregresseson

withdrawaloftherapy;disturbancesofliverfunctionsuchasincreasedtransaminaseorintra-

hepaticcholestasis;rarecasesofhypersensitivity-typejaundicehavebeenreported

Metabolic: initialhyperglycaemia

Skin: pruritus;urticaria;exanthema;erythema;exfoliativedermatitisandphotosensitivedermatitis;

gynaecomastiainoldermenonlongtermtherapy,whichusuallyregressesonwithdrawalof

therapy

Hypersensitivity: systemicallergicreactions

Musculo-skeletal: myalgia

Respiratory: dyspnoea

Specialsenses: visualdisturbances

Urogenital: increasedfrequencyofmicturition;impotencemayoccurrarely

Haemicandlymphaticsystem:purpura;agranulocytosis

Aswithothersustainedreleasedihydropyridines,exacerbationofanginapectorismayoccurrarelyatthestartof

treatmentwithsustainedreleaseformulationsofnifedipine.Theoccurrenceofmyocardialinfarctionhasbeendescribed

althoughitisnotpossibletodistinguishsuchaneventfromthenaturalcourseofischaemicheartdisease.

4.9Overdose

Clinicaleffects

Asfarastreatmentisconcerned,eliminationofactivesubstancesandtherestorationofstablecardiovascularconditions

havepriority.

Thesymptomsofoverdosagemayincludebradycardia,hypotension,hypoglycaemia,acutecardiacinsufficiencyand

bronchospasm.

Thesesignsmaynotbefullymanifesteduntilseveralhoursafteringestion.

Treatment

Generaltreatmentshouldincludeclosesupervision,treatmentinanintensivecareward,theuseofgastriclavage,

activatedcharcoalandalaxativetopreventabsorptionofanydrugstillpresentinthegastrointestinaltract,theuseof

plasmaandplasmasubstitutestotreathypotensionandshock.

Excessivebradycardiacanbecounteredwithatropine1-2mgintravenously.Ifnecessary,thismaybefollowedbya

bolusdoseofglucagon10mgintravenously.Ifrequired,thismayberepeatedorfollowedbyanintravenousinfusion

ofglucagon1-10mg/hourdependingonresponse.Intravenouscalciumgluconatecombinedwithmetaraminolmaybe

beneficialforhypotensioninducedbynifedipine.Ifnoresponsetoglucagonoccursorifglucagonisunavailable,a

beta-adrenoceptorstimulantsuchasdobutamine2.5–10microgram/kg/minutebyintravenousinfusionmaybegiven.

Dobutamine,duetoitspositiveinotropiceffectscouldalsobeusedtotreathypotensionandacutecardiac

insufficiency.Itislikelythatthesedoseswouldbeinadequatetoreversethecardiaceffectsofbeta-blockadeifalarge

overdosehasbeentaken.Thedoseofdobutamineshouldthereforebeincreasedifnecessarytoachievetherequired

responseaccordingtotheclinicalconditionofthepatient.

Forbronchospasm:inhalationofbeta

–stimulantssuchassalbutamol(2puffs),ororciprenalinesulphate(0.5-1.0mg)

slowlyi.v.Forgeneralisedconvulsions,administrationofdiazepamslowlyintravenouslyisrecommended.

Otherpossibletreatmentsincasesoflife-threateningintoxicationare:

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCcodes:

C08CA55

Selectivecalciumchannelblocker(Dihydropyridinederivative)withmainlyvasculareffects.

Nifedipine,combinations.

C07FB03

Betablockingagents,selective,andotherantihypertensives.

Atenololwithotherantihypertensives

Atenololisclassifiedasabeta

-selective(cardioselective)beta-adrenoceptorantagonistwithnomembrane-stabilising

activityandnopartialagonistactivity.Itisclearlythemosthydrophilicofthecurrentlyavailablebeta-blockers,and

thusdemonstratespoorpenetrationofcellmembranelipids.Atenololhasmarkednegativeinotropicandchronotropic

effects,therebyreducingcardiacoutput,myocardialoxygendemand,andbloodpressure,particularlyduringexercise.

Nifedipineisacalciumantagonistofthe1,4-dihydropyridinetype.Calciumantagonistsreducethetransmembrane

influxofcalciumionsthroughtheL-typecalciumchannelsintothecell.Nifedipineactsparticularlyonthecellsofthe

myocardiumandthesmoothmusclecellsofthecoronaryarteriesandtheperipheralresistancevessels.

Thefixedcombinationofnifedipine20mgandatenolol50mgisdesignedfortheantihypertensivetreatmentofpatients

whosebloodpressureisinadequatelycontrolledonmonotherapy.Thiscombinationofacardioselective,hydrophilic

beta

-adrenoceptorantagonist(atenolol),andapotent,specificcalciumantagonist(nifedipine)lowersbloodpressuretoa

greaterextentthaneitherofitsindividualcomponents.

Nifedipine’stendencytoincreaseheartrateandplasmareninactivityiscounteractedbybeta-adrenoceptorblockade,

whilethetendencyofatenololtoincreaseperipheralresistanceiscounterbalancedbythevasodilatationandreflex

increaseinsympathetictoneinducedbythecalciumantagonist.

Thereisnoevidenceofclinicallysignificantnegativeinotropic,dromotropicorchronotropiceffectswiththecombined

useofnifedipineandatenololinmancomparedwithtreatmentwithatenololalone.Similarly,thechronicrenal

pharmacodynamiceffectsofthefixedcombinationarenotdissimilartotheuseofatenololalone.

5.2Pharmacokineticproperties

Thefixedcombinationofnifedipine20mg(slowrelease)andatenolol50mgisbioequivalenttoitsindividualdrug

components,andthereisnoevidenceofpharmacokineticinteractionbetweenthetwodrugs.

Intheelderly,thehalflifeofnifedipinealoneisincreasedfromapproximately5½hoursto9hours,butpeakplasma

levelsareunchanged.

Thepharmacokineticsofatenolol50mgwhendosedinfreecombinationwithnifedipine20mg(slowrelease)inthe

elderlywereconsistentwiththepublishedatenololexperienceindemonstratinganapproximately45%increasein

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5.3Preclinicalsafetydata

Therearenopreclinicaldataofrelevancetotheprescriberwhichareadditionaltothosealreadyincludedinother

sectionsoftheSummaryofProductCharacteristics.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Nifedipinetablets:

Microcrystallinecellulose(E460)

Maizestarch

Lactosemonohydrate

Polysorbate80(E433)

Magnesiumstearate(E572)

Hypromellose(E464)

Macrogol4000

Titaniumdioxide(E171)

Redironoxide(E172)

Atenololgranules:

Magnesiumcarbonate,heavy

Maizestarch

Sodiumlaurilsulfate

Gelatin

Magnesiumstearate(E572)

Capsuleshell:

Redironoxide(E172)

Titaniumdioxide(E171)

Gelatin

Printingink:

Shellacglaze

Titaniumdioxide(E171)

Propyleneglycol(E1520)

Simethicone

6.2Incompatibilities

Notapplicable.

6.3Shelflife

BlisterpackscomposedofPVC/PVDCfoilbackedwithaluminiumfoil:3years.

Irish Medicines Board

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Date Printed 28/10/2011 CRN 2107332 page number: 10

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

BlisterpackscomposedofPPfoil,backedwithaluminiumfoil,eachcontaining28capsules.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

BayerLimited

TheAtrium

BlackthornRoad

Dublin18

8MARKETINGAUTHORISATIONNUMBER

PA1410/26/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:3 rd

October1988

Dateoflastrenewal:3 rd

October2008

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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Date Printed 28/10/2011 CRN 2107332 page number: 11