CARDILATE XL 40MG

Main information

  • Trade name:
  • CARDILATE XL 40MG
  • Dosage:
  • 40 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CARDILATE XL 40MG
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0282/070/003
  • Authorization date:
  • 27-07-1998
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0282/070/003

CaseNo:2069219

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

NortonHealthcareLimitedT/AIVAXPharmaceuticalsUK

RegentHouse,5-7BroadhurstGardens,SwissCottage,LondonNW63RZ,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

CardilateXL40mgProlonged-ReleaseTablet.

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom08/09/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CardilateXL40mgProlonged-ReleaseTablet.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

EachProlonged-ReleaseTabletcontains40mgNifedipine

Excipients:Eachtabletcontains30.0glactose

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Prolonged-ReleaseTablet.

Red-brownish,round,biconvexfilm-coatedtablets.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofmildtomoderatehypertension.

4.2Posologyandmethodofadministration

Adults:

Patientsshouldbetreatedindividuallydependingontheseverityofthediseaseandthetherapeuticresponse.The

followingrecommendationsfordosinginadultsandadolescentsover14yearsareapplicable:

TherecommendedstartingdoseisoneCardilateXLTabletevery24hours.Ifnecessarythisdosecanbeincreasedto

80mg(twotablets)every24hours.

Themodifiedreleasetabletsaretobetakenaftermeals,e.g.breakfast,withsomeliquid.Themodifiedreleasetablets

shouldbeswallowedwholewithhalfaglassofwater,andmustnotbebrokenorchewed.Nifedipineshouldnotbe

takenwithgrapefruitjuice(seeSection4.5,Interactionwithothermedicinalproductsandotherformsofinteraction).

ElderlyHepaticandRenalImpairment:

Thepharmacokineticsofnifedipinearealteredintheelderlysothatlowermaintenancedosesofnifedipinemaybe

requiredcomparedtoyoungerpatients.

Nifedipineisprimarilymetabolisedintheliverandthereforepatientswithliverdysfunctionshouldbecarefully

monitored.

Treatmentshouldbecommencedatadoseof5mgto10mgnifedipinetwicedailywithcarefulmonitoringofblood

levelstodeterminetheappropriatedoseregimen.Patientswithrenalimpairmentshouldnotrequireadjustmentof

dosage.

Children:

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4.3Contraindications

CardilateXLshouldnotbeadministeredtopatientswithanallergytonifedipineorothertabletconstituents,norto

patientswithcardiogenicshock.

CardilateXLiscontra-indicatedinwomenwithchild-bearingpotentialandthosebreast-feedingtheirbabies.

CardilateXLiscontra-indicatedinpatientswithclinicallysignificantaorticstenosis,unstableanginaorwithporphyria.

Efficacyandsafetyinmalignanthypertensionhasnotbeenestablished.

CardilateXLshouldnotbeusedforthetreatmentofacuteattacksofanginaorwithinonemonthofamyocardial

infarctorforthesecondarypreventionofmyocardialinfarction.

4.4Specialwarningsandprecautionsforuse

CardilateXLshouldonlybeadministeredtopatientswithlowcardiacreserveorwithseverehypotensionwith

caution.Patientsatriskofhypotensivecrisisshouldbeginanytherapyunderclosemedicalsupervision.

Inpatientsonhaemodialysiswithmalignanthypertensionandirreversiblerenalfailurewithhypovolaemia,nifedipine

shouldbegivenwithcaution.Anexaggeratedfallinbloodpressureduetovasodilationmayoccur.

Ischaemicpainhasbeenreportedinasmallproportionofpatientsfollowingtheintroductionofnifedipinetherapy.

Althougha‘steal’effecthasnotbeendemonstrated,patientsexperiencingthiseffectshoulddiscontinuenifedipine

therapy.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

CardilateXLcanbeadministeredconcomitantlywithotherantihypertensivesincludingbeta-receptorblockers.These

mayhaveadditiveantihypertensiveorpotentiatingeffectsandposturalhypotensionmaythereforeoccur.Concomitant

treatmentofnifedipinewithabeta-blockeroccasionallyresultsintheoccurrenceofheartfailure.Forthisreasona

combinationwithabeta-blockerisonlyrecommendedinpatientswithasufficientventricularfunction.After

discontinuationofthebeta-blockeradeteriorationwithregardtothesymptomsofanginapectorismayoccasionally

occur,duetotheabruptwithdrawalofthebeta-blocker.Therefore,itisnotrecommendedtoswitchabruptlyfroma

beta-blockertonifedipine.

CardilateXLwillnotpreventthepossibilitythattheremightbeareboundeffectwhenotherantihypertensivetreatment

isstopped.

Concomitanttherapywithcimetidinemaypotentiatetheantihypertensiveactionofnifedipine. Nifedipine

administrationmaysuppressserumlevelsofquinidine.Therefore,oncombinationtherapymonitoringofquinidine

levelsisrecommended.InitialreportsthatNifedipinemaycauseanincreaseinplasmadigoxinlevelsduetoreduced

renaldrugclearanceareunsupported.

CardilateXLmaymodifyinsulinandglucoseresponses,requiringadjustmentintherapyoftreateddiabetes.

CardilateXLshouldnotbeadministeredconcomitantlywithrifampicinaseffectiveplasmalevelsofnifedipinemay

notbeachievedowingtoenzymeinduction.

CardilateXLshouldnotbetakenwithgrapefruitjuiceasitsmetabolismmaybeinhibited.

4.6Pregnancyandlactation

CardilateXLiscontra-indicatedinpregnantwomenandwomenofchild-bearingpotentialbecausefoetalrisks,

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Nifedipineissecretedintobreastmilk,soCardilateXLshouldnotbeadministeredduringlactation.

4.7Effectsonabilitytodriveandusemachines

Nifedipinemaycauseheadache,dizziness,nauseaandtirednesstosuchadegreethatreactiontimeisaffected.These

effectscanbeaggravatedbyconcurrentalcohol.Ifthisoccurs,thepatientshouldbeadvisednottodriveoroperate

machines.

4.8Undesirableeffects

Undesirableeffects,usuallymildandtransientinnature,mayoccurandaremorefrequentatthebeginningoftherapy.

Frequently,headache,flush(facialreddening),dizziness,aswellasoedema,duetovasodilation,mayoccur.Less

commonsideeffectsincluderash,nausea,lethargyandurinaryfrequency.Inrarecases,inacutestudies,atransient

increaseinglucosehasbeenobserved.Thisshouldbeconsideredparticularlyinpatientswithdiabetesmellitus.

Nifedipinehasnodiabetogeniceffect.Rarelygingivalhyperplasiahasbeenobservedwhichwasreversibleafter

discontinuationoftherapy.Inelderlypatients,veryrarelyagynaecomastiahasbeenobservedwhichwasreversible

afterdiscontinuationoftherapy.

Additionally,uncommonandrareundesirableeffectswerealsoreported:

Thefollowingundesirableeffectswerereportedveryrarelyworldwide(>0.01%):gingivalhyperplasis,

agranulocytosis,erythromelalgia,exfoliativedermatitisandanaphylacticreaction.Therehasalsobeenreportsof

Uncommon(>0.1%<1%)

Bodyasawhole: Abdominalpain;chestpain:malaise;pain

Cardiovascular: Posturalhypotension:syncope;tachycardia

Digestive: Constipation, diarrhoea, dry mouth,

Dyspepsia,vomiting

Musculo-sketal: Arthralgia:myalgia

Nervous: Insomnia:nervousness:paraesthesia;Somnolence;

tremor;vertigo

Respiratory; Dyspnoea

Skin; Pruritus;rashskindisorder;sweating

Urogenitalsystem: Nocturia;polyuria

Exacerbationofanginapectorismayoccurattheinitialstageoftreatmentwithsustainedreleaseformulations

ofnifedipine.

Rare(>0.01%<0.1%)

Bodyasawhole: Enlarged abdomen; allergic reaction;

Photosensitivity reactions; hypersensitivity-type

jaundice

Cardiovascular: Hypotension

Digestive: Flatulence; gastrointestinal disorder; GGTP

increase;liverfunctiontestabnormalities.

HaemicandPurpura Lymphaticsystem;

Nervous; Hyperaesthesia;moodchanges

Skin; Urticaria

Specialsenses; Abnormalvision,ambylopia

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Casesofhypersensitivitytonifedipineresultinginjaundicehavebeenreported.

Listofundesirableeffectstobodysystem:

CardiovascularSystem:

Tachycardia,hypotension.Exacerbationofanginapectorismayoccuratthestartoftreatmentwithsustainedrelease

formulationsofnifedipine.Theoccurrenceofmyocardialinfarctionhasbeendescribed,althoughitisnotpossibleto

distinguishsuchaneventfromthenaturalcourseofischaemicheartdisease.

CentralNervousSystem:

Dizziness,tiredness,parasthesia,tremor.

Eyes:

Transientchangeinopticalperception.

Gastro-IntestinalTract:

Nausea,disturbances.

Skin:

Redness,itching,urticaria,exanthema,andexceptionallyexfoliativedermatitis.

UrinaryTract:

Anincreaseinthedailyamountofurinesothatnocturiamayoccur.

Legs:

Myalgia.

Liver:

Veryrarelyliverfunctiondisturbances(intrahepaticcholestatis,orincreasesintransaminases)haveoccurredwhich

werereversibleafterdiscontinuationoftherapy.

Miscellaneous:

Gingivalhyperplasia,gynaecomastia,increaseinglucoseinparticularinpatientswithdiabetesmellitus.

4.9Overdose

Toxiceffectsarisefromthethreemainactionsofnifedipineinoverdose:dilatationofvascularsmoothmuscles

(predominanteffect);decreasedmyocardialcontractility;anddepressionofAVnodalconduction.Hypotensionand

tachycardiaorbradycardiaarethemostlikelymanifestationsofoverdose.Othertoxiceffectsincludenausea,

vomiting,drowsiness,dizziness,confusion,lethargy,flushing,comaandconvulsions.Cardiaceffectsmayinclude

heartblock,AVdissociationandasystole;metabolicdisturbancesincludehyperglycaemia,acidosis,hypo-or

hyperkalaemiaandhypocalcaemia;pulmonaryoedemahasbeenreported.

Primarytreatmentinvolvesremovalofnifedipinebygastriclavageoripecacuanhaandadministrationofactivated

charcoal(50gadults;10-15gchildren).CardilateXLisamodifiedreleasematrixtablet,thereforeactivatedcharcoal

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Thepatientshouldbecloselymonitoredandtreatedaccordingtopredominantsigns:

Hypotension:thefeetshouldberaisedandplasmaexpandersgiven.Ifthisisnoteffective,10%calciumgluconateor

chloridecanbegivenintravenously(calciumchlorideshouldnotbegiventoacidoticpatients).Ifthisfails,dopamine

maybetried(largedosesmaybeneeded).Glucagonmayalsobeofvalue;

Bradycardia:treatmentwithatropine,isoprenalineandcardiacpacingshouldbegivenasrequired.

Thevalueofextracorporealmethodsofremovalofnifedipinehavenotbeenestablished.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

NifedipineisaCa-antagonistofthe1,4,-dihydropyridinetype.Ca-antagonistsinhibittheslowCa-channelfluxintothe

myocardialcells,thesmoothmusclecellsofthecoronaryarteriesandtheperipheralcapillaries.Nifedipinebrings

aboutasubstantialimprovementintheoxygensupplyofthemyocardiumwhilereducingoxygendemand.Ithasbeen

showntoexhibitanti-anginalproperties.Highbloodpressureisnormalisedduetoareductionintheperipheral

resistance(vasodilation).

5.2Pharmacokineticproperties

Absorption:CardilateXLisabsorbedrapidlyandalmostcompletelyfollowingoraladministration.CardilateXL

reachesmaximalconcentrations(29.4±12.0ng/ml)approximately5hoursafterdrugintakeatsteadystate.

ThereleaseofnifedipinefromtheCardilateXLmodifiedreleasetabletisalmostlinear,thismeansthatthedrugis

deliveredataconstantrate.

Therelativebioavailabilityofthemodifiedreleaseformcomparedtotheslowreleaseformsofnifedipineisnot

statisticallydifferentinsteadystate.

TroughlevelsafterCardilateXL(24hpost-dose)insteadystate(12.0+/-6.5ng/ml)areachievedafterthefirstdose.

Basedonitspharmacokineticprofile,aneffectduetoCardilateXLisexpectedover24hours.

Concomitantintakeoffoodresultsinhighermaximumplasmaconcentrationsofnifedipine,whichoccursearlier

comparedtoadministrationinfastedstate,buttheconcentrationsattheendofthedoseintervalaresimilar.

Distribution:TheproteinbindingofNifedipineamountsto94-99%.Animalstudieswithlabellednifedipinehave

shownthatdistributionofthefractionnotproteinboundisthroughoutallorgansandtissues,withhigher

concentrationsinmyocardiumthaninskeletalmuscle.Neithernifedipinenoritsmetabolitesarestoredselectivelyin

anytissue.

Metabolism:Nifedipineisalmostcompletelymetabolisedtoinactivemetabolites.

Elimination:Anapparenthalf-lifeof14.9+/-6.0hourswasfound.Theapparenthalf-lifeofCardilateXLdidnot

changeafterrepeateddosing.Only<1%ofthedoseisexcretedintheurineastheparentcompound.70-80%ofthe

doseisexcretedintheurineasmetabolites.Theremainderisexcretedasmetabolitesinthefaeces.Eliminationmay

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5.3Preclinicalsafetydata

Studiesinmice,ratsandrabbitsdemonstratedalowintraperitoneal,subcutaneousandoralacutetoxicity.No

significantsensibilitywasdetected:LD

inmicep.o.wasfoundtobe421-572mg/kg,inratsp.o.950-1087mg/kg,in

rabbitsp.o.250-500mg/kg,incatsp.o.100mg/kg.Toxicsymptomswererapidlyandcompletelyreversiblein

survivinganimals.Nomajordifferenceshavebeenobservedbetweenmaleandfemaleanimals.

Subacute,Subchronicandchronicoraltoxicitystudiesinratsdemonstratedalowtoxicityofhighdosesofnifedipine.

Withtheexceptionofadose-dependentincreaseinheartandliverweightsandphospholipidsinthesubchronicstudy,a

no-effectdosehasbeenevaluatedtobeequivalentto75timesthehumantherapeuticdose.Onlydosesof800(1200

HTD)andtosomeextent400mg/kg/day,werefoundtobeclearlytoxic.

Teratogenicitystudiesofnifedipineinratsandrabbitsdemonstratedateratogenicpotentialwhichjustifyittobe

contraindicatedinwomenwhoare,ormaybecomepregnant.

ExtensivemutagenicitystudiesinAmesSalmonellamutagenicitytestingsystemswereallnegative.

Nocarcinogenicpotentialhasoccurredduringthelongclinicalexperiencewiththecompoundandinthenegative

Ames.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore

microcrystallinecellulose

cellulose

hypromellose

lactose

magnesiumstearate

colloidalanhydroussilica

Tabletcoating

Macrogol400

Macrogol6000

ferricoxidered(E172)

titaniumdioxide(E171)

talc

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Fouryears.

6.4Specialprecautionsforstorage

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6.5Natureandcontentsofcontainer

Thermoformedblisterpacksofredtransparent,lightprotectivePVC/PVDC-film/aluminiuminboxesof7,14,21,

28,30,50,56,60,84,90,100,112,and120.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

NortonHealthcareLtd

T/AIVAXPharmaceuticalsUK

RegentHouse

5-7BroadhurstGardens

SwissCottage

London,NW63RZ

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA0282/070/003

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:26July1998

Dateoflastrenewal:26June2008

10DATEOFREVISIONOFTHETEXT

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