ADALAT RETARD 20 MG PROLONGED-RELEASE FILM-COATED TABLETS

Main information

  • Trade name:
  • ADALAT RETARD 20 MG PROLONGED-RELEASE FILM-COATED TABLETS
  • Dosage:
  • 20 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ADALAT RETARD 20 MG PROLONGED-RELEASE FILM-COATED TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/012/003E
  • Authorization date:
  • 12-08-1987
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AdalatRetard20mgProlonged-ReleaseFilm-CoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coated,prolongedreleasetabletcontains20mgnifedipine.

Excipient:Lactose

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Prolongedrelease,film-coatedtablet

ProductimportedfromtheUK:

Pink-greycirculartabletsimpressedwith‘IU’ononefaceandtheBayercrossonthereverse.

ProductimportedfromSpain:

Pink-greycirculartabletswith‘A20’embossedononefaceandtheBayercrossonthereverse.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Chronicstableangina

Mildtomoderatehypertension

4.2Posologyandmethodofadministration

TherecommendedstartingdoseofAdalatretard10mgand20mgis10mgevery12hoursswallowedwithwaterwith

subsequenttitrationofdosageaccordingtoresponse.Thedosemaybeadjustedto40mgevery12hours.

Thepharmacokineticsofnifedipinearealteredintheelderlysothatlowermaintenancedosesofnifedipinemaybe

requiredcomparedtoyoungerpatients.

Nifedipineismetabolisedprimarilybytheliverandthereforepatientswithliverdysfunctionshouldbecarefully

monitored.

Patientswithrenalimpairmentshouldnotrequireadjustmentofdosage.

Treatmentmaybecontinuedindefinitely.

Nifedipineisnotrecommendedforuseinchildren.

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4.3Contraindications

Adalatretard20mgshouldnotbeadministeredtopatientswithknownhypersensitivitytonifedipineorother

dihydropyridinesbecauseofthetheoreticalriskofcross-reactivity.

Adalatretard20mgshouldnotbeadministeredtowomencapableofchild-bearingortonursingmothers.

Adalatretard20mgshouldnotbeusedincardiogenicshock,clinicallysignificantaorticstenosis,unstableangina

pectoris,orduringorwithinonemonthofamyocardialinfarction.

Adalatretard20mgshouldnotbeusedforthetreatmentofacuteattacksofangina.

ThesafetyofAdalatretard20mginmalignanthypertensionhasnotbeenestablished.

Adalatretard20mgshouldnotbeusedforsecondarypreventionofmyocardialinfarction.

Adalatretard20mgshouldnotbeadministeredconcomitantlywithrifampicinsinceeffectiveplasmalevelsof

nifedipinemaynotbeachievedowingtoenzymeinduction(seeSection4.5)

4.4Specialwarningsandprecautionsforuse

Adalatretard20mgisnotabeta-blockerandthereforegivesnoprotectionagainstthedangersofabruptbeta-blocker

withdrawal;anysuchwithdrawalshouldbeagradualreductionofthedoseofbeta-blockerpreferablyover8-10days.

Adalatretard20mgmaybeusedincombinationwithbeta-blockingdrugsandotherantihypertensionagentsbutthe

possiblyofanadditiveeffectsresultinginposturalhypotensionshouldbeborneinmind.Adalatretard20mgwillnot

preventpossiblereboundeffectsaftercessationofotheranthihypertensivetherapy.

Adalatretard20mgshouldbeusedwithcautioninpatientswhosecardiacreserveispoor.Deteriorationofheart

failurehasoccasionallybeenobservedwithnifedipine.

Cautionshouldbeexercisedinpatientswithseverehypotension.

Ischaemicpainhasbeenreportedinasmallproportionofpatientswithinonetofourhoursoftheintroductionof

Adalatretard20mgtherapy.Althougha“steal”effecthasnotbeendemonstrated,patientsexperiencingthiseffect

shoulddiscontinueAdalatretard20mg.

DiabeticpatientstakingAdalatretard20mgmayrequireadjustmentoftheircontrol.

Indialysispatientswithmalignanthypertensionandhypovolaemia,amarkeddecreaseinbloodpressurecanoccur.

Whilstnifedipineiscontra-indicatedinpregnancy,particularcaremustbeexercisedwhenadministeringnifedipinein

combinationwithi.v.magnesiumsulphatetopregnantwomen.

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

nelfinavir,ritonavirandsaquinavirmaytheoreticallyresultinanincreaseinnifedipineplasmaconcentrations.Upon

co-administrationwithanyofthesecytochromeP4503A4inhibitors,bloodpressureshouldbemonitoredand,if

necessary,areductioninthenifedipinedoseconsidered(seeSection4.5)

Thisproductincludeslactose:Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactase

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

KnownInteractions

Aswithotherdihydropyridines,nifedipineshouldnotbetakenwithgrapefruitjuicebecausebioavailabilityis

increased.

TheantihypertensiveeffectofAdalatretard10mgand20mgmaybepotentiatedbysimultaneousadministrationof

cimetidine.

Whenusedincombinationwithnifedipine,serumquinidinelevelshavebeenshowntobesuppressedregardlessof

dosageofquinidine.

Thesimultaneousadministrationofnifedipineanddigoxinmayleadtoreduceddigoxinclearanceandhencean

increaseintheplasmadigoxinlevel.Plasmadigoxinlevelsshouldbemonitoredand,ifnecessary,thedigoxindose

reduced.

PhenytoininducesthecytochromeP4503A4system.Uponco-administrationwithphenytoin,thebioavailabilityof

nifedipineisreducedandthusitsefficacyweakened.Whenbothdrugsareconcomitantlyadministered,theclinical

responsetonifedipineshouldbemonitoredand,ifnecessary,anincreaseofthenifedipinedose,considered.Ifthedose

ofnifedipineisincreasedduringco-administrationofbothdrugs,areductionofthenifedipinedoseshouldbe

consideredwhenthetreatmentwithphenytoinisdiscontinued.

Diltiazemdecreasestheclearanceofnifedipineandhenceincreasesplasmanifedipinelevels.Therefore,cautionshould

betakenwhenbothdrugsareusedincombinationandareductionofthenifedipinedosemaybenecessary.

Nifedipinemayincreasethespetrophotometricvaluesofurinaryvanillymandelicacidfalsely.However,HPLC

measuresareunaffected.

Adalatretard10mgand20mgshouldbeadministeredconcomitantlywithrifampicinsinceeffectiveplasmalevelsof

nifedipinemaynotbeachievedowingtoenzymeinduction(seeSection4.3).

Stimultaneousadministrationofcisaprideandnifedipineorquinupristin/dalfopristinandnifedipinemayleadto

increasedplasmaconcentrationsofnifedipine.Consequently,thebloodpressureshouldbemonitoredand,if

necessary,thenifedipinedosereduced.

TheoreticalInteractions

NifedipineismetabolizedviathecytochromeP4503A4systemand,therefore,therearetheoreticalinteractionsfor

drugswhichareknowntoinhibitthisenzymesystem(e.g.erythromycin,ketoconazole,itraconazole,fluconazole,

fluoxetine,indinavir,nelfinavir,ritonavirandsaquinavir).Althoughnoformalinvivointeractionstudieshavebeen

performedwiththesedrugs,co-administrationwithnifedipinehasbeenshowninvitrotoincreasenifedipineplasma

concentrations.

Bloodpressureshouldthereforebemonitoredand,ifnecessary,areductioninthenifedipinedoseconsidered(see

Section4.4).

TacrolimushasbeenshowntobemetabolizedviathecytochromeP4503A4system.Uponco-administrationofboth

drugs,thetacrolimusplasmaconcentrationsshouldbemonitoredand,ifnecessary,areductioninthetacrolimusdose

considered.

Aclinicalstudyinvestigatingthepotentialofadruginteractionbetweennifedipineandnefazodonehasnotyetbeen

performed.

NefazodoneisknowntoinhibitthecytochromeP4503A4mediatedmetabolismofotherdrugs.Thereforeanincrease

innifedipineplasmaconcentrationsuponco-administrationofbothdrugscannotbeexcluded.Whennefazodoneis

giventogetherwithnifedipine,thebloodpressureshouldbemonitoredand,ifnecessary,areductioninthenifedipine

doseconsidered.

Althoughnoformalinteractionstudieshavebeenperformedbetweennifedipineandcarbamazipine,phenobarbitoneor

valproicacid,thesedrugshavebeenshowntoaltertheplasmaconcentrationsofastructurallysimilarcalciumchannel

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Drugsshownnottointeractwithnifedipine

Thefollowingdrugshavebeenshowntohavenoeffectonthepharmacokineticsofnifedipinewhenadministered

concomitantly:ajmaline,aspirin,benazepril,candesartancilexetil,debrisoquine,doxazosin,irbesartan,omeprazole,

orlistat,pantoprazole,ranitidine,rosiglitazone,talinololandtriamterenehydrochlorothiazide.

4.6Fertility,pregnancyandlactation

Adalatretard20mgarecontra-indicatedinwomencapableofchild-bearing.

ThesafetyofAdalatretard20mgforuseinhumanpregnancyhasnotbeenestablished.Evaluationofexperimental

animalstudieshasshownreproductivetoxicityconsistingofembryotoxicityandteratogeniceffectsatmaternallytoxic

doses.

Adalatretard20mgarecontra-indicatedinnursingmothers,asnifedipinemaybepresentinbreastmilk.

Insinglecasesofinvitrofertilisationcalciumantagonistslikenifedipinehavebeenassociatedwithreversible

biochemicalchangesinthespermatozoa’sheadsectionthatmayresultinimpairedspermfunction.Inthosemenwho

arerepeatedlyunsuccessfulinfatheringachildbyinvitrofertilisation,andwherenootherexplanationcanbefound,

calciumantagonistslikenifedipineshouldbeconsideredaspossiblecauses.

4.7Effectsonabilitytodriveandusemachines

Reactionstothedrug,whichvaryinintensityfromindividualtoindividual,mayimpairtheabilitytodriveorto

operatemachinery.Thisappliesparticularlyatthestartoftreatment,onchangingthemedicationandincombination

withalcohol.

4.8Undesirableeffects

Mostundesirableeffectsareconsequencesofthevasodilatoryeffectsofnifedipineandusuallyregressupon

withdrawaloftherapy.

Inallclinicalstudies(n=7243),thefollowingundesirableeffectswerecommonlyreported(>1%<10%incidence):

headache,vasodilatationandpalpitationswhichoccurmostfrequentlyintheearlystagesoftreatment,nausea,

dizziness,lethargy,oedemaandperipheraloedemanotassociatedwithheartfailureorweightgain.

Additionally,uncommonandrareundesirableeffectswerealsoreported:

Uncommon(>0.1%<1%)

Bodyasawhole: Abdominalpain;chestpain;malaise;pain

Cardiovascular: Posturalhypotension;syncope;tachycardia

Digestive: Constipation;diarrhoea;drymouth;dyspepsia;vomiting

Musculo-skeletal: Arthralgia;myalgia

Nervous: Insomnia;nervousness;paraesthesia;somnolence;tremor;vertigo

Respiratory: Dyspnoea

Skin: Pruritus;rash;skindisorder;sweating

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Aswithothersustainedreleasedihydropyridines,exacerbationofanginapectorismayoccuratthestartoftreatment

withsustainedreleaseformulationsofnifedipine.Theoccurrenceofmyocardialinfarctionhasbeendescribedalthough

itisnotpossibletodistinguishsuchaneventfromthenaturalcourseofischaemicheartdisease.

Rare(>0.01%<0.1%)

Bodyasawhole: Enlargedabdomen;allergicreaction;photosensitivityreactions;hypersensitivity-typejaundice.

Cardiovascular: Hypotension

Digestive: Flatulence;gastrointestinaldisorder;GGTPincrease;liverfunctiontestabnormalities.

Haemicand

Lymphaticsystem: Purpura.

Nervous: Hyperaesthesia;moodchanges

Skin: Urticaria

Specialsenses: Abnormalvision;ambylopia

Urogenital: Impotence

Forspontaneousreports(n=1841)thefollowingundesirableeffectswerereportedveryrarelyworldwide(<0.01%):

gingivalhyperplasia,agranulocytosis,erythromelalgia,exfoliativedermatitisandanaphylacticreaction.Therehave

alsobeenreportsofgynaecomastiainoldermenonlong-termtherapy,butthisusuallyregressesuponwithdrawalof

therapy.

4.9Overdose

Clinicaleffects

Reportsofnifedipineoverdosagesarelimitedandsymptomsarenotnecessarilydose-related.Severehypotensiondue

tovasodilatation,andtachycardiaorbradycardiaarethemostlikelymanifestationsofoverdose.

Metabolicdisturbancesincludehyperglycaemia,metabolicacidosisandhypo-orhyperkalaemia.

Cardiaceffectsmayincludeheartblock,AVdissociationandasystole,andcardiogenicshockwithpulmonaryoedema.

Othertoxiceffectsincludenausea,vomiting,drowsiness,dizziness,confusion,lethargy,flushing,hypoxiaand

unconsciousnesstothepointofcoma.

Treatment

Asfarastreatmentisconcerned,eliminationofnifedipineandtherestorationofstablecardiovascularconditionshave

priority.

Afteroralingestion,gastriclavageisindicated,ifnecessaryincombinationwithirrigationofthesmallintestine.

Ipecacuanhashouldbegiventochildren.

Eliminationmustbeascompleteaspossible,includingthesmallintestine,topreventtheotherwiseinevitable

subsequentabsorptionoftheactivesubstance.

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Bloodpressure,ECG,centralarterialpressure,pulmonarywedgepressure,ureaandelectrolytesshouldbemonitored.

Hypotensionasaresultofcardiogenicshockandarterialvasodilatationshouldbetreatedwithelevationofthefeetand

plasmaexpanders.Ifthesemeasuresareineffective,hypotensionmaybetreatedwith10%calciumgluconate10-20ml

intravenouslyover5-10minutes.Iftheeffectsareinadequate,thetreatmentcanbecontinued,withECGmonitoring.

Inaddition,beta-symathomimeticsmaybegiven,e.g.isoprenaline0.2mgslowlyi.v.orasacontinuousinfusionof5

µg/min.Ifaninsufficientincreaseinbloodpressureisachievedwithcalciumandisoprenaline,vasoconstricting

sympathomimeticssuchasdopamineornoradrenalineshouldbeadministered.Thedosageofthesedrugsshouldbe

determinedbythepatient’sresponse.

Bradycardiamaybetreatedwithatropine,beta-sympathomimeticsoratemporarycardiacpacemaker,asrequired.

Additionalfluidsshouldbeadministeredwithcautiontoavoidcardiacoverload.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCcode:C08CA05

SelectiveCalciumchannelblocker(Dihydropyridinederivative)withmainlyvasculareffects.

Nifedipineisaspecificandpotentcalciumantagonist.Inhypertension,themainactionofAdalatretard10mgand20

mgistocauseperipheralvasodilatationandthusreduceperipheralresistance.

Inangina,theAdalatretard10mgand20mgreducesperipheralandcoronaryvascularresistance,leadingtoan

increaseincoronarybloodflow,cardiacoutputandstrokevolume,whilstdecreasingafter-load.

Additionally,nifedipinedilatessubmaximallybothclearandatheroscleroticcoronaryarteries,thusprotectingtheheart

againstcoronaryarteryspasmandimprovingperfusiontotheischaemicmyocardium.

NifedipinereducesthefrequencyofpainfulattacksandtheischaemicECGchangesirrespectiveoftherelation

contributionfromcoronaryarteryspasmoratherosclerosis.

Adalatretard10mgand20mgadministeredtwice-dailyprovide24-hourcontrolofraisedbloodpressure.Adalat

retard10mgand20mgcausereductioninbloodpressuresuchthatthepercentageloweringisdirectlyrelatedtoits

initiallevel.Innormotensiveindividuals,Adalatretardtabletshavelittleornoeffectonbloodpressure.

5.2Pharmacokineticproperties

Nifedipineisabsorbedalmostcompletelyfromthegastro-intestinaltractregardlessoftheoralformulationusedand

undergoesextensivemetabolisminthelivertoinactivemetabolites,withlessthan1%oftheparentdrugappearing

unchangedintheurine.

Therateofabsorptiondeterminesthedrug’sapparentelimination.

Theapparenteliminationphasehalf-lifefortheAdalatretardtablethasbeenestimatedas6–18hours.

Afterenteralorintravenousdoses,70-80%ofactivityiseliminated(primarilyasmetabolites)viatheurine.Remaining

excretionisviathefaeces.

After24hours,90%oftheadministereddoseiseliminated.

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5.3Preclinicalsafetydata

Reproductiontoxicology

Nifedipineadministrationhasbeenassociatedwithavarietyofembryotoxic,placentotoxicandfoetotoxiceffectsin

rats,miceandrabbits.Allofthedosesassociatedwiththeteratogenic,embryotoxicorfoetotoxiceffectsinanimals

werematernallytoxicandseveraltimestherecommendedmaximumdoseforhumans.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose(E460)

Polysorbate80

Hypromellose

Lactose

Maizestarch

Macrogol

Magnesiumstearate

Titaniumdioxide(E171)

Ironoxide(E172)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelflifeexpirydateforthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25 o

Storeintheoriginalcontainer.

6.5Natureandcontentsofcontainer

Blisterpacksof56or60tabletscontainedinanoutercardboardcarton.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

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8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA0465/012/003

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 12 th

August1987

Dateoflastrenewal: 12 th

August2007

10DATEOFREVISIONOFTHETEXT

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