FELODIPINE 5 MG, PROLONGED RELEASE TABLETS

Main information

  • Trade name:
  • FELODIPINE 5 MG, PROLONGED RELEASE TABLETS
  • Dosage:
  • 5 Milligram
  • Pharmaceutical form:
  • Tablet Prolonged Release
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FELODIPINE 5 MG, PROLONGED RELEASE TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1363/003/001
  • Authorization date:
  • 24-11-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA1363/003/001

CaseNo:2079004

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

SelanaHealthcareLtd

GaradiceHouse,3-4Fairview,Dublin3

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Felodipine5mg,prolongedreleasetablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom26/05/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 26/05/2010 CRN 2079004 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Felodipine5mg,prolongedreleasetablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachprolongedreleasetabletcontains5mgoffelodipine.

Excipient:Eachprolongedreleasetabletcontains22.75mglactose.

Forafulllistofexcipients,see6.1.

3PHARMACEUTICALFORM

Prolongedreleasetablet

Lightpink,round,biconvex,film-coatedprolongedreleasetabletwithimprint5.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Essentialhypertension.

4.2Posologyandmethodofadministration

Felodipine5mgandFelodipine10mgshouldusuallybeadministeredasfollows:

Therecommendedstartingdoseis5mgfelodipineoncedaily.

Ifnecessarythedosemaybeincreasedto10mgfelodipineoncedailyoranotherantihypertensiveagentadded.Dose

increasesshouldoccuratintervalsofatleast2weeks.Theusualmaintenancedoseis5-10mgoncedaily.

Themaximumdailydoseis10mgfelodipine.

Thedoseshouldbeadjustedtotheindividualrequirementsofthepatient.

Elderly

Therecommendedstartingdoseshouldbeadaptedintheelderly.Subsequentdoseincreasesshouldbeundertakenwith

particularcaution.

Impairedhepaticfunction

Inpatientswithmildtomoderatehepaticimpairment,therecommendedstartingdoseshouldbeloweredtotheminimal

therapeuticeffectivedoseoffelodipine.Thedoseshouldonlybeincreasedaftercarefullybalancingthebenefitsagainst

therisks(see5.2).Itiscontraindicatedinpatientswithseverehepaticimpairment.

Impairedrenalfunction

Thepharmacokineticsarenotsignificantlyaffectedinpatientswithmildtomoderateimpairedrenalfunction.Caution

shouldbetakeninpatientswithsevererenalimpairment(seesections4.4and5.2).

Children

Thesafetyandefficacyoffelodipineinchildrenhasnotbeenestablished.

Administration

Theprolongedreleasetabletsshouldbetakeninthemorningwithasufficientamountoffluid(e.g.aglassofwater,but

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 26/05/2010 CRN 2079004 page number: 2

Theprolongedreleasetabletsshouldbeswallowedwholeandnotchewedorcrushed.

Thetabletsmaybetakenonemptystomachorwithalightmeal;howeverahigh-fatmealshouldbeavoided(see5.2).

4.3Contraindications

Felodipineiscontra-indicatedinpatientswith:

- Hypersensitivitytofelodipine(orotherdihydropyridines)ortoanyoftheexcipients.

Cardiogenicshock.

Severeaorticormitralstenosis.

Obstructivehypertrophiccardiomyopathy.

Unstableanginapectoris.

Acutemyocardialinfarction(within4-8weeksofamyocardialinfarction).

Decompensatedheartfailure.

Severehepaticimpairment.

Pregnancy(seesection4.6).

4.4Specialwarningsandprecautionsforuse

Felodipineshouldbeusedwithcautioninpatientswith:

Conductiondisorders,compensatedheartfailure,tachycardiaandaorticandormitralvalvestenosis.

Mildtomoderatehepaticimpairment,astheanti-hypertensiveeffectmaybeenhanced.Adjustmentofthe

dosageshouldbeconsidered.

Severerenalimpairment(GFR<30ml/min).

AVblockofthesecondorthirddegree.

Iftreatmentwithfelodipineisdiscontinuedabruptly,ahypertensivecrisismayoccurinindividualcases.

Felodipinecouldcausesignificanthypotension(vasodilationeffect)withconsecutivetachycardia,leadingto

myocardialischaemiainsensitivepatients,thereforepredisposedpatientsmaysufferfrommyocardialinfarction(see

section5.1).

Dihydropyridinesmaycauseacutehypotension.Insomecasethereisariskofhypoperfusionaccompaniedbyreflex

tachycardia(paradoxicalangor)(seesection5.1).

FelodipineismetabolisedbyCYP3A4enzymes.Therefore,combinationwithmedicinalproductswhicharepotent

CYP3A4inhibitorsorinducersshouldbeavoided(seesection4.5).Duetothesamereasontheconcomitantintakeof

grapefruitjuiceshouldbeavoided(seesection4.5).

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicinalproduct.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

FelodipineisaCYP3A4substrate.DrugsthatinduceorinhibitCYP3A4willhavelargeinfluenceonfelodipine

concentrations.

Theanti-hypertensiveeffectoffelodipinemaybeenhancedbyotheranti-hypertensivesandtricyclicantidepressants.

TheconcomitantintakeoffelodipineanddrugswhichinhibitthecytochromeP450isoenzyme3A4oftheliver(suchas

cimetidine,azoleantifungals[itraconazole,ketoconazole],macrolideantibiotic[erythromycin]orHIVprotease

inhibitorsleadstoincreasedfelodipineplasmalevels(seesection4.4).Grapefruitjuiceresultsinincreasedpeakplasma

levelsandbioavailabilitypossiblyduetointeractionwithflavonoidsinthefruitjuice.Thereforegrapefruitjuiceshould

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 26/05/2010 CRN 2079004 page number: 3

Concomitanttreatmentwithdrugssuchascarbamazepine,phenytoinandbarbiturates(e.g.phenobarbital)and

rifampicinreducestheplasmalevelsoffelodipineviaenzymeinductionintheliver(cytochromeP450-System).A

similareffectisexpectedwithSt.John’sWort.Thereforeadoseincreaseoffelodipinemaybenecessary.

Hydrochlorothiazidemayenhancetheanti-hypertensiveeffectoffelodipine.

FelodipinecaninduceanincreaseofCmaxofcyclosporine.Additionally,cyclosporinemayinhibitfelodipine

metabolism,whichmaycreateapotentialriskoffelodipinetoxicity.

Bloodlevelsofdigoxinincreaseduringconcomitantadministrationoffelodipine.Therefore,decreasingofdigoxin

dosageshouldbetakenintoaccountwhenthetwodrugsareadministeredconcurrently.

Felodipinemayincreasetheconcentrationoftacrolimus.Whenusedtogether,thetacrolimusserumconcentration

shouldbefollowedandthetacrolimusdosemayneedtobeadjusted.

4.6Pregnancyandlactation

Felodipineiscontra-indicatedduringtheentiredurationofpregnancy,asanimalexperimentshavedemonstratedfoetal

damage(see5.3).Pregnancymustbeexcludedbeforestartingtreatmentwithfelodipine.

Felodipineisexcretedinbreastmilk.Ifthebreast-feedingmotheristakingtherapeuticdosesoffelodipine,afully

breast-fedinfantabsorbsonlyaverylowdoseoftheactivesubstancewiththebreastmilk.Thereisnoexperienceof

theriskthismayposetothenewborn,thereforeasaprecautionbreast-feedingshouldbediscontinuedduringtreatment.

4.7Effectsonabilitytodriveandusemachines

Treatmentwithfelodipinerequiresregularmedicalsupervision.Felodipinecaninfluenceindividualreactionstosuch

anextentthattheabilitytotakeanactivepartinroadtrafficortooperatemachinesorworkwithoutsuitablesafeguards

maybeimpaired.Thisisparticularlythecaseatstartoftherapy,orwhenthedoseisincreased,ormedicationis

changedaswellasafterconcomitantingestionofalcohol.

4.8Undesirableeffects

Adversereactionshavebeenrankedunderheadingsoffrequencyusingthefollowingconvention:

Verycommon(1/10);common(1/100to<1/10);uncommon(1/1000to<1/100);rare(1/10000to<1/1000);

veryrare(<1/10000),notknown(cannotbeestimatedfromtheavailabledata).

Nervoussystemdisorders

Verycommon:Headache(particularlyatthebeginningoftreatment,whenthedoseisincreasedorwhenhighdoses

areadministered.Generally,thoseeffectssubsideoncontinuedtreatment).

Uncommon:Dizziness,syncope,paraesthesia,tremors,restlessness.

Earandlabyrinthdisorders

Verycommon:Tinnitus(particularlyatthebeginningoftreatment,whenthedoseisincreasedorwhenhighdosesare

administered.Generally,thoseeffectssubsideoncontinuedtreatment).

Cardiacdisorders

Common:Anginapectoris(particularlyatthebeginningoftreatment);increaseinthefrequency,durationandseverity

ofanginapectorisattacksinpatientswithpre-existinganginapectoris.

Uncommon:Palpitations,tachycardia.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 26/05/2010 CRN 2079004 page number: 4

Vasculardisorders

Verycommon:Flushing(particularlyatthebeginningoftreatment,whenthedoseisincreasedorwhenhighdosesare

administered.Generally,thoseeffectssubsideoncontinuedtreatment).

Uncommon:Hypotension.

Rare:Leucocytoclasticvasculitis.

Respiratory,thoracicandmediastinaldisorders

Uncommon:Dyspnoea.

Gastrointestinaldisorders

Uncommon:Gastro-intestinalcomplaints(e.g.nausea,vomiting,diarrhoea,constipation),gingivalhyperplasiaand

gingivitis.

Hepato-biliarydisorders

Veryrare:Hepaticfunctiondisorders(elevatedtransaminaselevels).

Skinandsubcutaneoustissuedisorders

Uncommon:Skinandhypersensitivityreactionssuchaspruritus,urticaria,exanthema,andphotosensitization.

Veryrare:Exfoliativedermatitis.

Musculoskeletal,connectivetissueandbonedisorders

Uncommon:Myalgia,arthralgia.

Renalandurinarydisorders

Uncommon:Pollakiuria.

Reproductivesystemandbreastdisorders

Veryrare:Erectiondisorders,gynaecomastia,menorrhagia.

Generaldisordersandadministrationsiteconditions

Common:Peripheraloedema(thedegreeofankleswellingisdoserelated).

Uncommon:Fatigue,weightgain,sweating.

Veryrare:Angioedema,fever.

4.9Overdose

Symptomsofintoxication

Overdosemayleadtoexcessiveperipheralvasodilatationwithmarkedhypotensionandinrarecasesbradycardia.

Managementofintoxication

Thetherapeuticmeasuresshouldfocusoneliminationoftheactiveingredientandmonitoringofthevitalsigns.If

severehypotensionoccurs,symptomatictreatmentshouldbeprovided,thepatientshouldbeplacedsupinewiththe

legselevated.Incaseofaccompanyingbradycardia,atropine(0.5–1.0mg)shouldbegivenintravenously.Additional

intravenousfluidsshouldbecautiouslyadministeredunderhaemodynamicsupervisiontopreventcardiacoverloading.

Sympathomimeticdrugswithpredominanteffectonthe

-adrenoreceptor(suchasdobutamin,dopamin,

norepinephrinoradrenalin)mayalsobegiven.Dosagedependsintheefficacyobtained.

Felodipineisonlydialysabletoaminimalextent(approx.9%).

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 26/05/2010 CRN 2079004 page number: 5

ATCcode:

C08CA02.

Felodipineisacalciumantagonistofthedihydropyridineclassofcalciumchannelblockers.Calciumantagonists

interferewiththevoltage-dependentL-type(slow)calciumchannelsintheplasmamembranesofsmoothmusclecells

andreducetheinflowofcalciumions.Thisresultsinvasodilatation.

Felodipinehasagreaterselectivityforvascularsmoothmusclethanmyocardialmuscle.Felodipineselectivelydilates

arterioleswithnoeffectsonvenousvessels.Felodipineleadstoadose-relatedloweringofbloodpressurevia

vasodilatationandconsequentlyareductionofperipheralvascularresistance.Itreducesbothsystolicanddiastolic

bloodpressure.Thehaemodynamiceffectoffelodipineisaccompaniedbyreflex(baroreceptor-mediated)tachycardia.

Intherapeuticdoses,felodipinehasnodirecteffectoneithercardiaccontractilityorcardiacconduction.Felodipine

reducesrenalvascularresistance.Theglomerularfiltrationrateremainsunchanged.

Felodipinehasaweaknatriuretic/diureticeffectanddoesnotprovokefluidretention.

Felodipinecanbeusedasamonotherapybutalsoconcomitantlywithbeta-blockers,diureticsandACEinhibitors.

Thereislimitedclinicaltrialexperienceoftheuseoffelodipineinhypertensivepaediatricpatients.Ina

randomised,double-blind,3-week,parallelgroupstudyinchildrenaged6-16yearswithprimaryhypertension,the

antihypertensiveeffectsofoncedailyfelodipine2.5mg(n=33),5mg(n=33)and10mg(n=31)werecomparedwith

placebo(n=35).Thestudyfailedtodemonstratetheefficacyoffelodipineinloweringbloodpressureinchildrenaged

6-16years.

Thelong-termeffectsoffelodipineongrowth,pubertyandgeneraldevelopmenthavenotbeenstudied.Thelong-term

efficacyofantihypertensivetherapyastherapyinchildhoodtoreducecardiovascularmorbidityandmortalityin

adulthoodhasalsonotbeenestablished.

5.2Pharmacokineticproperties

Absorption

Felodipineiscompletelyabsorbedfollowingoraladministration.Peakplasmalevelsarereachedwiththeprolonged

releaseformulationafter3–5hoursandresultinevenfelodipineplasmaconcentrationswithinthetherapeuticrange

for24hours.Steadystateisreachedapprox.3daysafterstartingtreatment.Duetoanextensivefirst-passeffect,only

approx.15%oftheadministereddoseissystemicallyavailable.

Distribution

Theplasmaproteinbindingoffelodipineis>99%.Thevolumeofdistributionisapproximately10l/kgatsteadystate,

sothatfelodipineisindicatinglargetissuedistribution.Thereisnosignificantaccumulationduringlong-term

treatment.

Metabolism

FelodipineisextensivelymetabolisedintheliverbyCYP3A4.Allidentifiedmetabolitesareinactive.

Elimination

Nounchangedparentsubstanceisdetectableintheurine.Theaveragehalf-lifeoffelodipineintheterminalphaseis25

hours.Theinactivehydrophilicmetabolitesformedbyhepaticbiotransformationaremainlyeliminatedrenally(to

approx.70%),andtheremainderisexcretedinthefaeces.Themeanplasmaclearanceis1100ml/landdependsonthe

hepaticbloodflow.

Inasingledose(felodipineprolongedrelease5mg)pharmacokineticstudywithalimitednumberofchildrenaged

between6and16years(n=12)therewasnoapparentrelationshipbetweentheageandAUC,C

orhalf-lifeof

felodipine.

Elderly

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 26/05/2010 CRN 2079004 page number: 6

Impairedhepaticfunction

Increasedplasmaconcentrationsofupto100%havebeenmeasuredinpatientswithimpairedhepaticfunction.

Impairedrenalfunction

Renalimpairmentdoesnotaffectthepharmacokineticsoffelodipine,althoughaccumulationofinactivemetabolites

occursinrenalfailure.

Effectoffood

Therate,butnottheextentofabsorptionisaffectedbythesimultaneousingestionoffattyfood.Cmaxwas2to2.5

timeshigherfollowingintakeofahigh-fatmealcomparedtoafastingstate.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicityandcarcinogenicpotential.Inanimalstudieswithrespecttothereproductionadverseeffects

werefound.Effectsinrats(prolongeddurationofpregnancyanddifficultlabour)andrabbits(impaireddevelopmentof

distalphalanges,presumablyduetodecreaseduteroplacentalperfusion)revealednoevidenceofadirectteratogenic

effect,butindicatesecondaryconsequencesofthepharmacodynamiceffect.Inmonkeysanabnormalpositionofthe

distalphalangeswasfound.Thesignificanceoftheseobservationsforhumansisunknown.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Lactosemonohydrate

Microcrystallinecellulose

Hypromellose

Povidone

Propylgallate

Colloidalanhydroussilica

Magnesiumstearate

Tabletcoat:

Hypromellose

Ironoxidered(E172)

Ironoxideyellow(E172)

Titaniumdioxide(E171)

Talcum

Propyleneglycol

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

5years.

6.4Specialprecautionsforstorage

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 26/05/2010 CRN 2079004 page number: 7

6.5Natureandcontentsofcontainer

PVC/PE/PVDCaluminiumblister.

Packsizes:10,14,20,28,30,50,56,60,90,98,100,250,500and1000prolongedreleasetablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

SelanaHealthcareLtd.

GaradiceHouse

3-4Fairview

Dublin3

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA1363/3/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:21May2004

Dateoflastrenewal:18January2006

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 26/05/2010 CRN 2079004 page number: 8