FREESTOM

Main information

  • Trade name:
  • FREESTOM Tablets Gastro-Resistant 20 Milligram
  • Dosage:
  • 20 Milligram
  • Pharmaceutical form:
  • Tablets Gastro-Resistant
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FREESTOM Tablets Gastro-Resistant 20 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0540/167/001
  • Authorization date:
  • 08-07-2011
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Freestom20mggastro-resistanttablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachgastro-resistanttabletcontains20mgpantoprazole(assodiumsesquihydrate).

Excipient:38.425mgMaltitoland0.345mgLecithin(derivedfromsoyaoil)(seesection4.4)

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Gastro-resistanttablet

Yellow,ovaltablet.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Short-termtreatmentofrefluxsymptoms(e.g.heartburn,acidregurgitation)inadults.

4.2Posologyandmethodofadministration

Posology

Therecommendeddoseis20mgpantoprazole(onetablet)perday.

Itmightbenecessarytotakethetabletsfor2-3consecutivedaystoachieveimprovementofsymptoms.Oncecomplete

reliefofsymptomshasoccurred,treatmentshouldbediscontinued.Thetreatmentshouldnotexceed4weekswithout

consultingadoctor.

Ifnosymptomreliefisobtainedwithin2weeksofcontinuoustreatment,thepatientshouldbeinstructedtoconsulta

doctor.

Specialpopulations

Nodoseadjustmentisnecessaryinelderlypatientsorinthosewithimpairedrenalorliverfunction.

Paediatricuse

PANTOPRAZOLEisnotrecommendedforuseinchildrenandadolescentsbelow18yearsofageduetoinsufficient

dataonsafetyandefficacy.

Methodofadministration

PANTOPRAZOLE20mggastro-resistanttabletsshouldnotbechewedorcrushed,andshouldbeswallowedwhole

withliquidbeforeameal.

4.3Contraindications

Hypersensitivitytotheactivesubstance,substitutedbenzimidazoles,lecithin(derivedfromsoyaoil)ortoanyofthe

excipients.

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4.4Specialwarningsandprecautionsforuse

Patientsshouldbeinstructedtoconsultadoctorif:

Theyhaveunintentionalweightloss,anaemia,gastrointestinalbleeding,dysphagia,persistentvomitingor

vomitingwithblood,sinceitmayalleviatesymptomsanddelaydiagnosisofaseverecondition.Inthesecases,

malignancyshouldbeexcluded.

Theyhavehadpreviousgastriculcerorgastrointestinalsurgery.

Theyareoncontinuoussymptomatictreatmentofindigestionorheartburnfor4ormoreweeks.

Theyhavejaundice,hepaticimpairment,orliverdisease.

Theyhaveanyotherseriousdiseaseaffectinggeneralwell-being.

Theyareagedover55yearswithneworrecentlychangedsymptoms.

Patientswithlong-termrecurrentsymptomsofindigestionorheartburnshouldseetheirdoctoratregularintervals.

Especially,patientsover55yearstakinganynon-prescriptionindigestionorheartburnremedyonadailybasisshould

informtheirpharmacistordoctor.

PatientsshouldnottakeanotherprotonpumpinhibitororH

antagonistconcomitantly.

Patientsshouldconsulttheirdoctorbeforetakingthismedicinalproductiftheyareduetohaveanendoscopyorurea

breathtest.

Patientsshouldbeadvisedthatthetabletsarenotintendedtoprovideimmediaterelief.

Patientsmaystarttoexperiencesymptomaticreliefafterapproximatelyonedayoftreatmentwithpantoprazole,butit

mightbenecessarytotakeitfor7daystoachievecompleteheartburncontrol.Patientsshouldnottakepantoprazoleas

apreventivemedicinalproduct.

Decreasedgastricacidity,duetoanymeans-includingprotonpumpinhibitors-increasesgastriccountsofbacteria

normallypresentinthegastrointestinaltract.Treatmentwithacid-reducingmedicinalproductsleadstoaslightly

increasedriskofgastrointestinalinfectionssuchasSalmonella,Campylobacter,orC.difficile.

Thismedicinalproductcontainsmaltitol.

Patientswithrarehereditaryproblemsoffructoseintoleranceshouldnottakethismedicinalproduct.

Thismedicinalproductcontainslecithinderivedfromsoyaoil.Ifyouareallergictopeanutorsoya,donotusethis

medicinalproduct.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

PANTOPRAZOLEmayreducetheabsorptionofactivesubstanceswhosebioavailabilityisdependentonthegastricpH

(e.g.ketoconazole).

Ithasbeenshownthatco-administrationofatazanavir300mg/ritonavir100mgwithomeprazole(40mgoncedaily)or

atazanavir400mgwithlansoprazole(60mgsingledose)tohealthyvolunteersresultedinasubstantialreductioninthe

bioavailabilityofatazanavir.TheabsorptionofatazanavirispH-dependent.Therefore,pantoprazolemustnotbeco-

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PantoprazoleismetabolizedintheliverviathecytochromeP450enzymesystem.Aninteractionofpantoprazolewith

othersubstanceswhicharemetabolizedbythesameenzymesystemcannotbeexcluded.However,noclinically

significantinteractionswereobservedinspecifictestswithcarbamazepine,caffeine,diazepam,diclofenac,digoxin,

ethanol,glibenclamide,metoprolol,naproxen,nifedipine,phenytoin,piroxicam,theophyllineandanoralcontraceptive

containinglevonorgestrelandethinyloestradiol.

Althoughnointeractionduringconcomitantadministrationofphenprocoumonorwarfarinhasbeenobservedinclinical

pharmacokineticstudies,afewisolatedcasesofchangesinInternationalNormalisedRatio(INR)havebeenreported

duringconcomitanttreatmentinthepost-marketingperiod.Therefore,inpatientstreatedwithcoumarinanticoagulants

(e.g.phenprocoumonorwarfarin),monitoringofprothrombintime/INRisrecommendedafterinitiation,terminationor

duringirregularuseofpantoprazole.

Therewerenointeractionswithconcomitantlyadministeredantacids.

4.6Fertility,pregnancyandlactation

Pregnancy

Therearenoadequatedatafromtheuseofpantoprazoleinpregnantwomen.Studiesinanimalshaveshown

reproductivetoxicity.Preclinicalstudiesrevealednoevidenceofimpairedfertilityorteratogeniceffects(seesection

5.3).Thepotentialriskforhumansisunknown.Thismedicinalproductshouldnotbeusedduringpregnancy.

Lactation

Itisunknownwhetherpantoprazoleisexcretedinhumanbreastmilk.Animalstudieshaveshownexcretionof

pantoprazoleinbreastmilk.Thismedicinalproductshouldnotbeusedduringbreast-feeding.

4.7Effectsonabilitytodriveandusemachines

Adversedrugreactionssuchasdizzinessandvisualdisturbancesmayoccur(seesection4.8).Ifaffected,patients

shouldnotdriveoroperatemachines.

4.8Undesirableeffects

Approximately5%ofpatientscanbeexpectedtoexperienceadversedrugreactions(ADRs).Themostcommonly

reportedADRsarediarrhoeaandheadache,bothoccuringinapproximately1%ofpatients.Thefollowingundesirable

effectshavebeenreportedwithpantoprazole.

Withinthefollowingtable,undesirableeffectsarerankedunderthefollowingfrequencyclassification:

Verycommon(1/10);common(1/100to<1/10);uncommon(1/1,000to<1/100);rare(1/10,000to<1/1,000);

veryrare(<1/10,000),notknown(cannotbeestimatedfromtheavailabledata).

Withineachfrequencygrouping,undesirableeffectsarepresentedinorderofdecreasingseriousness.

Table1.Undesirableeffectswithpantoprazoleinclinicaltrialsandpost-marketingexperience

Frequency

System

OrganClass Uncommon Rare Veryrare Notknown

Bloodand

lymphatic

system

disorders Thrombocytopenia;

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Immunesystem

disorders Hypersensitivity

(incl.

anaphylactic

reactionsand

anaphylactic

shock)

Metabolismand

nutrition

disorders Hyperlipidaemias

andlipid

increases

(triglycerides,

cholesterol);

Weightchanges Hyponatraemia

Psychiatric

disorders Sleepdisorders Depression(and

allaggravations) Disorientation

(andall

aggravations) Hallucination;

Confusion

(especiallyin

pre-disposed

patients,aswell

asthe

aggravationof

thesesymptoms

incaseof

pre-existence)

Nervoussystem

disorders Headache,

Dizziness

Eyedisorders Disturbancesin

vision/blurred

vision

Gastrointestinal

disorders Diarrhoea;

Nausea/

vomiting;

Abdominal

distensionand

bloating;

Constipation;

Drymouth;

Abdominal

pain

anddiscomfort

Hepatobiliary

disorders Liverenzymes

increased

(transaminases,

-GT) Bilirubin

increased Hepatocellular

injury;

Jaundice;

Hepatocellular

failure

Skinand

subcutaneous

tissuedisorders Rash/

exanthema/

eruption;

Pruritus Urticaria;

Angioedema Stevens-

Johnson

syndrome;

Lyell

syndrome;

Erythema

multiforme;

Photosensitivity

Musculoskeletal

andconnective

tissuedisorders Arthralgia;

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4.9Overdose

Therearenoknownsymptomsofoverdoseinman.

Dosesupto240mgadministeredintravenouslyover2minuteswerewelltolerated.

Aspantoprazoleisextensivelyproteinbound,itisnotreadilydialysable.

Inthecaseofoverdosewithclinicalsignsofintoxication,apartfromsymptomaticandsupportivetreatment,no

specifictherapeuticrecommendationscanbemade.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Protonpumpinhibitors,ATCcode:A02BC02

Mechanismofaction

Pantoprazoleisasubstitutedbenzimidazolewhichinhibitsthesecretionofhydrochloricacidinthestomachbyspecific

blockadeoftheprotonpumpsoftheparietalcells.

Pantoprazoleisconvertedtoitsactiveform,acyclicsulphenamide,intheacidicenvironmentintheparietalcellswhere

itinhibitstheH+,K+-ATPaseenzyme,i.e.thefinalstageintheproductionofhydrochloricacidinthestomach.

Theinhibitionisdose-dependentandaffectsbothbasalandstimulatedacidsecretion.Inmostpatients,freedomfrom

heartburnandacidrefluxsymptomsisachievedin1week.Pantoprazolereducesacidityinthestomachandthereby

increasesgastrininproportiontothereductioninacidity.Theincreaseingastrinisreversible.Sincepantoprazolebinds

totheenzymedistaltothereceptorlevel,itcaninhibithydrochloricacidsecretionindependentlyofstimulationby

othersubstances(acetylcholine,histamine,gastrin).Theeffectisthesamewhethertheactivesubstanceisgivenorally

orintravenously.

Thefastinggastrinvaluesincreaseunderpantoprazole.Onshort-termuse,inmostcasestheydonotexceedtheupper

limitofnormal.Duringlong-termtreatment,gastrinlevelsdoubleinmostcases.Anexcessiveincrease,however,

occursonlyinisolatedcases.Asaresult,amildtomoderateincreaseinthenumberofspecificendocrine(ECL)cells

inthestomachisobservedinaminorityofcasesduringlong-termtreatment(simpletoadenomatoidhyperplasia).

However,accordingtothestudiesconductedsofar,theformationofcarcinoidprecursors(atypicalhyperplasia)or

gastriccarcinoidsaswerefoundinanimalexperiments(seesection5.3)havenotbeenobservedinhumans.

Clinicalefficacy

Inaretrospectiveanalysisof17studiesin5960patientswithgastro-oesophagealrefluxdisease(GORD)whowere

treatedwith20mgpantoprazolemonotherapy,thesymptomsassociatedwithacidrefluxe.g.heartburnandacid

regurgitationwereevaluatedaccordingtoastandardisedmethodology.Studiesselectedhadtohaveatleastoneacid

refluxsymptomrecordingpointat2weeks.GORDdiagnosisinthesestudieswasbasedonendoscopicassessment,

withtheexceptionofonestudyinwhichtheinclusionofthepatientswasbasedonsymptomatologyalone.

Inthesestudies,thepercentageofpatientsexperiencingcompleterelieffromheartburnafter7dayswasbetween54.0%

and80.6%inthepantoprazolegroup.After14and28days,completeheartburnreliefwasexperiencedin62.9%to

Renaland

urinary

disorders Interstitial

nephritis

General

disorders

administration

siteconditions Asthenia,

fatigue

andmalaise Body

temperature

increased;

Oedema

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Forthecompleterelieffromacidregurgitation,similarresultswereobtainedasforheartburn.After7daysthe

percentageofpatientsexperiencingcompleterelieffromacidregurgitationwasbetween61.5%and84.4%,after14

daysbetween67.7%and90.4%,andafter28daysbetween75.2%and94.5%,respectively.

PantoprazolewasconsistentlyshowntobesuperiortoplaceboandH2RAandnon-inferiortootherPPIs.Acid-reflux

symptomreliefrateswerelargelyindependentoftheinitialGORDstage.

5.2Pharmacokineticproperties

Pharmacokineticsdonotvaryaftersingleorrepeatedadministration.Inthedoserangeof10to80mg,theplasma

kineticsofpantoprazolearelinearafterbothoralandintravenousadministration.

Absorption

Pantoprazoleiscompletelyandrapidlyabsorbedafteroraladministration.Theabsolutebioavailabilityfromthetablet

wasfoundtobeabout77%.Onaverage,atabout2.0h-2.5hpostadministration(t

)ofasingle20mgoraldose,

themaximumserumconcentrations(C

)ofabout1-1.5µg/mlareachieved,andthesevaluesremainconstantafter

multipleadministration.Concomitantintakeoffoodhadnoinfluenceonbioavailability(AUCorC

),butincreased

thevariabilityofthelag-time(t

Distribution

Volumeofdistributionisabout0.15l/kgandserumproteinbindingisabout98%.

Metabolismandexcretion

Clearanceisabout0.1l/h/kg,andterminalhalf-life(t

)about1h.Therewereafewcasesofsubjectswithdelayed

elimination.Duetothespecificbindingofpantoprazoletotheprotonpumpswithintheparietalcell,theelimination

half-lifedoesnotcorrelatewiththemuchlongerdurationofaction(inhibitionofacidsecretion).

Pantoprazoleisalmostexclusivelymetabolizedintheliver.Renaleliminationrepresentsthemajorrouteofexcretion

(about80%)forthemetabolitesofpantoprazole;therestisexcretedwiththefaeces.Themainmetaboliteinbothserum

andurineisdesmethylpantoprazole,whichisconjugatedwithsulphate.Thehalf-lifeofthemainmetabolite(about1.5

h)isnotmuchlongerthanthatofpantoprazole.

Specialpopulations

Renalimpairment

Nodosereductionisrecommendedwhenpantoprazoleisadministeredtopatientswithimpairedrenalfunction

(includingpatientsondialysis,whichremovesonlynegligibleamountsofpantoprazole).Aswithhealthysubjects,the

half-lifeofpantoprazoleisshort.Althoughthemainmetabolitehasalongerhalf-life(2-3h),excretionisstillrapidand

thusaccumulationdoesnotoccur.

Hepaticimpairment

Afteradministrationofpantoprazoletopatientswithliverimpairment(Child-PughclassesA,BandC)thehalf-life

valuesincreasedtobetween3and7handtheAUCvaluesincreasedbyafactorof3-6,whereastheC

only

increasedslightlybyafactorof1.3comparedwithhealthysubjects.

Elderly

TheslightincreaseinAUCandC

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5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardtohumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicityandgenotoxicity.

Inthe2-yearcarcinogenicitystudiesinrats,neuroendocrineneoplasmswerefound.Inaddition,squamouscell

papillomaswerefoundintheforestomachofratsinonestudy.Themechanismleadingtotheformationofgastric

carcinoidsbysubstitutedbenzimidazoleshasbeencarefullyinvestigatedandallowstheconclusionthatitisa

secondaryreactiontothemassivelyelevatedserumgastrinlevelsoccurringintheratduringchronichigh-dose

treatment.

Inthe2-yearrodentstudiesanincreasednumberoflivertumorswasobservedinrats(inoneratstudyonly)andin

femalemiceandwasinterpretedasbeingduetopantoprazole'shighmetabolicrateintheliver.

Aslightincreaseofneoplasticchangesofthethyroidwasobservedinthegroupofratsreceivingthehighestdose(200

mg/kg)inone2-yearstudy.Theoccurrenceoftheseneoplasmsisassociatedwiththepantoprazole-inducedchangesin

thebreakdownofthyroxineintheratliver.Asthetherapeuticdoseinmanislow,nosideeffectsonthethyroidglands

areexpected.

Inanimalstudies(rats)5mg/kgwastheobservedNOAEL(NoObservedAdverseEffectLevel)forembryotoxicity.

Investigationsrevealednoevidenceofimpairedfertilityorteratogeniceffects.Penetrationoftheplacentawas

investigatedintheratandwasfoundtoincreasewithadvancedgestation.Asaresult,concentrationofpantoprazolein

thefoetusisincreasedshortlybeforebirth.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore

maltitol(E965)

crospovidonetypeB

carmellosesodium

sodiumcarbonate,anhydrous

calciumstearate

Tabletcoating

poly(vinylalcohol)

talc

titaniumdioxide(E171)

macrogol3350

soyalecithin

ironoxideyellow(E172)

sodiumcarbonate,anhydrous

methacrylicacid-ethylacrylatecopolymer(1:1)

sodiumlaurilsulfate

polysorbate80

triethylcitrate

6.2Incompatibilities

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6.3Shelflife

ForAlu-Alublisters:4years

ForHDPEbottles:3years

Afterfirstopeningofthebottleusethemedicinalproductwithinthreemonths.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

oPA/Alu/PVC-Aluminiumblisterscontaining7or14gastro-resistanttabletsorHDPEbottleswithPPclosurewitha

desiccantcontainercontaining7or14gastro-resistanttablets.

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

Sanofi-AventisIrelandLimited

18Riverwalk

CitywestBusinessCampus

NaasRoad

Dublin24

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA540/167/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:8thJuly2011

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