CIMETIDINE

Main information

  • Trade name:
  • CIMETIDINE Coated Tablets 400 Milligram
  • Dosage:
  • 400 Milligram
  • Pharmaceutical form:
  • Coated Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CIMETIDINE Coated Tablets 400 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1046/009/002
  • Authorization date:
  • 14-03-2000
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cimetidine400mgFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains400mgofcimetidine.

Forexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet

Cimetidine400mgtabletsarefilmcoated,palegreen,capsuleshapedtabletsmarked‘S48’ononesideand‘Sterwin’

onthereverse.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inthetreatmentofbenignulcerationofoesophagus,stomach,upperintestinaltract(includingpost-operativestomal

area)andtheZollinger-EllisonSyndrome.

Inthemanagementofconditionsbenefitingfromreducedgastricacidsecretion.

Inthelongtermmaintenanceofbenignpepticulcerdiseaseunderregularsurveillance.

4.2Posologyandmethodofadministration

Thetotaldailydosebyanyrouteshouldnotnormallyexceed2.4g.Dosageshouldbereducedinpatientswithimpaired

renalfunction(seesection4.4).

Adults

Forpatientswithduodenalorbenigngastriculcerationasingledailydoseof800mgatbedtimeisrecommended.

Otherwisetheusualdosageis400mgtwiceadaywithbreakfastatbedtime.Regimensof200mgthricedailywith

mealsand400mgnocte(night)(1.0g/day)or,ifinadequate,400mgq.d.s.(fourtimesaday)(1.6g/day)withmealsand

atbedtimemayalsobeused.

Inoesophagealreflux400mgq.d.s.withmealsandatbedtimefor4to8weeksisrecommended.

Inpatientswithveryhighgastricacidsecretion(e.g.,Zollinger-EllisonSyndrome)itmaybenecessarytoincreasethe

doseto400mgq.d.s.oroccasionallyhigher.

Treatmentshouldbegiveninitiallyforatleast4weeks(6weeksinthecaseofbenignulcer,8weeksinulcer

associatedwithcontinuednon-steroidanti-flammatoryagents).Mostulcerswillhavehealedbythatstage,butthose

whichhavenotwillusuallydosoafterafurthercourseoftreatment.Treatmentmaybecontinuedforlongerperiodsin

thosepatientswhomaybenefitfromareductionofgastricsecretionandthedosagemaybereducedasappropriateto

400mgatbedtimeor400mginthemorningandatbedtime.

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bedtime;400mginthemorningandatbedtimehasalsobeenused.

Patientsonprolongedtreatment(particularlythosetreatedformorethanoneyear)shouldbekeptunderregular

surveillance.

Antacidsmaybeusedconcurrentlyifrequired.

Intheprophylaxisofhaemorrhagefrom‘stress’ulcerationdosesuptoamaximumof2.4gdailymaybegivenin

divideddoses.200–400mgdosescanbegivenevery4to6hoursbyoral,nasogastricorparenteralroutes(NBby

directintravenousinjectionadoseof200mgshouldnotbeexceeded–seeparenteraldosagerecommendations).

Intheprophylaxisofacidaspiration(Mendelson’sSyndrome)asingledoseof400mgmaybegiven90–120minutes

beforeinductionofgeneralanaesthesiaor,inobstetricpractice,atthestartoflabour.Whilesuchariskpersistsadose

ofupto400mgmayberepeated(parenterallyifappropriate)at4hourlyintervalsasrequired,uptotheusual

maximumof2.4g/day.

Intheshortbowelsyndrome,e.g.followingsubstantialresectionforCrohn’sdisease,theusualdosagerange(see

above)canbeusedaccordingtoindividualresponse.

Inpancreaticinsufficiency,forprotectionofpancreaticenzymesupplements,800–1600mgdailymaybegiven

accordingtoresponseinfourdivideddoses,onetooneandahalfhoursbeforemeals.

Elderly

Thenormaladultdosagemaybeusedunlessrenalfunctionismarkedlyimpaired(seesection4.4).

Children

Experienceinchildrenislessthanthatinadults.Inchildrenmorethan2yearsold,cimetidine25–30mg/kgbody

weight/dayindivideddosesmaybeadministeredbyeithertheoralorparenteralroutes.

Theuseofcimetidineinchildrenlessthan2yearsoldisnotfullyevaluated.

4.3Contraindications

Hypersensitivitytocimetidineoritsexcipients.

4.4Specialwarningsandprecautionsforuse

Dosageshouldbereducedinpatientswithimpairedrenalfunctionwhencreatinineclearanceisbelow50ml/minute.

Cimetidineisremovedbyhaemodialysis,butnottoanysignificantextentbyperitonealdialysis.

Clinicaltrialsofoversixyearscontinuoustreatmentandmorethan15yearswidespreadusehavenotrevealed

unexpectedadversereactionsrelatedtolongtermtherapy.Thesafetyofprolongeduseisnot,however,fully

establishedandcareshouldbetakentokeeppatientsonprolongedtreatment(particularlythosetreatedforgreaterthan

oneyear)underregularsurveillance.

Beforeinitiationofcimetidinetherapyforanygastriculcerationmalignancyshouldbeexcludedbyendoscopy,and

biopsyifpossible.Treatmentwithcimetidinecanmasksymptomsandassisttransienthealingofgastriccancer.The

consequencesofapotentialdelayindiagnosisshouldbekeptinmindparticularlyinpatientsofmiddleageoroveror

CreatinineClearance

30-50ml/minute

15-30ml/minute

0-15ml/minute DailyDosage

200mgq.d.s(fourtimesaday)

200mgt.d.s(threetimesaday)

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Careshouldbetakenthatpatientswithahistoryofpepticulcer,particularlytheelderly,beingtreatedwithcimetidine

andanon-steroidalanti-inflammatoryagentareobservedregularly.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Cimetidinecanprolongtheeliminationofdrugsmetabolisedbyoxidationintheliver.Pharmacologicalinteractions

withanumberofdrugse.g.,diazepam,propranolol,havebeendemonstrated;onlythosewithoralanticoagulants,

phenytoinandtheophyllineandintravenouslidocaineappeartodatetobeofclinicalsignificance.Closemonitoringof

patientsoncimetidinereceivingoralanticoagulants,phenytoin,theophyllineisrecommended.Areductionintheir

dosagemaybenecessary.

Inpatientsondrugtreatmentorwithillnesswhichcouldcausefallsinbloodcellcounts,thepossibilitythatH

receptorantagonismcouldpotentiatethiseffectshouldbeborneinmind.

4.6Pregnancyandlactation

Cimetidineshouldnotbeadministeredduringpregnancyorlactationinwomenbreast-feedinginfantsunless

consideredessentialbythephysician.Animalstudiesofreproductionhaveshownnodrug-relatedabnormality.

Significantlevelsofdrugreachbreastmilk.

4.7Effectsonabilitytodriveandusemachines

Ifdizziness,headacheortirednessoccurs,careshouldbetakenregardingdrivinganduseofmachinery.

4.8Undesirableeffects

Adversereactions:Morethan56millionpatientshavebeentreatedwithcimetidineworldwideandadversereactions

havebeeninfrequent.

Uncommonlyreportedadverseevents:

Gastrointestinaldisorders:diarrhoea.

Nervoussystemdisorders:dizziness.

Skinandsubcutaneoustissuedisorders:rash,usuallymildandtransient.

Generaldisordersandadministrationsiteconditions:tiredness.

Reproductivesystemandbreastdisorders:gynaecomastia,whichisalmostalwaysreversibleupondiscontinuing

treatment.

Rarelyreportedadverseevents:

Bloodandthelymphaticsystemdisorders:thrombocytopenia;leucopenia;agranulocytosis,(seesection4.4)whichare

reversibleonwithdrawaloftreatment.

Immunesystemdisorders:hypersensitivityvasculitis,whichisreversibleonwithdrawaloftreatment.

Psychiatricdisorders:reversibleconfusionalstates,usuallyinelderlyoralreadyveryillpatientse.g.thosewithrenal

failure;depression.

Hepato-biliarydisorders:biochemicalorbiopsyevidenceofreversibleliverdamage.

Veryrarelyreportedadverseevents:

Thefollowingadverseeventsareusuallyreversibleuponwithdrawaloftreatment:

Immunesystemdisorders:hypersensitivityreactionsincludinganaphylaxis.

Psychiatricdisorders:hallucinations.

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Nervoussystemdisorders:headache.

Cardiacdisorders:sinusbradycardia;tachycardia,heartblock.

Gastrointestinaldisorders:acutepancreatitis.

Musculoskeletal,connectivetissueandbonedisorders:myalgia;arthralgia.

Renalandurinarydisorders:interstitialnephritis.

Generaldisordersandadministrationsiteconditions:fever.

Alopeciahasbeenreportedbutnocausalrelationshiphasbeenestablished.Reversibleimpotencehasalsobeenvery

rarelyreportedbutnocausalrelationshiphasbeenestablishedatusualtherapeuticdoses.Isolatedincreasesofplasma

creatininehavebeenofnoclinicalsignificance.

4.9Overdose

Acuteoverdosageofupto20gramshasbeenreportedseveraltimeswithnosignificantilleffects.Inductionof

vomitingand/orgastriclavagemaybeemployedtogetherwithsymptomaticandsupportivetherapy.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticcategory:H

-Receptorantagonists,ATCCode:A02BA01.

AnH

receptorantagonistwellabsorbedafteroraldosing,metabolisedintheliverandexcretedmainlythroughthe

kidneywithaT½ofabout3-4hours.Theeffectsonacidsecretionareoflongerduration.

5.2Pharmacokineticproperties

Cimetidineisreadilyabsorbedfromthegastro-intestinaltractandpeakplasmaconcentrationsareobtainedaboutan

hourafteradministrationonanemptystomachandabout2hoursafteradministrationwithfood.Thebioavailabilityof

cimetidinefollowingoraladministrationisabout60-70%comparedtoanintravenousdoseduetofirstpass

metabolism.Theeliminationhalflifefromplasmaisaround2hoursandcimetidineisweaklybound,about20%,to

plasmaproteins.Cimetidineispartiallymetabolisedinthelivertothesulphoxideandtohydroxymethylcimetidinebut

mostisexcretedunchangedintheurine.Cimetidinecrossestheplacentalbarrierandisexcretedinbreastmilkwhen

concentrationsarereportedtobehigherthanthoseinplasma.Itdoesnotreadilycrosstheblood-brainbarrier.

5.3Preclinicalsafetydata

Therearenopre-clinicaldataofrelevancetotheprescriberwhichareadditionaltothatalreadyincludedinother

sectionsoftheSPC.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Maizestarch

Povidone

DalfcolGreen3203

-patentblueV(E131)

-quinolineyellow(E104)

Sodiumlaurilsulfate

Purifiedtalc

Magnesiumstearate

Croscarmellosesodium

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Macrogol400

MastercoteFA1507

-patentblueValuminiumlake(E131)

-quinolineyellowaluminiumlake(E104)

-titaniumdioxide(E171)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelflifeexpirydateforthisproductshallnotexceed3yearsfromthedateofitsmanufacture.

6.4Specialprecautionsforstorage

Donotstoreabove25 °

C.Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

PVCaluminiumfoilblisterscontainedincardboardcartonscontaining50,56,60,112and120tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

WinthropPharmaceuticalsUKLimited

OneOnslowStreet

Guildford

SurreyGU14YS

8MARKETINGAUTHORISATIONNUMBER

PA1046/9/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:14March1995

Dateoflastrenewal:14March2005

10DATEOFREVISIONOFTHETEXT

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