CIMELDINE

Main information

  • Trade name:
  • CIMELDINE Tablets 200 Milligram
  • Dosage:
  • 200 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CIMELDINE Tablets 200 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0126/077/001
  • Authorization date:
  • 06-11-1989
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cimeldine200mgFilm-coatedtablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

EachtabletcontainsCimetidine200mg.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablets.(Shortterm:Tablets)

Palegreen,circular,biconvex,film-coatedtabletwiththeClonmellogoononefaceandthecode‘274’onthereverse.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inthetreatmentofbenignulcerationofoesophagus,stomach,upperintestinaltract(includingpost-operativestomal

area)andtheZollinger-Ellisonsyndrome.

Inthemanagementofconditionsbenefitingfromreducedgastricacidsecretion.

Inthelongtermmaintenancemanagementofbenignpepticulcerdiseaseunderregularsurveillance.

4.2Posologyandmethodofadministration

Routeofadministration

Oral

Adults:Theusualdosageis400mgtwiceadaywithbreakfastandatbedtime.Alternativelypatientswithduodenalor

benigngastriculcerationmaybetreatedwithasingledoseof800mgatbedtime.Regimesof200mgthricedailywith

mealsand400mgnocteor,ifinadequate,400mgq.d.s.withmealsandatbedtimemayalsobeused.

Inoesophagealreflux400mgq.d.s.withmealsandatbedtimefor4to8weeksisrecommended.

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

doseto400mgq.d.s.oroccasionallyhigher.

Treatmentshouldbegiveninitiallyforatleast4weeks(6weeksinthecaseofbenignulcer).Inpatientswhomay

benefitfromareductionofgastricsecretion,dosagemaybereducedtoamaintenanceof400mgatbedtime,orinthe

morningandatbedtime.

Asimilarmaintenanceregimenmaybeusedtopreventrelapseinpatientswithbenignpepticulceration.Patientson

prolongedtreatment(particularlythosetreatedformorethanoneyear)shouldbekeptunderregularsurveillance.

Antacidsmaybeusedconcurrentlyifrequired.

Intheprophylaxisofhaemorrhagefromstressulceration,dosesupto2.4gdailymaybegivenindivideddoses.200–

400mgdosescanbegivenevery4to6hours.

Intheprophylaxisofacidaspiration(Mendelson’ssyndrome),asingledoseof400mgmaybegiven90–120minutes

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ofupto400mgmayberepeated(parenterallyifappropriate)at4hourlyintervalsasrequired,uptotheusual

maximumof2.4g/day.

Inpancreaticinsufficiency,forprotectionofpancreaticenzymesupplements,800–1,600mg/daymaybegiven

accordingtoresponseinfourdivideddoses,onetooneandhalfhoursbeforemeals.

Thetotaldailydosebyanyrouteshouldnotexceed2,400mg.

Dosageshouldbereducedinpatientswithimpairedrenalfunctionwhencreatinineclearanceisbelow50ml/minute.

CreatinineClearance DailyDosage

30–50ml/minute 200mgq.d.s.

15–30ml/minute 200mgt.d.s.

0–15ml/minute 200mgb.d.

Cimetidineisremovedbyhaemodialysis,butnottoanysignificantextentbyperitonealdialysis.

Elderly:Thenormaladultdosagemaybeusedunlessrenalfunctionismarkedlyimpaired.

Children:Experienceinchildrenislessthanthatinadults.Inchildrenmorethan2yearsold,cimetidine25-30mg/kg

bodyweightperdayindivideddosesmaybeadministeredbyeithertheoralorparenteralroutes.

Theuseofcimetidineinchildrenlessthan2yearsofageisnotfullyevaluated.

4.3Contraindications

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients(seesection6.1).

4.4Specialwarningsandprecautionsforuse

Confusionalstates,moodandbehaviouralchangesandinsomniamayoccurespeciallyintheelderlyorveryillpatients

orthosewithrenalfailure.Thoseonhighdosageareparticularlyatrisk.Thesestatesareusuallyreversible.

Beforeinitiationofcimetidinetherapyforanygastriculceration,malignancyshouldbeexcludedbyendoscopy,and

biopsyifpossible.Treatmentwithcimetidinecanmasksymptomsandassisttransienthealingofgastriccancer.The

consequencesofapotentialdelayindiagnosisshouldbekeptinmind,particularlyinpatientsofmiddleageoroveror

withneworrecentlychangeddyspepticsymptoms.

Patientsonprolongedcimetidinetherapy(particularlythosetreatedformorethanoneyear)shouldbekeptunder

regularsurveillancewithparticularattentiontothepathologyofthegastrointestinaltract.

Inpatientsondrugtreatmentorwithillnesseswhichcouldcausefallsinbloodcellcounts,thepossibilitythatH

receptorantagonismcouldpotentiatethiseffectshouldbeborneinmind.

Careshouldbetakenthatpatientswithahistoryofpepticulcer,particularlytheelderly,beingtreatedwithcimetidine

andanon-steroidalanti-inflammatoryagentareobservedregularly.

Closemonitoringofprothrombintimeisrecommendedwhencimetidineisconcurrentlyusedwithanticoagulants.

Co-administrationoftherapeuticagentswithanarrowtherapeuticindex,suchasphenytoinortheophylline,may

requiredosageadjustmentwhenstartingorstoppingconcomitantlyadministeredcimetidine(seeSection4.5).

Inpatientssuchastheelderly,personswithchroniclungdisease,diabetesortheimmunocompromised,theremaybe

anincreasedriskofdevelopingcommunityacquiredpneumonia.Alargeepidemiologicalstudyshowedanincreased

riskofdevelopingcommunityacquiredpneumoniaincurrentusersofH

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stoppedtreatment,withanobservedadjustedrelativeriskincreaseof1.63(95%CI,1.07-2.48).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Cimetidinecanprolongtheeliminationofdrugsmetabolisedbyoxidationintheliver.

Pharmacologicalinteractionswithanumberofdrugse.g.diazepam,propranololhavebeendemonstrated;onlythose

withoralanticoagulants,phenytoinandtheophyllineandintravenouslignocaineappeartodatetobeofclinical

significance.Closemonitoringofpatientsoncimetidinereceivingoralanticoagulants,phenytoinortheophyllineis

recommended.Areductionintheirdosagemaybenecessary.

Inpatientsondrugtreatmentorwithillnessesthatcouldcausefallsinbloodcellcount,thepossibilitythatH

-receptor

antagonismcouldpotentiatethiseffectshouldbeborneinmind.

Cimetidinehasthepotentialtoaffecttheabsorption,metabolismorrenalexcretionofotherdrugswhichisparticularly

importantwhendrugswithanarrowtherapeuticindexareadministeredconcurrently.Thealteredpharmokineticsmay

necessitatedosageadjustmentoftheaffecteddrugordiscontinuationoftreatment(seeSection4.4).

Interactionsmayoccurbyseveralmechanismsincluding:

InhibitionofcertaincytochromeP450enzymes(includingCYP1A2,CYP2C9,CYP2D6andCYP3A3/A4,

andCYP2C18).Inhibitionoftheseenzymesmayresultinincreasedplasmalevelsofcertaindrugsincludingwafarin-

typecoumarinanticoagulants(e.g.warfarin),tricyclicantidepressants(e.g.amitriptyline),classIantiarrhythmics(e.g.

lidocaine),calciumchannelblockers(e.g.nifedipine,diltiazem),oralsulfonylureas(e.g.glipizide),phenytoin,

theophyllineandmetoprolol.

Competitionforrenaltubularsecretion.Thismayresultinincreasedplasmalevelsofcertaindrugsincluding

procainamide,metformin,ciclosporinandtacrolimus.

AlterationofgastricpH.Thebioavailabilityofcertaindrugsmaybeaffected.Thiscanresultineitheran

increaseinabsorption(e.g.atazanavir)oradecreaseinabsorption(e.g.someazoleantifungalssuchasketoconazole,

itraconazoleorposaconazole).

Unknownmechanisms. Cimetidinemaypotentiatethemyelosuppressiveeffects(e.g.neutropenia,

agranulocytosis)ofchemotherapeuticagentssuchascarmustine,fluorouracil,epirbuicin,ortherapiessuchas

radiation.Isolatedcasesofclinicallyrelevantinteractionshavebeendocumentedwithnarcoticanalgesics(e.g.

morphine).

4.6Pregnancyandlactation

Cimetidineshouldnotbeadministeredduringpregnancyorlactationinwomenbreast-feedinginfantsunless

consideredessentialbythephysician.Animalstudiesofreproductionhaveshownnodrug-relatedabnormality.

Significantlevelsofdrugreachbreastmilk.

4.7Effectsonabilitytodriveandusemachines

Noneknown.

4.8Undesirableeffects

Adverseexperienceswithcimetidinearelistedbelowbysystemorganclassandfrequency.Frequenciesaredefinedas:

verycommon(>1/10),common(>1/100,<1/10),uncommon(>1/1000,<1/100),rare(>1/10000,<1/1000),veryrare

(<1/10000).

Bloodandlymphaticsystemdisorders

Uncommon:Leucopenia

Rare:Thrombocytopenia,aplasticanaemia

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Immunesystemdisorders

Veryrare:Anaphylacticreactionisusuallyclearedonwithdrawalofthedrug.

Psychiatricdisorders

Uncommon:Depression,hallucination.Confusionalstate,reversiblewithinafewdaysofwithdrawingcimetidine,has

beenreported,usuallyinelderlyorillpatients.

Nervoussystemdisorders

Common:Headache,dizziness

Cardiacdisorders

Uncommon:Tachycardia

Rare:Sinusbradycardia

Veryrare:Heartblock

Gastrointestinaldisorders

Common:Diarrhoea

Veryrare:Pancreatitis.Pancreatitisclearedonwithdrawalofthedrug.

Hepatobiliarydisorders

Uncommon:Hepatitis

Rare:Increasedserumtransaminaselevels.Hepatitisandincreasedserumtransaminaselevelsclearedonwithdrawalof

thedrug.

Skinandsubcutaneoustissuedisorders

Common:Rash

Veryrare:Alopeciaandhypersensitivityvasculitis.Hypersensitivityvasculitisusuallyclearedonwithdrawalofthe

drug.

Musculoskeletalandconnectivetissuedisorders

Common:Myalgia

Veryrare:Arthralgia

Renalandurinarydisorders

Uncommon:Bloodcreatinineincreased.

Rare:Interstitialnephritis.Interstitialnephritisclearedonwithdrawalofthedrug.Smallincreasesinbloodcreatinine

havebeenreported,unassociatedwithchangesinglomerularfiltrationrate.Theincreasesdonotprogresswith

continuedtherapyanddisappearattheendoftherapy.

Reproductivesystemandbreastdisorders

Uncommon:Gynaecomastiaandreversibleimpotence.Gynaecomastiaisusuallyreversibleupondiscontinuationof

cimetidinetherapy.Reversibleimpotencehasbeenreportedparticularlyinpatientsreceivinghighdoses(e.g.in

Zollinger-EllisonSyndrome).However,atregulardosage,theincidenceissimilartothatinthegeneralpopulation.

Veryrare:Galactorrhoea

Generaldisordersandadministrationsiteconditions

Common:Fatigue

Veryrare:Fever.Feverclearedonwithdrawalofthedrug.

4.9Overdose

Overdosageofupto20ghasbeenreportedwithnosignificantill-effects.Inductionofvomitingand/orgastriclavage

maybeemployedtogetherwithsymptomaticandsupportivetherapy.

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5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:H2-receptorantagonists

ATCcodeA02BA01

CimetidineisaH

antagonist.ItishighlyselectiveandactsbyantagonisingtheeffectsofhistamineandotherH

agonistsatH

receptorspresentonparietalcells.Thisactionofcimetidineiscompetitiveandresultsininhibitionof

gastricacidsecretioninadose-dependentmanner.Thedegreeofinhibitionparallelstheplasmaconcentrationofthe

drugoverawiderange.

Cimetidineinhibitsbasalandnocturnalsecretionaswellasstimulatedsecretion.Itreducesboththevolumeofgastric

juicesecretedanditshydrogenionconcentration(pH).Outputofpepsin,whichissecretedbythechiefcellsofthe

gastricglands,generallyfallsinparallelwiththereductioninvolumeofthegastricjuice.Concentrationsofgastrinin

theplasmaarenotsignificantlyalteredduringfastingconditions,however,thenormalprandialelevationofgastrinin

theplasmamaybeaugmented.

5.2Pharmacokineticproperties

Cimetidineisrapidlyandalmostcompletelyabsorbed.Hepaticfirst-passmetabolismresultsinbioavailabilityofabout

70%.Absorptionislittleimpairedbyfood.Peakplasmaconcentrationsareattainedinabout1to2hours.Equilibrium

dialysishasshown13to25percentofcimetidinetobeproteinboundinulcerpatients.Theeliminationhalf-lifeis

about2–3hours.Cimetidineiseliminatedprimarilybythekidneys,and60%ormoremayappearintheurine

unchangedwithmuchoftherestasoxidationproducts.Therearethreeknownmetabolicproducts:cimetidine

sulphoxide,hydroxymethylcimetidine,andguanylureacimetidinewhichmaybeformednon-enzymaticallyinvitro.

Smallamountsofcimetidinearerecoveredinthestool.

5.3Preclinicalsafetydata

Nofurtherinformationprovided.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

SodiumLaurilsulfate

MicrocrystallineCellulose

ColloidalAnhydrousSilica

SodiumStarchGlycolateTypeA

MagnesiumStearate

Povidone

FilmCoat

OpadryOY-5912-{Hypromellose

TitaniumDioxide(E171)

Macrogol

QuinolineYellowAluminiumLake(E104)

IronOxideyellow(E172)

FD&CBlue#2/IndigoCarmineAluminiumLake(E132)

6.2Incompatibilities

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6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Blisters

Storebelow25 o

Storeintheoriginalpackageinordertoprotectfrommoisture.

Keeptheblisterintheoutercarton.

6.5Natureandcontentsofcontainer

Blisterpacksconsistingof250µmclearPVCand20µmhardtemperaluminumfoilcontainedinacarton.

Packsizes:

100,120tablets

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

ClonmelHealthcareLimited,

WaterfordRoad,

Clonmel,

Co.Tipperary

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA0126/077/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:06November1989

Dateoflastrenewal:06November2009

10DATEOFREVISIONOFTHETEXT

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