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Ranitidine50mg/2mlSolutionforInjectionandInfusion
SummaryofProductCharacteristicsUpdated05May2015|AlliancePharmaceuticals

1.Nameofthemedicinalproduct
Ranitidine50mg/2mlSolutionforInjectionandInfusion

2.Qualitativeandquantitativecomposition
Eachonemlofsolutioncontains25mgranitidineasranitidinehydrochloride.Each2mlampoulecontains50mg
ranitidine.
Excipient(s)withknowneffect:
Disodiumhydrogenphosphatedihydrate
Sodiumchloride.
Forafulllistofexcipients,seesection6.1.

3.Pharmaceuticalform
SolutionforInjectionandInfusion
Clear,colourlesssolution.

4.Clinicalparticulars
4.1Therapeuticindications
RanitidineSolutionforInjectionisindicatedforthetreatmentofduodenalulcer,benigngastriculcer,postoperative
ulcer,andofZollingerEllisonSyndrome.Inthemanagementofconditionswherereductionofgastricsecretionand
acidoutputisdesirable,suchasrefluxoesphagitis.
Asprophylaxisagainst:
gastrointestinalhaemorrhagefromstressulcerationinseriouslyillpatients
recurrenthaemorrhageinpatientswithbleedingpepticulcers
acidaspiration(Mendelson'sSyndrome)beforeanaesthesiainpatientsatrisk,particularlyobstetricpatientsduring
labour.
Children(6monthsto18years)
shorttermtreatmentofpepticulcer
treatmentofgastrooesophagealreflux,includingrefluxoesophagitisandsymptomaticreliefofgastrooesophageal
refluxdisease.
4.2Posologyandmethodofadministration
(SeeSection5.2PharmacokineticPropertiesSpecialPatientPopulations)
Adults(includingelderly)andadolescents(12yearsandolder)
RanitidineSolutionforInjectionmaybegivenas:
aslowintravenousinjection(overtwominutes)uptoamaximumof50mg,afterdilutiontoavolumeof20mlper50
mgdose.Thisdosemayberepeatedevery6to8hoursor
asanintermittentintravenousinfusionatarateof25mgperhourfortwohours.Theinfusionmayberepeatedat6to
8hourintervalsor
asanintramuscularinjectionof50mg(2ml)every6to8hours.
Prophylaxisofhaemorrhagefromstressulcerationorrecurrenthaemorrhage:
Intheprophylaxisofhaemorrhagefromstressulcerationinseriouslyillpatientsortheprophylaxisofrecurrent
haemorrhageinpatientsbleedingfrompepticulceration,parenteraladministrationmaybecontinueduntiloralfeeding
commences.PatientsconsideredtobestillatriskmaythenbetreatedorallywithRanitidinetablets150mgtwicedaily.
Intheprophylaxisofuppergastrointestinalhaemorrhagefromstressulcerationinseriouslyillpatientsaprimingdose
of50mgasaslowintravenousinjectionfollowedbyacontinuousintravenousinfusionof0.1250.250mg/kg/hrmay
bepreferred.
ProphylaxisofMendelson'ssyndrome:
Inpatientsconsideredatriskofdevelopingacidaspiration(Mendelson's)syndrome,RanitidineSolutionforInjection50
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mgmaybegivenintramuscularlyorbyslowintravenousinjection,45to60minutesbeforeinductionofgeneral
anaesthesia.
Children/Infant(6monthsto11years)
Seesection5.2PharmacokineticPropertiesSpecialPatientPopulations
RanitidineInjectionmaybegivenasaslow(over2minutes)i.v.injectionuptoamaximumof50mgevery6to8hours.
PepticUlcerAcuteTreatmentandGastroOesophagealReflux
Intravenoustherapyinchildrenwithpepticulcerdiseaseisindicatedonlywhenoraltherapyisnotpossible.
Foracutetreatmentofpepticulcerdiseaseandgastrooesophagealrefluxinpaediatricpatients,Ranitidineinjection
maybeadministeredatdosesthathavebeenshowntobeeffectiveforthesediseasesinadultsandeffectiveforacid
suppressionincriticallyillchildren.Theinitialdose(2.0mg/kgor2.5mg/kg,maximum50mg)maybeadministeredas
aslowintravenousinfusionover10minutes,eitherwithasyringepumpfollowedbya3mlflushwithnormalsalineover
5min,orfollowingdilutionwithnormalsalineto20ml.MaintenanceofpH>4.0canbeachievedbyintermittentinfusion
of1.5mg/kgevery6hto8h.Alternativelytreatmentcanbecontinuous,administeringaloadingdoseof0.45mg/kg
followedbyacontinuousinfusionof0.15mg/kg/hr.
Neonates(under1month)
SeeSection5.2PharmacokineticPropertiesSpecialPatientPopulations.
Patientsover50yearsofage
SeeSection5.2Pharmacokineticproperties(SpecialPatientPopulations,Patientsover50yearsofage).
RenalImpairment
Accumulationofranitidinewithresultingelevatedplasmaconcentrationswilloccurinpatientswithrenalimpairment
(creatinineclearancelessthan50ml/min).Itisrecommendedinsuchpatientsthatranitidinebeadministeredindoses
of25mg.
RouteofAdministration
Intravenousorintramuscularinjection
4.3Contraindications
Hypersensitivitytotheactivesubstanceortoanyoftheexcipientslistedinsection6.1.
4.4Specialwarningsandprecautionsforuse
TreatmentwithahistamineH2antagonistmaymaskthesymptomsassociatedwithcarcinomaofthestomachand
maythereforedelaydiagnosisofthecondition.Wheregastriculcerissuspected,thepossibilityofmalignancyshould
beexcludedbeforetherapywithranitidineisstarted.
Ranitidineisexcretedviathekidneyandsoplasmalevelsofthedrugareincreasedinpatientswithrenalimpairment.
ThedosageshouldbeadjustedasdetailedinSection4.2PosologyandMethodofAdministration.
Bradycardiainassociationwithrapidadministrationofranitidineinjectionhasbeenreportedrarely,usuallyinpatients
withfactorspredisposingtocardiacrhythmdisturbances.Recommendedratesofadministrationshouldnotbe
exceeded.
IthasbeenreportedthattheuseofhigherthanrecommendeddosesofintravenousH2antagonistshasbeen
associatedwithrisesinliverenzymeswhentreatmenthasbeenextendedbeyondfivedays.
Althoughclinicalreportsofacuteintermittentporphyriaassociatedwithranitidineadministrationhavebeenrareand
inconclusive,ranitidineshouldbeavoidedinpatientswithahistoryofthiscondition.
Inpatientssuchastheelderly,personswithchroniclungdisease,diabetesortheimmunocompromised,theremaybe
anincreasedriskofdevelopingcommunityacquiredpneumonia.Alargeepidemiologicalstudyshowedanincreased
riskofdevelopingcommunityacquiredpneumoniaincurrentusersofH2receptorantagonistsversusthosewhohad
stoppedtreatment,withanobservedadjustedrelativeriskincreaseof1.82(95%CI,1.262.64)..
Postmarketingdataindicatereversiblementalconfusion,depression,andhallucinationshavebeenreportedmost
frequentlyinseverelyillandelderlypatients.(SeeSection4.8Undesirableeffects).
4.5Interactionwithothermedicinalproductsandotherformsofinteraction
Ranitidinehasthepotentialtoaffecttheabsorption,metabolismorrenalexcretionofotherdrugs.Thealtered
pharmacokineticsmaynecessitatedosageadjustmentoftheaffecteddrugordiscontinuationoftreatment.
Interactionsoccurbyseveralmechanismsincluding:
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1)InhibitionofcytochromeP450linkedmixedfunctionoxygenasesystem:
Ranitidine,atbloodlevelsproducedbystandarddoses,doesnotinhibitorinteractsignificantlywiththehepatic
cytochromeP450linkedmixedfunctionoxygenasesystem.
Accordingly,ranitidineinusualtherapeuticdoses,doesnotpotentiatetheactionsofdrugswhichareinactivatedbythis
enzymetheseincludediazepam,lidocaine,phenytoin,propranololandtheophylline.
Therehavebeenreportsofalteredprothrombintimewithcoumarinanticoagulants(e.g.warfarin).Duetothenarrow
therapeuticindex,closemonitoringofincreasedordecreasedprothrombintimeisrecommendedduringconcurrent
treatmentwithranitidine.
2)Competitionforrenaltubularsecretion:
Sinceranitidineispartiallyeliminatedbythecationicsystem,itmayaffecttheclearanceofotherdrugseliminatedby
thisroute.Highdosesofranitidine(e.g.suchasthoseusedinthetreatmentofZollingerEllisonsyndrome)mayreduce
theexcretionofprocainamideandNacetylprocainamideresultinginincreasedplasmalevelofthesedrugs.
3)AlterationofgastricpH:
Thebioavailabilityofcertaindrugsmaybeaffected.Thiscanresultineitheranincreaseinabsorption(e.g.triazolam,
midazolam,glipizide)oradecreaseinabsorption(e.g.ketoconazole,atazanavir,delaviridine,gefitnib).
4.6Fertility,pregnancyandlactation
Ranitidinecrossestheplacentabuttherapeuticdosesadministeredtoobstetricpatientsinlabourorundergoing
caesareansectionhavebeenwithoutanyadverseeffectonlabour,deliveryorsubsequentneonatalprogress.Ranitidine
isalsoexcretedinhumanbreastmilk.Likeotherdrugs,ranitidineshouldonlybeusedduringpregnancyorlactationif
consideredessentialbyaphysician.
Therearenotdataontheeffectsofranitidineonhumanfertility.Therewerenoeffectsonmaleandfemalefertilityin
animalstudies.
4.7Effectsonabilitytodriveandusemachines
Noneknown.
4.8Undesirableeffects
Thefollowingconventionhasbeenutilisedfortheclassificationofundesirableeffects:verycommon(1/10),common
(1/100,<1/10),uncommon(1/1000,1/100),rare(1/10,000,1/1000),veryrare(1/10,000).Adverseevent
frequencieshavebeenestimatedfromspontaneousreportsfrompostmarketingdata).
Blood&LymphaticSystemDisorders
Veryrare:

Bloodcountchanges(leucopenia,thrombocytopenia).Theseareusually
reversible.Agranulocytosisorpancytopenia,sometimeswithmarrowhypoplasia
ormarrowaplasia.

ImmuneSystemDisorders
Rare:

Hypersensitivityreactions(urticaria,angioneuroticoedema,fever,bronchospasm,
hypotensionandchestpain).

Veryrare:

Anaphylacticshock
Theseeventshavebeenreportedafterasingledose.

Unknown

Dyspnoea

PsychiatricDisorders
Veryrare:

Reversiblementalconfusion,depressionandhallucinations.
Theseadversereactionshavebeenreportedpredominantlyinseverelyill
patients,intheelderlyandinnephropathypatients.

NervousSystemDisorders
Veryrare:

Headache(sometimessevere),dizzinessandreversibleinvoluntarymovement
disorders.

EyeDisorders
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Veryrare:

Reversibleblurredvision.
Therehavebeenreportsofblurredvision,whichissuggestiveofachangein
accommodation.

CardiacDisorders
Veryrare:

AswithotherH2receptorantagonistsbradycardia,AVBlock,tachycardiaand
asystole.

VascularDisorders
Veryrare:

Vasculitis.

GastrointestinalDisorders
Uncommon:

Abdominalpain,constipation,nausea(thesesymptomsmostlyimprovedduring
continuedtreatment).

Veryrare:

Acutepancreatitis,diarrhoea.

HepatobiliaryDisorders
Rare:

Transientandreversiblechangesinliverfunctiontests.

Veryrare:

Hepatitis(hepatocellular,hepatocanalicularormixed)withorwithoutjaundice,
thesewereusuallyreversible.

SkinandSubcutaneousTissueDisorders
Rare:

SkinRash.

Veryrare:

Erythemamultiforme,alopecia.

MusculoskeletalandConnectiveTissueDisorders
Veryrare:

Musculoskeletalsymptomssuchasarthralgiaandmyalgia.

RenalandUrinaryDisorders
Rare:

Elevationofplasmacreatinine(usuallyslightnormalisedduringcontinued
treatment).

Veryrare:

Acuteinterstitialnephritis.

ReproductiveSystemandBreastDisorders
Veryrare:

Reversibleimpotence,breastsymptomsandbreastconditions(suchas
gynaecomastiaandgalactorrhoea).

Thesafetyofranitidinehasbeenassessedinchildrenaged0to16yearswithacidrelateddiseaseandwasgenerally
welltoleratedwithanadverseeventprofileresemblingthatinadults.Therearelimitedlongtermsafetydataavailable,
inparticularregardinggrowthanddevelopment.
Reportingofsuspectedadversereactions
Reportingsuspectedadversereactionsafterauthorisationofthemedicinalproductisimportant.Itallowscontinued
monitoringofthebenefit/riskbalanceofthemedicinalproduct.Healthcareprofessionalsareaskedtoreportany
suspectedadversereactionsviatheYellowCardSchemeat:www.mhra.gov.uk/yellowcard.
4.9Overdose
Ranitidineisveryspecificinactionandaccordingly,noparticularproblemsareexpectedfollowingoverdosagewiththe
drug.Symptomaticandsupportivetherapyshouldbegivenasappropriate.Ranitidinemayberemovedby
haemodialysis.

5.Pharmacologicalproperties
5.1Pharmacodynamicproperties
Pharmacotherapeuticgroup:H2receptorantagonist.
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ATCcode:A02BA02
Ranitidineisaspecific,rapidlyactinghistamineH2antagonist.Itinhibitsbasalandstimulatedsecretionofgastricacid,
reducingboththevolume,andtheacidandpepsincontentofthesecretion.
Theclinicaldataavailablementionstheuseofranitidineinchildrentopreventstressulcers.Nodirectevidencefor
preventionofstressulcersisavailable.TreatmentforthesepatientsisbasedontheobservationthatpHisabove4
afteradministrationofranitidine.Thevalueofthissurrogateparameterinchildrenwithstressulcersremainstobe
established.
5.2Pharmacokineticproperties
Absorption
Absorptionofranitidineafterintramuscularinjectionisrapidandpeakplasmaconcentrationsareusuallyachievedwithin
15minutesofadministration.
Distribution
Ranitidineisnotextensivelyboundtoplasmaproteins(15%),butexhibitsalargevolumeofdistributionrangingfrom96
to142L.
Metabolism
Ranitidineisnotextensivelymetabolised.Thefractionofthedoserecoveredasmetabolitesissimilarafterbothoral
andi.v.dosingandincludes6%ofthedoseinurineastheNoxide,2%astheSoxide,2%asdesmethylranitidineand
1to2%asthefuroicacidanalogue.
Elimination
Plasmaconcentrationsdeclinebiexponentially,withaterminalhalflifeof23hours.Themajorrouteofeliminationis
renal.AfterIVadministrationof150mg3Hranitidine,98%ofthedosewasrecovered,including5%infaecesand93%
inurine,ofwhich70%wasunchangedparentdrug.Afteroraladministrationof150mg3Hranitidine,96%ofthedose
wasrecovered,26%infaecesand70%inurineofwhich35%wasunchangedparentdrug.Lessthan3%ofthedoseis
excretedinbile.Renalclearanceisapproximately500mL/min,whichexceedsglomerularfiltrationindicatingnetrenal
tubularsecretion
SpecialPatientPopulations
Children/infants(6monthsandabove)
Limitedpharmacokineticdatashowthattherewerenosignificantdifferencesinhalflife(rangeforchildren3yearsand
above:1.72.2h)andplasmaclearance(rangeforchildren3yearsandabove:922ml/min/kg)betweenchildrenand
healthyadultsreceivingintravenousranitidinewhencorrectionismadeforbodyweight.Pharmacokineticdataininfants
isextremelylimitedbutappearstobeinlinewiththatforolderchildren.
Patientsover50yearsofage
Inpatientsover50yearsofage,halflifeisprolonged(34h)andclearanceisreduced,consistentwiththeagerelated
declineofrenalfunction.However,systemicexposureandaccumulationare50%higher.Thisdifferenceexceedsthe
effectofdecliningrenalfunction,andindicatesincreasedbioavailabilityinolderpatients.
Neonates(under1month)
LimitedpharmacokineticdatafromtermbabiesundergoingtreatmentwithExtracorporealMembraneOxygenation
(EMCO)suggeststhatplasmaclearancefollowingivadministrationmaybereduced(1.58.2ml/min/kg)andthehalflife
increasedinthenewborn.Clearanceofranitidineappearedtoberelatedtotheestimatedglomerularfiltrationrateinthe
neonates.
5.3Preclinicalsafetydata
Nonclinicaldatarevealednospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,
repeateddosetoxicity,genotoxicity,carcinogenicpotentialandtoxicitytoreproductionanddevelopment.

6.Pharmaceuticalparticulars
6.1Listofexcipients
Potassiumdihydrogenphosphate
Disodiumhydrogenphosphatedihydrate
Sodiumchloride
WaterforInjections
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6.2Incompatibilities
None
6.3Shelflife
2years
6.4Specialprecautionsforstorage
Donotstoreabove25C.Keepampoulesintheoutercartoninordertoprotectfromlight.
6.5Natureandcontentsofcontainer
2mlsolutioninamber,type1glassampoules.
Packsize:5ampoules
6.6Specialprecautionsfordisposalandotherhandling
RanitidineInjectionhasbeenshowntobecompatiblewiththefollowingintravenousinfusionfluids:
SodiumChloride0.9%w/v
Dextrose5%w/v
SodiumChloride0.18%w/vandDextrose4%w/v
SodiumBicarbonate4.2%w/v
Hartmann'ssolution
Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotusedimmediately,inusestorage
timesandconditionspriortousearetheresponsibilityoftheuserandwouldnormallynotbelongerthan24hoursat2
to8C,unlesspreparationofsolutionshastakenplaceincontrolledandvalidatedasepticconditions.
AllsolutionsofRanitidineSolutionforInjectionshouldbediscardedafteruse.

7.Marketingauthorisationholder
AlliancePharmaceuticalsLimited
AvonbridgeHouse
BathRoad
Chippenham
Wiltshire
SN152BB

8.Marketingauthorisationnumber(s)
PL16853/0130

9.Dateoffirstauthorisation/renewaloftheauthorisation
21October2008

10.Dateofrevisionofthetext
February2015

CompanyContactDetails
AlliancePharmaceuticals
http://www.alliancepharma.co.uk
Address
AvonbridgeHouse,BathRoad,Chippenham,
Wiltshire,SN152BB
Fax
+44(0)1249466977

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Telephone
+44(0)1249466966
MedicalInformationemail
medinfo@alliancepharma.co.uk

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