AMOXICILLIN SANDOZ

Main information

  • Trade name:
  • AMOXICILLIN SANDOZ
  • Dosage:
  • 250 Milligram
  • Pharmaceutical form:
  • Capsules Hard
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • AMOXICILLIN SANDOZ
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0111/004/001
  • Authorization date:
  • 23-02-2001
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0111/004/001

CaseNo:2064165

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

SandozGmbH

Biochemiestrasse10,A-6250Kundl,Austria

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

AmoxicillinSandoz250mgcapsules

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom22/07/2009until13/09/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 22/07/2009 CRN 2064165 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AmoxicillinSandoz250mgcapsules.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachcapsulecontains250mgamoxicillin(astrihydrate)

Forafulllistofexcipients,see6.1

3PHARMACEUTICALFORM

Capsule,hard

Yellow,opaquecapsuleswithblackimprintsalternately“AMX”and"250"axially

(ifappropriate)

4CLINICALPARTICULARS

4.1TherapeuticIndications

AmoxicillinSandozisindicatedfortheoraltreatmentofthefollowingbacterialinfectionscausedbyamoxicillin-

sensitivegram-positiveandgram-negativepathogens(seesection5.1.):

Infectionsoftheupperrespiratorytract,includinginfectionsoftheears,noseandthroat:Acuteotitismedia,

acutesinusitisandbacterialpharyngitis

Infectionsofthelowerrespiratorytract:Acuteexacerbationofchronicbronchitis,community-acquired

pneumonia

Infectionsofthelowerurinarytract:Cystitis

Endocarditis:Prophylaxisofendocarditisinpatientsatriski.e.surgeryintheoralcavityorupperairways.

Considerationshouldbegiventoofficiallocalguidance(e.g.nationalrecommendations)ontheappropriateuseof

antibacterialagents.

Susceptibilityofthecausativeorganismtothetreatmentshouldbetested(ifpossible),althoughtherapymaybe

initiatedbeforetheresultsareavailable.

4.2Posologyandmethodofadministration

Posology

Thedosageofamoxicillinisdependentonage,bodyweightandrenalfunctionofthepatient,ontheseriousnessand

localisationoftheinfectionandontheexpectedorprovedcausativeagent.

Standarddosage:

Adultsandadolescents(>40kgbodyweight):

Theusualdosagecoversarangefrom750mgto3gamoxicillindailyinthreedivideddoses.Insomeareas1500mg

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Specialdosagerecommendation

Acuteexacerbationofchronicbronchitisinadults:2x1gperday

Children(under12years)

Forinfantsandchildrenoralsuspensionscontainingamoxicillinarerecommended.

Dosageforthepreventionofendocarditis:

Forthepreventionofendocarditis,inpatientsnothavinggeneralanaesthetic,3gamoxicillinaregiveninthehour

precedingthesurgicalprocedure,followedby(6hourslater)afurther3gdose,ifconsiderednecessary.

Forfurtherdetailsanddescriptionofriskpatientslocalofficialguidelinesforthepreventionofendocarditisshouldbe

consulted

Dosageinimpairedrenalfunction:

Thedoseshouldbereducedinpatientswithsevererenalfunctionimpairment.Inpatientswitharenalclearanceofless

than30ml/minanincreaseinthedosageintervalorareductioninthesubsequentdosesisrecommended(seesection

4.4).Shortcoursetreatmentswithasingledoseof3gcannotbegivenincaseofrenalfailure.

Dosageinimpairedhepaticfunction

Nodosereductionisnecessaryaslongastherenalfunctionisnotimpaired.

Durationoftherapy:

Ingeneralthetherapyshouldbecontinuedfor2to3daysfollowingthedisappearanceofsymptoms.In-haemolytic

streptococcalinfectionsthedurationoftherapyshouldbeatleast10daysinordertoachieveeradicationofthe

organism.

Parenteraltherapyisindicatediftheoralrouteisconsideredimpracticableorunsuitable,andparticularlyfortheurgent

treatmentofsevereinfection.

Methodofadministration:

Thepreparationsareadministeredorally.

AmoxicillinSandozcapsulesshouldbetakenunchewedwithliquid(e.g.aglassofwater).

Theabsorptionofamoxicillinisnotreducedbyfoodintake.

4.3Contraindications

AmoxicillinSandoziscontraindicatedinpatientswith:

Hypersensitivitytopenicillin;across-allergytootherbeta-lactamssuchascephalosporinsshouldbetakeninto

account.

Adultsincludingelderlypatients

Creatinineclearance

ml/min Dose Interval;between

administration

>30 Noadjustmentnecessary

10-30 500mg 12h

<10 500mg 12h

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4.4Specialwarningsandprecautionsforuse

Beforeinitiatingtherapywithamoxicillin,carefulenquiryshouldbemadeconcerningprevioushypersensitivity

reactionstopenicillinsandcephalosporins.Thepossibilityofcross-hypersensitivity(10%-15%)withcephalosporins

shouldbetakenintoaccount.

Seriousandoccasionallyfatalhypersensitivity(anaphylactoid)reactionshavebeenreportedinpatientsonpenicillin

therapy.Thesereactionsaremorelikelytooccurinindividualswithahistoryofhypersensitivitytobeta-lactam

antibiotics.

Patientssufferingfromseveregastrointestinaldisturbanceswithdiarrhoeaandvomitingshouldnotbetreatedwith

AmoxicillinSandoz,duetotheriskofreducedabsorption.Inthesecasesaparenteraltreatmentwithamoxicillinis

advisable.

AmoxicillinSandozshouldbeusedwithcautioninpatientswithallergicdiathesisandasthma.

Inpatientswithrenalfunctionimpairmenttheexcretionofamoxicillinwillbedelayedand,dependingonthedegreeof

theimpairment,itmaybenecessarytoreducethetotaldailydosage(seesection4.2.).

Inpatientswithrenalfunctionimpairmenttheexcretionofamoxicillinwillbedelayedand,dependingonthedegreeof

theimpairment,itmaybenecessarytoreducethetotaldailydosage(seesection4.2.).

Theprolongeduseofamoxicillinmayoccasionallyresultinanovergrowthofnon-susceptibleorganismsoryeasts.

Patientsshouldthereforecarefullybewatchedforsuperinfections.

Theoccurrenceofanaphylacticshockandothersevereallergicreactionsisrarefollowingtheoraladministrationof

amoxicillin.

However,ifsuchreactionsoccur,appropriateemergencytreatmentmeasuresmustbetaken:I.v.administrationof

epinephrine,followedbyantihistaminicdrugs,volumesubstitutionandadministrationofglucocorticoids.Patients

shouldbekeptundercloseobservation,andfurthertherapeuticmeasures(artificialrespiration,oxygen)shouldbe

administeredasrequired.

Thepresenceofhighurinaryconcentrationsofamoxicillincancauseprecipitationoftheproductinurinarycatheters.

Therefore,cathetersshouldbevisuallyinspectedatintervals.

Athighdoses,adequatefluidintakeandurinaryoutputmustbemaintainedtominimisethepossibilityofamoxicillin

crystalluria.

AmoxicillinSandozshouldbeusedwithcautioninpatientswithviralinfections,acutelymphaticleukaemia,or

infectiousmononucleosis(duetoanincreasedriskoferythematousskinrashes).

Pseudomembranouscolitisshouldbeborneinmindifseverepersistentdiarrhoeaoccurs(inmostcasescausedby

Clostridiumdifficile).InthiscaseAmoxicillinSandozshouldbediscontinuedandanadequatetherapyhastobe

started.Theuseofantiperistalticsiscontraindicated.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Concomitantusenotrecommended

Allopurinol

Concomitantadministrationofallopurinolmaypromotetheoccurrenceofallergiccutaneousreactionsandistherefore

notadvised.

Digoxin

Anincreaseintheabsorptionofdigoxinispossibleonconcurrentadministrationwithamoxicillin.Adoseadjustment

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Disulfiram

Simultaneousadministrationofdisulfiramisnotrecommended.

Anticoagulants

Concomitantadministrationofamoxicillinandanticoagulantsfromthecoumarinclass,mayprolongthebleedingtime.

Adoseadjustmentofanticoagulantsmaybenecessary.

Probenecid

Byinhibitingtherenaleliminationofamoxicillintheconcomitantadministrationofprobenecidleadstoanincreasein

theconcentrationsofamoxicillininserumandbile.

Otherantibiotics

Ingeneralamoxicillinshouldnotbecombinedwithbacteriostaticchemotherapeutics/antibiotics(liketetracyclines,

macrolids,sulfonamidsorchloramphenicol),becauseinvitroantagonismisobserved.Whenusedsimultaneouslywith

aminoglycosidesasynergisticeffectmayoccur.

Methotrexate

Interactionbetweenamoxicillinandmethotrexateleadingtomethotrexatetoxicityhasbeenreported.Serum

methotrexatelevelsshouldbecloselymonitoredinpatientswhoreceiveamoxicillinandmethotrexatesimultaneously.

Amoxicillindecreasestherenalclearanceofmethotrexate,probablybycompetitionatthecommontubularsecretion

system.

Cautionisrecommendedwhenamoxicillinisgivenconcomitantlywith:

Oralhormonalcontraceptives

Administrationofamoxicillincantransientlydecreasetheplasmalevelofestrogensandprogesterone,andmayreduce

theefficacyoforalcontraceptives.Itisthereforerecommendedtotakesupplementalnon-hormonalcontraceptive

measures.

Otherformsofinteractions:

Forceddiuresisleadstoareductioninbloodconcentrationsbyincreasedeliminationofamoxicillin.

Theoccurrenceofdiarrhoeamayimpairtheabsorptionofothermedicamentsandconsequentlyadverselyaffect

theefficacy.

Itisrecommendedthatwhentestingforthepresenceofglucoseinurineduringamoxicillintreatment,enzymatic

glucoseoxidasemethodsshouldbeused.Duetothehighurinaryconcentrationsofamoxicillin,falsepositive

readingsarecommonwithchemicalmethods.

Amoxicillinmaydecreasetheamountofurinaryestriolinpregnantwomen.

Athighconcentrations,amoxicillinmaydiminishtheresultsofserumglycemialevels.

Amoxicillinmayinterferewithproteintestingwhencolormetricmethodsareused.

4.6Pregnancyandlactation

Amoxicillinpassestheplacentaandfoetalplasmaconcentrationsareapproximately25-30%ofthematernalplasma

concentrations.

Dataonalimitednumberofexposedpregnanciesindicatenoadverseeffectsofamoxicillinonpregnancyoronthe

healthofthefoetus/new-bornchild.Todate,nootherrelevantepidemiologicaldataareavailable.Animalstudiesdo

notindicatedirectorindirectharmfuleffectswithrespecttopregnancy,embryonal/foetaldevelopment,parturitionor

postnataldevelopment.Cautionshouldbeexercisedwhenprescribingtopregnantwomen.

Amoxicillindiffusesintothebreastmilk(approx.10%ofthecorrespondingserumconcentration)andinrarecasesthis

canleadtodiarrhoeaand/orfungalcolonisationofthemucosaintheinfant.Thepossibilityofsensitisationoftheinfant

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4.7Effectsonabilitytodriveandusemachines

Noeffectsontheabilitytodriveandusemachineshavebeenobserved.

4.8Undesirableeffects

Inthissectionundesirableeffectsaredefinedasfollows:

Verycommon1/10

Common1/100to<1/10

Uncommon1/1,000to<1/100

Rare1/10,000to<1/1,000

Veryrare <1/10,000,notknown(cannotbeestimatedfromtheavailabledata)

Infectionsandinfestations

Uncommon

Superinfectionsandcolonizationwithresistantorganismsoryeastssuchasoralandvaginalcandidiasisafterprolonged

andrepeateduseofamoxicillin.

Bloodandthelymphaticsystemdisorders

Rare

Eosinophiliaandhaemolyticanaemia.

Veryrare

Leucopenia,granulocytopenia,thrombocytopenia,pancytopenia,anaemia,myelosuppression,agranulocytosis,

prolongationofbleedingtime,andprolongationofprothrombintime.Allwerereversibleondiscontinuationof

therapy.

Immunesystemdisorders

Rare

Laryngealoedema,serumsickness,allergicvasculitis,anaphylaxisandanaphylacticshock.

Nervoussystemdisorders

Rare

CNSeffectsincludinghyperkinesia,dizzinessandconvulsions.Convulsionsmayoccurinpatientswithimpairedrenal

functionorinthosereceivinghighdoses.

Gastrointestinaldisorders:

Common

Gastriccomplaints,nausea,lossofappetite,vomiting,flatulence,softstools,diarrhoea,enanthemas(particularlyinthe

regionofthemouth),drymouth,tastedisturbances.Theseeffectsonthegastrointestinalsystemaremostlymildand

frequentlydisappeareitherduringthetreatmentorverysoonaftercompletionoftherapy.Theoccurrenceoftheseside

effectscangenerallybereducedbytakingamoxicillinduringmeals.

Rare

Superficialuperficialdiscolorationoftheteeth(especiallywiththesuspension).Usuallythediscolorationcanbe

removedbyteethbrushing.

Veryrare

Ifsevereandpersistentdiarrhoeaoccurs,theveryrarepossibilityofpseudomembranouscolitisshouldbeconsidered.

Theadministrationofanti-peristalticdrugiscontraindicated.

Developmentofablacktongue.

Hepato-biliarydisorders:

Uncommon

Moderateandtransientincreaseofliverenzymes.

Rare

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Skinandsubcutaneoustissuedisorders:

Common

Cutaneousreactionssuchasexanthema,pruritus,urticaria;thetypicalmorbilliformexanthemaoccurs5-11daysafter

startoftherapy.Immediateappearanceofurticariaindicatesanallergicreactiontoamoxicillinandtherapyshould

thereforebediscontinued.

Rare(seealsosection4.4)

Angioneuroticoedema(Quincke'soedema),erythemamultiformeexsudativum,acutegeneralizedpustulosis,Stevens-

Johnsonsyndrome,toxicepidermalnecrolysis,bullousandexfoliativedermatitis.

Renaldisorders

Rare

Acuteinterstitialnephritis.

Generaldisordersandadministrationsiteconditions

Rare

Drugfever.

4.9Overdose

Symptomsofoverdose:

Amoxicillinisnotgenerallyassociatedwithacutetoxiceffects,evenwhenaccidentallyconsumedinhighdoses.

Overdosagecanleadtosymptomssuchasgastrointestinaldisturbancesandfluidandelectrolyteimbalance.Inpatients

withseverelyimpairedrenalfunction,largeoverdosescanresultinsignsofrenaltoxicity;crystalluriaispossible.

Managementofoverdose:

Thereisnospecificantidoteforanoverdoseofamoxicillin.

Treatmentconsistsprimarilyofadministrationofactivatedcharcoal(agastriclavageisusuallynotnecessary)or

symptomaticmeasures.Particularattentionshouldbepaidtothewaterandelectrolytebalanceofthepatients.

Amoxicillincanbeeliminatedviahaemodialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATC-Code:J01CA04

Pharmacotherapeuticgroup:Beta-lactamantibacterials

Modeofaction

Amoxicillinisanaminobenzylpenicillinthathasabactericidalactionduetoitsinhibitionofthesynthesisofthe

bacterialcellwall.

Mechanismofresistance

Bacteriamayberesistanttoamoxicillin(and,thus,ampicillin)duetoproductionofbeta-lactamaseswhichhydrolyse

aminopenicillins(hydrolysiswhichcanbeinhibitedbyclavulanicacid),duetoalterationinpenicillin-bindingproteins,

duetoimpermeabilitytothedrug,orduetodrugeffluxpumps.Oneormoreofthesemechanismsmayco-existinthe

sameorganism,leadingtoavariableandunpredictablecross-resistancetootherbeta-lactamsandtoantibacterialdrugs

ofotherclasses.

Breakpoints(CLSI)

Enterobacteriaceae:S ≤8µg/ml;I=16µg/ml;R≥32µg/ml

Staphylococcusspp.: S ≤4µg/ml;R≥8µg/ml

Haemophilusspp.:S ≤1µg/ml;R≥4µg/ml

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Susceptibility:

Theprevalenceofresistancemayvarygeographicallyandwithtimeforselectedspeciesandlocalinformationon

resistanceisdesirable,particularlywhentreatingsevereinfections.Asnecessary,expertadviceshouldbesoughtwhen

thelocalprevalenceofresistanceissuchthattheutilityoftheagentinatleastsometypesofinfectionsisquestionable.

*Clinicalefficacyhasbeendemonstratedforsusceptibleisolatesinapprovedclinicalindications

Commonlysusceptiblespecies

AerobicGram-positive

Bacillusanthracis

Listeriamonocytogenes

Staphylococcusaureus(beta-lactamasenegative,methicillinsusceptible)

Streptococcusagalactiae

Streptococcusbovis

Streptococcuspyogenes*

AerobicGram-negative

Neisseriameningitidis

Anaerobes

Peptostreptococci

Speciesforwhichacquiredresistancemaybeaproblem

AerobicGram-positive

Corynebacteriumspp

Enterococcusfaecalis

Streptococcuspneumoniae* +

Streptococcusviridans

AerobicGram-negative

Haemophilusinfluenzae*

Haemophiluspara-influenzae*

Neisseriagonorrhoea

Proteusmirabilis

Anaerobes

Bacteroidesmelaninogenicus

Fusobacteriumspp

Inherentlyresistantorganisms

AerobicGram-positive

Staphylococcus(-lactamaseproducingstrains)

AerobicGram-negative

Acinetobacterspp

Citrobacterspp

Enterobacterspp

Escherichiacoli

Klebsiellaspp

Moraxellacatarrhalis*

Proteusspp(indolpositive)

Proteusvulgaris

Providenciaspp

Pseudomonasspp

Serratiaspp

Anaerobes

Bacteroidesfragilis

Others

Chlamydia

Mycoplasma

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5.2Pharmacokineticproperties

Absorption:

Theabsolutebioavailabilityofamoxicillindependsonthedoseandrangesbetween75and90%.Inthedoserange

between250mgand750mgthebioavailability(parameters:AUCand/orrecoveryinurine)islinearlyproportionalto

thedose.Athigherdosestheextentofabsorptiondecreases.Theabsorptionisnotaffectedbyconcomitantfoodintake.

Oraladministrationofasingledoseof500mgamoxicillinresultsinplasmaconcentrationsof6-11mg/l.After

administrationofasingledoseof3gamoxicillin,theplasmaconcentrationsreach27mg/l.Peakplasmaconcentrations

arepresentabout1-2hoursafteradministration.

Distribution:

Proteinbindingforamoxicillinisapproximately17%.Therapeuticdruglevelsarerapidlyachievedinserum,lung

tissue,bronchialsecretions,middleearfluid,bileandurine.Inhealthymeningesamoxicillindiffusesbadlyinliquor

cerebrospinalis.Ininflamedmeningestheconcentrationcanreachapproximately20%oftheconcentrationinblood.

Amoxicillincrossestheplacentaandasmallpercentageisexcretedintothebreastmilk.

Biotransformationandelimination:

Themainrouteofexcretionofamoxicillinisthekidney.About60-80%ofanoraldoseofamoxicillinareexcretedin

unchangedactiveformintheurinewithin6hoursofadministration,andasmallfractionisexcretedinthebile.

Approximately7-25%oftheadministereddoseismetabolisedtoinactivepenicilloicacid.Theserumhalf-lifein

patientswithnormalrenalfunctionisapproximately1–1,5hour.Inpatientswithend-stagerenalfailurethehalf-life

rangesbetween5to20hours.Thesubstanceishaemodialysable.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicityandtoxicitytoreproduction.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

CapsuleContents:

Magnesiumstearate

Cellulose,microcrystalline

CapsuleShell:

Yellowironoxide(E-172)

Titaniumdioxide(E-171)

Gelatin

Blackprintingink:

Shellac

Soybeanlecithin

Dimeticone

Blackironoxide(E-172)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

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6.4Specialprecautionsforstorage

Donotstoreabove25°C

6.5Natureandcontentsofcontainer

Nature: Blisterconsistingofaclearpolyvinylchloridefoilwithacoatingofpolyvinylidenechloride(PVC/PVDC)

236µmandaluminiumfoil20µm.

Contents: AmoxicillinSandoz250mgCapsules:

singlepacksfor12,21and100capsules

hospitalpacksfor500and1000capsules

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

None.

7MARKETINGAUTHORISATIONHOLDER

SandozGmbH

Biochemiestrasse10

A-6250Kundl

Austria

8MARKETINGAUTHORISATIONNUMBER

PA0111/004/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:23February2001

Dateoflastrenewal: 14September2005

10DATEOFREVISIONOFTHETEXT

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