ALLOPURINOL TEVA

Main information

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

Documents

Localization

  • Available in:
  • ALLOPURINOL TEVA
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0749/099/002
  • Authorization date:
  • 10-09-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AllopurinolTeva200mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

EachAllopurinoltabletcontains200mgofallopurinol.

Excipient(s):

Each200mgtabletcontainslactosemonohydrate,equivalentto114mglactose.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablets

White,roundbiconvextablets,debossed3K1ononeside,plainontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Adults

Childrenandadolescents

4.2Posologyandmethodofadministration

Fororaluse.

Methodofadministration:

Allopurinolmaybetakenorallyonceaday.Toincreasegastrointestinaltolerability,itshouldbetakenafterameal.If

thedailydosageexceeds300mgandgastrointestinalintoleranceisevident,adivideddosageregimenmaybe

appropriate.

Adults:

2-10mg/kgbodyweight/dayor100-200mgdailyinmildconditions,300-600mgdailyinmoderatelysevere

conditions,or700-900mgdailyinsevereconditions.Allopurinolshouldbeintroducedatlowdosagee.g.100mg/day

toreducetheriskofadversereactionsandincreasedonlyiftheserumurateresponseisunsatisfactory.Extracaution

shouldbeexercisedifrenalfunctionispoor(seeDosagerecommendationsinrenaldisorders).

Children(uptotheageof15)

Allformsofhyperuricaemianotcontrollablebydietincludingsecondaryhyperuricaemiaofdifferingoriginand

inclinicalcomplicationsofhyperuricaemicstates,particularlymanifestgout,uratenephropathyandforthe

dissolutionandpreventionofuricacidstones

Themanagementofrecurrentmixedcalciumoxalatestonesinconcurrenthyperuricaemia,whenfluid,dietaryand

similarmeasureshavefailed.

Secondaryhyperuricaemiaofdifferingorigin

Uricacidnephropathyduringtreatmentofleukaemia

Hereditaryenzymedeficiencydisorders,Lesch-Nyhansyndrome(partialortotalhypoxanthin-guanin

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Useinchildrenisrarelyindicatedexceptinmalignantconditions,especiallyinleukaemiaandcertainenzyme

disorders,forexampleLesch-Nyhansyndrome.

Elderly:

Nospecificdosagerecommendations,thelowestdosagewhichproducessatisfactoryuratereductionshouldbeused.

RefertodosageadviceunderDosagerecommendationsinrenaldisorders(alsoseesection4.4Specialwarningsand

precautionsforuse).

Dosagerecommendationsinrenaldisorders:

Allopurinolanditsmetabolitesareexcretedbythekidney;thereforeimpairmentofrenalfunctionmayleadtoretention

ofthedrugand/oritsmetabolites.Theplasmahalflivesmayasaconsequencebeprolonged.Thefollowingschedule

mayserveasguidancefordoseadjustmentsatrenalimpairment:

Creatinineclearance Dosage

>20ml/min normaldose

10-20ml/min 100-200mgperday

<10ml/min 100mg/dayorlongerdoseintervals

Seriousconsiderationshouldbegiveninthepresenceofimpairedrenalfunction,toinitiatingtreatmentwitha

maximumdoseof100mg/dayandincreasingitonlyiftheserumand/orurinaryrateresponseisunsatisfactory.In

severerenalinsufficiency,itmaybeadvisabletouselessthan100mg/dayortousesingledosesof100mgatlonger

intervalsthanoneday.

Ifplasmaoxipurinolconcentrationmonitoringisavailable,thedoseshouldbeadjustedtomaintainplasmaoxipurinol

levelsbelow100micromol/Litre(15.2microgram/ml).

Doserecommendationsinrenaldialysis:

Allopurinolanditsmetabolitesareremovedbyrenaldialysis.Ifdialysisisrequiredtwotothreetimesaweek

considerationshouldbegiventoanalternativedosagescheduleof300-400mgallopurinolimmediatelyaftereach

dialysiswithnoneintheinterim.

Dosageinhepaticimpairment:

Reduceddosesshouldbeusedinpatientswithhepaticimpairment.Periodicliverfunctiontestsarerecommended

duringtheearlystagesoftherapy.

Treatmentofhighurateturnoverconditionse.g.neoplasia,Lesch-Nyhansyndrome:

Itisadvisabletocorrectexistinghyperuricaemiaand/orhyperuricosuriawithallopurinolbeforecommencingcytotoxic

therapy.Itisimportanttoensureadequatehydrationtomaintainoptimumdiuresisandtoattemptalkalinisationof

urinetoincreasesolubilityofurinaryurate/uricacid.Thedoseofallopurinolshouldbeinthelowerrange.

Ifuratenephropathyorotherpathologyhascompromisedrenalfunction,adviceprovidedinDosagerecommendations

inrenaldisordershouldbefollowed.

Thesestepsmayreducetheriskofxanthineand/oroxipurinoldepositioncomplicatingtheclinicalsituation.(see

sections4.5Interactionwithothermedicinalproductsandotherformsofinteractionand4.8Undesirableeffects).

MonitoringAdvise:Dosageshouldbeadjustedbymonitoringserumurateconcentrationsandurinaryurate/uricacid

levelsatappropriateintervals.

4.3Contraindications

Hypersensitivitytoallopurinolortoanyoftheexcipients.

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Acutegoutyattacks:Allopurinoltreatmentshouldnotbestarteduntilanacuteattackofgouthascompletelysubsided,

asfurtherattacksmaybeprecipitated.

Intheearlystagesoftreatmentwithallopurinol,aswithuricosuricagents,anacuteattackofgoutyarthritismaybe

precipitated.Thereforeitisadvisabletogiveprophylaxiswithasuitableanti-inflammatoryagentorcolchicineforat

leastonemonth.Theliteratureshouldbeconsultedfordetailsofappropriatedosageandprecautionsandwarnings.

Ifacuteattacksdevelopinpatientsreceivingallopurinol,treatmentshouldcontinueatthesamedosagewhiletheacute

attackistreatedwithasuitableanti-inflammatoryagent.

Allopurinolshouldnotbeprescribedtopatientstreatedwithazathioprineor6-mercaptopurineunlessthedoseofthese

drugsisreducedtoone-quarterofthepreviouslyprescribeddose(seesection4.5).

Allopurinolshouldbewithdrawnimmediatelywhenaskinrashorotherevidenceofsensitivityoccurs.Reduceddoses

shouldbeusedinpatientswithhepaticorrenalimpairment.Patientsundertreatmentforhypertensionorcardiac

insufficiency,forexamplewithdiureticsorACEinhibitors,mayhavesomeconcomitantimpairmentofrenalfunction

andallopurinolshouldbeusedwithcareinthisgroup.

Asymptomatichyperuricaemiaperseisgenerallynotconsideredanindicationforuseofallopurinol.Fluidanddietary

modificationwithmanagementoftheunderlyingcausemaycorrectthecondition.

Xanthinedeposition:Inconditionswheretherateofurateformationisgreatlyincreased(e.g.malignantdiseaseandits

treatment,Lesch-Nyhansyndrome)theabsoluteconcentrationofxanthineinurinecould,inrarecases,risesufficiently

toallowdepositionintheurinarytract.Thisriskmaybeminimisedbyadequatehydrationtoachieveoptimalurine

dilution.

Impactionofuricacidrenalstones:Adequatetherapywithallopurinolwillleadtodissolutionoflargeuricacidrenal

pelvicstones,withtheremotepossibilityofimpactionintheureter.

Inthetreatmentofrenalgoutanduricacidstones,thevolumeofurineproducedshouldbeatleast2litresperdayand

theurinarypHshouldbekeptintherangeof6.4–6.8.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactosedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

6-mercaptopurineandazathioprine:Atconcomitantadministrationwithallopurinol,thedoseof6-mercaptopurineor

azathioprineshouldbereducedto25%oftheusualdose.Allopurinolisaninhibitorofxanthineoxidaseand

counteractsthemetabolicinactivationofazathioprineand6-mercaptopurine.Serumconcentrationsofthesemedicinal

productscanreachtoxiclevelsunlessdosereductionisundertaken.

Vidarabine(AdenineArabinoside):Evidencesuggeststhattheplasmahalf-lifeofvidarabineisincreasedinthe

presenceofallopurinol.Whenthetwoproductsareusedconcomitantlyextravigilanceisnecessary,torecognise

enhancedtoxiceffects.

Salicylatesanduricosuricagents:Oxipurinol,themajormetaboliteofallopurinolanditselftherapeuticallyactive,is

excretedbythekidneyinasimilarwaytourate.Hence,drugswithuricosuricactivitysuchasprobenecidorlarge

dosesofsalicylatemayacceleratetheexcretionofoxipurinol.Thismaydecreasethetherapeuticactivityof

allopurinol,butthesignificanceneedstobeassessedineachcase.

Chlorpropamide:Ifallopurinolisgivenconcomitantlywithchlorpropamidewhenrenalfunctionispoor,theremaybe

anincreasedriskofprolongedhypoglycaemicactivitybecauseallopurinolandchlorpropamidemaycompetefor

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Coumarinanticoagulants:Therehavebeenrarereportsofincreasedeffectofwarfarinandothercoumarin

anticoagulantswhenco-administeredwithallopurinoltherefore,allpatientsreceivinganticoagulantsmustbecarefully

monitored.

Phenytoin:Allopurinolmayinhibithepaticoxidationofphenytoinbuttheclinicalsignificancehasnotbeen

demonstrated.

Theophylline:Inhibitionofthemetabolismoftheophyllinehasbeenreported.Themechanismoftheinteractionmay

beexplainedbyxanthineoxidasebeinginvolvedinthebiotransformationoftheophyllineinman.Theophyllinelevels

shouldbemonitoredinpatientsstartingorincreasingallopurinoltherapy.

Ampicillin/Amoxicillin:Anincreaseinfrequencyofskinrashhasbeenreportedamongpatientsreceivingampicillinor

amoxicillinconcurrentlywithallopurinolcomparedtopatientswhoarenotreceivingbothdrugs.Thecauseofthe

reportedassociationhasnotbeenestablished.However,itisrecommendedthatinpatientsreceivingallopurinolan

alternativetoampicillinoramoxicillinisusedwhereavailable.

Cyclophosphamide,doxorubicin,bleomycin,procarbazine,mechloroethamine:Enhancedbonemarrowsuppressionby

cyclophosphamideandothercytotoxicagentshasbeenreportedamongpatientswithneoplasticdisease(otherthan

leukaemia),inthepresenceofallopurinol. However,inawell-controlledstudyofpatientstreatedwith

cyclophosphamide,doxorubicin,bleomycin,procarbazineand/ormechloroethamine(chlormethinehydrochloride)

allopurinoldidnotappeartoincreasethetoxicreactionofthesecytotoxicagents.

Ciclosporin:Reportssuggestthattheplasmaconcentrationofciclosporinmaybeincreasedduringconcomitant

treatmentwithallopurinol.Thepossibilityofenhancedciclosporintoxicityshouldbeconsideredifthedrugsareco-

administered.

Didanosine:InhealthyvolunteersandHIVpatientsreceivingdidanosine,plasmadidanosineC

andAUCvalues

wereapproximatelydoubledwithconcomitantallopurinoltreatment(300mgdaily)withoutaffectingterminalhalf

life.Co-administrationofthese2drugsisgenerallynotrecommended.Ifconcomitantuseisunavoidable,adose

reductionofdidanosinemayberequired,andpatientsshouldbecloselymonitored.

Captopril:Withconcomitantadministrationofallopurinolandcaptopril,theriskofskinreactionscanberaised,

especiallyincasesofchronicrenalfailure.

4.6Pregnancyandlactation

Thereisinsufficientevidenceofthesafetyofallopurinolinhumanpregnancy.Animalreproductivetoxicitystudies

haveshownconflictingresults(seesection5.3).

Allopurinolshouldbeusedinpregnancyonlywherethereisnosaferalternativeandwhenthediseaseitselfcarries

risksforthemotherorchild.

Reportsindicatethatallopurinolandoxipurinolareexcretedinhumanbreastmilk.Concentrationsof1.4mg/litre

allopurinoland53.7mg/litreoxipurinolhavebeendemonstratedinbreastmilkfromwomantakingallopurinol300

mg/day.However,therearenodataconcerningtheeffectsofallopurinoloritsmetabolitesonthebreast-fedbaby.

Adecisionmustbemadewhethertodiscontinuebreast-feedingortodiscontinue/abstainfromallopurinoltherapy

takingintoaccountthebenefitofbreastfeedingforthechildandthebenefitoftherapyforthewoman.

4.7Effectsonabilitytodriveandusemachines

Sinceadversereactionssuchasvertigo,somnolenceandataxiahavebeenreportedinpatientsreceivingallopurinol,

patientsshouldexercisecautionbeforedriving,usingmachineryorparticipatingindangerousactivitiesuntiltheyare

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4.8Undesirableeffects

Forthisproductthereisnomodernclinicaldocumentationwhichcanbeusedassupportfordeterminingthefrequency

ofundesirableeffects.Undesirableeffectsmayvaryintheirincidencedependingonthedosereceivedandalsowhen

givenincombinationwithothertherapeuticagents.

Thefrequencycategoriesassignedtotheadversedrugreactionsbelowareestimates:formostreactions,suitabledata

forcalculatingincidencearenotavailable.Adversedrugreactionsidentifiedthroughpost-marketingsurveillancewere

consideredtoberareorveryrare.Thefollowingconventionhasbeenusedfortheclassificationoffrequency:

Verycommon( ≥1/10);

Common( ≥1/100to<1/10);

Uncommon( ≥1/1,000to1/100);

Rare( ≥1/10,000to1/1,000);

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

Theincidenceofadversereactionsishigherinthepresenceofrenaland/orhepaticdisorder.

Infectionsandinfestations

Veryrare:furunculosis.

Bloodandlymphaticsystemdisorders

Veryrare:agranulocytosis,granulocytosis,aplasticanaemia,thrombocytopenia,leukopenia,leukocytosis,eosinophilia

andpureredcellaplasia

Veryrarereportshavebeenreceivedofthrombocytopenia,agranulocytosisandaplasticanaemia,particularlyin

individualswithimpairedrenaland/orhepaticfunction,reinforcingtheneedforparticularcareinthisgroupof

patients.

Immunesystemdisorders

Uncommon:hypersensitivityreactions.

Veryrare:angioimmunoblasticlymphadenopathy.

Serioushypersensitivityreactions,includingskinreactionsassociatedwithexfoliation,fever,lymphadenopathy,

arthralgiaand/oreosinophiliaincludingStevens-JohnsonSyndromeandToxicEpidermalNecrolysisoccurrarely(see

Skinandsubcutaneoustissuedisorders).Associatedvasculitisandtissueresponsemaybemanifestedinvariousways

includinghepatitis,renalimpairment,acutecholangitis,xanthinestonesandveryrarely,seizures.Veryrarelyacute

anaphylacticshockhasbeenreported.Ifsuchreactionsdooccur,itmaybeatanytimeduringtreatment,allopurinol

shouldbewithdrawnimmediatelyandpermanently.

Corticosteroidsmaybebeneficialinovercominghypersensitivityskinreactions.Whengeneralisedhypersensitivity

reactionshaveoccurred,renaland/orhepaticdisorderhasusuallybeenpresentparticularlywhentheoutcomehasbeen

fatal.

Angioimmunoblasticlymphadenopathyhasbeendescribedveryrarelyfollowingbiopsyofageneralised

lymphadenopathy.Itappearstobereversibleonwithdrawalofallopurinol.

Metabolismandnutritiondisorders

Veryrare:diabetesmellitus,hyperlipidaemia.

Psychiatricdisorders

Veryrare:depression.

Nervoussystemdisorders

Veryrare:coma,paralysis,ataxia,neuropathy,paraesthesiae,somnolence,headache,tasteperversion.

Eyedisorders

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Earandlabyrinthdisorders

Veryrare:vertigo.

Cardiacdisorders

Veryrare:angina,bradycardia.

Vasculardisorders

Veryrare:hypertension.

Gastrointestinaldisorders

Uncommon:vomiting,nausea,diarrhoea

Veryrare:recurrenthaematemesis,steatorrhoea,stomatitis,changedbowelhabit.

Inearlyclinicalstudies,nauseaandvomitingwerereported.Toincreasegastrointestinaltolerability,allopurinolshould

betakenafterameal.

Hepatobiliarydisorders

Uncommon:asymptomaticincreasesinliverfunctiontests.

Rare:hepatitis(includinghepaticnecrosisandgranulomatoushepatitis).

Hepaticdysfunctionhasbeenreportedwithoutovertevidenceofmoregeneralisedhypersensitivity.

Skinandsubcutaneoustissuedisorders

Common:rash.

Veryrare:angioedema,fixeddrugeruption,alopecia,discolouredhair.

Skinreactionsarethemostcommonreactionsandmayoccuratanytimeduringtreatment.Theymaybepruritic,

maculopapular,sometimesscaly,sometimespurpuricandrarelyexfoliative.Allopurinolshouldbewithdrawn

immediatelyshouldsuchreactionsoccur.Afterrecoveryfrommildreactions,Allopurinolmay,ifdesired,bere-

introducedatasmalldose(e.g.50mg/day)andgraduallyincreased.Iftherashrecurs,Allopurinolshouldbe

permanentlywithdrawnasmoreseverehypersensitivitymayoccur(seeImmunesystemdisorders).

Angioedemahasbeenreportedtooccurwithandwithoutsignsandsymptomsofamoregeneralisedhypersensitivity

reaction.

Musculoskeletalandconnectivetissuedisorders

Veryrare:musclepain

Renalandurinarydisorders

Rare:Urolithiasis

Veryrare:haematuria,uraemia.

Reproductivesystemandbreastdisorders

Veryrare:maleinfertility,erectiledysfunction,gynaecomastia.

Generaldisordersandadministrationsiteconditions

Veryrare:oedema,generalmalaise,asthenia,fever.

FeverhasbeenreportedtooccurwithandwithoutsignsandsymptomsofamoregeneralisedAllopurinol

hypersensitivityreaction(seeImmunesystemdisorders).

4.9Overdose

Ingestionofupto22.5gallopurinolwithoutadverseeffecthasbeenreported.Symptomsandsignsincludingnausea,

vomiting,diarrhoeaanddizzinesshavebeenreportedinapatientwhoingested20gallopurinol.Recoveryfollowed

generalsupportivemeasures.Massiveabsorptionofallopurinolmayleadtoconsiderableinhibitionofxanthine

oxidaseactivity,whichshouldhavenountowardeffectsunlessaffectingconcomitantmedication,especiallywith6-

mercaptopurineand/orazathioprine.Adequatehydrationtomaintainoptimumdiuresisfacilitatesexcretionof

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacokineticgroup:Preparationsinhibitinguricacidproduction.

ATCCode:M04AA01

Allopurinolisaxanthine-oxidaseinhibitor.Allopurinolanditsmainmetaboliteoxipurinollowerthelevelofuricacid

inplasmaandurinebyinhibitionofxanthineoxidase,theenzymecatalyzingtheoxidationofhypoxanthinetoxanthine

andxanthinetouricacid.Inadditiontotheinhibitionofpurinecatabolisminsomebutnotallhyperuricaemicpatients,

denovopurinebiosynthesisisdepressedviafeedbackinhibitionofhypoxanthine-guaninephosphoribosyltransferase.

Othermetabolitesofallopurinolincludeallopurinol-ribosideandoxipurinol-7riboside.

5.2Pharmacokineticproperties

Allopurinolisactivewhengivenorallyandisrapidlyabsorbedfromtheuppergastrointestinaltract.Studieshave

detectedallopurinolintheblood30-60minutesafterdosing.Estimatesofbioavailabilityvaryfrom67%to90%.Peak

plasmalevelsofallopurinolgenerallyoccurapproximately1.5hoursafteroraladministrationofAllopurinol,butfall

rapidlyandarebarelydetectableafter6hours.Peaklevelsofoxipurinolgenerallyoccurafter3-5hoursafteroral

administrationofAllopurinolandaremuchmoresustained.

Allopurinolisnegligiblyboundbyplasmaproteinsandthereforevariationsinproteinbindingarenotthoughtto

significantlyalterclearance.Theapparentvolumeofdistributionofallopurinolisapproximately1.6litre/kg,which

suggestsrelativelyextensiveuptakebytissues.Tissueconcentrationsofallopurinolhavenotbeenreportedinhumans,

butitislikelythatallopurinolandoxipurinolwillbepresentinthehighestconcentrationsintheliverandintestinal

mucosawherexanthineoxidaseactivityishigh.

Approximately20%oftheingestedallopurinolisexcretedinthefaecesin48-72hours.Eliminationofallopurinolis

mainlybymetabolicconversiontooxipurinolbyxanthineoxidaseandaldehydeoxidase,withlessthan10%ofthe

unchangeddrugexcretedintheurine.Allopurinolhasaplasmahalf-lifeofabout1to2hours.

Oxipurinolisalesspotentinhibitorofxanthineoxidasethanallopurinol,buttheplasmahalf-lifeofoxipurinolisfar

moreprolonged.Estimatesrangefrom13to30hoursinman.Thereforeeffectiveinhibitionofxanthineoxidaseis

maintainedovera24hourperiodwithasingledailydoseofAllopurinol.Patientswithnormalrenalfunctionwill

graduallyaccumulateoxipurinoluntilasteady-stateplasmaoxipurinolconcentrationisreached.Suchpatients,taking

300mgofallopurinolperdaywillgenerallyhaveplasmaoxipurinolconcentrationsof5-10mg/litre.

Oxipurinoliseliminatedunchangedintheurinebuthasalongeliminationhalf-lifebecauseitundergoestubular

reabsorption.Reportedvaluesfortheeliminationhalf-liferangefrom13.6hoursto29hours.Thelargediscrepanciesin

thesevaluesmaybeaccountedforbyvariationsinstudydesignand/orcreatinineclearanceinthepatients.

Pharmacokineticsinpatientswithrenalimpairment.

Allopurinolandoxipurinolclearanceisgreatlyreducedinpatientswithpoorrenalfunctionresultinginhigherplasma

levelsinchronictherapy.Patientswithrenalimpairment,wherecreatinineclearancevalueswerebetween10and

20ml/min,showedplasmaoxipurinolconcentrationsofapproximately30mg/litreafterprolongedtreatmentwith300

mgallopurinolperday.Thisisapproximatelytheconcentrationwhichwouldbeachievedbydosesof600mg/dayin

thosewithnormalrenalfunction.AreductioninthedoseofAllopurinolisthereforerequiredinpatientswithrenal

impairment.

Pharmacokineticsinelderlypatients.

Thekineticsofthedrugarenotlikelytobealteredotherthanduetodeteriorationinrenalfunction(see

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5.3Preclinicalsafetydata

Teratogenicity

Onestudyinmicereceivingintraperitonealdosesof50or100mg/kgondays10or13ofgestationresultedinfoetal

abnormalities,howeverinasimilarstudyinratsat120mg/kgonday12ofgestationnoabnormalitieswereobserved.

Extensivestudiesofhighoraldosesofallopurinolinmiceupto100mg/kg/day,ratsupto200mg/kg/dayandrabbits

upto150mg/kg/dayduringdays8to16ofgestationproducednoteratogeniceffects.

Aninvitrostudyusingfoetalmousesalivaryglandsinculturetodetectembryotoxicityindicatedthatallopurinol

wouldnotbeexpectedtocauseembryotoxicitywithoutalsocausingmaternaltoxicity.

Inanimalexperiments,long-termapplicationofhighdosesofallopurinolresultedinformationofxanthinprecipitates

(urolithiasis),whichledtomorphologicalchangesinuriniferousorgans

Therearenoadditionalnon-clinicaldataconsideredrelevanttoclinicalsafetybeyondthoseincludedinothersections

ofthisSPC.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

LactoseMonohydrate

Silicacolloidalanhydrous

MaizeStarch

Powderedcellulose

SodiumStarchGlycolate(TypeA)

Sodiumlaurilsulfate

PovidoneK30

MagnesiumStearate(E470b)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions

6.5Natureandcontentsofcontainer

TransparentPVC/PVdC/Aluminiumblister.Thepacksizesavailableare:

20,28,30,50,60,100andHospitalPackof50

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

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7MARKETINGAUTHORISATIONHOLDER

TevaPharmaB.V.

Computerweg10

3542DRUtrecht

TheNetherlands

8MARKETINGAUTHORISATIONNUMBER

PA749/99/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:10thSeptember2010

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