CEFUROXIME ACTAVIS 500 Base Milligrams Film Coated Tablet

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
CEFUROXIME AXETIL
Available from:
Actavis Group PTC ehf
ATC code:
J01DC02
INN (International Name):
CEFUROXIME AXETIL
Dosage:
500 Base Milligrams
Pharmaceutical form:
Film Coated Tablet
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
Second-generation cephalosporins
Authorization status:
Authorised
Authorization number:
PA1380/055/002
Authorization date:
2010-03-31

PACKAGE LEAFLET:INFORMATIONFORTHE USER

Cefuroxime Actavis250mgfilm-coatedtablets

Cefuroxime Actavis500mgfilm-coatedtablets

Cefuroxime

Readallofthisleafletcarefullybefore youstarttakingthismedicine.

- Keepthisleaflet.Youmayneedtoreadit again.

- Ifyou haveanyfurtherquestions, askyourdoctororpharmacist.

- Thismedicinehasbeen prescribedforyou. Do notpassiton to others.Itmayharmthem,

eveniftheirsymptomsare the same asyours.

- If anyofthe side effectsgetsserious, orifyou noticeanysideeffectsnotlisted in thisleaflet,

please tellyourdoctororpharmacist.

Inthisleaflet:

1. WhatCefuroxime Actavisisand whatitisused for

2. Beforeyoutake Cefuroxime Actavis

3. Howto takeCefuroxime Actavis

4. Possible side effects

5. Howto storeCefuroxime Actavis

6. Furtherinformation

1. WHATCEFUROXIMEACTAVISISAND WHATITISUSED FOR

Cefuroxime Actavisisanantibiotic.It belongstoagroupofantibioticsthat arecalled

cephalosporins. Thesetypesofantibioticsaresimilartopenicillin.Cefuroxime Actaviskills

bacteriaand itcan beused againstvarioussortsofinfections.

Likeall antibioticsCefuroxime Actavisisonlyeffectiveagainstsometypesofbacteria. So, itis

onlysuitablefortreatingsometypesofinfection.

Cefuroxime Actaviscanbe usedtotreat:

ear, sinusand throatinfections

chestinfectionssuchasbronchitis

infectionsofthebladder

infectionsin theskin and thelayersjustundertheskin (such asfuruncles, impetigo-an

infection on thesurfaceoftheskin)

earlyLyme disease (froma tickbite)andtopreventlate complicationsinadultsandchildren

abovetheageof12.

2. BEFOREYOU TAKECEFUROXIMEACTAVIS

Do nottakeCefuroxime Actavis

-ifyouare hypersensitive(allergic)totheactive substance cefuroxime ortoanyofthe other

ingredientsofCefuroxime Actavis.

-ifyou arehypersensitiveto othertypeofcephalosporinsantibiotic.

-ifyouhaveeverhadasevereallergicreactiontoanysort ofpenicillinantibiotic.

Notallpeople whoare allergic topenicillinsarealsoallergic tocephalosporins.

However,you should nottakethismedicineifyouhaveeverhadasevereallergicreactiontoany

penicillin.Thisisbecauseyoumight alsobeallergictothismedicine.

Take specialcare withCefuroxime Actavis

Pleaseinformyourdoctorif:

- youhave everhadanallergicreactiontopenicillins.

- youhave severeandpersistentdiarrhea while usingorafterusingCefuroximeActavisyou

should notuseanymedicinesfordiarrheathatinhibitperistalsis;

- you arevomitingorhavediarrhoea.

- youget feverandfeel ill ashort timeafterusingCefuroxime Actavisforthetreatment of

Lyme disease (thisisa signofa disease calledJarischHerxheimerdisease)

- youare alsousingmedicinesthatdecrease stomachacidity.(see:“Usingothermedicines”);

Some childrenhaveexperiencedmildtomoderatehearinglossduringtreatment withcefuroxime

sodium

HavingacourseofCefuroximeActaviscantemporarilyincrease thechancethatyoucanget

infectionscaused byothersortsofgerms.Forexample, thrush mayoccur.

Takingother medicines

Please informyourdoctororpharmacistifyouaretaking, orhaverecentlytaken anyother

medicines, includingmedicinesobtained withoutprescription.

Pleasetellyourdoctorifyouaretaking:

- medicinesthatdecrease stomachacidity(medicinesforheartburn);

- certain othermedicinesfortheprevention orcontrolofinfections(antibiotics), such as

tetracyclines, macrolides,chloramphenicol, aminoglycosids;

- probenecid(amedicineforgoutand otherailments).

- watertabletsorinjections(diuretics)

- certainmedicinesagainstfungal infections(Amphotericin)

Cefuroxime Actavismayinterferewithcertaintests,suchastestsfordeterminingtheamount of

glucose(sugar)in theblood orurineand testsfordeterminingsomesubstancesin theblood

(Coombstest).

Underantibiotictreatment, disordersoftheintestinalfloramayoccur. Thismayreducethe

absorption ofoestrogen.Takethisinto account, ifyou takeoralcontraceptives(the“pill”).

Therefore, dueto possiblyreducedefficacyofcontraception, additionalcontraceptive measures

should beused.

TakingCefuroxime Actaviswith foodand drink

Take Cefuroxime Actavistabletsaftermeals.

Pregnancy andbreast-feeding

Askyourdoctororpharmacistsforadvicebeforetakinganymedicine.

Pregnancy

Pleaseinformyourdoctorifyouarepregnantorthinkyou mightbepregnant,you doctorwill

decideifyou should discontinuethetreatmentorchangeyou to anothermedicinalproduct

Breast-feeding

Pleaseinformyourdoctorifyouarebreast-feeding. You should notbreast-feedwhile ontreatment

withCefuroxime Actavis

Drivingand usingmachines

Cefuroxime Actavismaycausedizziness,you should becautiouswhen drivingavehicleor

operatingmachinery.

3. HOWTO TAKECEFUROXIMEACTAVIS

AlwaystakeCefuroximeActavistabletsexactlyasyourdoctorhastoldyou. You should check with

yourdoctororpharmacistifyou arenotsure.

Foran individualdosage,Cefuroxime Actavis250 mgand 500mgfilm-coatedtabletsareavailable.

Generaldosage recommendationsforCefuroxime Actavisdepend on thesensitivityofthe

respectivepathogen (germ)and thesiteofinfection.

Cefuroxime Actavisshould betaken with somefluid shortlyafteramealto ensureidealabsorption.

Thefilm-coated tabletsshould betaken in intervalsof12 hours.

Duetothebittertaste,CefuroximeActavisshould notbebroken, crushed, orchewed.

Dosageforadultsand children(over12 yearsofage):

Theusual treatment durationis5-10 days. Someinfectionsmayrequirelongertreatmentinorder to

prevent latecomplications.

Forear, sinusand throatinfections:

1 tabletofCefuroxime Actavis250 mgor500 mgtwiceadayfor5-10 days.

Forchestinfectionssuchasbronchitisand pneumonia:

1 tabletofCefuroxime Actavis500 mgtwiceadayfor 5-10 days.

Forbladderinfections:

1 tabletofCefuroxime Actavis250 mgtwiceadayfor5-10 days.

Forskin infectionsand infectionsin thelayersjustundertheskin:

1 tabletofCefuroxime Actavis250 mgor500 mgtwiceadayfor5-10 days.

Forthe treatmentofearly Lyme disease(an infection spread byinfected ticks):

1 tabletofCefuroxime Actavis500 mgtwiceadayfor20 days.

Dosageforchildren(5-12years):

Fortheconditionslisted above:

125 - 250 mgtwiceadayfor5-10 days.

Foracuteotitismedia (infection ofthemiddleearspace, behind theeardrum):

1 tabletofCefuroxime Actavis250 mgtwiceadayfor5-10 days.

Children between 5and12yearsshould notreceivemorethan adailydoseof500mgcefuroxime.

Foryoungerchildren,administration ofasuspension ismoresuitable.

There isnoexperience inthe use ofcefuroximaxetilin childrenbelow3monthsofage.

Dosageinelderlypatientsandpatientswithimpairedrenal function:

Ifatotaldailydoseof1000mgcefuroximeisnotexceeded, doseadjustmentisnotrequired.

Patientsonhaemodialysis

Additionaldosesmaybeeneeded attheend ofeach dialysis.

IfyoutakemoreCefuroxime Actavisthan you should

Ifyou havetaken moreofthismedicinethanyoushould, talk toyourdoctorstraightawayorgo to

the nearesthospitalaccidentandemergencydepartment.

OverdoseofCefuroxime Actaviscan lead to convulsion.

Ifyouforgetto takeCefuroximeActavis

Ifyou forgetto takeadoseofthismedicineattherighttime,takeit assoonasyouremember.Do

nottakeadoubledosetomakeup foraforgotten dose.

Ifyou stop takingthismedicine

Itisimportantthatyou takethismedicineuntilyou finish theprescribedcourse. You should not

stop themedicinejustbecauseyou feelbetter.Ifyou stop too soon, theinfection maystartup again.

Ifyou stillfeelsunwellattheend oftheprescribed courseoftreatment, orfeelsworseduring

treatment,tellyourdoctor.

Ifyou haveanyfurtherquestionson theuseofthisproduct, askyourdoctororpharmacist.

4. POSSIBLE SIDE EFFECTS

Likeall medicines,Cefuroxime Actaviscancauseside effects, although noteverybodygetsthem.If

anyofthesideeffectsgetsserious,orifyounoticeanysideeffectsnot listedinthisleaflet,please

tellyourdoctororpharmacist.

Ifyounoticeany ofthefollowingserioussideeffects, stoptakingCefuroxime Actavisand

contactadoctor immediately:

- Sudden wheezing, swellingofyourlips, faceorbody, rash, faintingordifficultiesswallowing

(severe allergic reaction).Thiseffectisveryrare,affectinglessthan 1 in 10,000 users.

- Yellowskin, dark urineand tirednesswhich can besymptomsofliverproblems. Thiseffectis

veryrare, affectinglessthan 1 in 10,000 users.

- Reddeningoftheskin with blistersorpeelingandmaybe associatedwithahighfeverand

jointpains.There mayalsobe severeblistersandbleedingin thelips, eyes,mouth, noseand

genitals.Thiscouldbyerythemamultiforme,Stevens-Johnson syndromeortoxicepidermal

necrolysis. Thiseffectisveryrare, affectinglessthan 1 in 10,000 users.

Common (affecting lessthan 1 in 10 people):

- increasein sometypeofwhiteblood cells(eosinophilia)

- headache, dizziness

- stomach problems, diarrhoea, nauseaand vomiting.

- kidneyand urinaryproblems:ifyou havebeen told thatyourkidneysdo notwork verywell,

changesin kidneyfunction mayoccur(higherlevelsofcreatinineand ureain theblood).

- skin rash with orwithoutsevereitchingand whealformation

- feverandfeelinggenerallybeingunwell ashort timeaftertakingCefuroximeActavisfor the

treatmentofLyme disease (Jarisch-Herxheimerreaction)

- temporaryincreaseofsomeliverenzymes, which ismeasured byblood tests

Uncommon(affecting lessthan 1 in 100 people):

- decreasein whiteblood cells(leucopenia)orsometypesofwhiteblood cells (neutropenia)or

plateletsinyourblood

- acutekidneyinflammation

Rare(affecting lessthan 1 in 1000 people):

- decreased haemoglobin concentration in theblood. Haemoglobin isin thered-blood cellsand

transportsoxygen andcarbon dioxidein thebloodstream

- pseudomembranouscolitis, infection ofthecolon,Theillnessischaracterized bydiarrhoea,

fever,and abdominalpain.

- aswithotherantibioticsprolonged usemaylead to secondarysuperinfectionscaused by

insusceptibleorganisms, e.g.Candida, EnterococciandClostridiumdifficiles

- afeverassociated with an allergicreaction whichdisappearson discontinuation

- serumsickness,hypersensitive reactioncharacterizedbyfever,swelling,skinrash,and

enlargementofthelymph nodes.

Very rare(affecting lessthan 1 in 10 000 people):

- haemolyticanaemia(reductioninredbloodcells)symptomssuch asnosebleeds, bleeding

gums, shortnessofbreath, fatigue, rapid heartbeat,paleskin colororyellowskin color

(jaundice),chills, and dark-colored urine.

- restlessness, nervousness, confusion, hallucinations

- allergic reactionsincluding suddenwheezing, swellingoflips, faceorbody, rash, faintingor

difficultiesswallowing

- reddeningoftheskin with blistersorpeelingandsometimeswith ahigh feverand jointpains.

Theremayalso besevereblistersand bleedingin thelips, eyes, mouth, noseandgenitals

(erythemamultiforme,Stevens-Johnson syndrome(SJS), toxicepidermalnecrolysis(TEN))

- hepatitiswithsymptomssuchasyellowdiscoloration ofskin oreyes(jaundice), fever, liver

enlargement,and abdominalpain, obstructivejaundice

Investigations

Certain testsfordeterminingsomesubstancesinyourblood mightshowdifferentresultswhileyou

take Cefuroxime Actavis(Coombstest).

5. HOWTO STORECEFUROXIMEACTAVIS

Keep outofthereach and sightofchildren.

Thismedicinalproductdoesnotrequireanyspecialstorageconditions

Do notuseCefuroxime Actavisafterthe expirydate whichisstatedonthepackage afterEXP.The

expirydatereferstothelast dayofthat month.

Medicinesshould notbedisposed ofviawastewaterorhousehold waste. Askyourpharmacisthow

to disposeofmedicinesno longerrequired. Thesemeasureswillhelp to protecttheenvironment.

6. FURTHER INFORMATION

WhatCefuroxime Actaviscontains

-The active substance is:250mgor500mgcefuroxime ascefuroxime axetil.

-Otheringredientsare:

Core:pregelatinisedstarch,croscarmellosesodium,sodium lauril sulfate,microcrystalline

cellulose,silica colloidalanhydrous,hydrogenatedvegetable oil.

Coating:Opadryblue:hydroxypropylmethylcellulose(E464), titaniumdioxide(E171),

propyleneglycol, brilliantbluealuminiumcoating (E133), indigocarminealuminiumcoating

(E132).

WhatCefuroxime Actavislookslikeand contentsofthepack

250mg:Lightbluecoloured filmcoated,capsuleshaped tabletsmarked “250”on onesideand

“P125”on theotherside.

500mg:Lightbluecoloured filmcoated,capsuleshaped tabletsmarked “500”on onesideand

“P126”on theotherside.

Pack sizes:

Blisters:10, 12, 14, 16, 20 and 50film-coatedtablets.

Tabletcontainers:20and60 film-coatedtablets.

Notallpacksizesmaybe marketed.

MarketingAuthorisationHolder andManufacturer

Marketing Authorisation Holder

ActavisGroup PTCehf.

Reykjavíkurvegur76-78

IS-220 Hafnarfjörður

Iceland

Manufacturer:

OrchidEuropeLimited

Building3, Chiswick Park

566 Chiswick High Road

Chiswick

London, W4 5YA

UNITED KINGDOM

ActavisGroup PTCehf.

Reykjavíkurvegur76-78

IS-220 Hafnarfjörður

Iceland

ThisleafletwaslastrevisedinOctober2013.

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CefuroximeActavis500mgFilm -coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains500mgcefuroximeascefuroximeaxetil

Forthefulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

Lightbluecolouredfilm-coatedcapsuleshapedtabletsmarked“500”ononesideand“P126”ontheotherside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

CefuroximeActavisisindicatedforthetreatmentoftheinfectionslistedbelowinadultsandchildrenfromtheageof3

months(seesections4.4and5.1).

Acutestreptococcaltonsillitisandpharyngitis.

Acutebacterialsinusitis.

Acuteotitismedia.

Acuteexacerbationsofchronicbronchitis.

Cystitis.

Pyelonephritis.

Uncomplicatedskinandsofttissueinfections.

TreatmentofearlyLymedisease.

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.2Posologyandmethodofadministration

Posology

Theusualcourseoftherapyissevendays(mayrangefromfivetotendays).

Table1.Adultsandchildren(40kg)

Indication Dosage

Acutetonsillitisandpharyngitis,acutebacterialsinusitis 250mgtwicedaily

Acuteotitismedia 500mgtwicedaily

Acuteexacerbationsofchronicbronchitis 500mgtwicedaily

Cystitis 250mgtwicedaily

Pyelonephritis 250mgtwicedaily

Uncomplicatedskinandsofttissueinfections 250mgtwicedaily

Lymedisease 500mgtwicedailyfor14days(rangeof10to21

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Table2.Children(<40kg)

ThereisnoexperienceofusingCefuroximeActavisinchildrenundertheageof3months.

Cefuroximeaxetiltabletsandcefuroximeaxetilgranulesfororalsuspensionarenotbioequivalentandarenot

substitutableonamilligram-per-milligrambasis(seesection5.2).

Renalimpairment

Thesafetyandefficacyofcefuroximeaxetilinpatientswithrenalfailurehavenotbeenestablished.Cefuroximeis

primarilyexcretedbythekidneys.Inpatientswithmarkedlyimpairedrenalfunctionitisrecommendedthatthedosage

ofcefuroximeshouldbereducedtocompensateforitsslowerexcretion.Cefuroximeiseffectivelyremovedbydialysis.

Table3.RecommendeddosesforCefuroximeActavisinrenalimpairment

Hepaticimpairment

Therearenodataavailableforpatientswithhepaticimpairment.Sincecefuroximeisprimarilyeliminatedbythe

kidney,thepresenceofhepaticdysfunctionisexpectedtohavenoeffectonthepharmacokineticsofcefuroxime.

Methodofadministration

Oraluse

CefuroximeActavistabletsshouldbetakenafterfoodforoptimumabsorption.

CefuroximeActavistabletsshouldnotbebroken,crushedorchewedandarethereforeunsuitablefortreatmentof

patientswhocannotswallowtablets.Oralsuspensionmaybeavailableforchildren.

4.3Contraindications

Indication Dosage

Acutetonsillitisandpharyngitis,acutebacterialsinusitis 10mg/kgtwicedailytoamaximumof125mg

twicedaily

Childrenagedtwoyearsorolderwithotitismediaor,where

appropriate,withmoresevereinfections 15mg/kgtwicedailytoamaximumof250mg

twicedaily

Cystitis 15mg/kgtwicedailytoamaximumof250mg

twicedaily

Pyelonephritis 15mg/kgtwicedailytoamaximumof250mg

twicedailyfor10to14days

Uncomplicatedskinandsofttissueinfections 15mg/kgtwicedailytoamaximumof250mg

twicedaily

Lymedisease 15mg/kgtwicedailytoamaximumof250mg

twicedailyfor14days(10to21days)

Creatinineclearance T1/2(hrs) Recommendeddosage

30mL/min/1.73m 2 1.4-2.4 nodoseadjustmentnecessary

(standarddoseof125mgto500mg

giventwicedaily)

10-29mL/min/1.73m 2 4.6 standardindividualdosegivenevery

24hours

<10mL/min/1.73m 2 16.8 standardindividualdosegivenevery

48hours

Patientsonhaemodialysis 2-4 afurtherstandardindividualdose

shouldbegivenattheendofeach

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Patientswithknownhypersensitivitytocephalosporinantibiotics.

Historyofseverehypersensitivity(e.g.anaphylacticreaction)toanyothertypeofbetalactamantibacterialagen

(penicillins,monobactamsandcarbapenems).

4.4Specialwarningsandprecautionsforuse

Hypersensitivityreactions

Specialcareisindicatedinpatientswhohaveexperiencedanallergicreactiontopenicillinsorotherbeta-lactam

antibioticsbecausethereisariskofcross-sensitivity.Aswithallbeta-lactamantibacterialagents,seriousand

occasionallyfatalhypersensitivityreactionshavebeenreported.Incaseofseverehypersensitivityreactions,treatment

withcefuroximemustbediscontinuedimmediatelyandadequateemergencymeasuresmustbeinitiated.

Beforebeginningtreatment,itshouldbeestablishedwhetherthepatienthasahistoryofseverehypersensitivity

reactionstocefuroxime,toothercephalosporinsortoanyothertypeofbeta-lactamagent.Cautionshouldbeusedif

cefuroximeisgiventopatientswithahistoryofnon-severehypersensitivitytootherbeta-lactamagents.

Jarisch-Herxheimerreaction

TheJarisch-HerxheimerreactionhasbeenseenfollowingcefuroximeaxetiltreatmentofLymedisease.Itresults

directlyfromthebactericidalactivityofcefuroximeaxetilonthecausativebacteriaofLymedisease,thespirochaete

Borreliaburgdorferi.Patientsshouldbereassuredthatthisisacommonandusuallyself-limitingconsequenceof

antibiotictreatmentofLymedisease(seesection4.8).

Overgrowthofnon-susceptiblemicroorganisms

Aswithotherantibiotics,useofcefuroximeaxetilmayresultintheovergrowthofCandida.Prolongedusemayalso

resultintheovergrowthofothernon-susceptiblemicroorganisms(e.g.enterococciandClostridiumdifficile),which

mayrequireinterruptionoftreatment(seesection4.8).

Antibacterialagent–associatedpseudomembranouscolitishavebeenreportedwithnearlyallantibacterialagents,

includingcefuroximeandmayrangeinseverityfrommildtolifethreatening.Thisdiagnosisshouldbeconsideredin

patientswithdiarrhoeaduringorsubsequenttotheadministrationofcefuroxime(seesection4.8).Discontinuationof

therapywithcefuroximeandtheadministrationofspecifictreatmentforClostridiumdifficileshouldbeconsidered.

Medicinalproductsthatinhibitperistalsisshouldnotbegiven(seesection4.8).

Interferencewithdiagnostictests

ThedevelopmentofapositiveCoomb´sTestassociatedwiththeuseofcefuroximemayinterferewithcrossmatching

ofblood(seesection4.8).

Asafalsenegativeresultmayoccurintheferricyanidetest,itisrecommendedthateithertheglucoseoxidaseor

hexokinasemethodsareusedtodetermineblood/plasmaglucoselevelsinpatientsreceivingcefuroximeaxetil.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Drugswhichreducegastricaciditymayresultinalowerbioavailabilityofcefuroximeaxetilcomparedwiththatofthe

fastingstateandtendtocanceltheeffectofenhancedabsorptionafterfood.

Cefuroximeisexcretedbyglomerularfiltrationandtubularsecretion.Concomitantuseofprobenicidisnot

recommended.Concurrentadministrationofprobenecidsignificantlyincreasesthepeakconcentration,areaunderthe

serumconcentrationtimecurveandeliminationhalf-lifeofcefuroxime.

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4.6Fertility,pregnancyandlactation

Pregnancy

Therearelimiteddatafromtheuseofcefuroximeinpregnantwomen.Studiesinanimalshaveshownnoharmful

effectsonpregnancy,embryonalorfoetaldevelopment,parturitionorpostnataldevelopment.CefuroximeActavis

shouldbeprescribedtopregnantwomenonlyifthebenefitoutweighstherisk.

Breastfeeding

Cefuroximeisexcretedinhumanmilkinsmallquantities.Adverseeffectsattherapeuticdosesarenotexpected,

althoughariskofdiarrhoeaandfungusinfectionofthemucousmembranescannotbeexcluded.Breastfeedingmight

havetobediscontinuedduetotheseeffects.Thepossibilityofsensitisationshouldbetakenintoaccount.Cefuroxime

shouldonlybeusedduringbreastfeedingafterbenefit/riskassessmentbythephysicianincharge.

Fertility

Therearenodataontheeffectsofcefuroximeaxetilonfertilityinhumans.Reproductivestudiesinanimalshave

shownnoeffectsonfertility.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.However,asthismedicinemay

causedizziness,patientsshouldbewarnedtobecautiouswhendrivingoroperatingmachinery.

4.8Undesirableeffects

ThemostcommonadversereactionsareCandidaovergrowth,eosinophilia,headache,dizziness,gastrointestinal

disturbancesandtransientriseinliverenzymes.

Thefrequencycategoriesassignedtotheadversereactionsbelowareestimates,asformostreactionssuitabledata(for

examplefromplacebo-controlledstudies)forcalculatingincidencewerenotavailable.Inadditiontheincidenceof

adversereactionsassociatedwithcefuroximeaxetilmayvaryaccordingtotheindication.

Datafromlargeclinicalstudieswereusedtodeterminethefrequencyofverycommontorareundesirableeffects.The

frequenciesassignedtoallotherundesirableeffects(i.e.thoseoccurringat<1/10,000)weremainlydeterminedusing

post-marketingdataandrefertoareportingrateratherthantruefrequency.Placebo-controlledtrialdatawerenot

available.Whereincidenceshavebeencalculatedfromclinicaltrialdata,thesewerebasedondrug-related(investigator

assessed)data.Withineachfrequencygrouping,undesirableeffectsarepresentedinorderofdecreasingseriousness.

Treatmentrelatedadversereactions,allgrades,arelistedbelowbyMedDRAbodysystemorganclass,frequencyand

gradeofseverity.Thefollowingconventionhasbeenutilisedfortheclassificationoffrequency:verycommon 1/10;

common 1/100to<1/10,uncommon 1/1,000to<1/100;rare 1/10,000to<1/1,000;veryrare<1/10,000andnot

known(cannotbeestimatedfromtheavailabledata).

Systemorganclass Common Uncommon NotKnown

Infectionsandinfestations Candidaovergrowth Clostridiumdifficile

overgrowth

Bloodandlymphatic

systemdisorders eosinophilia positiveCoomb’stest,

thrombocytopenia

leukopenia(sometimes

profound) haemolyticanaemia

Immunesystemdisorder drugfever,serumsickness,

anaphylaxis,Jarisch-

Herxheimerreaction

Nervoussystemdisorders headache

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Paediatricpopulation

Thesafetyprofileforcefuroximeaxetilinchildrenisconsistentwiththeprofileinadults.

Reportingsuspectedadversereactions

Reportingsuspectedadversereactionsafterauthorisationofthemedicinalproductisimportant.Itallowscontinued

monitoringofthebenefit/riskbalanceofthemedicinalproduct.Healthcareprofessionalsareaskedtoreportany

suspectedadversereactionsviaHPRAPharmacovigilance,EarlsfortTerrace,IRL-Dublin2;Tel:+35316764971;

Fax:+35316762517.Website: www.hpra.ie ;E-mail: medsafety@hpra.ie

4.9Overdose

Overdosecanleadtoneurologicalsequelaeincludingencephalopathy,convulsionsandcoma.Symptomsofoverdose

canoccurifthedoseisnotreducedappropriatelyinpatientswithrenalimpairment(seesections4.2and4.4).

Serumlevelsofcefuroximecanbereducedbyhaemodialysisandperitonealdialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:antibacterialsforsystemicuse,second-generationcephalosporins,ATC-code:J01DC02

Mechanismofaction

Cefuroximeaxetilundergoeshydrolysisbyesteraseenzymestotheactiveantibiotic,cefuroxime.Cefuroximeinhibits

bacterialcellwallsynthesisfollowingattachmenttopenicillinbindingproteins(PBPs).Thisresultsintheinterruption

ofcellwall(peptidoglycan)biosynthesis,whichleadstobacterialcelllysisanddeath.

Mechanismofresistance

Bacterialresistancetocefuroximemaybeduetooneormoreofthefollowingmechanisms:

hydrolysisbybeta-lactamases;including(butnotlimitedto)byextended-spectrumbeta-lactamases(ESBLs)and

AmpCenzymesthatmaybeinducedorstablyderepressedincertainaerobicGram-negativebacteriaspecies;

reducedaffinityofpenicillin-bindingproteinsforcefuroxime;

outermembraneimpermeability,whichrestrictsaccessofcefuroximetopenicillinbindingproteinsinGram-

negativebacteria;

Gastrointestinaldisorders diarrhoea

nausea

abdominalpain vomiting pseudomembranouscolitis

Hepatobiliarydisorders transientincreasesof

hepaticenzymelevels jaundice(predominantly

cholestatic),hepatitis

Skinandsubcutaneous

tissuedisorders Skinrashes Urticaria,pruritus,

erythemamultiforme,

Stevens-Johnson

syndrome,toxicepidermal

necrolysis(exanthematic

necrolysis)(seeImmune

systemdisorders),

angioneuroticoedema

Descriptionofselectedadversereactions

Cephalosporinsasaclasstendtobeabsorbedontothesurfaceofredcellsmembranesandreactwithantibodies

directedagainstthedrugtoproduceapositiveCoombs’test(whichcaninterferewithcross-matchingofblood)and

veryrarelyhaemolyticanaemia.

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Organismsthathaveacquiredresistancetootherinjectablecephalosporinsareexpectedtoberesistanttocefuroxime.

Dependingonthemechanismofresistance,organismswithacquiredresistancetopenicillinsmaydemonstratereduced

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Cefuroximeaxetilbreakpoints

Minimuminhibitoryconcentration(MIC)breakpointsestablishedbytheEuropeanCommitteeonAntimicrobial

SusceptibilityTesting(EUCAST)areasfollows:

S=susceptible,R=resistant

Microbiologicalsusceptibility

Theprevalenceofacquiredresistancemayvarygeographicallyandwithtimeforselectedspeciesandlocalinformation

onresistanceisdesirable,particularlywhentreatingsevereinfections.Asnecessary,expertadviceshouldbesought

whenthelocalprevalenceofresistanceissuchthattheutilityofcefuroximeaxetilinatleastsometypesofinfectionsis

questionable.

Microorganism Breakpoints(mg/L)

Enterobacteriaceae 1,2 8 >8

Staphylococcusspp. Note 3 Note 3

StreptococcusA,B,CandG Note 4 Note 4

Streptococcuspneumonia 0.25 >0.5

Moraxellacatarrhalis 0.125 >4

Haemophilusinfluenza 0.125 >1

Non-speciesrelatedbreakpoints 1 IE 5 IE 5

ThecephalosporinbreakpointsforEnterobacteriaceaewilldetectallclinicallyimportantresistancemechanisms(includingESBLand

plasmidmediatedAmpC).Somestrainsthatproducebeta-lactamasesaresusceptibleorintermediateto3rdor4thgenerationcephalosporins

withthesebreakpointsandshouldbereportedasfound,i.e.thepresenceorabsenceofanESBLdoesnotinitselfinfluencethe

categorizationofsusceptibility.Inmanyareas,ESBLdetectionandcharacterizationisrecommendedormandatoryforinfectioncontrol

purposes.

UncomplicatedUTI(cystitis)only(seesection4.1).

Susceptibilityofstaphylococcitocephalosporinsisinferredfromthemethicillinsusceptibilityexceptforceftazidmeandcefiximeand

ceftibuten,whichdonothavebreakpointsandshouldnotbeusedforstaphylococcalinfections.

Thebeta-lactamsusceptabilityofbeta-haemolyticstreptococcigroupsA,B,CandGisinferredfromthepenicillinsusceptibility.

Insufficientevidencethatthespeciesinquestionisagoodtargetfortherapywiththedrug.AnMICwithacommentbutwithoutan

accompanyingSorR-categorizationmaybereported.

Commonlysusceptiblespecies

Gram-positiveaerobes:

Staphylococcusaureus(methicillinsusceptible)*

Streptococcuspyogenes

Streptococcusagalactiae

Gram-negativeaerobes:

Haemophilusinfluenzae

Haemophilusparainfluenzae

Moraxellacatarrhalis

Spirochaetes:

Borreliaburgdorferi

Microorganismsforwhichacquiredresistancemaybeaproblem

Gram-positiveaerobes:

Streptococcuspneumoniae

Gram-negativeaerobes:

Citrobacterfreundii

Enterobacteraerogenes

Enterobactercloacae

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*Allmethicillin-resistantS.aureusareresistanttocefuroxime.

5.2Pharmacokineticproperties

Absorption

Afteroraladministrationcefuroximeaxetilisabsorbedfromthegastrointestinaltractandrapidlyhydrolysedinthe

intestinalmucosaandbloodtoreleasecefuroximeintothecirculation.Optimumabsorptionoccurswhenitis

administeredshortlyafterameal.

Followingadministrationofcefuroximeaxetiltabletspeakserumlevels(2.9µg/mLfora125mgdose,4.4µg/mLfora

250mgdose,7.7µg/mLfora500mgdoseand13.6µg/mLfora1000mgdose)occurapproximately2.4hoursafter

dosingwhentakenwithfood.Therateofabsorptionofcefuroximefromthesuspensionisreducedcomparedwiththe

tablets,leadingtolater,lowerpeakserumlevelsandreducedsystemicbioavailability(4to17%less).Cefuroxime

axetiloralsuspensionwasnotbioequivalenttocefuroximeaxetiltabletswhentestedinhealthyadultsandthereforeis

notsubstitutableonamilligram-per-milligrambasis(seesection4.2).Thepharmacokineticsofcefuroximeislinear

overtheoraldosagerangeof125to1000mg.Noaccumulationofcefuroximeoccurredfollowingrepeatoraldosesof

250to500mg.

Distribution

Proteinbindinghasbeenstatedas33to50%dependingonthemethodologyused.Followingasingledoseof

cefuroximeaxetil500mgtabletto12healthyvolunteers,theapparentvolumeofdistributionwas50L(CV%=28%).

Concentrationsofcefuroximeinexcessoftheminimuminhibitorylevelsforcommonpathogenscanbeachievedinthe

tonsilla,sinustissues,bronchialmucosa,bone,pleuralfluid,jointfluid,synovialfluid,interstitialfluid,bile,sputum

andaqueoushumor.Cefuroximepassestheblood-brainbarrierwhenthemeningesareinflamed.

Biotransformation

Klebsiellapneumoniae

Proteusmirabilis

Proteusspp.(otherthanP.vulgaris)

Providenciaspp.

Gram-positiveanaerobes:

Peptostreptococcusspp.

Propionibacteriumspp.

Gram-negativeanaerobes:

Fusobacteriumspp.

Bacteroidesspp.

Inherentlyresistantmicroorganisms

Gram-positiveaerobes:

Enterococcusfaecalis

Enterococcusfaecium

Gram-negativeaerobes:

Acinetobacterspp.

Campylobacterspp.

Morganellamorganii

Proteusvulgaris

Pseudomonasaeruginosa

Serratiamarcescens

Gram-negativeanaerobes:

Bacteroidesfragilis

Others:

Chlamydiaspp.

Mycoplasmaspp.

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Elimination

Theserumhalf-lifeisbetween1and1.5hours.Cefuroximeisexcretedbyglomerularfiltrationandtubularsecretion.

Therenalclearanceisintheregionof125to148mL/min/1.73m.

Specialpatientpopulations

Gender

Nodifferencesinthepharmacokineticsofcefuroximewereobservedbetweenmalesandfemales.

Elderly

Nospecialprecautionisnecessaryintheelderlypatientswithnormalrenalfunctionatdosagesuptothenormal

maximumof1gperday.Elderlypatientsaremorelikelytohavedecreasedrenalfunction;therefore,thedoseshould

beadjustedinaccordancewiththerenalfunctionintheelderly(seesection4.2).

Paediatrics

Inolderinfants(aged>3months)andinchildren,thepharmacokineticsofcefuroximearesimilartothatobservedin

adults.

Thereisnoclinicaltrialdataavailableontheuseofcefuroximeaxetilinchildrenundertheageof3months.

Renalimpairment

Thesafetyandefficacyofcefuroximeaxetilinpatientswithrenalfailurehavenotbeenestablished.

Cefuroximeisprimarilyexcretedbythekidneys.Therefore,aswithallsuchantibiotics,inpatientswithmarkedly

impairedrenalfunction(i.e.C1<30mL/minute)itisrecommendedthatthedosageofcefuroximeshouldbereduced

tocompensateforitsslowerexcretion(seesection4.2).Cefuroximeiseffectivelyremovedbydialysis.

Hepaticimpairment

Therearenodataavailableforpatientswithhepaticimpairment.Sincecefuroximeisprimarilyeliminatedbythe

kidney,thepresenceofhepaticdysfunctionisexpectedtohavenoeffectonthepharmacokineticsofcefuroxime.

PK/PDrelationship

Forcephalosporins,themostimportantpharmacokinetic-pharmacodynamicindexcorrelatingwithinvivoefficacyhas

beenshowntobethepercentageofthedosinginterval(%T)thattheunboundconcentrationremainsabovethe

minimuminhibitoryconcentration(MIC)ofcefuroximeforindividualtargetspecies(i.e.%T>MIC).

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonstudiesofsafetypharmacology,repeateddosetoxicity,

genotoxicityandtoxicitytoreproductionanddevelopment.Nocarcinogenicitystudieshavebeenperformed;however,

thereisnoevidencetosuggestcarcinogenicpotential.

Gammaglutamyltranspeptidaseactivityinraturineisinhibitedbyvariouscephalosporins,howeverthelevelof

inhibitionislesswithcefuroxime.Thismayhavesignificanceintheinterferenceinclinicallaboratorytestsinhumans.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Core:

Pregelatinisedstarch,

Croscarmellosesodium,

Sodiumlaurilsulfate,

Microcrystallinecellulose,

Silicacolloidalanhydrous,

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Coating:

Opadryblue:

Hydroxypropylmethylcellulose(E464),

Titaniumdioxide(E171),

Propyleneglycol,

BrilliantBluealuminiumcoating(E133),

IndigoCarminealuminiumcoating(E132).

6.2Incompatibilities

Notapplicable

6.3Shelflife

3years

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions

6.5Natureandcontentsofcontainer

Thefilm-coatedtabletsarepackedinaPVC/Aclar-blisterandtabletcontainer(HDPE)withchild-resistantplasticcap

(PE)withpulpandheatsealliner(aluminium).

Packsizes:

Blisters:10,12,14,16,20and50film-coatedtablets

Tabletcontainers:20and60film -coatedtablets

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Nospecialrequirements

7MARKETINGAUTHORISATIONHOLDER

ActavisGroupPTCehf

Reykjavikurvegi76-78

220Hafnarfjordur

Iceland

8MARKETINGAUTHORISATIONNUMBER

PA1380/55/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:31March2010

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10DATEOFREVISIONOFTHETEXT

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