CEFUROXIME ACTAVIS 250 Base Milligrams Pdr for Soln for Injection

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
CEFUROXIME SODIUM
Available from:
Actavis Group PTC ehf
ATC code:
J01DC02
INN (International Name):
CEFUROXIME SODIUM
Dosage:
250 Base Milligrams
Pharmaceutical form:
Pdr for Soln for Injection
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
Second-generation cephalosporins
Authorization status:
Authorised
Authorization number:
PA1380/066/001
Authorization date:
2010-11-26

PACKAGELEAFLET:INFORMATIONFOR THEUSER

Cefuroxime Actavis250mg powderfor solutionfor injection

Cefuroxime Actavis750mg powderfor solutionfor injection

Cefuroxime Actavis1.5gpowderfor solutionforinjectionor infusion

Cefuroxime

Readallofthis leafletcarefully before youstartreceiving thismedicine.

- Keep thisleaflet. You mayneedto readitagain.

- Ifyou have anyfurtherquestions,askyourdoctororpharmacist.

- This medicine hasbeen prescribedforyou. Do notpass iton to others. Itmayharmthem, even

iftheirsymptoms are thesame as yours.

- Ifanyofthe side effects gets serious, orifyou noticeanyside effects notlistedinthis leaflet,

pleasetellyourdoctororpharmacist.

In this leaflet:

1. WhatCefuroxime Actavisis and whatitis usedfor

2. Before you are givenCefuroxime Actavis

3. HowCefuroxime Actavisis given

4. Possibleside effects

5. Howto storeCefuroxime Actavis

6. Furtherinformation

1. WHATCEFUROXIMEACTAVISIS ANDWHATIT IS USEDFOR

Cefuroximebelongs to a group ofantibioticscalled cephalosporins.

Antibiotics are used to killthe bacteriaor‘germs’thatcauseinfections.

Cefuroxime is apowderwhichis madeinto asolutionto be given byinjection intoa vein orinto a

muscle.

Cefuroxime Actavisis given forthe treatmentofinfectionsincludinginfectionsofthe chestand

kidneys.

Adoctormayalso give ittoyou before an operationtoprotectyou frominfection.

2. BEFOREYOUAREGIVENCEFUROXIMEACTAVIS

Do not useCefuroxime Actavis:

ifyou are allergic(hypersensitive)to cefuroxime (seesection6 foralistoftheingredients).

ifyou have hadan allergicreaction to antibiotics suchaspenicillinorcephalosporins(an

allergicreaction mayinclude arash,itchingorbreathingdifficulties).

Take specialcarewithCefuroxime Actavis:

ifyou have kidneydiseaseorifyou areon dialysis.

ifyou have liverproblems.

ifyou have anyblood tests,Cefuroxime Actaviscancausechangestotheresults.

Longtime use ofCefuroxime Actaviscan resultininfectionscaused byorganisms thatare not

sensitive toCefuroxime Actavis.

Diarrhoeamaydevelop while you are on antibiotics,includingCefuroxime Actavis, oreven several

weeks afteryou have stopped usingthem.Ifitbecomessevereorpersistentoryou noticethatyour

stoolcontainsblood ormucus tellyourdoctorimmediately.Cefuroxime Actavistreatmentwillhave

to bestoppedimmediately, asthiscan be life-threatening. Do nottake medicinesthatstoporslow

down bowelmovements.

Taking othermedicines

Please tellyourdoctororpharmacistifyou aretakingorhave recentlytaken anyothermedicines,

includingmedicinesobtained withouta prescription.

Thedoctorwilltake specialcareifyou areusinganyofthe followingmedicines atthe same time:

- Diuretics(watertablets),e.g. furosemide

- Probenecid (usedtotreatgout)

- Otherantibiotics(e.g. amphotericin,aminoglycosides,tetracyclines, macrolidesor

chloramphenicol)

Pregnancyandbreast-feeding

Askyourdoctororpharmacistforadvice before takinganymedicine.

Thereis no evidenceofharmfuleffects causedbyCefuroxime Actavisinpregnancy. But,Cefuroxime

Actavisshould onlybe given duringpregnancyaftercarefulconsiderationoftherisks and benefits. If

you are pregnantorthinkyou maybe pregnantoryouaretryingto become pregnant,tellyou doctor

orpharmacistbeforetakingthis medicine.

Cefuroxime Actavisisexcretedin breastmilkand should be given with careto breast-feeding

mothers. Please tellyou doctorifyou arebreast-feeding.

Driving andusingmachines

In rare casesCefuroxime Actavismaycausedizziness,nervousnessorconfusion.Ifyou feelatall

unwellafterbeinggivenCefuroxime Actavisyou should notattempttodrive oruse machines.

Importantinformation about some ofthe ingredients ofCefuroxime Actavis

50 mgvialThis medicinalproductcontains lessthan1mmolsodium(23 mg)pervial, i.e. essentially

‘sodium-free’.

For 750 mgvialThis medicinalproductcontains 1.8 mmol(42 mg)sodiumpervial.To be taken into

consideration bypatientson a controlled sodiumdiet

For 1500 mgvialThis medicinalproductcontains 3.7mmol(84 mg)sodiumpervial.To betakeninto

consideration bypatientson a controlled sodiumdiet

3. HOWCEFUROXIMEACTAVISIS GIVEN

Yourdoctorwilldecide onthe doseand the durationoftreatment.This medicinewillnormallybe

given byaninjectionofa solutioninto a veinoramuscle.The usualdoseis:

Adolescents (aged12yearsto 17years), adults and elderly:

750mgto 1500 mgthreetimesa day.Formore severeinfections this maybe increasedto750 mgto

1500mgfourtimesa day.

Yourdoctormaygiveyou 1500mgCefuroxime Actavisbefore surgeryto protectyou frominfection.

You maygetfurtherdosesof750mgofcefuroxime aftertheoperation.

Infants (aged 28 daysto 23months)andchildren (2yearsto 11 years):The doseis based on body

weightandis normallybetween 30 mgto 100 mg(usually60mg)foreach kilogramoftheirbody

weighteach day.This willbe divided into dosesofthreeorfourtimesa day.

Patients with kidney disorders

Ifyou have kidneyproblems, you maybe givenalowerdosejustonceortwiceadaydependingon

yourkidneyfunction.

Ifyoumissa doseor receive toomuchofCefuroxime Actavis

As this medicine willbe given to you whilstyou are in hospital,itis unlikelythatyou willmissa dose

orbegiven too much however, ifyou have anyconcerns discuss this withyourdoctorornurse.

While you arereceivingCefuroxime Actavis

Ifyou have anyfurtherquestions onthe useofthis product,askyourdoctororpharmacist.

4. POSSIBLESIDEEFFECTS

Like allmedicines,Cefuroxime Actaviscancausesideeffects, although noteverybodygets them. Itis

importantthatyou are aware ofwhatthese side effectsmaybe.

Ifyou noticeany ofthefollowing serious side effects, stoptakingCefuroximeActavisand

contacta doctor immediately:

Reddeningofthe skin withblisters orpeeling. There mayalso besevereblisters and bleedingin

thelips, eyes, mouth, noseand genitals.This could be“Stevens-Johnson syndrome”or“toxic

epidermalnecrolysis”.

Severe prolonged diarrhoea, which mayhave blood ormucusin it, accompaniedwith stomach

painand fever.This couldbe “pseudomembranouscolitis”.

Theseeffects arerare, affectinglessthan 1in 1,000 people.

Sudden wheezing, swellingofyourlips,tongue and throatorbody, rash,faintingordifficulties

to swallow(severe allergicreaction).

Yellowskin, darkurineandtirednesswhichcan besymptoms ofliverproblems(jaundice).

Theseeffects are veryrare,affectinglessthan 1in 10,000 people.

Otherside effectsinclude:

Common sideeffects (affects 1 to10 usersin 100):

Diarrhoea, nauseaorvomiting.

Skin rash,itchyskin.

Increaseinsome substances in you blood (creatinineand urea)especiallyin patients with

kidneyproblems.

Painorswellingwheretheneedle wentintothe veinormuscle.

Uncommon side effects (affects1 to10 usersin 1,000):

Abnormalincreaseinacertaintype ofwhitebloodcellsinyourblood(eosinophilia). Symptoms

include weightloss, nightsweatsandfever.

Abnormaldecreasein some typesofwhite bloodcellsinyourblood(leucopenia and

neutropenia), which can make youmore likelyto getinfections.

Unusualbleedingorbruisingcaused bya reduction inthe numberofplatelets in the blood

(thrombocytopenia).

Headache, dizziness.

Severe kidneyproblems(especiallyin elderlypatientsand patients with previouskidney

disorders).

Changestotestused to measurefunctioningofthe liver.

Rare sideeffects (affects1 to 10 usersin 10,000)

Abnormaldecreaseina certaintype ofwhite bloodcells in you blood(agranulocytosis)which

which can make youmore likelyto getinfections.

Abnormaldecreaseofhaemoglobin in yourblood(anaemia).Symptoms includetiredness,

paleness, weakness,dizziness, shortness ofbreathandfastheartbeat.

Various skin eruptions orrashes(e.g. thepotentiallyfatalStevens-Johnson syndrome ortoxic

epidermalnecrolysis).

Fever.

Delayedallergic reaction (serumsickness)where symptomsmayincludefever, hives, skin rash,

jointpains, enlarged glands, shortnessofbreath and generallyfeelingunwell. Symptoms can

take 1–2 weeks to appearafterthestartoftreatment.

Whitefurry, soretongue and mouth (oralthrush).

Sore,itchyvagina and/ordischarge (vaginalthrush).

Veryrareside effects(affects lessthan 1 userin 10,000)

Abnormalbreakdownofred bloodcells(haemolytic anaemia).Symtoms includetiredness,

paleness, yellowingofskin,weakness, dizziness, shortness ofbreath and fastheartbeat.

Vertigo(feelingofdizziness orspinning), restlessness,nervousness, confusion.

Notknown:frequencycannotbeestimatedfrom the availabledata:

Some blood tests maybecome falsepositive (e.gCombs test).

Severe allergic reaction (angio-oedema)with swellingofthe face(e.g. lips and eyelids),tongue,

handsand feetanddifficultybreathing.

Reportingofsuspected adversereactions

Ifyou getanyside effects, talkto yourdoctor, pharmacistornurse.This includesanypossible side

effects notlistedinthis leaflet.You can also reportside effects directlyvia HPRAPharmacovigilance,

EarlsfortTerrace, IRL-Dublin2;Tel:+3531 6764971;Fax:+353 1 6762517.Website:www.hpra.ie;

E-mail:medsafety@hpra.ie.

Byreportingsideeffects you can helpprovide moreinformation onthe safetyofthis medicine.

5. HOW TOSTORECEFUROXIMEACTAVIS

Keep outofthesightand reach ofchildren.

This medicine doesnotrequireanyspecialstorage conditions.

Reconstituted/diluted solution should beused immediately.

Fromthe microbiologicalpointofview,the productshould be used immediately.

Ifnotusedimmediately, in-usestorage timesandconditions priortousearethe responsibilityofthe

userand would normallynotbelongerthan24hoursat2°Cto 8°C, unlessreconstitution/dilution has

taken placein controlledand validatedconditions.

Do notuseCefuroxime Actavisaftertheexpirydate whichisstatedon thecarton.

For single use only.

Discard anyunused solution.

Medicinesshould notbe disposedofvia wastewaterorhousehold waste. Askyourpharmacisthowto

disposeofmedicinesno longerrequired.Thesemeasureswillhelp to protecttheenvironment.

6. FURTHERINFORMATION

WhatCefuroxime Actaviscontains

- Theactive ingredientis cefuroxime 250mgor750mg or1500mg(assodiumsalt).

- Otheringredients:None.

WhatCefuroxime Actavislookslike and contents ofthe pack

Cefuroxime is whitetofaintlyyellowpowderto whichappropriate amounts ofwaterareadded to

prepareanoff-white to paleyellowopaque suspensionforintramuscularuseora yellowishsolution

forintraveneous administration.

250mg, 750mgpowderforsolutionforinjection:

20mltypeIglass vials,sealed with greybromo butylrubberstopperandcolouredflip offseal.

1.5gpowderforsolution forinjection orinfusion:

20mltypeIglass vials(forinjection)and 100mltypeIglass vials(forinfusion),sealed with grey

bromo butylrubberstopperand colouredflip offseal.

Packsizes:

250mgpowderforsolution forinjection:

1 vial, 5 vials, 10 vials

750mgpowderforsolution forinjection:

1 vial, 5 vials, 10 vials

1.5gpowderforsolution forinjection orinfusion:

20mlvials (injection):1 vial, 5 vials, 10 vials

100mlvials (infusion):1 vial,5 vials, 10 vials

Notallpacksizesmaybe marketed.

MarketingAuthorisationHolderandManufacturer

Marketing Authorisation Holder

Actavis Group PTCehf

Reykjavikurvegi76-78

220 Hafnarfjordur

Iceland

Manufacturer

Actavis Group PTCehf

Reykjavikurvegi76-78

220 Hafnarfjordur

Iceland

Thismedicinalproductisauthorisedinthe MemberStatesoftheEEAunderthefollowing

names:

Cefuroxime 250mgpowderforsolution forinjection

Cefuroxime 750mgpowderforsolution forinjection

Cefuroxime 1.5gpowderforsolutionforinjection/infusion

Cefuroxime Actavis 250mg powderforsolutionforinjection

Cefuroxime Actavis 750mg powderforsolutionforinjection

Cefuroxime Actavis 1.5 gpowderforsolution forinjectionorinfusion

Thisleafletwaslastapproved inFebruary 2016.

Thefollowinginformationis intendedformedicalorhealthcare professionals only:

For singleuse only. Discard anyunusedsolution.

Thedilutionisto be madeunderaseptic conditions.The solutionisto beinspected visuallyfor

particulate matterand discoloration priorto administration.Thesolutionshould onlybe usedifthe

solution is clearandfreefromparticles.

Preparation ofsolution

Intramuscular

Add 1mlwaterforinjections to250mgCefuroxime Actavisor3mlwaterforinjections to 750mg

Cefuroxime Actavis. Shake gentlyto produce an opaque suspension.

Intravenous

DissolveCefuroxime Actavisin waterforinjections using2mlfor250mg, 6mlfor750mgor15ml

for1500mg(1.5g). For shortintravenous infusion(e.g. up to 30minutes), 1500mg(1.5g)maybe

dissolved in50mlwaterforinjections.Thesesolutions maybegiven directlyintothe veinor

introducedintothe tubingofthe givingsetifthe patientisreceivingparenteralfluids.The

reconstituted solutionshould appearyellowish.

Cefuroxime is compatiblewith mostcommonlyused intravenous fluids and electrolyte solutions.

Waterforinjectionsis recommended forreconstitution, followedbydilution (priortointravenous

administration)with waterforinjections, 5%glucose injection or0.9%sodiumchlorideinjection.

Cefuroxime Actavisisalsocompatible withHartmann's solutionand0.18%sodiumchloride+

4%glucose.

Reconstituted product:

Chemicalandphysicalin-usestabilityhasbeen demonstrated for24 hours at2°Cto8°C.

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CefuroximeActavis250mgpowderforsolutionforinjection

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachvialcontainscefuroximesodiumequivalentto250mgcefuroxime.

Eachvialcontainsapproximately14mgsodium.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Powderforsolutionforinjection.

Cefuroximeiswhitetofaintlyyellowpowder.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Cefuroximeisindicatedforthetreatmentofthefollowinginfectionswhencausedbysusceptibleorganisms.

Respiratorytractinfections:acuteexacerbationofchronicbronchitis,hospitalacquiredpneumonia,severecommunity

acquiredpneumonia.

Upperurinarytractinfections:pyelonephritis.

Peri-operativeprophylaxisagainstinfectioninabdominal,orthopaedicandcardiacsurgery.

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.2Posologyandmethodofadministration

Usualdosageforadolescents(aged12yearsto17years),adultsandtheelderly:

Thedosageis1.5g/dayto6g/day.Inmostinfectionsasufficientdoseis750mgevery8hours.Inmoresevere

infectionsthedoseshouldbeincreasedto1.5gevery8hoursbyintravenousinjection.

Ifnecessary,thedosagefrequencycanbeincreasedtoevery6hoursuptototaldailydoseof6g.

Prophylaxis

Theusualdoseis1.5gintravenouslywithinductionofanaesthesiaforabdominalandorthopaedicoperations,butmay

besupplementedwithtwo750mgintramusculardoseseightandsixteenhourslater.Incardiacoperations,theusual

doseis1.5gintravenouslywithinductionofanaesthesiacontinuingwith750mgintramuscularlythreetimesdailyfor

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Dosageinimpairedrenalfunctionforadolescents,adultsandelderly

Itisnotnecessarytoreducethedoseifcreatinineclearanceismorethan20ml/min.Therecommendedmaintenance

doseinimpairedrenalfunctionisasfollows:

Specialprecautionsarerequiredifcreatinineclearanceis<10ml/minuteandtreatmentshouldtakeplaceunder

appropriateexpertsupervision(seesection4.4).

Serumconcentrationofcefuroximeshouldbemonitoredinpatientswithsevererenalimpairment.

Forpatientsonhaemodialysisafurther750mgdose,byintravenousorintramuscularinjection,shouldbegivenatthe

endofeachsession.

Forlow-fluxhaemofiltrationfollowthedosagerecommendedunderimpairedrenalfunction.

Paediatricpatients

Preterm(bornat<36weeksofgestation)andtermnewborninfants(age0–27days):

Cefuroximeisnotrecommendedfortheuseintheseagegroupsduetoinsufficientdataonsafetyandefficacy.Inthe

firstweeksoflifetheserumhalf-lifeofcefuroximecanbethreetofivetimesthatinadults(seesection5.2).

Infants,toddlers(age28daysto23months)andchildren(2yearsto11years):

Therecommendeddosagerangeis30to100mg/kg/daygivenasthreeorfourdivideddoses.Mostinfectionswill

respondtoadoseof60mg/kg/day.

Infants,toddlers(28daysto23months)andchildren(2yearsto11years)withimpairedrenalfunction:

Thereareinsufficientdataregardinguseofcefuroximeinpaediatricrenalinsufficiencyandthereforesuchuseisnot

recommended.

RouteofAdministration:

CefuroximeActavismaybeadministeredbyintramuscularinjectionorintravenousinjection(within3–5minutes),see

section6.6.

Intramuscularadministrationshouldbelimitedonspecialindicationand/orexceptionalclinicalsituationsafter

benefit/riskassessment.Intramuscularadministration3timesadayisnotrecommended.

Dosesabove750mgofcefuroximeshouldnotbeadministeredintramuscularly.

Creatinineclearance

(ml/min) Recommendeddosageofcefuroxime

(mg) Frequencyofdosage

(hours)

>20 Normaldose

10-20 750 12

<10 750 24

Patientsoncontinuous

arteriovenous

haemofiltration/haemo-

dialysis 750 12

Hypersensitivitytocefuroximeortoanyofthecephalosporins.

Previousimmediateand/orseverehypersensitivityreactiontopenicillinortoanyother

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4.4Specialwarningsandprecautionsforuse

Specialcareisindicatedinpatientswhohaveexperiencedanallergicreactiontopenicillinsorbeta-lactamantibiotics

ascross-reactionsmayoccur(forcontraindicationsduetoknownhypersensitivityreactionsseesection4.3).

Ifafteradministrationofcefuroximesodiumhypersensitivityreactionsoccur,theuseofcefuroximesodiumshouldbe

discontinuedimmediatelyandanappropriatetreatmentmeasuresshouldbeinitiated.

Specialcareshouldbetakeninpatientswithhepaticdysfunction.

Aswithotherantibiotics,useofcefuroximesodiummayresultintheovergrowthofCandida.Prolongedusemayalso

resultintheovergrowthofothernon-susceptibleorganisms(e.g.EnterococciandClostridiumdifficile),whichmay

requireinterruptionoftreatment.

Inpatientswhodevelopseverediarrhoeaduringorafteruseofcefuroximesodium,theriskoflifethreateningpseudo-

membranouscolitisshouldbetakenintoaccount.Theuseofcefuroximesodiumshouldbediscontinuedandthe

appropriatetreatmentestablished.Anti-peristalticsarecontra-indicated.

Cefuroximesolutionisincompatiblewithaminoglycosideantibiotics(seesection6.2).

TheuseofcefuroximemaybeaccompaniedbyafalsepositiveCoombstest.Thismayinterferewiththeperformance

ofcrossmatchingtestswithblood(seesection4.8).

Cefuroximeisexcretedviathekidneys.Thereforeadoseadjustmentisrequiredinpatientswithimpairedrenal

function(seesection4.2).

Duetoanincreasedriskofcefuroximeaccumulationinserumaccompaniedbyanincreasedriskforundesirableeffects

patientswithacreatinineclearance<10ml/minshouldbetreatedunderexpertsupervision.

Asaprecaution,renalfunctionshouldbemonitoredifrenalfunctionisalreadyimpaired.

Thesodiumcontentofcefuroximeshouldbetakenintoaccountwhenprescribedtopatientsrequiringsodium

restriction.

Thereareinsufficientdataregardinguseofcefuroximeinpaediatricrenalinsufficiencyandthereforesuchuseisnot

recommended.

Thismedicinalproductcontainslessthan1mmolsodium(23mg)pervial,i.e.essentially‘sodium-free’.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Cephalosporinantibioticsathighdosageshouldbegivenwithcautiontopatientsreceivingconcurrenttreatmentwith

potentdiureticssuchasfurosemide,amphotericinandaminoglycosides,asconcomitantuseincreasestheriskof

nephrotoxicity.

Bacteriostaticantibioticsmayinterferewiththebactericidalactionofcephalosporins.Therefore,itisadvisabletoavoid

givingtetracyclines,macrolides,orchloramphenicolinconjunctionwithcefuroxime.

Probenicidinhibitsthetubularexcretionofcefuroxime.Whenprobenicidisadministeredconcomitantlyplasma

concentrationsofcefuroximeareenhanced.

Cefuroximedoesnotinterfereinenzyme-basedtestsforglycosuria.Slightinterferencewithcopperreductionmethods

(Benedict's,Fehling's,Clinitest)maybeobserved.However,thisshouldnotleadtofalse-positiveresults,asmaybe

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Itisrecommendedthateithertheglucoseoxidaseorhexokinasemethodsareusedtodetermineblood/plasmaglucose

levelsinpatientsreceivingcefuroxime.Thisantibioticdoesnotinterfereinthealkalinepicrateassayforcreatinine.

4.6Fertility,pregnancyandlactation

Pregnancy

Dataonalimitednumberofexposedpregnanciesindicatenoadverseeffectsofcefuroximeonthepregnancyoronthe

healthofthefetus/newbornchild.Todatenootherrelevantepidemiologicaldataareavailable.Animalstudiesdonot

showanyharmfuleffectsonembryonalandfetaldevelopment(seesection5.3).Cefuroximereachestheembryo/fetus

viatheplacenta.DuetothelimitedclinicalexperienceCefuroximeActavisshouldonlybeusedduringpregnancyafter

carefulrisk/benefit,especiallyduringthefirsttrimester.

Lactation

Cefuroximeisexcretedinhumanmilk.CefuroximeActavisshouldonlybeusedduringlactationaftercareful

risk/benefitassessment.Diarrhoeaandfungusinfectionofthemucousmembranescouldoccurinthebreast-fedinfant,

sothatnursingmighthavetobediscontinued.Thepossibilityofsensitisationshouldbeborneinmind.

4.7Effectsonabilitytodriveandusemachines

Cefuroximemaysometimesbeassociatedwithsideeffects,suchasdizziness,thatmayimpairtheabilitytodrivea

vehicle,operatemachineryortoworksafely.

4.8Undesirableeffects

Thefollowingconventionhasbeenusedfortheclassificationoffrequency:

Verycommon1/10

Common1/100to<1/10

Uncommon1/1,000to<1/100

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

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

Dependentonthedoseanddurationofthetreatmentapproximately3%ofalltreatedpatientsareexpectedto

experienceoneorseveraloftheadversereactionsmentionedbelow.

SystemOrganClass Frequency Undesirableeffects

Infectionsand

infestations Rare Pseudomembranouscolitis.Aswithotherantibiotics

prolongedusemayleadtosecondarysuperinfections

causedbyinsusceptibleorganisms,e.g.Candida,

EnterococciandClostridiumdifficile(seesection4.4).

Bloodandlymphatic

systemdisorder Uncommon Eosinophilia,leucopenia,neutropenia,thrombocytopenia

Rare Decreasedhaemoglobinconcentration,agranulocytosis

Veryrare Haemolyticanemia

Immunesystem

disorders Rare Serumsickness

Veryrare Anaphylaxis(seesection4.4)

Notknown Angioneutroticoedema

Nervoussystem

disorders Uncommon Headache,dizziness

Veryrare Vertigo,restlessness,nervousness,confusion

Gastrointestinal

disorders Common Gastrointestinaldisturbancessuchasdiarrhoea,nauseaand

vomiting

Hepatobiliary

disorders Uncommon Transientincreasesofhepaticenzymelevels(AST,ALT

andLDH)andserumbilirubin

Veryrare Jaundice

Skinandsubcutaneous

tissuedisorders Common Skinrashes,urticaria,pruritus

Rare Erythemamultiforme,Stevens-Johnsonsyndromeand

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Reportingofsuspectedadversereactions

Reportingsuspectedadversereactionsafterauthorisationofthemedicinalproductisimportant.Itallowscontinued

monitoringofthebenefit/riskbalanceofthemedicinalproduct.Healthcareprofessionalsareaskedtoreportany

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

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

4.9Overdose

Overdosageofcephalosporinscancausecerebralirritationleadingtoconvulsions.Serumlevelsofcefuroximecanbe

reducedbyhaemodialysisorperitonealdialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Secondgenerationcephalosporin

ATCcode:J01DC02

Modeofaction

Allcephalosporins(-lactamantibiotics)inhibitcellwallproductionandareselectiveinhibitorsofpeptidoglycan

synthesis.Theinitialstepindrugactionconsistsofbindingofthedrugtocellreceptors,calledPenicillin-Binding

Proteins.Aftera-lactamantibiotichasboundtothesereceptors,thetranspeptidationreactionisinhibitedand

peptidoglycansynthesisisblocked,resultinginbacteriallysis.

PK/PDrelationship

Theefficacyismainlydeterminedbythelengthoftime,duringwhichthedruglevelisabovetheminimalinhibitory

concentrationofthepathogen.

Mechanismofresistance

Renalandurinary

disorders Common Increasedlevelsofcreatinineandureainserum,especially

inpatientswithimpairedrenalfunction(seesection4.2and

4.4)

Uncommon Acuteinterstitialnephritis.Nephrotoxicity.Acuterenal

tubularnecrosishasfollowedexcessivedosageandhas

alsobeenassociatedwithitsuseinolderpatientsorthose

withpre-existingrenalimpairment(seesection4.2and

4.4).

Generaldisordersand

administrationsite

conditions Common Painattheinjectionsitefollowingintramuscular

administration,thrombophlebitisandpainfollowing

intravenousinjection,afterrapidintravenous

administrationheatsensationsornauseamayoccur

Rare Drugfever

Investigations Notknown Theuseofcefuroximemaybeaccompaniedbyafalse

positiveCoombstest.Thismayinterferewiththe

performanceofcrossmatchingtestswithblood.

hydrolysisbybeta-lactamases.Cefuroximemaybeefficientlyhydrolysedbycertainofthe

extended-spectrumbeta-lactamases(ESBLs)andbythechromosomally-encoded(AmpC)

enzymethatmaybeinducedorstablydepressedincertainaerobicgram-negativebacterial

species

reducedaffinityofpenicillin-bindingproteinsforcefuroxime

outermembraneimpermeability,whichrestrictsaccessofcefuroximetopenicillinbinding

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Methicillin-resistantstaphylococci(MRS)areresistanttoallcurrentlyavailable-lactamantibioticsincluding

cefuroxime.

Penicillin-resistantStreptococcuspneumoniaearecross-resistanttocephalosporinssuchascefuroximethrough

alterationofpenicillinbindingproteins.

Beta-lactamasenegative,ampicillinresistant(BLNAR)strainsofH.influenzaeshouldbeconsideredresistantto

cefuroximedespiteapparentinvitrosusceptibility.

StrainsofEnterobacteriaceae,inparticularKlebsiellaspp.andEscherichiacolithatproduceESBLs(extended

spectrum-lactamase)maybeclinicallyresistanttotherapywithcephalosporinsdespiteapparentinvitrosusceptibility

andshouldbeconsideredasresistant.

Breakpoints

EUCAST(EuropeanCommitteeonAntimicrobialSusceptibilityTesting)breakpoints:

Thebreakpointpertainstoadosageof1.5gx3andtoE.coliandKlebsiellaspponly.

*Susceptibilityofstaphylococcitocefuroximeisinferredfromthemethicillinsusceptibility.

Methicillin(Oxacillin)-resistantstaphylococciareresistanttocephalosporines.

**Basedonserumpharmacokinetic.

Susceptability

Theprevalenceofacquiredresistancemayvarygeographicallyandwithtimeforselectedspeciesandlocalinformation

onresistanceisdesirable,particularlywhentreatingsevereinfections.Asnecessary,expertadviceshouldbesought

whenthelocalprevalenceofresistanceissuchthattheutilityoftheagentinatleastsometypesofinfectionsis

drugeffluxpumps

Organisms Susceptible Resistant

Enterobacteriaceae 1 8mg/l >8mg/l

Staphylococcusspp. –* –*

Streptococcusspp.(A,B,C,

0,5mg/l >0,5mg/l

Streptococcuspneumoniae 0,5mg/l >1mg/l

Haemophilusinfluenzae 1mg/l >2mg/l

Moraxellacatarrhalis 1mg/l >2mg/l

Non-speciesrelated** 4mg/l >8mg/l

Commonlysusceptiblespecies

Grampositiveaerobes

Staphylococcusaureus(methicillin-susceptible)

Staphylococcussaprophyticus°

Streptococcusagalactiae

Streptococcuspyogenes

Gramnegativeaerobes

Proteusmirabilis

Speciesforwhichacquiredresistancemaybeaproblem

Grampositiveaerobes

Staphylococcusepidermidis +

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°ReferstoGermandata(March2007):Atthetimeofpublicationofthetablenocurrentdatawereavailable.In

primaryliterature,standardtextbooks,andtreatmentrecommendationssusceptibilityisanticipated.

Prevalenceofbacterialresistanceis>50%atleastinoneEuropeancountryorregion.

Frequencyofmethicillinresistanceisabout30to50%forallstaphylococciinFranceandisusuallyobservedin

hospital.

Staphylococcusresistanttomethicillinareresistanttootherbeta-lactams.

Streptococcusresistanttopenicillinarealwaysresistanttocefuroxime.

5.2Pharmacokineticproperties

Absorption

Cefuroximeispoorlyabsorbedfromthegastro-intestinaltractandisgivenbyintramuscularorintravenousinjectionor

infusionasthesodiumsalt.Followingintravenousdosesof750mgand1.5g,serumpeakconcentrations(C

)were

approximately50µg/mland100µg/ml,respectively,after15minutes(t

Staphylococcushominis +

Streptococcuspneumoniae +,3

Gramnegativeaerobes

Citrobacterfreundii +

Citrobacterkoseri +

Enterobacteraerogenes +

Enterobactercloacae +

Escherichiacoli

Haemophilusinfluenzae

Klebsiellaoxytoca

Klebsiellapneumoniae +

Moraxellacatarrhalis

Inherentlyresistantorganisms

Grampositiveaerobes

Enterococcusspp.

Listeriamonocytogenes

Staphylococcusaureus(methicillin-resistant) (1),(2)

Staphylococcusepidermidis(methicillin-resistant)

Gramnegativeaerobes

Acinetobacterbaumannii

Burkholderiacepacia

Campylobacterspp.

Morganellamorganii

Proteusvulgaris

Pseudomonasaeruginosa

Serratiaspp.

Stenotrophomonasmaltophilia

Anaerobes

Bacteroidesspp.

Clostridiumdifficile

Others

Chlamydiaspp.

Chlamydophilaspp.

Legionellaspp.

Mycobacteriumspp.

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mgwithmeasurableamountspresent8hoursafteradose.

Distribution

Cefuroximeiswidelydistributedinthebodyandlevels,thatexceedtheMIC-valuesofmostpathogens,areachieved

pleuralfluid,sputum,bone,synovialfluid,andaqueoushumour,butonlyachievestherapeuticconcentrationsinthe

CSFwhenthemeningesareinflamed.Thevolumeofdistributionrangesbetween9.3and15.8l/1.73m 2

inhealthy

adults.About33%to50%ofcefuroximeinthecirculationisboundtoplasmaproteins.Itdiffusesacrosstheplacenta

andhasbeendetectedinbreastmilk.

Biotransformation

Cefuroximeismetabolizedonlytoaminorextent(<5%).

Elimination

Theeliminationhalf-liferangesbetweenabout70and80minafterintramuscularorintravenousadministrationin

healthyadults.Mostofthedoseofcefuroximeisexcretedunchangedinactiveform.About50%isexcretedby

glomerularfiltrationandabout50%throughrenaltubularsecretionwithin24hours,withthemajoritybeingeliminated

within6hours;highconcentrationsareachievedintheurine.Smallamountsofcefuroximeareexcretedinbile.The

renalclearanceis136.0and169.6ml/min/1.73m 2

after0.5and1gcefuroximeintravenousand137.9and146.3

ml/min/1.73m 2

after0.750and1gcefuroximeintramuscular,respectively.Theeliminationisimpairedinpatients

withimpairedrenalfunction.

Concomitantadministrationoforalprobenecidslowstubularsecretionofcefuroximeanddecreasesrenalclearanceby

approximately40%.

Oralprobenecid(1g)prolongedthehalf-lifeby63%andincreasedtheareaundertheconcentration-timecurveof

intravenouscefuroxime(750mg)byupto50%.

Cefuroximeisdialysableandsmallamountsareremovedbyperitonealdialysis.

Linearity/non-linearity

Thepeakplasmaconcentrationandtheareaundertheconcentrationcurveincreasewithincreasingdose.

Pharmacokineticsinspecialpatientgroups

Thehalf-lifeofcefuroximeisprolongedinpatientswithrenalimpairmentassociatedwiththeriskofaccumulation.

Theserumhalf-lifeis4.2hoursatacreatinineclearanceof23ml/minand22.3hoursatacreatinineclearanceof5

ml/min.Thereforedoseadjustmentisrequiredinpatientswithimpairedrenalfunction(seesection4.2).

Theserumhalf-lifeisprolongedinpretermandtermnewborninfantsduringthefirstweeksoflife(3to5timesthe

valueinadults).

5.3Preclinicalsafetydata

Effectsinnon-clinicalstudieswereobservedonlyatexposuresconsideredsufficientlyinexcessofthemaximum

humanexposureindicatinglittlerelevancetoclinicaluse.Preclinicalnephrotoxicitystudiesshowedtheproductcan

causerenaldamageinsomespecieswhenadministeredinveryhighdoses.Itsnephrotoxicityincreaseswhen

administeredincombinationwithglycerolandfurosemide.

Themostprominenttreatment-relatedeffectwastissuedamageattheinjectionsites.

Acefuroximeesterdidnotshowclinicallyrelevanteffectswhentestedinvitroandinvivoforgenotoxicpotential.No

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Investigationsinrabbitsandmicedidnotdemonstratereproductivetoxicityorteratogenic-effects.Cefuroximehas

beenshowntopasstheplacenta.

Gamma-glutamyltranspeptidaseactivityinraturineisinhibitedbyvariouscephalosporins,however,thelevelof

inhibitionislesswithcefuroxime.Thismayhavesignificanceintheinterferenceinclinicallaboratorytestsinhumans.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

None

6.2Incompatibilities

Thismedicinalproductmustnotbemixedwithothermedicinalproductsexceptthosementionedinsection6.6.

ThepHof2.74%w/vsodiumbicarbonateinjectionBPconsiderablyaffectsthecolourofsolutionsandthereforethis

solutionisnotrecommendedforthedilutionofcefuroximepowderforsolutionforinjection.However,ifrequired,for

patientsreceivingsodiumbicarbonateinjectionbyinfusionthecefuroximepowderforsolutionforinjectionmaybe

introducedintothetubeofthegivingset.

Cefuroximepowderforsolutionforinjectionshouldnotbemixedinthesyringewithaminoglycosideantibiotics.

6.3Shelflife

2years.

Reconstitutedproduct:

Chemicalandphysicalin-usestabilityhasbeendemonstratedfor24hoursat2°Cto8°C.

Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotusedimmediately,in-usestorage

timesandconditionspriortousearetheresponsibilityoftheuserandwouldnormallynotbelongerthan24hoursat2°

Cto8°C,unlessreconstitutionhastakenplaceincontrolledandvalidatedasepticconditions.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

Forstorageconditionsofthereconstitutedmedicinalproduct,seesection6.3.

6.5Natureandcontentsofcontainer

20mltypeIglassvials,sealedwithgreybromobutylrubberstopperandcolouredflipoffseal.

Packsizes:

1vial,5vials,10vials

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Forsingleuseonly.Discardanyunusedsolution.

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

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discolorationpriortoadministration.Thesolutionshouldonlybeusedifthesolutionisclearandfreefromparticles.

Preparationofsolution

Intramuscular

Add1mlwaterforinjectionsto250mg CefuroximeActavis.Shakegentlytoproduceanopaquesuspension.

Intravenous

DissolveCefuroximeActavisinwaterforinjectionsusing2mlfor250mg.Thereconstitutedsolutionshouldappear

yellowish.

Thecontentsandconcentrationsofcefuroximeassolutionareshowninthetablebelow.

Cefuroximeiscompatiblewithmostcommonlyusedintravenousfluidsandelectrolytesolutions.Waterforinjections

isrecommendedforreconstitution,followedbydilution(priortointravenousadministration)withwaterforinjections,

5%glucoseinjectionor0.9%sodiumchlorideinjection.

CefuroximesodiumisalsocompatiblewithHartmann'ssolutionand0.18%sodiumchloride+4%glucose.

7MARKETINGAUTHORISATIONHOLDER

ActavisGroupPTCehf

Reykjavikurvegi76-78

220Hafnarfjordur

Iceland

8MARKETINGAUTHORISATIONNUMBER

PA1380/66/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:26thNovember2010

10DATEOFREVISIONOFTHETEXT

Cefuroxime

pervial(mg) Routeof

administration Volumeofsolvent

tobeadded(ml) Finalvolumeof

solution(ml) Concentrationof

solution(mg/ml)

IVBolus 2 2.2 114

IVBolus 6 6.7 112

1500 IVBolus 15 16.2 93

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