CIPROFLOXACIN TEVA

Main information

  • Trade name:
  • CIPROFLOXACIN TEVA
  • Dosage:
  • 750 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0749/031/004
  • Authorization date:
  • 20-04-2007
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CiprofloxacinTeva750mgFilm-CoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains750mgciprofloxacinasciprofloxacinhydrochloride.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

White,capsuleshapedfilm-coatedtablets,debossed“CIP750”ononesideandplainontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Adults

Treatmentofthefollowinginfectionsinadultswhencausedbyciprofloxacin-susceptibleorganisms:

Infectionsof:

-Therespiratorytract.CiprofloxacinmaybeindicatedfortreatingpneumoniaduetoaerobicGram-negative

pathogens.Inpneumococcalpneumoniaciprofloxacinisnotthedrugoffirstchoice.

-Theurinarytract:acuteuncomplicatedcystitis,complicatedinfectionsandpyelonephritis.

-Thegenitalorgans:acute,uncomplicatedgonorrhoea,prostatitis.

-Severebacterialenteritis.

-SkinandsofttissueinfectionscausedbyGram-negativebacteria.

-OsteomyelitiscausedbyGram-negativebacteria.

-SeveresystemicinfectionscausedbyGram-negativebacteriae.g.septicaemia,peritonitis(withadditionofan

antibacterialagenttocoveranaerobes),infectionsinimmunosuppressedpatients.

Childrenandadolescents

Acutepulmonaryexacerbationofcysticfibrosisinchildrenandadolescents(5-17years)causedbyPseudomonas

aeruginosa.

Ciprofloxacinisnotrecommendedforotherindicationsinthisagegroup.

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.2Posologyandmethodofadministration

Thedoseofciprofloxacinisdeterminedbytheseverityandtypeofinfectionandtheage,weightandrenalfunctionof

thepatient.Treatmentmaybeinitiatedwithtabletsorintravenousinjectionaccordingtotheconditionofthepatient

Thedurationoftreatmentdependsontheseverityofthedisorderandontheclinicalandbacteriologicalcourse.

Inprinciple,treatmentshouldbemaintainedforatleast3daysafterbodytemperaturehasreturnedtonormal,or

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Thefollowingdoserecommendationsareprovidedasaguidelineandrefertooraldosingonly(Notethatdifferentdose

recommendationsmayapplytointravenousadministrationofciprofloxacin).

Adults:Thedoserangeforadultsis100-750mgtwicedaily.

*Inparticularlysevere,life-threateninginfections(especiallythoseinvolvingPseudomonas,staphylococcior

streptococci,e.g.osteomyelitis,septicaemia,pneumococcalpneumonia,recurrentboutsofinfectionincysticfibrosis

patients,severeskinandsofttissueinfectionsorperitonitis)therecommendeddoseforadultsis750mgciprofloxacin

twicedaily.

Elderlypatients:

Elderlypatientsshouldreceiveadosedependingontheseverityofthedisorderandoncreatinineclearance.

Impairedrenalorhepaticfunction

Adults

Impairedrenalfunction

*Inpatientswithsevereinfectionsandsevererenalimpairmentaunitdoseof750mgcanbegiven.

Patientsshouldbecarefullymonitored.Dosageintervalsshouldremainthesameasinpatientswithnormalrenal

function.

Impairedrenalfunctionandhaemodialysis

Recommendeddose:500mgperdayadministeredasasingledosefollowinghaemodialysis.

Impairedrenalfunctionandcontinuousambulatoryperitonealdialysis(CAPD)

Recommendeddose:500mgperdayadministeredasasingledosefollowingCAPD.

Impairedhepaticfunction

Doseadjustmentisnotnecessaryinmildormoderatehepaticfailurebutmaybeconsiderednecessaryinseverehepatic

Indication Dailydose* Usualdurationoftreatment

Acuteuncomplicatedcystitis

inwomen 100-250mgtwicedaily 3days

Complicated urinary tract

infectionsandpyelonephritis 250–500mgtwicedaily 7to14days

Acute, uncomplicated

gonorrhoea (urethritis and

cervicitis) 250–500mg Singledose

Prostatitis 500mgtwicedaily Upto28days

Respiratorytractinfections 250–500mgtwicedaily. 7to14days

Skinandsofttissueinfections 500mgtwicedaily 5to10days

Osteomyelitis 500mgtwicedaily 4to6weeksorlonger

Severebacterialenteritis 500mgtwicedaily 3to7days

Severe systemic infections

caused by Gram-negative

bacteria 500–750mgtwicedaily Asrequired

Childrenandadolescents(5-17years)

Acutepulmonaryexacerbation

ofcysticfibrosiscausedby

Pseudomonasaeruginosa. 40mg/kg/24hdividedintotwo

dosesi.e.20mg/kgtwicedaily

(maximum1500mgdaily) 10to14days

Creatinineclearance Serumcreatininelevel Dose

31–60ml/min/1.73m 2 120–170µmol(1.4–1.9

mg/dl) Maximumdose1000mg/day

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Impairedrenalandhepaticfunction

Doseadjustmentasunderimpairedrenalfunction.Patientsshouldbecarefullymonitored.Inspecificcases,itmaybe

appropriatetoassayserumlevelsofciprofloxacin.

Childrenandadolescents(5-17years):

Dosageinchildrenwithreducedrenalandliverfunctionhasnotbeeninvestigated.

Methodofadministration:

Thetabletsaretobeswallowedwithliquid.Theycanbetakenatanytimeregardlessofmeals.Ingestiononanempty

stomachacceleratestheabsorptionofactivesubstance.

Dairyproductswithahighcalciumcontent(milk,yoghurt)mayreduceciprofloxacinabsorption(seesection4.5).

4.3Contraindications

Hypersensitivitytociprofloxacin,otherquinolonesortoanyoftheexcipients.

Pregnancy,lactation(seesection4.6).

Inpatientswithahistoryoftendondisordersrelatedtofluoroquinoloneadministration(seesection4.4).

Childrenandgrowingadolescents(5-17years):ciprofloxaciniscontraindicatedexceptforthetreatmentofacute

pulmonaryexacerbationofcysticfibrosis(seesections4.1,4.2and4.4).

Childrenunder5years.

Patientsconcomitantlyreceivingtizanidine(seesection4.5).

4.4Specialwarningsandprecautionsforuse

Hypersensitivityreactionsandallergicreactionsoccurredinsomecasesafterthefirstadministrationofciprofloxacin.

Ifsuchreactionsoccur,ciprofloxacintreatmentmustbediscontinued.

Useinpatientswithepilepsyandothercentralnervoussystem(CNS)disorders:

Inpatientswithepilepsyorotherlesionsofthecentralnervoussystem(e.g.reducedconvulsionthreshold,ahistoryof

seizures,diminishedcerebralbloodflow,changesinbrainstructureorstroke),ciprofloxacinshouldbeusedwith

caution,becauseofthepossibilityofcentralnervoussideeffects

UndesirableCNSeffectsmayoccurafterthefirstadministrationofciprofloxacin.Depressionorpsychoseshaveledto

self-endangeringbehaviourinsomecases.Ifsuchreactionsoccur,treatmentwithciprofloxacinmustbediscontinued

immediately.

Crystalluriarelatedtotheuseofciprofloxacinhasbeenreported.Patientsreceivingciprofloxacinshouldbewell

hydratedandexcessivealkalinityoftheurineshouldbeavoided.

Pseudomembranouscolitisisaparticularformofenterocolitisthatcanoccurwithantibiotics(inmostcasesdueto

Clostridiumdifficile).Ifsevereandpersistentdiarrhoeaoccursduringoraftertreatment,thedoctorshouldbe

consulted.EvenifClostridiumdifficileisonlysuspected,administrationofciprofloxacinshouldbediscontinued

immediatelyandappropriatetreatmentgiven.

Patientswithafamilyhistoryoforactualdefectsinglucose-6-phosphatedehydrogenaseactivityareproneto

haemolyticreactionswithquinolones,andsociprofloxacinshouldbeusedwithcautioninthesepatients.

Ciprofloxacinshouldbeusedwithcautioninpatientswithsignificantrenalorhepaticdisorders.

Ciprofloxacinusehasrarelybeenassociatedwithphotosensitivity.However,patientsshouldbeadvisedtoavoid

prolongedexposuretosunlightorUVradiationduringtreatmentwithciprofloxacin.

Tendonitisand/orruptureoftendons(whichmainlyaffectstheAchillestendon)havebeenobservedduringtreatment

withquinoloneantibiotics.

Theseproblemsaremostoftenobservedinelderlypatientsandpatientstreatedwithcorticosteroids.Atthefirstsignof

painorinflammation,thetreatmentshouldbediscontinuedandtheaffectedextremityshouldbemadenon-weight

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IfthesymptomsoriginatefromtheAchillestendon,careshouldbetakentoavoidruptureofbothtendons(i.e.byuse

ofsplintstobothAchillestendonsorsupportofbothheels)(seesection4.3).

BecauseciprofloxacinhassomeactivityagainstMycobacteriumtuberculosis,false-negativeculturesmayoccurwhen

specimensareobtainedduringciprofloxacintreatment.

Ciprofloxacinshouldbeusedwithcautioninpatientswithmyastheniagravis.

Studiesinimmatureanimalsshowedciprofloxacinmaycausearthropathyinweight-bearingjoints.However,reviewof

safetydatainpatientsyoungerthan18years(mainlycysticfibrosispatients)revealednosignsofdrugrelateddamages

ofcartilageorjoints.

Ciprofloxacinhasbeenshowntocausearthropathyinweight-bearingjointsofimmatureanimals.Safetydatafroma

randomizeddoubleblindstudyonciprofloxacinuseinchildren(Ciprofloxacin:n=335,meanage=6.3years;

comparators:n=349,meanage=6.2years;agerange=1to17years)revealedanincidenceofsuspecteddrugrelated

arthropathy(discernedfromjoint-relatedclinicalsignsandsymptoms)byDay+42of7.2%and4.6%.Respectively,an

incidenceofdrug-relatedarthropathyby1-yearfollow-upwas9.0%and5.7%.Theincreaseofsuspecteddrugrelated

arthropathyoverthetimewasnotstatisticallysignificantbetweengroups.

Theuseofciprofloxacinforindicationsotherthanthetreatmentofacutepulmonaryexacerbationofcysticfibrosis

causedbyP.aeruginosainfection(childrenaged5–17years)hasnotbeenevaluatedinclinicaltrialsandtheclinical

experienceislimited.

FluoroquinoloneshavebeenassociatedwithprolongationoftheQTcinterval.Ciprofloxacinbelongstothegroupwith

asmallpotentialtothisadverseevent.Cautionshouldbeexercisedwhentreatingpatientsatriskfortorsadedepointes

arrhythmia(seesection4.8).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Xanthinederivatives

Concurrentadministrationofciprofloxacinandtheophyllinemaycauseincreasedplasmaconcentrationsof

theophylline.Thismayleadtotheophyllineinducedundesirablereactions,whichinveryrarecasesarelifethreatening.

Duringconcurrentadministrationoftheophylline,theplasmaconcentrationsshouldbemonitored,andthetheophylline

doseshouldbeadjustedadequately.Onconcurrentadministrationofciprofloxacinandcaffeineorpentoxifylline,

raisedserumconcentrationsofthesexanthinederivativeswerereported.

CYP1A2

CiprofloxacininhibitsCYP1A2andthusmaycauseincreasedserumconcentrationofconcomitantlyadministered

substancesmetabolisedbythisenzyme(e.g.theophylline,clozapine,tacrine,ropinirol,tizanidine).Theconcomitant

administrationofciprofloxacinandtizanidineiscontraindicated(seesection4.3).Patientstakinganyotherdrugsthat

aresubstratesforthisisoenzymeconcomitantlywithciprofloxacinshouldbemonitoredcloselyforclinicalsignsof

overdose,anddeterminationofserumconcentrations,especiallyoftheophylline,maybenecessary.

Antacids,sucralfate,iron,zinc,calcium,magnesium,aluminium,didanosine,oralnutritionalsolutions,dairyproducts

Absorptionofciprofloxacinisreducedwheniron,zinc,sucralfateorantacidsandhighlybufferedpharmaceuticals,

containingmagnesium,aluminiumorcalcium,areadministeredsimultaneously.Thisalsoappliestosucralfate,

antiviralmedicinalproductscontainingbuffereddidanosineformulations,oralnutritionalsolutionsandlargequantities

ofdairyproducts(milkorliquidmilkproductssuchasyoghurt).Thereforeciprofloxacinshouldbeadministeredeither

1to2hoursbeforeoratleast4hoursaftertheabove-mentionedproducts.Thisrestrictiondoesnotapplytothegroup

ofH

receptor-blockingantacids.

NSAIDs

Animaltrialshaveshownthatconcurrentadministrationofveryhighdosesofaquinoloneandcertainnon-steroidal

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Ciclosporin

Atransientincreaseintheconcentrationofplasmacreatinineisseenwhenciprofloxacinandciclosporinare

administeredsimultaneously.Plasmacreatinineconcentrationsshouldbecheckedregularlyinthesepatients.

Oralanticoagulants

Ciprofloxacin,likeotherquinolones,mayenhancetheeffectofcoumarinderivativesincludingwarfarin.Inthecaseof

concomitantadministrationoftheseproducts,prothrombintime(PT)orothersuitablecoagulationtestsshouldbe

monitored.Ifnecessary,theoralanticoagulantdosageshouldbeadjustedasappropriate.

Glibenclamide

Simultaneousadministrationofciprofloxacinandglibenclamidemayincreasetheeffectofglibenclamide.

Probenecid

Probenecidinhibitstherenalexcretionofciprofloxacinresultinginanincreaseoftheplasmaconcentrationof

ciprofloxacin.

Metoclopramide

Metoclopramideacceleratestheabsorptionofciprofloxacin.Themaximumplasmaconcentrationisthereforeachieved

morerapidly.Thebioavailabilityofciprofloxacinisnotaffected.

Mexiletine

Simultaneousadministrationofciprofloxacinandmexiletinecanleadtoincreasedconcentrationsofmexiletine.

Phenytoin

Simultaneousadministrationofciprofloxacinandphenytoinmayresultinincreasedorreducedserumlevelsof

phenytoinsuchthatmonitoringofdruglevelsisrecommended.

Premedicants

Itisrecommendedthatopiatepremedicants,(e.g.papaveretum)oropiatepremedicantsusedwithanticholinergic

premedicants,(e.g.atropineorhyoscine)arenotusedconcomitantlywithciprofloxacin,astheserumlevelsof

ciprofloxacinarereduced.

Co-administrationofciprofloxacinandbenzodiazepinepremedicantshasbeenshownnottoaffectciprofloxacin

plasmalevels.However,sincedecreasedclearanceofdiazepam,withaprolongedhalf-life,hasbeenreportedduring

co-administrationofciprofloxacinanddiazepam,andinanisolatedcasewithmidazolam,carefulmonitoringof

benzodiazepinetherapyisrecommended.

Ropinirole

Apotentialexistsforincreasedplasmalevelsofropinirolewithpossibleincreaseinadversereactions.Incaseof

combineduse,increasedclinicalmonitoringanddosageadjustmentofropinirolemayberequired.

Buffereddidanosineformulations

Clinicallyimportantinteractionshavebeenreportedwithbuffereddidanosineformulations(pleaserefertothefirst

paragraphofthissection).

Methotrexate

Renaltubulartransportofmethotrexatemaybeinhibitedbyconcomitantadministrationofciprofloxacinpotentially

leadingtoincreasedplasmalevelsofmethotrexate.Thismayincreasetheriskofmethotrexateassociatedtoxic

reactions.Therefore,patientsreceivingmethotrexatetherapyshouldbecarefullymonitoredwhenconcomitant

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4.6Fertility,pregnancyandlactation

(seesection4.3)

Useduringpregnancyiscontraindicated.Aswithotherquinolones,ciprofloxacinhasbeenshowntocausearthropathy

inimmatureanimals,andthereforeitsuseduringpregnancyiscontraindicated.

Administrationtonursingmothersiscontraindicatedsincequinolonesadministeredattherapeuticdosesareexcretedin

breastmilkinquantitiesthatcanbeexpectedtoaffecttheinfant.

4.7Effectsonabilitytodriveandusemachines

Ciprofloxacinhasminorormoderateinfluenceontheabilitytodriveandusemachines.

Ciprofloxacincanalterthecapacityforreactionstoanextentthatimpairstheabilitytodriveavehicle,tooperate

machineryortoworksafely.Thisappliestoagreaterdegreeatthestartoftreatment,whenthedoseisincreased,and

whenswitchingmedications,aswellinconjunctionwithalcohol.

4.8Undesirableeffects

Adversereactionshavebeenreportedin5-14%ofpatientsreceivingciprofloxacin.

Themostfrequentlyreportedadversereactionsarenausea,diarrhoeaandrash.

Adversereactionsarelistedbyfrequency:common>1/100,<1/10);uncommon>1/1,000,<1/100);rare>1/10,000,<

1/1,000);veryrare(<1/10,000).

Thefollowingadversereactionshavebeenobserved:

Infectionsandinfestations

Uncommon:moniliasis

Rare:moniliasis(oral),vaginalmoniliasis

Veryrare:moniliasis(gastrointestinal)

Bloodandthelymphaticsystemdisorders

Uncommon:eosinophilia,leukopenia

Rare:anaemia,leukopenia(granulocytopenia),leucocytosis,thrombocytopenia,thrombocythaemia(thrombocytosis)

Veryrare:hemolyticanaemia,agranulocytosis,pancytopenia(life-threatening),bonemarrowdepression(life-

threatening)

Immunesystemdisorders

Rare:allergicreaction,anaphylactoid(anaphylactic)reaction,dyspnoea,larynxoedema.

Veryrare:shock(anaphylactic/anaphylactoidreactionsprogressinginveryrarecasestolife-threateningshock),serum

sicknesslikereaction,angioedema,pruriticrash

Metabolismandnutritiondisorders

Uncommon:anorexia

Rare:hyperglycaemia

Psychiatricandnervoussystemdisorders

Uncommon:headache,dizziness,insomnia,agitation,confusion,tasteperversion(usuallyreversibleupon

discontinuationoftreatment)

Rare:hallucination,paresthesia(peripheralparalgesia),abnormaldreams(nightmares),depression,tremor,convulsion,

hypesthesia,somnolence,exacerbationofsymptomsofmyastheniagravis

Veryrare:grandmalconvulsion,abnormalgait,psychosis(whichmayprogresstoself-endangeringbehaviour),

intracranialhypertension,ataxia,hyperesthesia,hypertonia,parosmia(impairedsmell),anosmia(usuallyreversibleon

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Eyedisorders

Veryrare:abnormalvision(visualdisturbances),diplopia,chromatopsia

Earandlabyrinthdisorders

Veryrare:tinnitus,transitorydeafness(especiallyathighfrequencies)

Cardiacandvasculardisorders

Rare:tachycardia,syncope(fainting),vasodilation(hotflushes),hypotension

Veryrare:vasculitis(petechiae,haemorrhagicbullae,papules,crustformation);ventriculararrhythmia,torsadede

pointes,QTprolongation(theseeventswereobservedpredominantlyamongpatientswithfurtherriskfactorsforQTc

prolongation(seesection4.4)).

Gastrointestinaldisorders

Common:nausea,diarrhoea

Uncommon:vomiting,dyspepsia,flatulence,abdominalpain

Rare:dysphagia,pseudomembranouscolitis(refertoSection4.4),pancreatitis

Veryrare:life-threateningpseudomembranouscolitiswithpossiblefataloutcome(refertoSection4.4)

Hepato-biliarydisorders

Uncommon:bilirubinaemia,

Rare:jaundice,cholestaticjaundice,livernecrosis(rarelyprogressingtolife-threateninghepaticfailure)

Veryrare:hepatitis

Skinandsubcutaneoustissuedisorders

Common:rash

Uncommon:pruritis,maculopapularrash,urticaria

Rare:photosensitivityreaction,erythemamutliforme(minor),erythemanodosum

Veryrare:Stevens-Johnson-Syndrome,epidermalnecrolysis(Lyell-Syndrome),fixeddrugreaction,petechia

Musculoskeletal,connectivetissueandbonedisorders

Uncommon:arthralgia

Rare:myalgia,jointdisorder(jointswelling),paininextremeties,backpain,myasthenia

Veryrare:twitching,tendinitis(predominantlyachillotendinitisincludingtenosynovitis),partialorcompletetendon

rupture(predominantlyAchillestendon)(seesection4.4)

Renalandurinarydisorders

Rare:acutekidneyfailure,abnormalkidneyfunction,haematuria,crystalluria,interstitialnephritis

Generaldisordersandadministrationsiteconditions

Uncommon:asthenia(generalfeelingofweakness,tiredness).

Rare:pain,chestpain,sweating,drugfever,oedema(peripheral,vascular,face)

Investigations

Uncommon:SGOTincreased,SGPTincreased,abnormalliverfunctiontest,alkalinephosphataseincreased,increases

increatinine,increasesinBUN(urea)

Rare:alteredprothrombinvalues

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4.9Overdose

Toxicity

Limitedexperienceonoverdose,butisconsideredtobeoflowtoxicity.

Symptoms

Dizziness,tremor,headaches,tiredness,seizures,hallucinations,confusion,gastrointestinalupset,liverandkidney

abnormalities,crystalluria,hematuria.

Treatment

Inacuteandextremeoverdose,reversiblekidneydamageisseen.Gastriclavagemaybeconsidered.Activated

charcoal,MgorCa-containingantacidsmaybeadministeredinordertoreducetheabsorptionofciprofloxacin.The

patientshouldbekeptundercloseobservationwhilereceivingbothsymptomaticandsupportivetreatment.Renal

functionshouldbemonitored.Athaemodialysisorperitonealdialysisonlyamodestamountofciprofloxacin(<10%)is

eliminated.Adequatehydrationmustbemaintainedtominimisetheriskofcrystalluria.

QTcprolongationisdosedependentthereforeinoverdosageQTcprolongationcanoccur.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Fluoroquinolones

ATCcode:J01MA02

Activity

Ciprofloxacinisasynthetic4-quinolonederivativeantibacterialagentofthefluoroquinoloneclass.

MechanismofAction:

Asafluoroquinoloneantibacterialagent,ciprofloxacinactsontheDNA-DNA-gyrasecomplexandtopoisomeraseIV.

Breakpoints:

EUCAST: S ≤0.5mg/l;R>1mg/l

Exceptions:

Acinetobacterspp.,Staphylococcusspp.:

≤1mg/l;R>1mg/l

Streptococcuspneumoniae:

≤0.03mg/l;R>0.06mg/l

Haemophilusinfluenzae,Moraxellacatarrhalis:

≤0.5mg/l;R>0.5mg/l

Neisseriagonorrhoeae,Neisseriameningitidis:

≤0.03mg/l;R>0.06mg/l

Mechanismofresistance

Invitroinvestigationshaveshownthatresistancetociprofloxaciniscommonlyduetomutationsinbacterial

topoisomerasesandusuallydevelopsgradually("multiple-step"type).Transferableplasmid-mediatedquinolone

resistancehasbeendetectedinsomequinolone-resistantclinicalstrainsofE.coliandKlebsiellaspp.

Cross-resistancebetweenfluoroquinolonesmayoccurwhenthemechanismofresistanceisduetomutationsin

bacterialgyrases.Singlemutationsmaynotresultinclinicalresistance,butmultiplemutationsgenerallydoresultin

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Impermeabilityand/ordrugeffluxpumpmechanismsofresistancemayhaveavariableeffectonbacterial

susceptibilitytoindividualfluoroquinolones,whichdependsonthephysicochemicalpropertiesofthevariousdrugs

withintheclassandtheaffinityoftransportsystemsforeachdrug.

Susceptibility

Theprevalenceofacquiredresistancecanvaryforsomespeciesgeographicallyandwithtime.Therefore,itis

importanttoobtaininformationonlocalresistancepatterns,particularlywhentreatingmoresevereinfections.

Commonlysusceptiblespecies

Gram-negativebacteria

Aeromonashydrophila

Brucellamelitensis

Citrobacterfreundii

Enterobacterspp.

Escherichiacoli

Haemophilusinfluenzae

Moraxellacatarrhalis

Morganellamorganii

Plesiomonasshigelloides

Proteusmirabilis

Proteusvulgaris

Providenciaspp.

Shigellaspp.

Vibriospp.

Yersiniaenterocolitica

Anaerobes^

Peptococcusspp.

Peptostreptococcusspp.

Veillonellaparvula

Otherpathogens

Legionellapneumophila

Speciesforwhichacquiredresistancemaybeaproblem

Gram-positivebacteria

Staphylococcusaureus(methicillinsensitive)

Staphylococcusaureus(methicillinresistant)*

Streptococcusagalactiae

Streptococcuspneumoniae+

Streptococcuspyogenes+

Gram-negativebacteria

Acinetobacterspp.

Klebsiellaspp.

Neisseriagonorrhoeae

Pseudomonasaeruginosa

Serratiaspp.

Otherpathogens

Chlamydiaspp.+

Inherentlyresistantorganisms

Gram-positiveaerobes

Enterococcusspp

Gram-negativeaerobes

Stenotrophomonasmaltophila

Flavobacteriummeningosepticum

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*MRSAareverylikelytoberesistanttociprofloxacinandciprofloxacinshouldnotbeusedtotreatpresumedorknownMRSA

infectionsunlesstheorganismisknowntobesusceptible.

+mightberegardedasbeingofintermediatesusceptibilitytociprofloxacin.

^Ciprofloxacinisnotconsideredtobethedrugoffirstchoicefortreatmentofinfectionswithanaerobes.

5.2Pharmacokineticproperties

Absorption

Afteroraladministration,ciprofloxacinispredominantlyabsorbedfromtheduodenumandupperjejunumandreaches

peakserumconcentrationswithin60-90min.Aftersingledosesof250mgand500mg,C

valuesareabout0.8-2.0

mg/land1.5-2.9mg/l,respectively.Theabsolutebioavailabilityisapproximately70to80%;C

andAUCvaluesare

proportionallyincreasedwiththedose.

Foodintake(exceptasmentionedinsection4.5)hasnoeffectontheplasmaconcentrationprofileofciprofloxacin.

Distribution

Thesteady-statevolumeofdistributionofciprofloxacinis2-3l/kg.Sincetheproteinbindingofciprofloxacinislow

(20-30%)andthesubstanceispredominatelypresentinplasmainnon-ionisedform,almosttheentirequantityofthe

administereddosecandiffusefreelyintotheextravascularspace.Asaresult,theconcentrationsincertainbodyfluids

andtissuesmaybemarkedlyhigherthanthecorrespondingserumconcentrations.

Metabolism/Elimination

Ciprofloxacinisessentiallyexcretedinunchangedform,mostlyintheurine.Renalclearanceliesbetween3and5

ml/min/kg,andtotalclearanceamountsto8-10ml/min/kg.Bothglomerularfiltrationandtubularsecretionplayapart

intheeliminationofciprofloxacin.Smallconcentrationsof4metaboliteswerefound:desethyleneciprofloxacin(M1),

sulphociprofloxacin(M2),oxociprofloxacin(M3)andformylciprofloxacin(M4).M1toM3showantibacterialactivity

comparablewithorsmallerthannalidixicacid.M4,withthelowestquantity,hasanantimicrobialactivitysimilarto

thatofnorfloxacin.

Excretionafteroraladministration(in%oftheciprofloxacindose)

Thehalf-lifeofciprofloxacinliesbetween3and5hours,bothafteroralandafterintravenousadministration.

Sinceciprofloxacinisexcretednotonlyviathekidneys,butalsotoamajorextentviathegut,renalfunctionmustbe

substantiallyimpairedbeforeincreasesinserumeliminationhalf-lifeofupto12hoursareobserved.

Children

Thepharmacokineticsofciprofloxacininchildrenwithcysticfibrosisdiffersfromthatinchildrenwithoutcystic

fibrosis,anddosingrecommendationsareonlyapplicableforchildrenwithcysticfibrosis.Oraladministrationof20

mg/kgtwicedailytochildrenwithcysticfibrosisgivesanexposurewhichiscomparabletothatinadultsfollowingan

oraldoseof750mgtwicedaily.

5.3Preclinicalsafetydata

Articulartolerabilitystudies

Asreportedforothergyraseinhibitors,ciprofloxacincausesdamagetothelargeweight-bearingjointsinimmature

animals.Theextentofthecartilagedamagevariesaccordingtoage,speciesanddose;thedamagecanbereducedby

Anaerobes

Bacteroidesfragilis

Bacteroidesthetaiotaomicron

Clostridiumdifficile

Urine Faeces

Ciprofloxacin 44.7 25.0

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Inastudyinyoungbeagledogsciprofloxacincausedseverearticularchangesattherapeuticdosesaftertwoweeksof

treatment,whichwerestillobservedafter5months.Otherpreclinicaleffectswereobservedonlyatexposures

sufficientlyinexcessofthemaximumhumanexposurethatmakeconcernforhumansafetynegligibleinrespectof

animaldata.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Microcrystallinecellulose

PovidoneK-30

Croscarmellosesodium

Colloidalanhydroussilica

Magnesiumstearate

Film-coating:

Hypromellose

Titaniumdioxide(E171)

Macrogol400

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

TransparentorwhiteopaquePVC/PVdC/aluminiumblisterincardboardboxes.

Packsizes:8,10,12,16,20,30,100&160film-coatedtablets.Hospitalpacksof50,100&160film-coatedtablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

TevaPharmaB.V.

Computerweg10

3542DRUtrecht

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8MARKETINGAUTHORISATIONNUMBER

PA749/31/4

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateforauthorisation:20 th

April2007

Dateoflastrenewal:25 th

August2009

10DATEOFREVISIONOFTHETEXT

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