CIPROXIN

Main information

  • Trade name:
  • CIPROXIN Film Coated Tablet 500 Base Milligrams
  • Dosage:
  • 500 Base Milligrams
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CIPROXIN Film Coated Tablet 500 Base Milligrams
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/082/002A
  • Authorization date:
  • 22-03-2002
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Ciproxin500mgFilm-coatedTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains500mgciprofloxacin(ashydrochloride).

Forfulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

ProductimportedfromtheNetherlands,GreeceandHungary:

White,oblongtabletswith‘Bayer’impressedononesideand‘CIP’,abreaklineand‘500’ontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Ciprofloxacinisindicatedforthetreatmentofthefollowinginfectionscausedbysensitivebacteria:

Adults:

Respiratorytractinfections:e.g.lobarandbronchopneumonia,acuteandchronicbronchitis,acuteexacerbationof

cysticfibrosis,bronchiectasis,empysema.Ciprofloxacinisnotrecommendedasfirst-linetherapyforthetreatmentof

pneumococcalpneumonia.Incircumstanceswhereaphysicianconsidersitappropriatetouseciprofloxacininpatients

withpneumococcalpneumonia,adoseof750mgtwicedailyshouldprovideadequatecoverinthemajorityofcases

(seeDosageandAdministrationsection).CiprofloxacinmaybeusedfortreatingGram-negativepneumonia.

Urinarytractinfections:e.g.uncomplicatedandcomplicatedurethritis,cystitis,pyelonephritis,prostatitis,epididymitis.

Gastro-intestinalinfections:e.g.entericfever,infectivediarrhoea.

Gonorrhoea:includingurethral,rectalandpharyngealgonorrhoeacausedbyß-lactamaseproducingorganismsor

organismsmoderatelysensitivetopenicillin.

Children:ForthetreatmentofacutepulmonaryexacerbationofcysticfibrosisassociatedwithP.aeruginosainfection

inpaediatricpatientsaged5-17years.

InhalationAnthraxinAdultsandChildren:Toreducetheincidenceorprogressionofdiseasefollowingconfirmationor

suspectedexposuretoaerosolizedBacillusanthracis.

4.2Posologyandmethodofadministration

Generaldosagerecommendations:ThedosageofCiproxintabletsisdeterminedbytheseverityandtypeofinfection,

thesensitivityofthecausativeorganism(s)andtheage,weightandrenalfunctionofthepatient.Ciproxintablets

shouldbeswallowedwholewithanadequateamountofliquid.

IfciproxinTabletsaretakenonanemptystomach,theactivesubstanceisabsorbedmorerapidly.Inthiscase,the

tabletsshouldnotbetakenconcurrentlywithdairyproductsorwithmineralfortifieddrinksalone(e.g.milk,yoghurt,

calciumfortifiedorangejuice).However,anormaldietthtwillcontiansmallamountsofcalcium,doesnot

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Adults:Thedosagerangeforadultsis100-750mgtwicedaily.Thefollowingdosagesforspecifictypesofinfectionare

recommended:

RecommendedAdultDosage:

Indication Dose

Gonorrhoea: 250mgsingledose

100mgb.d.or250mgb.d.**

Upperandlowerurinarytractinfections

(dependingonseverity): 250-500mgb.d.

Upperandlowerrespiratorytractinfections

(dependingonseverity): 250-750mgb.d.

Pneumococcalpneumonia(second-line): 750mgb.d.

Cysticfibrosispatientswithpseudomonal

lowerRTI*: 750mgb.d.

Otherinfectionsasdetailedunder4.1: 500-750mgb.d.

Severeinfections,particularlyduetoPseudomonas,

staphylococciandstreptococci: 750mgb.d.

inhalationanthrax: 500mgb.d

*Asthepharmacokineticsofciprofloxacinremainunchangedinpatientswithcysticfibrosis,thelowbodyweightof

thesepatientsshouldbetakenintoconsiderationwhendeterminingdosage.

**Bothdosesareequallyeffectiveintreatingacute,uncomplicatedcystitis.

ImpairedRenalFunction:

Dosageadjustmentsarenotusuallyrequired,exceptinpatientswithsevererenalimpairment(serumcreatinine>265

micromole/lorcreatinineclearance<20ml/minute).Ifadjustmentisnecessary,thismaybeachievedbyreducingthe

totaldailydosebyhalf,althoughmonitoringofdrugserumlevelsprovidesthemostreliablebasisfordoseadjustment.

Dialysisreducesserumlevelsofciprofloxacin.

Elderly:

Althoughhigherciprofloxacinserumlevelsarefoundintheelderly,noadjustmentofdosageisnecessary.

Adolescentsandchildren:

Aswithotherdrugsinitsclass,ciprofloxacinhasbeenshowntocausearthropathyinweight-bearingjointsof

immatureanimals.Althoughaanalysisofavailablesafetydatafromciprofloxacinuseinpatientslessthan18yearsof

age,themajotityofwhomhadcysticfibrosis,didnotdiscloseanyevidenceofdrug-relatedcartilageorarticular

damage,itsuseinthepaediatricpopulationisgenerallynotrecommended.

Clinicalandpharmacokineticdatasupporttheuseofsiprofloxacininpaediatriccysticfibrosispatients(aged5-17

years)withacutepulmonaryexacerbationassociatedwithP.aeruginosainfection,atadoseof20mg/kgorallytwice

daily(maximumdailydose1500mg).

Fortheindicationofinhalationanthrax,theriskbenefitassesmentindicatesthatadministrationofsiprofloxacinto

paediatircpatientsatadoseof15mg/kgorallytwicedailt(maximumdailydoseof1000mg)isappropriate.

Forindicationsotherthantreatmentofpulmonaryexacerbationsincysticfibrosisandinhalationanthrax,ciprofloxacin

maybeusedinchildrenandadolescentswherethebenefitisconsideredtooutweighthepotentialrisks.

Dosinginchildrenwithimpairedrenaland/orhepaticfunctionhasnotbeenstudied.

DurationofTreatment:

Thedurationoftreatmentdependsupontheseverityofinfection,clinicalresponseandbacteriologicalfindings.

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Tablets.

Inotheracuteinfectionstheusualtreatmentperiodis5to7dayswithCiproininfusionor5to10dayswithCiproxin

Tablets.Generally,treatmentshouldbecontinuedforatleastthreedaysaftersignsandsymptomsoftheinfectionhave

disappeared.

Prolongedtreatmentoruseinchronicconditionsshouldonlybeinitiatedunderconsultantdirectionwithregular

surveillance.

ForacutepulmonaryexacerbationofcysticfibrosisassociatedwithP.aeruginosainfectioninpaediatricpatients(aged

5-17years),thedurationoftreatmentis10-14days.

Forinhalationanthrax,drugadministrationshouldbeginassoonaspossibleafterconfirmedorsuspectedexposureand

shouldbecontinuedfor60days.

4.3Contraindications

Ciprofloxaciniscontraindicatedinpatientswhohaveshownhypersensitivitytociprofloxacinorotherquinoloneanti-

infectivesorwhohaveahistoryofquinolone-inducedtendondisorder.

Ciprofloxacinisalsocontraindicatedinchildrenandgrowingadolescentsunlessepiphysealclosuresoflongbones

haveoccurredorexceptwherethebenefitsoftreatmentexceedtherisks.

See4.2,AdolescentsandChildren

4.4Specialwarningsandprecautionsforuse

Intheeventofhypersensitivity,therapyshouldbediscontinued.

CiprofloxacinshouldbeusedwithcautioninepilepticsandpatientswithahistoryofCNSdisordersandonlyifthe

benefitsoftreatmentareconsideredtooutweightheriskofpossibleCNSside-effects,depressionorpsychosesleadto

self-endangeringbehaviour(seealsoSection4.8).

Crystalluriarelatedtotheuseofciprofloxacinhasbeenreported.Patientsreceivingciprofloxacinshouldbewell

hydratedandexcessivealkalinityoftheurineshouldbeavoided.

Patientswithafamilyhistoryoforactualdefectsinglucose-6-phosphatedehydrogenaseactivityareproneto

haemolyticreactionswithquinolones,andsociprofloxacinshouldbeusedwithcautioninthesepatients.

Ciprofloxacinisnotrecommendedasfirst-linetherapyforthetreatmentofpneumococcalpneumonia.Streptococcus

pneumoniaeisthemostfrequentpathogenresponsibleforcommunityacquiredpneumonia.

Tendoninflammationandrupturemayoccurwithquinoloneantibiotics.Suchreactionshavebeenobserved

particularlyinolderpatientsandinthosetreatedconcurrentlywithcorticosteroids.Atthefirstsignofpainor

inflammation,patientsshoulddiscontinueciprofloxacinandresttheaffectedlimbs.

Toxicologicalstudieshaveshownthatadministrationofoxyquinoloneantibacterialagentsatdoseshigherthanthe

therapeuticrangecanproduceerosionofthecartilageinweight-bearingjointsinimmatureanimalsofsomespecies.

Nosuchlesionshavebeenshowntooccurinmantodate.Thisproductshouldnotbeprescribedforchildrenorthosein

whombonegrowthiscontinuing,withtheexceptionofpaediatriccysticfibrosispatients,unlessthebenfitofshort-

termuseisregardedasexceedingtherisk.

Patientswithpre-existentsignificantrenalorhepaticdisordersshouldbecarefullymonitoredtodetectany

deteriorationinfunction.Itshouldonlybeadministeredwithgreatcautiontopersonswithrenalinsufficiency,or

severedehydration.

Thereisariskofpseudomembranouscolitiswithbroad-spectrumantibiotics.Itisimportanttoconsiderthisinpatients

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pseudomembranouscolitisissuspectedtreatmentwithciprofloxacinshouldbestoppedandappropriatetreatmentgiven

(e.g.oralvancomycin).

Aswithotherquinolones,patientsshouldavoidprolongedexposuretostrongsunlightorUVradiationduring

treatment.

Laboratorytestsmaygiveabnormalfindingsifperformedwhilstpatientsarereceivingciprofloxacin,e.g.increased

alkalinephosphatase;increasesinliverfunctiontests,e.g.transaminasesandcholestaticjaundice,especiallyinpatients

withpreviousliverdamage.

EradicationofinfectionduetoPseudomonasinpersonswithcysticfibrosisonlyoccursinaminorityofcases,

particularlyafterrepeatcoursesoftreatmentwithciprofloxacin.Cyclicaloralternatingantibacterialtherapiesmay

helpreducethenumberofresistantstrains.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Increasedplasmalevelsoftheophyllinehavebeenobservedfollowingconcurrentadministrationwithciprofloxacin.It

isrecommendedthatthedoseoftheophyllineshouldbereducedandplasmalevelsoftheophyllinemonitored.Where

monitoringofplasmalevelsisnotpossible,theuseofciprofloxacinshouldbeavoidedinpatientsreceiving

theophylline.Particularcautionisadvisedinthosepatientswithconvulsivedisorders.

PhenytoinlevelsmaybealteredwhenCiproxinisusedconcomitantly.

CiproxinTabletsshouldnotbeadministeredwithin4multivalentcationicdrugsandmineralsupplements(e.g.

calcium,magnesium,aluiniumoriron),sucralfateorantacidsandhighlybuffeddrugs(e.g.antiretrovirals)as

interferencewithabsorptionmayoccur.Whenappropriate,patientsshouldbeadvisednottoself-medicatewith

preparationscontainingthesecompoundsduringtherpaywithciprofloxacin.Thisreactiondoesnotapplytotheclassof

H2receptorblockerdrugs.

Theconcurrentadministrationofdairyproductsorfortifieddrinksalone(e.g.milk,yoghurt,calcium,fortifiedorange

juice)andciprofloxacinshouldbeavoidedbecauseabsorptionofciprofloxacinmaybereduce.Howeveranormaldiet,

thatwillcontainsmallamountsofcalcium,doesnotsignificantlyaffectciprofloxacinabsorption.

Prolongationofclottingtimehasbeenreportedduringconcomitantadministrationofciprofloxacinandoralanti-

coagulants.

Ciprofloxacinmayinterferewithestimationsofurinary17-ketosteroids,orvanillylmandelicacid.

Animaldatahaveshownthathighdosesofquinolonesincombinationwithsomenon-steroidalanti-inflammatory

drugs,(e.g.fenbufen,butnotacetylsalicylicacid)canleadtoconvulsions.

Transientincreasesinserumcreatininehavebeenseenfollowingconcomitantadministrationofciprofloxacinand

cyclosporin.Therefore,monitoringofserumcreatininelevelsisadvisable.

Concomitantusewithsomephenylpropionicacid-derivednon-steroidalanti-inflammatorydrugsmayleadtotoxicity

possiblebecauseofrenaleffects.

Thesimultaneousadministrationofquinolonesandglibenclamidecanonoccasionpotentiatetheeffectof

glibenclamideresultinginhypoglycaemia.

Renaltubulartransportofmethotrexatemaybeinhibitedbyconcomitantadministrationofciprofloxacinpotentially

leadingtoincreasedplasmalevelsofmethotrexate.Thismayincreasetheriskofmethotrexateassociatedtoxic

reactions.Therfore,patientsreceivingmethotrexatetherpayshouldbecarefullymonitoredwhenconcomitant

ciprofloxacintherapyisindicated.

Concomitantusewithprobenecidreducestherenalclearanceofciprofloxacin,resultinginincreasedquinoloneplasma

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Theuseofmetoclopramidewithciprofloxacinmayacceleratetheabsorptionofciprofloxacin.

4.6Fertility,pregnancyandlactation

Ciprofloxacinshouldnotbeusedduringpregnancy,orinwomenatriskofpregnancynorduringlactation.

Reproductionstudiesperformedinmice,ratsandrabbitsusingparenteralandoraladministrationdidnotrevealany

evidenceofteratogenicity,impairmentoffertilityorimpairmentofperi-/post-nataldevelopment.However,aswith

otherquinolones,ciprofloxacinhasbeenshowntocausearthropathyinimmatureanimals,andthereforeitsuseduring

pregnancyorinwomencapableofchild-bearingisnotrecommended.Studieshaveindicatedthatciprofloxacinis

secretedinbreastmilk.Administrationtonursingmothersisthusnotrecommended.

4.7Effectsonabilitytodriveandusemachines

Ciprofloxacincouldresultinimpairmentofthepatient'sabilitytodriveoroperatemachinery,particularlyin

conjunctionwithalcohol.

4.8Undesirableeffects

Ciprofloxacinisgenerallywelltolerated.Themostfrequentlyreportedadversereactionsarenausea,diarrhoeaand

rash.

Thefollowingadversereactionshavebeenobserved:

Hypersensitivity/skin,e.g.rash,pruritus,urticaria,photosensitivity,drug-inducedfever,anaphylactic/anaphylactoid

reactionsincludingangioedemaanddyspnoea.Rarely,erythemanodosumanderythemamultiforme.Veryrarely,

petechiae,haemorrhagicbullae,vasculitis,serumsickness-likereaction,fixeddrugreactions,Stevens-Johnson

SyndromeandLyellsSyndrome.Treatmentwithciprofloxacinshouldbediscontinuedifanyoftheaboveoccurupon

firstadministration.

General,e.g.moniliasis,asthenia,hyperglycaemiaandabnormalgait,pain,paininextremeties,backpain,chestapin.

Thrombophlebitis.

CNS,e.g.headache,restlessness,depression,dizziness,tremor,convulsions,confusion,hallucinations,somnolence,

sleepdisorders,insomnia.Veryrarely,migraine,hyperesthesia,ataxia,hypertonia,twitchingorandanxietystates.

Isolatedcasesofciprofloxacin-inducedpsychoseshavebeenreported,whichmayprogresstoself-endangering

behaviour.Thereareisolatedreportsofintracranialhypertensionassociatedwithquinolonetherapy.Paraesthesiahas

beenreported.

Gastro-intestinal,e.g.nausea,diarrhoea,vomiting,dyspepsia,abdominalpain,anorexia,flatulence,dysphagia.

Rarely,pancreatitisorpseudomembranouscolitis.

Cardiovascular,e.g.tachycardia,oedema,fainting,hotflushes,hypotensionandsweating,‘VeryrareprolongedQTc

intervalandventriculararrhythmia(includingtorsadedepointes).

Effectsonhaematologicalparameters,e.g.anaemia,eosinophilia,increasesordecreasesinwhitecelland/orplatelet

count,alteredprothrombinlevels,and,veryrarely,haemolyticanaemia,agranulocytosisorpancytopeniaorbone

marrowdepression.Pancytopeniaandbonemarrowdepressionmaybepotentiallylifethreating.

Hepatic,e.g.transientincreasesinliverenzymesorserumbilirubin(particularlyinpatientswithpreviousliver

damage),hepatitis,jaundice/cholestasisandmajorliverdisordersincludinghepaticnecrosis,whichmayrarelyprogress

tohepaticfailure.

Renal,e.g.transientincreasesinbloodureaorserumcreatinine,renalfailure,crystalluria,haematuria,nephritis.

Musculoskeletal,e.g.reversiblearthralgia,jointswellingandmyalgia.Rarely,tenosynovitis.Tendoninflammation

(predominantlyoftheAchillestendon)hasbeenreportedwhichmayleadtotendonrupture.Treatmentshouldbe

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Rarely,exacerbationofthesymptomsofmyastheniagravishasbeenreported.

Specialsenses,e.g.veryrarely,visualdisturbancesincludingdiplopiaandcolourdisturbances,impairedtasteand

smellusuallyreversibleupondiscontinuationoftreatment,tinnitus,transientimpairmentofhearingparticularlyathigh

frequencies.

Abnormallaboratoryfindings,e.g.increasedalkalinephosphatase,amylaseandlipase,increasesinliverfunctiontests,

e.gtransaminases,andcholestaticjaundice,especiallyinpatientswithpreviousliverdamage.

4.9Overdose

Basedonthelimitedinformationavailableintwocasesofingestionofover18gofciprofloxacin,reversiblerenal

toxicityhasoccurred.Therefore,apartfromroutineemergencymeasures,itisrecommendedtomonitorrenalfunction,

includingurinarypHandacidify,ifrequired,topreventcrystalluria.

Patientsmustbekeptwellhydratedand,inthecaseofrenaldamageresultinginprolongedoliguria,dialysisshouldbe

initiated.

CalciumormagnesiumantacidsmaybeadministeredassoonaspossibleafteringestionofCiproxintabletsinorderto

reducetheabsorptionofciprofloxacin.

Serumlevelsofciprofloxacinarereducedbydialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCCodeJ01MA02

Ciprofloxacinisasynthetic4-quinolonederivative,withbactericidalactivity.ItactsviainhibitionofbacterialDNA

gyrase,ultimatelyresultingininterferencewithDNAfunction.Ciprofloxacinishighlyactiveagainstawiderangeof

Gram-positiveandGram-negativeorganismsandhasshownactivityagainstsomeanaerobes,Chlamydiaspp.and

Mycoplasmaspp.Killingcurvesdemonstratetherapidbactericidaleffectagainstsensitiveorganismsanditisoften

foundthatminimumbactericidalconcentrationsareintherangeofminimuminhibitoryconcentrations

CiprofloxacinhasbeenshowntohavenoactivityagainstTreponemapallidumandUrealasmaurealyticum,Nocaria

asteroidesandEnterococcusfaeciumareresistant.

Breakpoints

1µg/ml,R 4µg/ml

Susceptibilty:

Theprelevanceofresistancemayvarygeographicallyandwithtimeforselectedspeciesandlocalareainformationon

resistanceisdesirable,particularlywhentreatingsevereinfections.Thisinformationgivesonlyanapproximate

guidanceonwhethermicro-organismswillbesusceptibletociprofloxacinornot.

Organism Prevalence of

resistance

Sensitive:

Gram-postivebacteria

Corynebacteriumdiphtheriae 0%

Corynebacteriumspp. -

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Staphylococcusaureus(methicillinaresistant) 48-90%

Streptococcusagalactiae 0-17%

Bacillusanthracis -

Gram-negativebacteria

Acinetobacterbaumanii 6-93%

Acinetobacterspp. 14-70%

Aeromonashydrophilia 0%

Aeromonasspp. -

Bordetellapertussis 0%

Brucellamelitensis 0%

Campylobacterjejuni/coli 0.82%

Campylobacterspp. 0%

Citrobacterfreundii 0-4%

Citrobacterspp. 0%

Edwardsiellatarda 0%

Enterobacteraerogenes 0%

Enterobactercloacae 0-3%

Enterobacterspp. 3-13%

Escherichiacoli 2-7%

Escherichiacoli,EHECandEPEC -

Haemphilusinfluenzae 0-1%

Haemphilusinfluenzae(-lactamnegative) 0%

Haemphilusinfluenzae(-lactampostive) 0%

Haemphilusparainfluenzae 0%

Hafniaalvei 0%

Klebsiellaoxytoca 0%

Klebsiellapneumoniae 2-5.8%

Klebsiellaspp. 2-21%

Legionellapneumophila 0%

Legionellaspp. 0%

Moraxellacatarrhalis 0%

Morganellamorganii 1-2%

Neisseriagonorrhoeae 0%

Neisseriagonorrhoeae,-lactamase 0%

Neisseriagonorrhoeae,-lactamasepositive 0%

Neisseriameningitidis 0%

Neisseriameningitidis,-lactamasenegative 0%

Plesiomonasshigelloides 0%

Proteusmirabillis 0-10%

Proteusvulgaris 4%

Providencerettgeri -

Providencespp. 4%

Providencestuartii -

Pseudomonasaeruginosa 1-28%

Salmonellaspp. 0%

Salmonellatyphi 0-2%

Serratisliquefaciens -

Serratiamarcescens 23%

Serratiaspp. 0-21%

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Vibriocholerae 0%

Vibrioparahaemolyticus 0%

Vibriospp. 0%

Yershiniaenterocolitica 0%

Anaerobes

Bacteroidesureolyticus 0%

Clostridiumperfringens -

Peptococcusspp. 0%

Pepotostreptococcusspp. -

Peptostreptococcusmagnus 0%

Veillonellaparvula 0%

Otherpathogens

Chlamydiaspp. -

Heilicobacterpylori -

Mycobacteriumfortuitum 0%

Mycobacteriumtuberculosis 0%

Mycoplasmahominis 16%

Intermediate

Gram-positveaerobes

Enterococci 5%

Enterococcusfaecalis 9-34%

Staphylococcusepidermis,methicillinsenstive 10-16%

Staphylococcusepidermis,methicillinresistant 26-56%

Staphylococcushaemolyticus -

Staphylococcushaemolyticus,methicillinsensitive 8%

Staphylococcushaemolyticus,methicillinresistant 73%

Streptococcusanginosus 9%

Streptococcusbovis -

Streptococcusmilleri 5%

Streptococcusmitis -

Streptococcuspneumoniae,penicillinsenstive 0-1%

Streptococcuspneumoniae,penicillinintermediate -

Streptococcuspneumoniae,penicillinintermediate

andresistant 2.8%

Streptococcuspneumoniae,penicillinresistant -

Streptococcupyogenes 0-28%

Streptococcus,viridansgroup -

Streptococcusviridans,penicillinsensitive -

Streptococcusviridans,penicillinresistant -

Streptococcu,-haemolyticgroupsA,CandG 0%

Gram-negativeaerobes

Alcaligenesspp. -

Listeriamonocytogenes 0%

Listeriaspp. 0%

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Reistance

Plasmid-relatedtransferofresistancehasnotbeenobservedwithciprofloxacinandtheoverallfrequencyof

developmentofresistanceislow(10-9-10-7).Cross-resistancetopenicillins,cephalosporins,aminoglycosidesand

tetracyclineshasnotbeenobservedandorganismsresistanttotheseantibioticsaregenerallysensitivetociprofloxacin.

Ciprofloxacinisalsosuitableforuseincombinationwiththeseantibiotics,andadditivebehaviourisusuallyobserved.

5.2Pharmacokineticproperties

Absorptionoforaldosesofciprofloxacintabletformulationoccursrapidly,mainlyfromthesmallintestine,thehalf-

lifeofabsorptionbeing2-15minutes.Plasmalevelsaredose-relatedandpeak0.5-2.0hoursafterdosing.TheAUC

alsoincreasesdoseproportionatelyafteradministrationofbothsingleandrepeatedoral(tablet)andintravenousdoses.

Theabsolutebioavailabilityisreportedtobe52-83%andciprofloxacinissubjecttoonlyslightfirstpassmetabolism.

Theoralbioavailabilityisapproximately70-80%.

Theintakeoffoodatthesametimeasadministrationoforalciprofloxacinhasamarginalbutclinicallynotrelevant

effectonthepharmacokineticparametersCmaxandAUC.Nospecificrecommendationsarenecessarywithregardto

timeofadministrationoforalciprofloxacinrelativetofoodintake.

Distributionofciprofloxacinwithintissuesiswideandthevolumeofdistributionhigh,thoughslightlylowerinthe

elderly.Proteinbindingislow(between19-40%).

Only10-20%ofasingleoralorintravenousdoseiseliminatedasmetabolites(whichexhibitloweractivitythanthe

parentdrug).Fourdifferentantimicrobiallyactivemetaboliteshavebeenreported,desethyleneciprofloxacin(M1),

sulphociprofloxacin(M2),oxaciprofloxacin(M3)andformylciprofloxacin(M4).M2andM3accountforonethird

eachofmetabolisedsubstanceandM1isfoundinsmallamounts(1.3-2.6%ofthedose).M4hasbeenfoundinvery

smallquantities(<0.1%ofthedose).M1-M3haveantimicrobialactivitycomparabletonalidixicacidandM4foundin

thesmallestquantityhasantimicrobialactivitysimilartothatofnorfloxacin.

Eliminationofciprofloxacinanditsmetabolitesoccursrapidly,primarilybythekidney.Aftersingleoraland

intravenousdosesofciprofloxacin,55%and75%respectivelyareeliminatedbythekidneyand39%and14%inthe

faeceswithin5days.Renaleliminationtakesplacemainlyduringthefirst12hoursafterdosingandrenalclearance

Fusobacteriumspp. -

Gardnerellavaginalis 0%

Preotellaspp. -

Otherpathogens

Ureaplasmaurealyticum 11%

Resistant

Gram-postiveaerobes

Enterococcusfaecium -

Stenotrophomonasmaltophilla 94%

Strepotococcussamguis -

Gram-negativeaerobes

Flavobacteriummeningosepticum -

Nocardiaasteroides -

Anaerobes

Bacteroidesfragilis -

Bacteroidesthetaiotaomicron -

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clearanceisbetween0.18–0.3l/h.kgandtotalbodyclearancebetween0.48–0.60l/h.kg.Approximately1%ofa

ciprofloxacindoseisexcretedviathebiliaryroute.Theeliminationkineticsarelinearandafterrepeateddosingat12

hourlyintervals,nofurtheraccumulationisdetectedafterthedistributionequilibriumisattained(at4-5half-lives).The

eliminationhalf-lifeofunchangedciprofloxacinoveraperiodof24-48hourspost-doseis3.1-5.1hours.

Somestudiescarriedoutwithciprofloxacininseverelyrenallyimpairedpatients(serumcreatinine>265micromole/lor

creatinineclearance<20ml/minute)demonstratedeitheradoublingoftheeliminationhalf-life,orfluctuationsinhalf-

lifeincomparisonwithhealthyvolunteers,whereasotherstudiesshowednosignificantcorrelationbetween

eliminationhalf-lifeandcreatinineclearance.However,itisrecommendedthatinseverelyrenallyimpairedpatients,

thetotaldailydoseshouldbereducedbyhalf,althoughmonitoringofdrugserumlevelsprovidesthemostreliable

basisfordoseadjustmentasnecessary.

Resultsofpharmacokineticstudiesinpaediatriccysticfibrosispatientshaveshowndosagesof20mg/kgorallytwice

dailyor10mg/kgivthreetimesdailyarerecommendedtoachieveplasmaconcentration/timeprofilescomparableto

thoseachievedintheadultpopulationatthecurrentlyrecommendeddosageregimen.

Inhalationanthrax:Ciprofloxacinserumconcentrationsachievedinhumansserveasasurrogateendpointreasonably

likelytopredictclinicalbenefitandprovidethebasisfortherecommendeddoses.

5.3Preclinicalsafetydata

Followingextensiveoralandintravenoustoxicologytestingwithciprofloxacin,onlytwofindingswhichmaybe

consideredrelevanttotheuseofciprofloxacininmanwereobserved.Crystalluriawasnotedinthosespeciesof

animalswhichhadanormallyalkalineurine.Kidneydamagewithoutthepresenceofcrystalluriawasnotobserved.

Thiseffectisconsideredasecondaryinflammatoryforeign-bodyreaction,duetotheprecipitationofacrystalline

complexofciprofloxacin,magnesiumandproteininthedistaltubulesystemofthekidneys.Thisisconsiderednotto

beaprobleminman,becausetheurineisnormallyacidic.However,toavoidtheoccurrenceofcrystalluria,patients

shouldbewellhydratedandexcessivealkalinityoftheurineavoided.

Aswithotherquinolones,damagetotheweight-bearingjointsofonlyjuvenileratsanddogstreatedwithciprofloxacin

wasnotedinrepeatdosetoxicitytesting.Thiswasmorenoticeableinthedog.Althoughanalysisofavailablesafety

datafromciprofloxacinuseinpaediatricpatientsdidnotdiscloseanyevidenceofdrugrelatedcartilageorarticular

damage,theuseofciprofloxacininchildrenandgrowingadolescentsisgenerallynotrecommended,unlessthebenefits

areconsideredtooutweighthepotentialrisks(withtheexceptionoftreatmentofcysticfibrosis).Additionally,because

ofthepotentialofarthropathy,theuseofciprofloxacinduringpregnancyandlactationisnotrecommended.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Maizestarch

Microcrystallinecellulose

Crospovidone

Colloidalanhydroussilica

Magnesiumstearate

Hypromellose

Macrogol4000

Titaniumdioxide(E171)

6.2Incompatibilities

Notapplicable.

Irish Medicines Board

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Date Printed 27/06/2011 CRN 2101974 page number: 10

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Blisterpacksof10and20tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA0465/082/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:22March2002

Dateoflastrenewal:22March2007

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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Date Printed 27/06/2011 CRN 2101974 page number: 11