CIFLOXAGER

Main information

  • Trade name:
  • CIFLOXAGER Coated Tablets 750 Milligram
  • Dosage:
  • 750 Milligram
  • Pharmaceutical form:
  • Coated Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CIFLOXAGER Coated Tablets 750 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0577/069/003
  • Authorization date:
  • 04-02-2005
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cifloxager750mgfilm-coatedtablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontainsciprofloxacinhydrochlorideequivalentto750mgciprofloxacin.

ForexcipientsseeSection6.1

3PHARMACEUTICALFORM

Film-coatedtablet

White,biconvexcapsulesshaped,film-coatedtabletmarked'CF750'oneithersideofascorelineononesideand'G'

ontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Ciprofloxacinisindicatedforthetreatmentofthefollowinginfectionscausedbysensitivebacteria.

Respiratorytractinfections:e.g.lobarandbronchopneumonia,acuteandchronicbronchitis,acuteexacerbationof

cysticfibrosis,bronchiectasis,emphysema.Ciprofloxacinisnotrecommendedasfirstlinetherapyforthetreatmentof

pneumococcalpneumonia(seeSpecialwarningsandprecautionsforuse).Incircumstanceswhereaphysician

considersitappropriatetouseciprofloxacininpatientswithpneumococcalpneumoniaadoseof750mgtwicedaily

shouldprovideadequatecoverinthemajorityofcases(seePosologyandmethodofadministration).Ciprofloxacin

maybeusedfortreatingGram-negativepneumonia.

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

epididymitis.

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

Gonorrhoea:includingurethral,rectalandpharyngealgonorrhoeacausedbybeta-lactamaseproducingorganismsor

organismsmoderatelysensitivetopenicillin.

4.2Posologyandmethodofadminstration

PosologyandMethodofAdministration

GeneralDosageRecommendations:thedosageofCiprofloxacinisdeterminedbytheseverityandtypeofinfection,the

sensitivityofthecausativeorganism(s)andtheage,weightandrenalfunctionofthepatient.CifloxagerFilm-Coated

Tabletsshouldbeswallowedwholewithanadequateamountofliquid.

Adults:Thedosagerangeforadultsis100–750mgtwicedaily.Thefollowingdosagesforspecifictypesofinfection

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Table1:RecommendedAdultDosage

*Asthepharmacokineticsofciprofloxacinremainunchangedinpatientswithcysticfibrosisthelowbodyweightof

thesepatientsshouldbetakenintoconsiderationwhendeterminingdosage.

Impairedrenalfunction:Dosageadjustmentsarenotusuallyrequiredexceptinpatientswithsevererenalimpairment

(serumcreatinine>265micromole/lorcreatinineclearance<20ml/minute).Ifadjustmentisnecessarythismaybe

achievedbyreducingthetotaldailydosebyhalfalthoughmonitoringofdrugserumlevelsprovidesthemostreliable

basisfordoseadjustment.Dialysisreducesserumlevelsofciprofloxacin.

Elderly:Althoughhigherciprofloxacinserumlevelsarefoundintheelderly,noadjustmentofdosageisnecessary.

Adolescentsandchildren:Aswithotherdrugsinitsclass,ciprofloxacinhasbeenshowntocausearthropathyin

weight-bearingjointsofimmatureanimals.

Althoughtherelevanceofthistomanisunknown,itsuseinchildrenandgrowingadolescentsisnotrecommended.

However,wherethebenefitofusingciprofloxacinisconsideredtooutweighthispotentialrisk,thedosagedepends

upontheseverityofinfection,andshouldbeadministeredintwodivideddoses.

DurationofTreatment:Thedurationoftreatmentdependsupontheseverityofinfection,clinicalresponseand

bacteriologicalfindings.InacuteanduncomplicatedcystitisthetreatmentperiodisthreedayswithCifloxagerFilm-

Coated100mgTablets.Inotheracuteinfectionstheusualtreatmentperiodis5to7dayswithciprofloxacininfusionor

5to10dayswithCifloxagerFilm-CoatedTablets.Generally,treatmentshouldbecontinuedforatleastthreedaysafter

thesignsandsymptomsofinfectionhavedisappeared.Prolongedtreatmentoruseinchronicconditionsshouldonlybe

initiatedunderconsultantdirectionwithregularsurveillance.

Initialintravenousadministrationmaybefollowedbytreatmentwithoralciprofloxacin.

InacuteuncomplicatedcystitisthetreatmentperiodisthreedayswithCifloxagertablets.

InitialintravenousadministrationmaybefollowedbytreatmentwithoralCiprofloxacin.

4.3Contraindications

Ciprofloxaciniscontraindicatedinpatientswhohaveshownhypersensitivitytociprofloxacinorsimilarquinolone

drugs.

Ciprofloxaciniscontraindicatedinpatientswithahistoryofquinolone-inducedtendondisorder.

Ciprofloxacinisalsocontraindicatedinchildrenandgrowingadolescentsunlessepiphysealclosuresoflongbones

haveoccurred,orexceptwherethebenefitsoftreatmentexceedtherisks.

4.4Specialwarningsandprecautionsforuse

Indication Dosage(mgCiprofloxacin)

Gonorrhoea 250mgsingledose

Acute,uncomplicatedcystitis 250mgb.d.

Upperandlowerurinarytractinfections(dependingon

severity) 250mg-500mgb.d.

Upperandlowerrespiratorytractinfections(dependingon

severity) 250mg-750mgb.d.

Pneumococcalpneumonia(second-linewherephysician

considersitappropriate) 750mgb.d.

CysticfibrosispatientswithpseudomonallowerRTI* 750mgb.d.

Otherinfections 500–750mgb.d.

Severeinfections,particularlyduetoPseudomonas,

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includingepilepsy,orhistoryofconvulsivedisease.

Crystalluriarelatedtotheuseofciprofloxacinhasbeenreported.Patientsreceivingciprofloxacinshouldbewell

hydratedandexcessivealkalinityoftheurineshouldbeavoided.

Personswithlatentoractualdefectsinglucose-6-phosphatedehydrogenaseactivityarepronetohaemolyticreactions

withquinoloneantibacterialsandsociprofloxacinshouldbeusedwithcautioninthesepatients.

Ciprofloxacinisnotrecommendedasfirst-linetherapyforthetreatmentofpneumococcalpneumonia.Streptococcus

pneumoniaeisthemostfrequentpathogenresponsibleofcommunityacquiredpneumonia.

Tendoninflammationandrupturemayoccurwithquinoloneantibiotics.Suchreactionshavebeenobserved

particularlyinolderpatientsandinthosetreatedconcurrentlywithcorticosteroids.Atthefirstsignofpainor

inflammation,patientsshoulddiscontinueciprofloxacinandresttheaffectedlimbs.

Toxicologicalstudieshaveshownthatadministrationofoxyquinoloneantibacterialagentsatdoseshigherthanthe

therapeuticrangecanproduceerosionofthecartilageinweight-bearingjointsinimmatureanimalsofsomespecies.

Nosuchlesionshavebeenshowntooccurinmantodate.Thisproductshouldnotbeprescribedforchildrenorthosein

whombonegrowthiscontinuingunlessthebenefitofshort-termuseisregardedasexceedingtherisk.

Patientswithpre-existentsignificantrenalorhepaticdisordersshouldbecarefullymonitoredtodetectany

deteriorationinfunction.Itshouldonlybeadministeredwithgreatcautiontopersonswithrenalinsufficiencyorsevere

dehydration.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Increasedplasmalevelsoftheophyllinehavebeenobservedfollowingconcurrentadministrationwithciprofloxacin.It

isrecommendedthatthedoseoftheophyllineshouldbereducedandplasmalevelsoftheophyllinemonitored.Where

monitoringofplasmalevelsisnotpossibletheuseofciprofloxacinshouldbeavoidedinpatientsreceiving

theophylline.Particularcautionisadvisedinthosepatientswithconvulsivedisorders.CifloxagerFilm-CoatedTablets

shouldnotbeadministeredwithinfourhoursofmedicationscontainingmagnesium,aluminium,calciumorironsalts

asinterferencewithabsorptionmayoccur.Whenappropriate,patientsshouldbeadvisednottoself-medicatewith

preparationscontainingthesecompoundsduringtherapywithciprofloxacin.

Prolongationofbleedingtimehasbeenreportedduringconcomitantadministrationofciprofloxacinandoralanti-

coagulants.

Ciprofloxacinmayinterferewithestimationsofurinary17-ketosteroids,orvanillylmandelicacid.Animaldatahave

shownthathighdosesofquinolonesincombinationwithsomenon-steroidalanti-inflammatorydrugs(e.g.fenbufen

butnotacetylsalicylicacid)canleadtoconvulsions.

Transientincreasesinserumcreatininehavebeenseenfollowingconcomitantadministrationofciprofloxacinand

cyclosporin.Thereforemonitoringofserumcreatininelevelsisadvisable.

Concomitantusewithsomephenylpropionicacidderivednon-steroidalanti-inflammatorydrugsmayleadtotoxicity

possiblybecauseofrenaleffects.Thesimultaneousadministrationofquinolonesandglibenclamidecanonoccasion

potentiatetheeffectofglibenclamideresultinginhypoglycaemia.Concomitantusewithprobenecidreducestherenal

clearanceofciprofloxacin,resultinginincreasedquinoloneplasmalevels.

Theuseofmetoclopramidewithciprofloxacinmayacceleratetheabsorptionofciprofloxacin.

4.6Pregnancyandlactation

Ciprofloxacinshouldnotbeusedduringpregnancy,orinwomenatriskofpregnancy,norduringlactation.

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drugsofthisseries.Thedrugproducedtheseeffectsinanimalsinreproductionstudies.Itcrossestheplacentaandis

excretedinbreastmilkandamnioticfluid.Administrationtonursingmothersisthusnotrecommended.

4.7Effectsonabilitytodriveandusemachines

Ciprofloxacincouldresultinimpairmentofthepatient’sabilitytodriveoroperatemachineryparticularlyin

conjunctionwithalcohol.

4.8Undesirableeffects

Side-effectsinclude;Gastro-intestinaldisturbancesincludingrarely,pseudomembranouscolitis.

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

reactions.Rarely,erythemanodosumanderythemamultiforme.

Veryrarely,petechiae,haemorrhagicbullae,vasculitis,Stevens-JohnsonSyndromeandLyell’sSyndrome.Treatment

withciprofloxacinshouldbediscontinuedifanyoftheaboveoccuruponfirstadministration.

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

somnolence.Veryrarelysleepdisordersandanxietystates.Isolatedcasesofciprofloxacin-inducedpsychosishave

beenreported.Thereareisolatedreportsofintracranialhypertensionassociatedwithquinolonetherapy.

Hepaticdisturbancese.g.transientincreasesinliverenzymesorserumbilirubin(particularlyispatientswithprevious

liverdamage),hepatitis,jaundiceandmajorliverdisordersincludinghepaticnecrosiswhichmayrarelyprogressto

hepaticfailure.

RenalDisturbances

Musculoskeletaldisturbancese.g.reversiblearthralgia,jointswellingandmyalgia,rarelytenosynovitisandveryrarely,

tendoninflammationwhichmayleadtotendonrupture.

Effectsonhaematologicalparameters,e.g.eosinophilia,leucopenia,granulocytopenia,thrombocytopenia,

thrombocytosis,alteredprothrombinlevelsandveryrarely,haemolyticanaemia.

Specialsensedisturbancese.g.veryrarely,visualdisturbances,impairedtasteandsmell,tinnitus,transientimpairment

ofhearingparticularlyathighfrequencies.

Tachycardia,oedema,fainting,hotflushes,hypotensionandsweatinghavebeenreported.

4.9Overdose

Basedonthelimitedinformationavailableintwocasesofingestionofover18gofciprofloxacinreversiblerenal

toxicityhasoccurred.Thereforeapartfromroutineemergencymeasures,itisrecommendedtomonitorrenalfunction,

includingurinarypHandacidity,ifrequiredtopreventcrystalluria.Patientsmustbekeptwellhydratedandinthecase

ofrenaldamageresultinginprolongedoliguria,dialysisshouldbeinitiated.

CalciumormagnesiumantacidsmaybeadministeredassoonaspossibleafteringestionofCifloxagerFilm-Coated

Tabletsinordertoreducetheabsorptionofciprofloxacin.

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Ciprofloxacinisasynthetic4-quinlonederivative,withbactericidalactivity.ItactsviainhibitionofbacterialDNA

gyraseultimatelyresultingininterferenceofbacterialDNAgyrase.UltimatelyresultingininterferencewithDNA

function.CiprofloxacinishighlyactiveagainstawiderangeofGram-positiveandGram-negativeorganismsandhas

shownactivityagainstsomeanaerobes.ChlamydiasppandMycoplasmasppkillingcurvesdemonstratetherapid

bactericidaleffectagainstsensitiveorganismsanditisoftenfoundthatminimumbactericidalconcentrationsareinthe

rangeofminimuminhibitoryconcentrations.CiprofloxacinhasbeenshowntohavenoactivityagainstTreponema

pallidumandUreaplasmaurealyticum.NocardiaasteroidesandEnterococcusfaeciumareresistant.

Plasmid-relatedtransferofresistancehasnotbeenobservedwithciprofloxacinandtheoverallfrequencyof

developmentofresistanceislow(10 -8

–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.

Plasmalevelspeakapproximately1.5–2.5hoursafterdosingandtheAUC

isintherangeof5–12mg.h/l.The

absolutebioavailabilityisreportedtobe52-83%andciprofloxacinissubjecttoonlyslightfirstpassmetabolism.The

oralbioavailabilityisapproximately70-80%.

Theintakeoffoodatthesametimeasadministrationoforalciprofloxacinhasamarginalbutclinicallynotrelevant

effectonthepharmacokineticparametersC

andAUC.Nospecificrecommendationsarenecessarywithregardto

timetoadministrationoforalciprofloxacinrelativetofoodintake.

Distributionofciprofloxacinwithinissuesiswideandthevolumeofdistributionhigh,thoughslightlylowerinthe

elderly.Proteinbindingislow(between19–40%).

Only10-20%ofasingleoralorintravenousdoseiseliminatedasmetabolites(whichexhibitloweractivitythanthe

parentdrug).Fourdifferentantimicrobiallyactivemetaboliteshavebeenreporteddesethyleneciprofloxacin(M1).

Sulphociprofloxacin(M2).Oxaciprofloxacin(M3)andformylciprofloxacin(M4).M2andM3accountforonethird

eachofmetabolisedsubstanceandM1isfoundinsmallamounts(13-26%ofthedose).M4hasbeenfoundinvery

smallquantities(<0.1%ofthedose).M1-M3haveantimicrobialactivitycomparabletonalidixicacidandM4foundin

thesmallestquantityhasantimicrobialactivitysimilartothatofnorfloxacin.Eliminationofciprofloxacinandits

metabolitesoccursrapidly,primarilybythekidney.Aftersingleoralandintravenousdosesofciprofloxacin55%and

75%respectivelyareeliminatedbythekidneyand39%and14%inthefaeceswithin5days.Renaleliminationtakes

placemainlyduringthefirst12hoursafterdosingandrenalclearancelevelssuggestthatactivesecretionbytherenal

tubulesoccursinadditiontonormalglomerularfiltration.Renalclearanceisbetween0.18-0.3l/h.kgandtotalbody

clearanceisbetween0.48-0.6l/h.kg.Approximately1%ofaciprofloxacindoseisexcretedviathebiliaryroute.The

eliminationkineticsarelinearandafterrepeateddosingat12hourlyintervalsnofurtheraccumulationisdetectedafter

thedistributionequilibriumisattained(at4.5half-lives).Theeliminationhalf-lifeofunchangedciprofloxacinovera

periodof24–48hourspostdoseis3.1-5.1hours.Somestudiescarriedoutwithciprofloxacininseverelyrenally

impairedpatients(serumcreatinine>265micromole/lorcreatinineclearance<20ml/minutes)demonstratedeithera

doublingoftheeliminationhalf-lifeorfluctuationsinhalf-lifeincomparisonwithhealthyvolunteers,whereasother

studiesshowednosignificantcorrelationbetweeneliminationhalf-lifeandcreatinineclearance.However,itis

recommendedthatinseverelyrenallyimpairedpatients,thetotaldailydoseshouldbereducedbyhalf,although

monitoringofalthoughmonitoringofdrugserumlevelsprovidesthemostreliablebasisfordoseadjustmentas

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5.3Preclinicalsafetydata

Followingextensiveoralandintravenoustoxicologytestingwithciprofloxacinonlytwofindingswhichmaybe

consideredrelevanttotheuseofciprofloxacininmanwereobserved.Crystalluriawasnotedinthosespeciesof

animalswhichhadnormallyalkalineurine.Kidneydamagewithoutthepresenceofcrystalluriawasnotobserved.This

effectisconsideredasecondaryinflammatoryforeign-bodyreactionduetotheprecipitationofcrystallinecomplexof

ciprofloxacin,magnesiumandproteininthedistaltubulesystemofthekidneys.Thisisconsiderednottobeaproblem

inmanbecausetheurineisnormallyacidic.Howevertoavoidtheoccurrenceofcrystalluria,patientsshouldbewell

hydratedandexcessivealkalinityoftheurineavoided.

Aswithotherquinolones,damagetotheweightbearingjointsofonlyjuvenileratsanddogstreatedwithciprofloxacin

wasnotedinrepeatdosetoxicitytesting.Thiswasmorenoticeableinthedog.Althoughtherelevanceofthistomanis

unknown,theuseofciprofloxacininchildrenandgrowingadolescentsisnotrecommendedunlessthebenefitsare

consideredtooutweighthepotentialrisks.Additionally,becauseofthepotentialofarthropathy,theuseof

ciprofloxacinduringpregnancy,inwomencapableofchildbearingandinnursingmothersisnotrecommended.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

Maizestarch

Crospovidone

Starch,pregelatinised

Silica,colloidalanhydrous

Magnesiumstearate

Coating:

OpadryIIWhiteY-22-7719consistingof(HydroxypropylMethylcellulose,TitaniumDioxide,Polydextrose,Glycerol

Triacetate,Macrogol).

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Nospecialstorageconditions.

6.5Natureandcontentsofcontainer

PVDC/PVCAluminiumFoilblistersof10tabletspackedincartons.

Cartonscontainatotalof10or20tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7MARKETINGAUTHORISATIONHOLDER

McDermottLaboratoriesLtd

T/AGerardLaboratories

35-36BaldoyleIndustrialEstate

GrangeRoad

Dublin13

8MARKETINGAUTHORISATIONNUMBER

PA577/69/3

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:04February2005

10DATEOFREVISIONOFTHETEXT

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