CETRICURE

Main information

  • Trade name:
  • CETRICURE Film Coated Tablet 10 Milligram
  • Dosage:
  • 10 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CETRICURE Film Coated Tablet 10 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0688/003/001
  • Authorization date:
  • 26-05-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cetricure10mgFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

EachtabletcontainsCetirizinedihydrochloride10mg.

Alsocontainslactose

Forafulllistofexcipientssee6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

Whitecircularbiconvexfilm-coatedtablets,embossed`A`ononesideandadeepscoreontheother.

Thetabletcanbedividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inadultsandpaediatricpatients6yearandabove:

-Cetirizineisindicatedforthereliefofnasalandocularsymptomsofseasonalandperennial

allergicrhinitis.

-Cetirizineisindicatedforthereliefofsymptomsofchronicidiopathicurticaria.

4.2Posologyandmethodofadministration

Childrenagedfrom6to12years:5mgtwicedaily(ahalftablettwicedaily).

Adultsandadolescentsover12yearsofage:10mgoncedaily(1tablet).

Thetabletsneedtobeswallowedwithaglassofliquid.

Elderlysubjects:datadonotsuggestthatthedoseneedstobereducedinelderlysubjectsprovidedthattherenal

functionisnormal.

Patientswithmoderatetosevererenalimpairment:therearenodatatodocumenttheefficacy/safetyratioinpatients

withrenalimpairment.Sincecetirizineismainlyexcretedviarenalroute(seesection5.2),incasesnoalternative

treatmentcanbeused,thedosingintervalsmustbeindividualizedaccordingtorenalfunction.Refertothefollowing

tableandadjustthedoseasindicated.Tousethisdosingtable,anestimateofthepatient’screatinineclearance(CLcr)

inml/minisneeded.TheCLcr(ml/min)maybeestimatedfromserumcreatinine(mg/dl)determinationusingthe

followingformula:

Dosingadjustmentsforadultpatientswithimpairedrenalfunction

CLcr= [140-age(years)]xweight(kg) (x0.85forwomen)

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Inpaediatricpatientssufferingfromrenalimpairment,thedosewillhavetobeadjustedonanindividualbasistaking

accounttherenalclearanceofthepatientandhisbodyweight.

Patientswithhepaticimpairment:nodoseadjustmentisneededinpatientswithsolelyhepaticimpairment.

Patientswithhepaticimpairmentandrenalimpairment:doseadjustmentisrecommended(seePatientswithmoderate

tosevererenalimpairmentabove).

4.3Contraindications

Historyofhypersensitivitytotheactivesubstance,toanyoftheexcipients,tohydroxyzineortoanypiperazine

derivatives.

Patientswithsevererenalimpairmentatlessthan10ml/mincreatinineclearance.

4.4Specialwarningsandprecautionsforuse

Attherapeuticdoses,noclinicallysignificantinteractionshavebeendemonstratedwithalcohol(forabloodalcohol

levelof0.5g/L).Nevertheless,precautionisrecommendedifalcoholistakenconcomitantly.

Cautioninepilepticpatientsandpatientsatriskofconvulsionsisrecommended.

Theuseofthefilm-coatedtabletformulationisnotrecommendedinchildrenagedlessthan6yearssincethis

formulationdoesnotallowforappropriatedoseadaptation.

Allergyskintestsareinhibitedbyantihistaminesandawash-outperiod(of3days)isrequiredbeforeperformingthem.

Cetirizinetabletscontainlactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactase

deficiencyorglucose-galactosemalabsorptionshouldnottakecetirizinefilm-coatedtablet.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Duetothepharmacokinetic,pharmacodynamicandtoleranceprofileofcetirizine,nointeractionsareexpectedwiththis

antihistamine.Actually,neitherpharmacodynamicnorsignificantpharmacokineticinteractionwasreportedindrug-

druginteractionsstudiesperformed,notablywithpseudoephedrineortheophylline(400mg/day).

Theextentofabsorptionofcetirizineisnotreducedwithfood,althoughtherateofabsorptionisdecreased.

4.6Fertility,pregnancyandlactation

Pregnancy

Forcetirizineveryrareclinicaldataonexposedpregnanciesareavailable.Animalstudiesdonotindicatedirector

indirectharmfuleffectswithrespecttopregnancy,embryonal/fetaldevelopment,parturitionorpostnataldevelopment.

Group Creatinineclearance

(ml/min) Dosageandfrequency

Normal ≥80 10mgoncedaily

Mild 50-79 10mgoncedaily

Moderate 30-49 5mgoncedaily

Severe <30 5mgonceevery2days

End-stagerenal

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Lactation

Cetirizineisexcretedinhumanmilkatconcentrationsrepresenting0.25to0.90thosemeasuredinplasma,depending

onsamplingtimeafteradministration.Therefore,cautionshouldbeexercisedwhenprescribingcetirizinetolactating

women.

4.7Effectsonabilitytodriveandusemachines

Objectivemeasurementsofdrivingability,sleeplatencyandassemblylineperformancehavenotdemonstratedany

clinicallyrelevanteffectsattherecommendeddoseof10mg.

Patientsintendingtodrive,engaginginpotentiallyhazardousactivitiesoroperatingmachineryshouldnotexceedthe

recommendeddoseandshouldtaketheirresponsetothemedicinalproductintoaccount.Inthesesensitivepatients,

concurrentusewithalcoholorotherCNSdepressantsmaycauseadditionalreductionsinalertnessandimpairmentof

performance.

4.8Undesirableeffects

ClinicalstudieshaveshownthatcetirizineattherecommendeddosagehasminoradverseeffectsontheCNS,including

somnolence,fatigue,dizzinessandheadache.Insomecases,paradoxicalCNSstimulationhasbeenreported.

AlthoughcetirizineisaselectiveantagonistofperipheralH1-receptorsandisrelativelyfreeofanticholinergicactivity,

isolatedcasesofmicturitiondifficulty,eyeaccommodationdisordersanddrymouthhavebeenreported.

Instancesofabnormalhepaticfunctionwithelevatedhepaticenzymesaccompaniedbyelevatedbilirubinhavebeen

reported.Mostlythisresolvesupondiscontinuationofthetreatmentwithcetirizinedihydrochloride.

a)Clinicaltrials

Doubleblindcontrolledclinicalorpharmacoclinicaltrialscomparingcetirizinetoplaceboorotherantihistaminesatthe

recommendeddosage(10mgdailyforcetirizine),ofwhichquantifiedsafetydataareavailable,includedmorethan

3200subjectsexposedtocetirizine.

Fromthispooling,thefollowingadverseeventswerereportedforcetirizine10mgintheplacebo-controlledtrialsat

ratesof1.0%orgreater:

Althoughstatisticallymorecommonthanunderplacebo,somnolencewasmildtomoderateinthemajorityofcases.

Objectivetestsasdemonstratedbyotherstudieshavedemonstratedthatusualdailyactivitiesareunaffectedatthe

Adverseevent

(WHO-ART) Cetirizine10mg

(n=3260) Placebo

(n=3061)

Bodyasawhole–generaldisorders

Fatigue 1.63% 0.95%

Centralandperipheralnervous

systemdisorders

Dizziness

Headache 1.10%

7.42% 0.98%

8.07%

Gastro-intestinalsystemdisorders

Abdominalpain

Drymouth

Nausea 0.98%

2.09%

1.07% 1.08%

0.82%

1.14%

Psychiatricdisorders

Somnolence 9.63% 5.00%

Respiratorysystemdisorders

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Adversedrugreactionsatratesof1%orgreaterinchildrenagedfrom6monthsto12years,includedinplacebo-

controlledclinicalorpharmacoclinicaltrialsare:

b)Post-marketingexperience

Inadditiontotheadverseeffectsreportedduringclinicalstudiesandlistedabove,isolatedcasesofthefollowing

undesirableeffectshavebeenreportedinpost-marketingexperience.Frequenciesaredefinedasfollows:verycommon

(>1/10);common(>1/100to<1/10);uncommon(>1/1,000to<1/100);rare(>1/10,000to<1/1,000);veryrare

(<1/10,000),notknown(cannotbeestimatedfromavailabledata).

Bloodandlymphaticdisorders:

Veryrare:thrombocytopenia

Immunesystemdisorders:

Rare:hypersensitivity

Veryrare:anaphylacticshock

Psychiatricdisorders:

Uncommon:agitation

Rare:aggression,confusion,depression,hallucination,insomnia

Veryrare:tics

Nervoussystemdisorders:

Uncommon:paraesthesia

Rare:convulsions

Veryrare:dysgeusia,syncope,tremor,dystonia,dyskinesia

Notknown:amnesia,memoryimpairment

Eyedisorders:

Veryrare:accommodationdisorder,blurredvision,oculogyration

Cardiacdisorders:

Rare:tachycardia

Gastro-intestinaldisorders:

Uncommon:diarrhoea

Hepatobiliarydisorders:

Adversedrugreactions

(WHO-ART) Cetirizine10mg

(n=1656) Placebo

(n=1294)

Gastro-intestinalsystemdisorders

Diarrhoea 1.0% 0.6%

Psychiatricdisorders

Somnolence 1.8% 1.4%

Respiratorysystemdisorders

Rhinitis 1.4% 1.1%

Bodyasawhole–generaldisorders

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Skinandsubcutaneoustissuedisorders:

Uncommon:pruritus,rash

Rare:urticaria

Veryrare:angioneuroticoedema,fixeddrugeruption

Renalandurinarydisorders:

Veryrare:dysuria,enuresis

Generaldisordersandadministrationsiteconditions:

Uncommon:asthenia,malaise

Rare:oedema

Investigations:

Rare:weightincreased

4.9Overdose

a)Symptoms

SymptomsobservedafteranimportantoverdoseofcetirizinearemainlyassociatedwithCNSeffectsorwitheffects

thatcouldsuggestananticholinergiceffect.

Adverseeventsreportedafteranintakeofatleast5timestherecommendeddailydoseare:confusion,diarrhoea,

dizziness,fatigue,headache,malaise,mydriasis,pruritus,restlessness,sedation,somnolence,stupor,tachycardia,

tremor,andurinaryretention.

b)Management

Thereisnoknownspecificantidotetocetirizine.

Shouldoverdoseoccur,symptomaticorsupportivetreatmentisrecommended.Gastriclavageshouldbeconsidered

followingingestionofashortoccurrence.

Cetirizineisnoteffectivelyremovedbydialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Piperazinederivatives,ATCcode:R06AE07

Cetirizine,ahumanmetaboliteofhydroxyzine,isapotentandselectiveantagonistofperipheralH1-receptors.Invitro

receptorbindingstudieshaveshownnomeasurableaffinityforotherthanH1-receptors.

Inadditiontoitsanti-H1effect,cetirizinewasshowntodisplayanti-allergicactivities:atadoseof10mgonceortwice

daily,itinhibitsthelatephaserecruitmentofeosinophils,intheskinandconjunctivaofatopicsubjectssubmittedto

allergenchallenge.

Studiesinhealthyvolunteersshowthatcetirizine,atdosesof5and10mgstronglyinhibitsthewhealandflare

reactionsinducedbyveryhighconcentrationsofhistamineintotheskin,butthecorrelationwithefficacyisnot

established.

Ina35-daystudyinchildrenaged5to12,notolerancetotheantihistaminiceffect(suppressionofwhealandflare)of

cetirizinewasfound.Whenatreatmentwithcetirizineisstoppedafterrepeatedadministration,theskinrecoversits

normalreactivitytohistaminewithin3days.

Inasix-week,placebo-controlledstudyof186patientswithallergicrhinitisandconcomitantmildtomoderateasthma,

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Thisstudysupportsthesafetyofadministeringcetirizinetoallergicpatientswithmildtomoderateasthma.

Inaplacebo-controlledstudy,cetirizinegivenatthehighdailydoseof60mgforsevendaysdidnotcausestatistically

significantprolongationofQTinterval.

Attherecommendeddosage,cetirizinehasdemonstratedthatitimprovesthequalityoflifeofpatientswithperennial

andseasonalallergicrhinitis.

5.2Pharmacokineticproperties

Thesteady-statepeakplasmaconcentrationsisapproximately300ng/mlandisachievedwithin1.0 ±

0.5h.No

accumulationisobservedforcetirizinefollowingdailydosesof10mgfor10days.

Thedistributionofpharmacokineticparameterssuchaspeakplasmaconcentration(Cmax)andareaundercurve

(AUC),isunimodalinhumanvolunteers.

Theextentofabsorptionofcetirizineisnotreducedwithfood,althoughtherateofabsorptionisdecreased.Theextent

ofbioavailabilityissimilarwhencetirizineisgivenassolutions,capsulesortablets.

Theapparentvolumeofdistributionis0.50l/kg.Plasmaproteinbindingofcetirizineis93 ±

0.3%.Cetirizinedoesnot

modifytheproteinbindingofwarfarin.

Cetirizinedoesnotundergoextensivefirstpassmetabolism.Abouttwothirdofthedoseareexcretedunchangedin

urine.Theterminalhalf-lifeisapproximately10hours.

Cetirizineexhibitslinearkineticsovertherangeof5to60mg.

Specialpopulations

Elderly:Followingasingle10mgoraldose,half-lifeincreasedbyabout50%andclearancedecreasedby40%in16

elderlysubjectscomparedtothenormalsubjects.Thedecreaseincetirizineclearanceintheseelderlyvolunteers

appearedtoberelatedtotheirdecreasedrenalfunction.

Children,infantsandtoddlers:Thehalf-lifeofcetirizinewasabout6hoursinchildrenof6-12yearsand5hoursin

children2-6years.Ininfantsandtoddlersaged6to24months,itisreducedto3.1hours

Renallyimpairedpatients:Thepharmacokineticsofthedrugweresimilarinpatientswithmildimpairment(creatinine

clearancehigherthan40ml/min)andhealthyvolunteers.Patientswithmoderaterenalimpairmenthada3-foldincrease

inhalf-lifeand70%decreaseinclearancecomparedtohealthyvolunteers.

Patientsonhemodialysis(creatinineclearancelessthan7ml/min)givenasingleoral10mgdoseofcetirizinehada3-

foldincreaseinhalf-lifeanda70%decreaseinclearancecomparedtonormals.

Cetirizinewaspoorlyclearedbyhaemodialysis.Dosingadjustmentisnecessaryinpatientswithmoderateorsevere

renalimpairment(seesection4.2).

Hepaticallyimpairedpatients:Patientswithchronicliverdiseases(hepatocellular,cholestatic,andbiliarycirrhosis)

given10or20mgofcetirizineasasingledosehada50%increaseinhalf-lifealongwitha40%decreaseinclearance

comparedtohealthysubjects.

Dosingadjustmentisonlynecessaryinhepaticallyimpairedpatientsifconcomitantrenalimpairmentispresent.

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafety

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

MicrocrystallineCellulose

MaizeStarch

ColloidalAnhydrousSilica

MagnesiumStearate

Talc

Film-coat:

Hypromellose

Lactosemonohydrate

Titaniumdioxide(E171)

Macrogol4000

SodiumCitrate

6.2Incompatibilities

Notapplicable

6.3Shelflife

3years

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialprecautionsforstorage.

6.5Natureandcontentsofcontainer

BlisterstripscomposedoftransparentPVCandaluminiumfoil.

Packsizes:7tablets

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements

7MARKETINGAUTHORISATIONHOLDER

ChanelleMedical,

Loughrea,

Co.Galway,

Ireland.

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:26thMay2006

Dateoflastauthorisation:26thMay2011

10DATEOFREVISIONOFTHETEXT

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