CETIRIZINE 10MG FILM-COATED TABLETS.

Main information

  • Trade name:
  • CETIRIZINE 10MG FILM-COATED TABLETS.
  • Dosage:
  • 10 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CETIRIZINE 10MG FILM-COATED TABLETS.
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0577/085/001
  • Authorization date:
  • 13-06-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PA0577/085/001

CaseNo:2085502

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

McDermottLaboratoriesLtdt/aGerardLaboratories

35-36BaldoyleIndustrialEstate,GrangeRoad,Dublin13,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Cetirizine10mgfilm-coatedtablets

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom30/07/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cetirizine10mgfilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onefilm-coatedtabletcontains10mgcetirizinedihydrochloride.

Excipients:onefilm-coatedtabletcontains74.3mglactose-monohydrate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablets.

White,capsuleshaped,filmcoatedtabletwithbreaklineandmarked‘CZ’and‘10’ononesideandmarked‘G’onthe

reverse.

Thebreaklineistofacilitatebreakingforeaseofswallowingandnottodivideintoequaldoses.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inadultsandpaediatricpatients6yearandabove:

Cetirizineisindicatedforthereliefofnasalandocularsymptomsofseasonalandperennialallergicrhinitis.

Cetirizineisindicatedforthereliefofsymptomsofchronicidiopathicurticaria.

4.2Posologyandmethodofadministration

Childrenagedfrom6to12years:5mgtwicedaily(ahalftablettwicedaily).

Adultsandadolescentsover12yearsofage:10mgoncedaily(1tablet).

Thetabletsneedtobeswallowedwithaglassofliquid.

Elderlysubjects:datadonotsuggestthatthedoseneedstobereducedinelderlysubjectsprovidedthattherenal

functionisnormal.

Patientswithmoderatetosevererenalimpairment:therearenodatatodocumenttheefficacy/safetyratioinpatients

withrenalimpairement.Sincecetirizineismainlyexcretedviarenalroute(seesection5.2),incasesnoalternative

treatmentcanbeused,thedosingintervalsmustbeindividualizedaccordingtorenalfunction.Refertothefollowing

tableandadjustthedoseasindicated.Tousethisdosingtable,anestimateofthepatient’screatinineclearance(CLcr)

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

followingformula:

[140-age(years)]xweight(kg)

=_____________________________(x0.85forwomen)

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Dosingadjustmentsforadultpatientswithimpairedrenalfunction

Inpaediatricpatientssufferingfromrenalimpairment,thedosewillhavetobeadjustedonanindividualbasistaking

intoaccounttherenalclearanceofthepatient,hisageandhisbodyweight.

Patientswithhepaticimpairment:nodoseadjustmentisneededinpatientswithsolelyhepaticimpairment.

Patientswithhepaticimpairmentandrenalimpairment:doseadjustmentisrecommended(see

Patientswithmoderatetosevererenalimpairmentabove).

4.3Contraindications

Hypersensitivitytotheactivesubstance,toanyoftheexcipients,tohydroxyzineortoanypiperazinederivatives.

Patientswithsevererenalimpairmentatlessthan10ml/mincreatinineclearance.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyor

glucose-galactosemalabsorptionshouldnottakecetirizinefilm-coatedtablet.

4.4Specialwarningsandprecautionsforuse

Attherapeuticdoses,noclinicallysignificantinteractionshavebeendemonstratedwithalcohol(forabloodalcohol

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

Cautioninepilepticpatientsandpatientsatriskofconvulsionsisrecommended.

Theuseofthefilm-coatedtabletformulationisnotrecommendedinchildrenagedlessthan6yearssincethis

formulationdoesnotallowforappropriatedoseadaptation.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Duetothepharmacokinetic,pharmacodynamicandtoleranceprofileofcetirizine,nointeractionsareexpectedwiththis

antihistamine.Actually,neitherpharmacodynamicnorsignificantpharmacokineticinteractionwasreportedindrug-

druginteractionsstudiesperformed,notablywithpseudoephedrineortheophylline(400mg/day).

Theextentofabsorptionofcetirizineisnotreducedwithfood,althoughtherateofabsorptionisdecreased.

4.6Pregnancyandlactation

Forcetirizineveryrareclinicaldataonexposedpregnanciesareavailable.Animalstudiesdonotindicatedirector

indirectharmfuleffectswithrespecttopregnancy,embryonal/fetaldevelopment,parturitionorpostnataldevelopment.

Cautionshouldbeexercisedwhenprescribingtopregnantorbreastfeedingwomenbecausecetirizinepassesinto

Group CreatinineClearance(ml/min) Doasgeandfrequency

Normal ≥80 10mgoncedaily

Mild 50–79 10mgoncedaily

Moderate 30–49 5mgoncedaily

Severe <30 5mgonceevery2days

End-stageRenalDisease-

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4.7Effectsonabilitytodriveandusemachines

Objectivemeasurementsofdrivingability,sleeplatencyandassemblylineperformancehavenotdemonstratedany

clinicallyrelevanteffectsattherecommendeddoseof10mg.Patientsintendingtodrive,engaginginpotentially

hazardousactivitiesoroperatingmachineryshouldnotexceedtherecommendeddoseandshouldtaketheirresponseto

themedicinalproductintoaccount.Inthesesensitivepatients,concurrentusewithalcoholorotherCNSdepressants

maycauseadditionalreductionsinalertnessandimpairmentofperformance.

4.8Undesirableeffects

ClinicalstudieshaveshownthatcetirizineattherecommendeddosagehasminorundesirableeffectsontheCNS,

includingsomnolence,fatigue,dizzinessandheadache.Insomecases,paradoxicalCNSstimulationhasbeenreported.

AlthoughcetirizineisaselectiveantagonistofperipheralH

-receptorsandisrelativelyfreeofanticholinergicactivity,

isolatedcasesofmicturitiondifficulty,eyeaccommodationdisordersanddrymouthhavebeenreported.

Instancesofabnormalhepaticfunctionwithelevatedhepaticenzymesaccompaniedbyelevatedbilirubinhavebeen

reported.Mostlythisresolvesupondiscontinuationofthetreatmentwithcetirizinedihydrochloride.

Clinicaltrials

Doubleblindcontrolledclinicalorpharmacoclinicaltrialscomparingcetirizinetoplaceboorotherantihistaminesatthe

recommendeddosage(10mgdailyforcetirizine),ofwhichquantifiedsafetydataareavailable,includedmorethan

3200subjectsexposedtocetirizine.

Fromthispooling,thefollowingadverseeventswerereportedforcetirizine10mgintheplacebo-controlledtrialsat

ratesof1.0%orgreater:

Althoughstatisticallymorecommonthanunderplacebo,somnolencewasmildtomoderateinthemajorityofcases.

Adverseevent

(WHO-ART) Cetirizine10mg

(n=3260) Placebo

(n=3061)

Bodyasawhole–general

disorders

Fatigue

1.63% 0.95%

Centralandperipheralnervous

systemdisorders

Dizziness

Headache 1.10%

7.42% 0.98%

8.07%

Gastro-intestinalsystem

disorders

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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recommendeddailydoseinhealthyyoungvolunteers.

Adversedrugreactionsatratesof1%orgreaterinchildrenagedfrom6monthsto12years,includedinplacebo-

controlledclinicalorpharmacoclinicaltrialsare:

Post-marketingexperience

Inadditiontotheadverseeffectsreportedduringclinicalstudiesandlistedabove,isolatedcasesofthefollowing

adversedrugreactionshavebeenreportedinpost-marketingexperience.Fortheselessfrequentlyreportedundesirable

effects,theestimatedfrequencies(uncommon: ≥1/1,000to1/100,rare:≥1/10,000to1/1,000,veryrare:1/10,000)are

madebasedonpost-marketingexperience.

Bloodandlymphaticdisorders:

Veryrare:thrombocytopenia

Immunesystemdisorders:

Rare:hypersensitivity

Veryrare:anaphylacticshock

Psychiatricdisorders:

Uncommon:agitation

Rare:aggression,confusion,depression,hallucination,insomnia

Veryrare:tic

Nervoussystemdisorders:

Uncommon:paraesthesia

Rare:convulsions,movementsdisorders

Adversedrugreactions

(WHO-ART) Cetirizine

(n=1656) Placebo

(n=1294)

Gastro-intestinalsystem

disorders

Diarrhoea

1.0% 0.6%

Psychiatricdisorders

Somnolence 1.8% 1.4%

Respiratorysystemdisorders

Rhinitis 1.4% 1.1%

Bodyasawhole–general

disorders

Fatigue

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Eyedisorders:

Veryrare:accommodationdisorder,blurredvision,oculogyration

Cardiacdisorders:

Rare:tachycardia

Gastro-intestinaldisorders:

Uncommon:diarrhoea

Hepatobiliarydisorders:

Rare:hepaticfunctionabnormal(increasedtransaminases,alkalinephosphatase,-GTandbilirubin)

Skinandsubcutaneoustissuedisorders:

Uncommon:pruritus,rash

Rare:urticaria

Veryrare:angioneuroticoedema,fixeddrugeruption

Renalandurinarydisorders:

Veryrare:dysuria,enuresis

Generaldisordersandadministrationsiteconditions:

Uncommon:asthenia,malaise

Rare:oedema

Investigations:

Rare:weightincreased

4.9Overdose

Symptoms

SymptomsobservedafteranoverdoseofcetirizinearemainlyassociatedwithCNSeffectsorwitheffectsthatcould

suggestananticholinergiceffect.

Adverseeventsreportedafteranintakeofatleast5timestherecommendeddailydoseare:confusion,diarrhoea,

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

tremor,andurinaryretention.

Management

Thereisnoknownspecificantidotetocetirizine.

Shouldoverdoseoccur,symptomaticorsupportivetreatmentisrecommended.

Gastriclavageshouldbeconsideredfollowingingestionofashortoccurrence.Cetirizineisnoteffectivelyremovedby

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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,

cetirizine10mgoncedailyimprovedrhinitissymptomsanddidnotalterpulmonaryfunction.Thisstudysupportsthe

safetyofadministeringcetirizinetoallergicpatientswithmildtomoderateasthma.

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%andclearance

decreasedby40%in16elderlysubjectscomparedtothenormalsubjects.Thedecreaseincetirizineclearanceinthese

elderlyvolunteersappearedtoberelatedtotheirdecreasedrenalfunction.

Children,infantsandtoddlers:Thehalf-lifeofcetirizinewasabout6hoursinchildrenof6-12yearsand5hoursin

children2-6years.Ininfantsandtoddlersaged6to24months,itisreducedto3.1hours

Renallyimpairedpatients:Thepharmacokineticsofthedrugweresimilarinpatientswithmildimpairment(creatinine

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inhalf-lifeand70%decreaseinclearancecomparedtohealthyvolunteers.

Patientsonhemodialysis(creatinineclearancelessthan7ml/min)givenasingleoral10mgdoseofcetirizinehada3-

foldincreaseinhalf-lifeanda70%decreaseinclearancecomparedtonormals.Cetirizinewaspoorlyclearedby

haemodialysis.Dosingadjustmentisnecessaryinpatientswithmoderateorsevererenalimpairment(seesection4.2).

Hepaticallyimpairedpatients:Patientswithchronicliverdiseases(hepatocellular,cholestatic,andbiliarycirrhosis)

given10or20mgofcetirizineasasingledosehada50%increaseinhalf-lifealongwitha40%decreaseinclearance

comparedtohealthysubjects.

Dosingadjustmentisonlynecessaryinhepaticallyimpairedpatientsifconcomitantrenalimpairmentispresent.

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicity,carcinogenicpotential,toxicitytoreproduction.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

LactoseMonohydrate,

PregelatinisedMaizeStarch,

PovidoneK29/32,

MagnesiumStearate,

Tabletcoating

Opadry-Y-1-7000,containing:

TitaniumDioxide(E171),

Hypromellose5cP(E464),

Macrogol400.

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

2years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

Polypropylenecontainerwithtamper-evidentpolyethylenecap:30,100,250tablets.

PVdCcoatedPVCblisterwithaluminumfoillidding:7,10,14,15,20,30,50,60,90,100,100(10x10x1)and50(50

x1)unit-dose.

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

McDermottLaboratoriesLimited(t/aGerardLaboratories)

35/36BaldoyleIndustrialEstate

GrangeRoad,

Dublin13

8MARKETINGAUTHORISATIONNUMBER

PA0577/085/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation: 13June2006

Dateoflastrenewal: 30November2007

10DATEOFREVISIONOFTHETEXT

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