CETIRELIEF ALLERGY 10 MG FILM-COATED TABLETS

Main information

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

Documents

Localization

  • Available in:
  • CETIRELIEF ALLERGY 10 MG FILM-COATED TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1427/002/001
  • Authorization date:
  • 19-10-2007
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA1427/002/001

CaseNo:2077067

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

EireceuticaLimited

Unit2,BlockE,NutgroveBusinessPark,Dublin14,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

CetireliefAllergy10mgFilm-coatedTablets.

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom16/02/2010until29/06/2011.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CetireliefAllergy10mgFilm-coatedTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

EachFilmcoatedtabletcontainsCetirizinedihydrochloride10mg

Forexcipientssee6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

Film-coated,whiteoralmostwhiteconvex,ovalshaped,tablets.Scoredononeside.Thetabletsaremarked“C”onone

side,“J”and“E”oneithersideofacentraldivisionlineonthereverse.

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)

(72xserumcreatinine(mg/dl)

Dosingadjustmentsforadultpatientswithimpairedrenalfunction

Group Creatinineclearance

(ml/min) Dosageandfrequency

Normal ≥80 10mgoncedaily

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Inpediatricpatientssufferingfromrenalimpairment,thedosewillhavetobeadjustedonanindividualbasistaking

intoaccounttherenalclearanceofthepatient,hisageandhisbodyweight.

Patientswithhepaticimpairment:nodoseadjustmentisneededinpatientswithsolelyhepaticimpairment.

Patientswithhepaticimpairmentandrenalimpairment:doseadjustmentisrecommended(seePatientswithmoderateto

severerenalimpairmentabove).

4.3Contraindications

Hypersensitivitytotheactivesubstance,toanyoftheexcipients,tohydroxyzineortoanypiperazinederivatives.

Patientswithsevererenalimpairmentatlessthan10ml/mincreatinineclearance.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakecetirizinefilm-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

breastmilk.

4.7Effectsonabilitytodriveandusemachines

Objectivemeasurementsofdrivingability,sleeplatencyandassemblylineperformancehavenotdemonstratedany

clinicallyrelevanteffectsattherecommendeddoseof10mg.

Patientsintendingtodrive,engaginginpotentiallyhazardousactivitiesoroperatingmachineryshouldnotexceedthe

recommendeddoseandshouldtaketheirresponsetothemedicinalproductintoaccount.Inthesesensitivepatients,

concurrentusewithalcoholorotherCNSdepressantsmaycauseadditionalreductionsinalertnessandimpairmentof

Moderate 30–49 5mgoncedaily

Severe 30 5mgonceevery2days

End-stagerenaldisease 10 Contra-indicated

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4.8Undesirableeffects

ClinicalstudieshaveshownthatcetirizineattherecommendeddosagehasminorundesirableeffectsontheCNS,

includingsomnolence,fatigue,dizzinessandheadache.Insomecases,paradoxicalCNSstimulationhasbeenreported.

AlthoughcetirizineisaselectiveantagonistofperipheralH1-receptorsandisrelativelyfreeofanticholinergicactivity,

isolatedcasesofmicturitiondifficulty,eyeaccommodationdisordersanddrymouthhavebeenreported.

Instancesofabnormalhepaticfunctionwithelevatedhepaticenzymesaccompaniedbyelevatedbilirubinhavebeen

reported.Mostlythisresolvesupondiscontinuationofthetreatmentwithcetirizinedihydrochloride.

Clinicaltrials

Doubleblindcontrolledclinicalorpharmacoclinicaltrialscomparingcetirizinetoplaceboorotherantihistaminesatthe

recommendeddosage(10mgdailyforcetirizine),ofwhichquantifiedsafetydataareavailable,includedmorethan

3200subjectsexposedtocetirizine.

Fromthispooling,thefollowingadverseeventswerereportedforcetirizine10mgintheplacebocontrolledtrialsat

ratesof1.0%orgreater:

Althoughstatisticallymorecommonthanunderplacebo,somnolencewasmildtomoderateinthemajorityofcases.

Objectivetestsasdemonstratedbyotherstudieshavedemonstratedthatusualdailyactivitiesareunaffectedatthe

recommendeddailydoseinhealthyyoungvolunteers.

Adversedrugreactionsatratesof1%orgreaterinchildrenagedfrom6monthsto12years,includedinplacebo-

controlledclinicalorpharmacoclinicaltrialsare:

Post-marketingexperience

Inadditiontotheadverseeffectsreportedduringclinicalstudiesandlistedabove,isolatedcasesofthefollowing

Adverseevent

(WHO-ART) Cetirizine10mg

(n=3260) Placebo

(n=3061)

Bodyasawhole–generaldisorders

Fatigue 1.63% 0.95%

Centralandperipheralnervoussystemdisorders

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

Pharyngitis 1.29% 1.34%

Adversedrugreactions

(WHO-ART) Cetirizine

(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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Fortheselessfrequentlyreportedundesirableeffects,theestimatedfrequencies(uncommon: ≥1/1,000to1/100,rare:≥

1/10,000to1/1,000,veryrare:1/10,000)aremadebasedonpost-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

Veryrare:dysgeusia,syncope,tremor,dystonia,dyskinesia

Eyedisorders:

Veryrare:accommodationdisorder,blurredvision,oculogyration

Cardiacdisorders:

Rare:tachycardia

Gastro-intestinaldisorders:

Uncommon:diarrhea

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,

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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:atadoseof

10mgonceortwicedaily,itinhibitsthelatephaserecruitmentofeosinophils,intheskinand

conjunctivaofatopicsubjectssubmittedtoallergenchallenge.

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/mlandisachievedwithin

1.0+/-0.5h.Noaccumulationisobservedforcetirizinefollowingdailydosesof10mgfor10days.

Thedistributionofpharmacokineticparameterssuchaspeakplasmaconcentration(Cmax)andareaundercurve

(AUC),isunimodalinhumanvolunteers.

Theextentofabsorptionofcetirizineisnotreducedwithfood,althoughtherateofabsorptionis

decreased.Theextentofbioavailabilityissimilarwhencetirizineisgivenassolutions,capsulesortablets.

Theapparentvolumeofdistributionis0.50l/kg.Plasmaproteinbindingofcetirizineis93 0.3%.Cetirizinedoes

notmodifytheproteinbindingofwarfarin.

Cetirizinedoesnotundergoextensivefirstpassmetabolism.Abouttwothirdofthedoseareexcretedunchangedin

urine.Theterminalhalf-lifeisapproximately10hours.

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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.Cetirizinewaspoorlyclearedby

haemodialysis.Dosingadjustmentisnecessaryinpatientswithmoderateorsevererenalimpairment(seesection4.2).

Hepaticallyimpairedpatients:Patientswithchronicliverdiseases(hepatocellular,cholestatic,andbiliarycirrhosis)

given10or20mgofcetirizineasasingledosehada50%increaseinhalf-lifealongwitha40%decreaseinclearance

comparedtohealthysubjects.

Dosingadjustmentisonlynecessaryinhepaticallyimpairedpatientsifconcomitantrenalimpairmentispresent.

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafety

pharmacology,repeateddosetoxicity,genotoxicity,carcinogenicpotential,toxicitytoreproduction.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Cellulose,microcrystalline

Lactosemonohydrate

Crospovidone

Silica,colloidalanhydrous

Magnesiumstearate

Filmcoating:

Hypromellose

Macrogolstearate

Cellulose,microcrystalline

Propyleneglycol

Titaniumdioxide,E171

6.2Incompatibilities

Noneknown.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

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6.5Natureandcontentsofcontainer

Aluminium/PVCblisters

Aluminium/Aluminiumblisters

HDPEtabletcontainers.

Packsize:30Tablets

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

ÉireceuticaLtd

Unit2

BlockE

NutgroveBusinessPark

Dublin14

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA1427/2/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:30June2006

10DATEOFREVISIONOFTHETEXT

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