CETIRIZINE AUROBINDO

Main information

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

Documents

Localization

  • Available in:
  • CETIRIZINE AUROBINDO
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1445/004/001
  • Authorization date:
  • 03-07-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CetirizineAurobindo10mgfilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontains10mgcetirizinedihydrochloride.

Excipient:155.2mglactosemonohydrate/film-coatedtablet

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

Whitetooff-white,film-coated,off-rectangulartablets,debossedwith‘X’ononesidewith‘20’ontheotherside.

Scorelinebetween‘2’and‘0’.

Thetabletcanbedividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inadultsandpaediatricpatients6yearsandabove:

Cetirizineisindicatedforthereliefofnasalandocularsymptomsofseasonalandperennialallergicrhinitis.

Cetirizineisindicatedforthereliefofsymptomsofchronicidiopathicurticaria.

4.2Posologyandmethodofadministration

Oraluse.

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(CL

inml/minisneeded.TheCL

(ml/min)maybeestimatedfromserumcreatinine(mg/dl)determinationusingthe

followingformula:

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

---------------------------------------(X0.85forwomen)

72Xserumcreatinine(mg/dl)

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Inpaediatricpatientssufferingfromrenalimpairment,thedosewillhavetobeadjustedonanindividualbasistaking

intoaccounttherenalclearanceofthepatient,hisageandhisbodyweight.

Patientswithhepaticimpairment:nodoseadjustmentisneededinpatientswithsolelyhepaticimpairment.

Patientswithhepaticimpairmentandrenalimpairment:doseadjustmentisrecommended(seePatientswithmoderate

tosevererenalimpairmentabove).

4.3Contraindications

Hypersensitivitytotheactivesubstance,toanyoftheexcipients,tohydroxyzineortoanypiperazinederivatives.

Patientswithsevererenalimpairmentatlessthan10ml/mincreatinineclearance.

4.4Specialwarningsandprecautionsforuse

Attherapeuticdoses,noclinicallysignificantinteractionshavebeendemonstratedwithalcohol(forabloodalcohol

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

Cautioninepilepticpatientsandpatientsatriskofconvulsionsisrecommended.

Theuseofthefilm-coatedtabletformulationisnotrecommendedinchildrenagedlessthan6yearssincethis

formulationdoesnotallowforappropriatedoseadaptation.

Allergyskintestsareinhibitedbyantihistaminesandawash-outperiod(of3days)isrequiredbeforeperformingthem.

CetirizineAurobindo10mgfilm-coatedtabletscontainlactose.Patientswithrarehereditaryproblemsofgalactose

intolerance,theLapplactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Duetothepharmacokinetic,pharmacodynamicandtoleranceprofileofcetirizine,nointeractionsareexpectedwiththis

antihistamine.Actually,neitherpharmacodynamicnorsignificantpharmacokineticinteractionwasreportedindrug-

druginteractionsstudiesperformed,notablywithpseudoephedrineortheophylline(400mg/day).

Theextentofabsorptionofcetirizineisnotreducedwithfood,althoughtherateofabsorptionisdecreased.

4.6Fertility,pregnancyandlactation

Pregnancy:

Forcetirizineveryrareclinicaldataonexposedpregnanciesareavailable.Animalstudiesdonotindicatedirector

indirectharmfuleffectswithrespecttopregnancy,embryonal/fetaldevelopment,parturitionorpostnataldevelopment.

Cautionshouldbeexercisedwhenprescribingtopregnantwomen.

Group Creatinineclearance

(ml/min) Dosageandfrequency

Normal 80 10mgoncedaily

Mild 50–79 10mgoncedaily

Moderate 30–49 5mgoncedaily

Severe <30 5mgonceevery2days

End-stagerenaldisease-

Patientsundergoing

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Cetirizineisexcretedinhumanmilkatconcentrationsrepresenting0.25to0.90thosemeasuredinplasma,depending

onsamplingtimeafteradministration.Therefore,cautionshouldbeexercisedwhenprescribingcetirizinetolactating

women.

4.7Effectsonabilitytodriveandusemachines

Objectivemeasurementsofdrivingability,sleeplatencyandassemblylineperformancehavenotdemonstratedany

clinicallyrelevanteffectsattherecommendeddoseof10mg.

Patientsintendingtodrive,engaginginpotentiallyhazardousactivitiesoroperatingmachineryshouldnotexceedthe

recommendeddoseandshouldtaketheirresponsetothemedicinalproductintoaccount.Inthesesensitivepatients,

concurrentusewithalcoholorotherCNSdepressantsmaycauseadditionalreductionsinalertnessandimpairmentof

performance.

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.

Objectivetestsasdemonstratedbyotherstudieshavedemonstratedthatusualdailyactivitiesareunaffectedatthe

Adverseevent

(WHO-ART) Cetirizine10mg(n=

3260) Placebo(n=

3061)

Bodyasawhole-generaldisorders

Fatigue 1.63% 0.95%

Centralandperipheralnervoussystemdisorders

Dizziness 1.10% 0.98%

Headache 7.42% 8.07%

Gastro-intestinalsystemdisorders

Abdominalpain 0.98% 1.08%

Drymouth 2.09% 0.82%

Nausea 1.07% 1.14%

Psychiatricdisorders

Somnolence 9.63% 5.00%

Respiratorysystemdisorders

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Adversedrugreactionsatratesof1%orgreaterinchildrenagedfrom6monthsto12years,includedinplacebo-

controlledclinicalorpharmacologicaltrialsare:

Post-marketingexperience

Inadditiontotheadverseeffectsreportedduringclinicalstudiesandlistedabove,isolatedcasesofthefollowing

adversedrugreactionshavebeenreportedinpost-marketingexperience.Fortheselessfrequentlyreportedundesirable

effects,theestimatedfrequencies(uncommon: 1/1,000to<1/100,rare: 1/10,000to<1/1,000),veryrare:

<1/10,000),notknown(cannotbeestimatedfromtheavailabledata)aremadebasedonpost-marketingexperience.

Investigations:

Rare: weightincreased

Cardiacdisorders:

Rare: tachycardia

Bloodandlymphaticdisorders:

Veryrare: thrombocytopenia

Nervoussystemdisorders:

Uncommon: paraesthesia

Rare: convulsions,movementdisorders

Veryrare: dysgeusia,syncope,tremor,dystonia,dyskinesia

Notknown: amnesia,memoryimpairment

Eyedisorders:

Veryrare: accommodationdisorder,blurredvision,oculogyration

Gastrointestinaldisorders:

Uncommon: diarrhoea

Renalandurinarydisorders:

Veryrare: dysuria,enuresis

Skinandsubcutaneoustissuedisorders:

Uncommon: pruritus,rash

Rare: urticaria.

Veryrare: angioneuroticoedema,fixeddrugeruption

Generaldisordersandadministrationsiteconditions:

Uncommon: asthenia,malaise

Rare: oedema

Immunesystemdisorders

Rare: hypersensitivity

Adverseevent

(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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Hepato-billiarydisorders:

Rare: hepaticfunctionabnormal(increasedtransaminases,alkalinephosphatase,-GTandbilirubin)

Psychiatricdisorders:

Uncommon: agitation

Rare: aggression,confusion,depression,hallucination,insomnia

Veryrare: tics

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.Gastriclavageshouldbeconsidered

followingingestionofashortoccurrence.

Cetirizineisnoteffectivelyremovedbydialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Piperazinederivatives,ATCcode:R06AE07

Cetirizine,ahumanmetaboliteofhydroxyzine,isapotentandselectiveantagonistofperipheralH

-receptors.Invitro

receptorsbindingstudieshaveshownnomeasurableaffinityforotherthanH

-receptors.

Inadditiontoitsanti-H

effect,cetirizinewasshowntodisplayanti-allergicactivities:atadoseof10mgonceortwice

daily,itinhibitsthelatephaserecruitmentofeosinophils,intheskinandconjunctivaofatopicsubjectssubmittedto

allergenchallenge.

Studiesinhealthyvolunteersshowthatcetirizine,atdosesof5and10mgstronglyinhibitsthewhealandflarereactions

inducedbyveryhighconcentrationsofhistamineintotheskin,butthecorrelationwithefficacyisnotestablished.

Ina35-daystudyinchildrenaged5to12,notolerancetotheantihistaminiceffect(suppressionofwhealandflare)of

cetirizinewasfound.Whenatreatmentwithcetirizineisstoppedafterrepeatedadministration,theskinrecoversits

normalreactivitytohistaminewithin3days.

Inasix-week,placebo-controlledstudyof186patientswithallergicrhinitisandconcomitantmildtomoderateasthma,

cetirizine10mgoncedailyimprovedrhinitissymptomsanddidnotalterpulmonaryfunction.Thisstudysupportsthe

safetyofadministeringcetirizinetoallergicpatientswithmildtomoderateasthma.

Inaplacebo-controlledstudy,cetirizinegivenatthehighdailydoseof60mgforsevendaysdidnotcausestatistically

significantprolongationofQTinterval.

Attherecommendeddosage,cetirizinehasdemonstratedthatitimprovesthequalityoflifeofpatientswithperennial

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5.2Pharmacokineticproperties

Thesteady-statepeakplasmaconcentrationsisapproximately300ng/mlandisachievedwithin1.0±0.5h.No

accumulationisobservedforcetirizinefollowingdailydosesof10mgfor10days.Thedistributionofpharmacokinetic

parameterssuchaspeakplasmaconcentration(C

)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-lifeanda70%decreaseinclearancecomparedtohealthyvolunteers.

Patientsonhaemodialysis(creatinineclearancelessthan7ml/min)givenasingleoral10mgdoseofcetirizinehada3-

foldincreaseinhalf-lifeanda70%decreaseinclearancecomparedtonormals.Cetirizinewaspoorlyclearedby

haemodialysis.Dosingadjustmentisnecessaryinpatientswithmoderateorsevererenalimpairment(seesection4.2).

Hepaticallyimpairedpatients:Patientswithchronicliverdisease(hepatocellular,cholestatic,andbiliarycirrhosis)

given10or20mgofcetirizineasasingledosehada50%increaseinhalf-lifealongwitha40%decreaseinclearance

comparedtohealthysubjects.

Dosingadjustmentisonlynecessaryinhepaticallyimpairedpatientsifconcomitantrenalimpairmentispresent.

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicity,carcinogenicpotentialortoxicitytoreproduction.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Lactosemonohydrate

Crospovidone

Starch,pregelatinised(maize)

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Film-coat:

Hypromellose

Titaniumdioxide

Macrogol400

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Blisterpack:1year

HDPEbottlepack:18months

6.4Specialprecautionsforstorage

Storebelow25°C.

6.5Natureandcontentsofcontainer

PVC-PVDCAluminiumblisters:1,2,7,10,14,15,20,21,30,50,60,90,98and100film-coatedtablets.

HDPEbottle:250film-coatedtablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

AurobindoPharma(Malta)Limited

46/2,Southstreet

Valletta

VLT11

Malta

8MARKETINGAUTHORISATIONNUMBER

PA1445/4/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:3 rd

July2009

10DATEOFREVISIONOFTHETEXT

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