Information för alternativet: Cetiristad 1 Mg/Ml Oral Lösning, visa andra alternativ

Välj alternativ:

1. Cetiristad 1 Mg/Ml Oral Lösning
2. Cetiristad 10 Mg Filmdragerad Tablett

Document: Cetiristad oral solution ENG SmPC change

• Cetiristad oral solution SmPC
• Cetiristad oral solution ENG SmPC

---

summary of product characteristics

Cetiristad 1 mg/ml, oral solution

1 ml oral solution contains 1 mg of cetirizine dihydrochloride.

Excipients with known effect: Each ml of the oral solution contains 1.35 mg methylparahydroxybenzoate, 0.15 mg propylparahydroxybenzoate, 450 mg sorbitol.

For the full list of excipients, see section 6.1.

Oral solution

Clear colourless liquid with banana flavour

Inadultsandchildren2yearandabove:

• Cetirizine is indicated for the relief of nasal and ocular symptoms of seasonal and perennial allergic rhinitis.

• Cetirizine is indicated for the relief of symptoms of chronic idiopathic urticaria.

Posology

Childrenagedfrom2to6years

2.5mgtwicedaily(2.5mloralsolutiontwicedaily(ahalfspoon twicedaily)).

Childrenagedfrom6to12years

5mgtwicedaily(5mloralsolutionbid(afullspoontwicedaily)).

Adultsandadolescentsover12yearsofage

10mgoncedaily(10mloralsolution(2fullspoons)).

Older people

Datadonotsuggestthatthedoseneedstobereducedinelderlysubjectsprovided thattherenalfunctionisnormal.

Patientswithmoderatetosevererenalimpairment

Therearenodatatodocumenttheefficacy/safety ratioinpatientswithrenalimpairment.Sincecetirizineismainlyexcretedviarenalroute(see section5.2),incasesnoalternativetreatmentcanbeused,thedosingintervalsmustbeindividualized accordingtorenalfunction.Refertothefollowingtableandadjustthedoseasindicated.Tousethis dosingtable,anestimateofthepatient’screatinineclearance(CL_cr)inml/minisneeded.TheCL_cr(ml/min)maybeestimatedfromserumcreatinine(mg/dl)determinationusingthefollowingformula:

Dosing adjustments for adult patients with impaired renal function

Group:	Creatinine clearance (ml/min):	Dosage and frequency:
Normal	≥80	10 mg once daily
Mild	50 – 79	10 mg once daily
Moderate	30 – 49	5 mg once daily
Severe	< 30	5 mg once every 2 days
End-stage renal disease -	< 10	Contra-indicated
Patients undergoing dialysis

Inpaediatricpatientssufferingfromrenalimpairment,thedosewillhavetobeadjustedonan individualbasistakingintoaccounttherenalclearanceofthepatient,hisageandhisbodyweight.

Patientswithhepaticimpairment

Nodoseadjustmentisneededinpatientswithsolelyhepatic impairment.

Patientswithhepaticimpairmentandrenalimpairment

Doseadjustmentisrecommended(see Patientswithmoderatetosevererenalimpairmentabove).

Method of administration

The solution can be swallowed as such.

Hypersensitivitytotheactivesubstance,tohydroxyzineortoanypiperazine derivatives or to any of the excipients listed in section 6.1.

Patientswithsevererenalimpairmentat lessthan10ml/mincreatinineclearance.

Patientswithrarehereditaryproblemsoffructose intoleranceshouldnottakecetirizine1mg/mloral solution.

Attherapeuticdoses,noclinicallysignificantinteractionshavebeendemonstratedwithalcohol(fora bloodalcohollevelof0.5g/L).Nevertheless,precautionisrecommendedifalcoholistaken concomitantly.

Caution should be taken in patients with predisposition factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia) as cetirizine may increase the risk of urinary retention.

Cautioninepilepticpatientsandpatients atriskofconvulsionsisrecommended.

Methylparahydroxybenzoateandpropylparahydroxybenzoatemaycauseallergicreactions(possibly delayed).

Allergy skin tests are inhibited by antihistamines and a wash-out period (of 3 days) is required before performing them.

Paediatric population

Theuseoftheproductisnotrecommendedinchildrenagedlessthan2years.

Due to the pharmacokinetic, pharmacodynamic and tolerance profile of cetirizine, no interactions are expected with this antihistamine. Actually, neither pharmacodynamic nor significant pharmacokinetic interaction was reported in drug-drug interactions studies performed, notably with pseudoephedrine or theophylline (400 mg/day).

The extent of absorption of cetirizine is not reduced with food, although the rate of absorption is decreased.

Pregnancy

Forcetirizineveryrareclinicaldataonexposed pregnanciesareavailable.Animalstudiesdonot indicatedirectorindirectharmfuleffectswithrespectto pregnancy,embryonal/foetaldevelopment, parturitionorpostnataldevelopment.Cautionshouldbeexercisedwhenprescribingtopregnantwomen.

Breast-feeding

Cetirizine is excreted in human milk at concentrations representing 25 % to 90 % of those measured in plasma, depending on sampling time after administration. Therefore, caution should be exercised when prescribing cetirizine to lactating women.

Objectivemeasurementsofdrivingability,sleeplatencyandassemblylineperformancehavenot demonstratedanyclinicallyrelevanteffectsattherecommendeddoseof10mg.

Patientsintendingtodrive,engaginginpotentiallyhazardousactivitiesoroperatingmachineryshould notexceedtherecommendeddoseandshouldtake theirresponsetothemedicinalproductinto account.

Insensitivepatients,concurrentuse withalcoholorotherCNSdepressantsmaycause additionalreductionsinalertnessandimpairmentofperformance.

Clinicalstudieshaveshownthatcetirizineattherecommendeddosagehasminorundesirable effects ontheCNS,includingsomnolence,fatigue,dizzinessandheadache.Insomecases,paradoxicalCNS stimulationhasbeenreported.

AlthoughcetirizineisaselectiveantagonistofperipheralH₁-receptors andisrelativelyfreeof anticholinergicactivity,isolatedcasesofmicturitiondifficulty,eyeaccommodationdisordersanddry mouthhavebeenreported.

Instancesofabnormalhepaticfunctionwithelevatedhepaticenzymesaccompaniedbyelevated bilirubinhavebeenreported.Mostlythisresolvesupondiscontinuationofthetreatmentwith cetirizinedihydrochloride.

Clinicaltrials

Doubleblindcontrolledclinicaltrialscomparingcetirizinetoplaceboorother antihistaminesattherecommendeddosage(10mgdailyforcetirizine),ofwhichquantifiedsafety dataareavailable,includedmorethan3200subjectsexposedtocetirizine.

Fromthispooling,thefollowingadversereactions werereportedforcetirizine10mgintheplacebo-controlledtrialsatratesof1.0%orgreater:

Althoughstatisticallymorecommonthanunderplacebo,somnolencewasmildtomoderateinthe majorityofcases.Objectivetestsasdemonstratedbyotherstudieshavedemonstratedthatusualdaily activitiesareunaffectedattherecommendeddailydoseinhealthyyoungvolunteers.

Adversereactionsatratesof1%orgreater inchildrenagedfrom6monthsto12years,included inplacebo-controlledclinicalor pharmacoclinicaltrialsare:

Post-marketingexperience

Inadditiontotheadversereactionsreportedduringclinicalstudiesandlistedabove,thefollowingundesirable effects havebeenreportedinpost-marketingexperience.

Undesirable effects are described according to MedDRA System Organ Class and by estimated frequency based on post-marketing experience.

Frequencies are defined as follows: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

Bloodandlymphaticdisorders:

Veryrare:thrombocytopenia

Immunesystemdisorders:

Rare:hypersensitivity

Veryrare:anaphylacticshock

Metabolism and nutrition disorders

Not known: increased appetite

Psychiatricdisorders:

Uncommon:agitation

Rare:aggression,confusion,depression,hallucination,insomnia

Veryrare:tics

Not known: suicidal ideation

Nervoussystemdisorders:

Uncommon:paraesthesia

Rare:convulsions,movementsdisorders

Veryrare:dysgeusia,syncope,tremor,dystonia,dyskinesia

Not known: amnesia, memory impairment

Eyedisorders:

Veryrare:accommodationdisorder,blurredvision,oculogyration

Ear and labyrinth disorders

Not known: vertigo

Cardiacdisorders:

Rare:tachycardia

Gastro-intestinaldisorders:

Uncommon:diarrhoea

Hepatobiliarydisorders:

Rare:hepaticfunctionabnormal(increasedtransaminases,alkalinephosphatase,γ-GTandbilirubin)

Skinandsubcutaneoustissuedisorders:

Uncommon:pruritus,rash

Rare:urticaria

Veryrare:angioneuroticoedema,fixeddrugeruption

Renalandurinarydisorders:

Veryrare:dysuria,enuresis

Not known: urinary retention

Generaldisordersandadministrationsiteconditions:

Uncommon:asthenia,malaise

Rare:oedema

Investigations:

Rare:weightincreased

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via {to be completed nationally: the national reporting system listed in Appendix V}.

Symptoms

SymptomsobservedafteranoverdoseofcetirizinearemainlyassociatedwithCNSeffectsorwith effectsthatcouldsuggestananticholinergiceffect.

Adverseeventsreportedafteranintakeofatleast5timestherecommendeddailydoseare:confusion, diarrhoea,dizziness,fatigue,headache,malaise,mydriasis,pruritus,restlessness,sedation, somnolence,stupor,tachycardia,tremor,andurinaryretention.

Management

Thereisnoknownspecificantidotetocetirizine.

Shouldoverdoseoccur,symptomaticorsupportivetreatmentisrecommended.Gastriclavageshould beconsideredfollowingingestionofashortoccurrence.

Cetirizineisnoteffectivelyremovedbydialysis.

Pharmacotherapeuticgroup:Piperazinederivatives

ATCcode:R06AE07

Cetirizine,ahumanmetaboliteofhydroxyzine,isapotentandselectiveantagonistofperipheralH₁-receptors.InvitroreceptorbindingstudieshaveshownnomeasurableaffinityforotherthanH₁-receptors.

Inadditiontoitsanti-H₁effect,cetirizinewasshowntodisplayanti-allergicactivities:atadoseof 10mgonceortwicedaily,itinhibitsthelatephaserecruitmentofeosinophils,intheskinand conjunctivaofatopicsubjectssubmittedtoallergenchallenge.

Studiesinhealthyvolunteersshowthatcetirizine,atdosesof5and10mgstronglyinhibitsthewheal andflarereactionsinducedbyveryhighconcentrationsofhistamineintotheskin,butthecorrelation withefficacyisnotestablished.

Ina35-daystudyinchildrenaged5to12,notolerancetotheantihistaminiceffect(suppressionof whealandflare)ofcetirizinewasfound.Whena treatmentwithcetirizineisstoppedafterrepeated administration,theskinrecoversitsnormalreactivitytohistaminewithin3days.

Inasix-week,placebo-controlledstudyof186patientswithallergicrhinitisandconcomitantmildto moderateasthma,cetirizine10mgoncedailyimprovedrhinitissymptomsanddidnotalterpulmonary function.Thisstudysupportsthesafetyofadministeringcetirizinetoallergicpatientswithmildto moderateasthma.

Inaplacebo-controlledstudy,cetirizinegivenatthehighdailydoseof60mgforsevendaysdidnot causestatisticallysignificantprolongationofQTinterval.

Attherecommendeddosage,cetirizinehasdemonstrated thatitimprovesthequalityoflifeofpatients withperennialandseasonalallergicrhinitis.

Thesteady-statepeakplasmaconcentrationis approximately300ng/mlandisachievedwithin 1.0±0.5h.Noaccumulationisobservedforcetirizinefollowingdailydosesof10mgfor10days. Thedistributionofpharmacokineticparameters suchaspeakplasmaconcentration(C_max)andarea undercurve(AUC),isunimodalinhumanvolunteers. Theextentofabsorptionofcetirizineisnotreducedwithfood,althoughtherateofabsorptionis decreased.Theextentofbioavailabilityissimilarwhencetirizineisgivenassolutions,capsulesor tablets.

Theapparentvolumeofdistributionis0.50l/kg.Plasmaproteinbindingofcetirizineis93±0.3%. Cetirizinedoesnotmodifytheproteinbindingofwarfarin.

Cetirizinedoesnotundergoextensivefirstpassmetabolism.Abouttwothirdofthedoseareexcreted unchangedinurine.Theterminalhalf-lifeisapproximately10hours.

Cetirizineexhibitslinearkineticsovertherangeof5to60mg.

Specialpopulations

Older people

Followingasingle10mgoraldose,half-lifeincreasedbyabout50%andclearance decreasedby40%in16elderlysubjectscomparedto thenormalsubjects.Thedecreaseincetirizine clearanceintheseelderlyvolunteersappearedto berelatedtotheirdecreasedrenalfunction.

Paediatric population

Thehalf-lifeofcetirizinewasabout6hoursinchildrenof6-12years and5hoursinchildren2-6years.Ininfantsandtoddlersaged6to24months,itisreducedto 3.1hours.

Patients with renal impairment

Thepharmacokineticsofthedrugweresimilarinpatientswithmild impairment(creatinineclearancehigherthan40 ml/min)andhealthyvolunteers.Patientswith moderaterenalimpairmenthada3-foldincreaseinhalf-lifeand70%decreaseinclearancecompared tohealthyvolunteers. Patientsonhemodialysis(creatinineclearancelessthan7ml/min)givenasingleoral10mgdoseof cetirizinehada3-foldincreaseinhalf-lifeand a70%decreaseinclearancecomparedtonormals. Cetirizinewaspoorlyclearedbyhaemodialysis.Dosingadjustmentisnecessaryinpatientswith moderateorsevererenalimpairment(seesection4.2).

Patients with hepatic impairment

Patientswithchronicliverdiseases(hepatocellular,cholestatic,and biliarycirrhosis)given10or20mgofcetirizineas asingledosehada50%increaseinhalf-lifealong witha40%decreaseinclearancecomparedtohealthysubjects.

Dosingadjustmentisonlynecessaryinhepaticallyimpairedpatientsifconcomitantrenalimpairment ispresent.

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafety pharmacology,repeateddosetoxicity,genotoxicity,carcinogenicpotential,toxicitytoreproduction.

Sorbitol solution 70%

Glycerol

Propylene glycol

Sodium acetate

Saccharin sodium

Acetic acid glacial

Banana flavour

Purified water

Methylparahydroxybenzoate (E 218),

Propylparahydroxybenzoate (E216)

Not applicable

5 years

After first opening the solution should be used within 12 weeks.

Store in original container.

Amber glass bottles (Type III) with child-proof white plastic (PP) closures, containing 75 and 150 ml oral solution.

Not all pack sizes will be marketed in all countries.

The legal category of each pack size will be determined nationally.

No special requirements

Stada Arzneimittel AG

Stadastraße 2-18

D-61118 Bad Vilbel

Germany

16475

22/02/2002

26 September 2014