ADVANTAN CREAM 0.1% W/ W

Main information

  • Trade name:
  • ADVANTAN CREAM 0.1% W/ W
  • Dosage:
  • 0.1%w/ w %w/ w
  • Pharmaceutical form:
  • Cream
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ADVANTAN CREAM 0.1% W/W
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1407/001/001
  • Authorization date:
  • 27-07-2007
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA1407/001/001

CaseNo:2042218

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

IntendisGmbH

Max-Dohrn-Str.10,D-10589Berlin,Germany

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

AdvantanCream0.1%w/w

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom03/04/2008.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 09/07/2008 CRN 2042218 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Advantan0.1%w/wcream

2QUALITATIVEANDQUANTITATIVECOMPOSITION

1gcreamcontains1mg(0.1%)methylprednisoloneaceponate.

Excipients:AlsocontainsCetostearylAlcoholandButylhydroxytoluene(E321)

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Cream

Whiteopaquecream.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Topicaltreatmentofcorticosteroidsensitivedermatoses.

4.2Posologyandmethodofadministration

Ingeneral,theAdvantanformulationappropriatetotheskinconditionisappliedthinlyonceperdaytothediseased

areasofskin.

Ingeneral,thedurationofuseshouldnotexceed12weeksinadultsand4weeksinchildren.

4.3Contraindications

Useinthepresenceofuntreatedinfectionsofbacterial,tuberculous,treponemal,viralorfungalorigin.Hypersensitivity

tothepreparation.Useinacnevulgaris,rosaceaorinperioraldermatosis.Useinchildrenundertheageofthreeyears.

4.4Specialwarningsandprecautionsforuse

Donotuseonchildrenunder12yearsofagewithoutmedicalsupervision.

Additional,specfictherapyisrequiredinbacteriallyinfectedskindiseasesand/orinfungalinfections.

IftheskindriesoutexcessivelyunderprotracteduseofAdvantancream,aswitchshouldbemadetooneofthefattier

formulations(AdvantanointmentorAdvantanfattyointment).

Advantanshouldnotbeallowedtocomeintocontactwiththeeyeswhenbeingappliedtotheface.

Noimpairmentofadrenocorticalfunctionhasbeenobservedeitherinadultsorinchildrenonlarge-area(40-60%of

theskinsurface)orevenocclusivetreatmentwithAdvantan.Nevertheless,thedurationofuseshouldbekeptasbrief

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 09/07/2008 CRN 2042218 page number: 2

Extensiveapplicationoftopicalcorticosteroidstolargeareasofthebodyorforprolongedperiodsoftime,inparticular

underocclusion,significantlyincreasestheriskofsideeffects.

Asknownfromsystemiccorticoids,glaucomamayalsodevelopfromusinglocalcorticoids(e.g.afterlarge-dosedor

extensiveapplicationoveraprolongedperiod,occlusivedressingtechniques,orapplicationtotheskinaroundthe

eyes).

Thisproductcontainsbutylhydroxytoluene(E321)whichmaycauselocalskinreactions(e.g.contactdermatitis),or

irritationtotheeyesandmucousmembranesandcetylstearylalcoholwhichmaycauselocalskinreactions(e.g.contact

dermatitis).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Nonesofarknown.

4.6Pregnancyandlactation

Animalexperimentalstudieswithglucocorticosteroidshaveshownreproductivetoxicity(cf.section“5.3Preclinical

safetydata”).

Anumberofepidemiologicalstudiessuggestthattherecouldpossiblybeanincreasedriskoforalcleftsamong

newbornsofwomenwhoweretreatedwithsystemicglucocorticosteroidsduringthefirsttrimesterofpregnancy.Oral

cleftsareararedisorderandifsystemicglucocorticosteroidsareteratogenic,thesemayaccountforanincreaseofonly

oneortwocasesper1000womentreatedwhilepregnant.Dataconcerningtopicalglucocorticosteroiduseduring

pregnancyareinsufficient;however,alowerriskmightbeexpectedsincesystemicavailabilityoftopicallyapplied

glucocorticosteroidsisverylow.

Asageneralrule,topicalpreparationscontainingcorticoidsshouldnotbeappliedduringthefirsttrimesterof

pregnancy.TheclinicalindicationfortreatmentwithAdvantanmustbecarefullyreviewedandthebenefitsweighed

againsttherisksinpregnantandlactatingwomen.Inparticular,large-areaorprolongedusemustbeavoided.

Nursingmothersshouldnotbetreatedonthebreasts.

4.7Effectsonabilitytodriveandusemachines

Notapplicable.

4.8Undesirableeffects

Localconcomitantsymptomssuchasitching,burning,erythemaorvesiculationmayoccurinisolatedcasesunder

treatmentwithAdvantan.

Thefollowingreactionmayoccurwhentopicalpreparationscontainingcorticoidsareappliedtolargeareasofthebody

(about10%andmore)orforprolongedperiodsoftime(morethan4weeks):localsymptomssuchasatrophyofthe

skin,telangiectasia,striae,acneformchangesoftheskinandsystemiceffectsofthecorticoidduetoabsorption.During

theclinicalinvestigation,noneofthesesideeffectsoccurredunderAdvantanontreatmentupto12weeks(adults)and

4weeks(children).

Aswithothercorticoidsfortopicalapplication,thefollowingsideeffectsmayoccurinrarecases:

Folliculitis,hypertrichosis,perioraldermatitis,skindiscolouration,allergicskinreactionstooneoftheingredientsof

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 09/07/2008 CRN 2042218 page number: 3

4.9Overdose

Symptomsofintoxication

Symptomsofcutaneousatrophysuchasthinningoftheskin,telangiectasiasandstriae(particularlyintertriginous)may

occurassignsofexcessivelylongorintensivetopicalapplicationofcorticoidformulations.

Therapyofintoxication

Thetreatmentmustbediscontinuedifsuchsymptomsofcutaneousatrophyoccurasaresultoftopical"overdosage".

Ingeneral,thesymptomsthenregresswithin10to14days.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Aftertopicalapplication,Advantansuppressesinflammatoryandallergicskinreactionsaswellasreactionsassociated

withhyperproliferation,leadingtoregressionoftheobjectivesymptoms(erythema,oedema,infiltration,

lichenification)andthesubjectivecomplaints(itching,burning,pain).

Onapplicationofmethylprednisoloneaceponateintopicallyeffectivedosage,thesystemiceffectisminimalinboth

manandanimals.Afterlarge-areatreatmentofpatientswithskindisorders,theplasmacortisolvaluesremainwithin

thenormalrange,circadiancortisolrhythmismaintainedandnoreductionofcortisolhasbeenascertainedin24-hour

urine.

Asforallotherglucocorticoids,sofarthemechanismofactionofmethylprednisoloneaceponateisnotcompletely

understood.Itisknownthatmethylprednisoloneaceponateitselfbindstotheintracellularglucocorticoidreceptorand

thisisespeciallytrueoftheprincipalmetabolite6-alpha-methylprednisolone-17-propionate,whichisformedafter

cleavageintheskin.

ThesteroidreceptorcomplexbindstocertainregionsofDNA,therebytriggeringaseriesofbiologicaleffects.

Theunderstandingofthemechanismoftheanti-inflammatoryactionismoreprecise.Bindingofthesteroidreceptor

complexresultsininductionofmacrocortinsynthesis.Macrocortininhibitsthereleaseofarachidonicacidandthusthe

formationofinflammationmediatorssuchasprostaglandinsandleukotrienes.

Theimmunosuppressiveactionofglucocorticoidscanbeexplainedbyinhibitionofchemotaxis(inhibitionof

leukotrienesynthesis)andanantimitoticeffect,whichsofarisnotwellunderstood.

Inhibitionofthesynthesisofvasodilatingprostaglandinsorpotentiationofthevasoconstrictiveeffectofadrenaline

finallyresultinthevasoconstrictiveactivityofglucocorticoids.

TherespectivebasesareofmajorimportancetothetherapeuticeffectoftheAdvantanformulations.

Advantancream

Asalow-fatformulationwithahighwatercontent,Advantancreamisparticularlysuitableforacuteandweeping

stagesofeczema,forverygreasyskinandforuseonexposedorhairypartsofthebody.

Advantanointment

Skinconditionswhichareneitherweepingnorverydryrequireabasewithbalancedproportionsoffatandwater.

Advantanointmentmakestheskinslightlygreasywithoutretainingwarmthandfluid.Ofthethreeformulations,

Advantanointmenthasthewidestfieldofuse.

Advantanfattyointment

Verydryskinconditionsandchronicstagesofskindiseasesrequireananhydrousbase.Theocclusiveeffectofthe

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 09/07/2008 CRN 2042218 page number: 4

5.2Pharmacokineticproperties

Methylprednisoloneaceponatebecomesavailableintheskinfromallformulations(cream,ointment,fattyointment).

Theconcentrationinthestratumcorneumandlivingskindecreasesfromoutsidetoinside.

Methylprednisoloneaceponateishydrolysedintheepidermisanddermistothemainmetabolite6-alpha-

methylprednisolone-17-propionatewhichbindsmorefirmlytothecorticoidreceptor-anindicationof"bioactivation"

intheskin.

Thedegreeofpercutaneousabsorptiondependsonthestateoftheskin,theformulationandtheconditionsof

application(open/occlusion).Studiesinjuvenileandadultpatientswithneurodermatitisandpsoriasishaveshownthat

thepercutaneousabsorptiononopenapplicationwasonlyslightly(2.5%)greaterthanthepercutaneousabsorptionin

volunteerswithnormalskin(0.5-1.5%).

Whenthehornylayerisremovedbeforetheapplication,thecorticoidlevelsintheskinareaboutthreetimeshigher

thanafterapplicationtointactskin.

Afterreachingthesystemiccirculation,theprimaryhydrolysisproductofMPA,6-alpha-methylprednisolone-17-

propionate,isquicklyconjugatedwithglucuronicacidandinactivatedasaresult.

ThemetabolitesofMPA(mainmetabolite:6-alpha-methylprednisolone-17-propionate-21-glucuronide)areeliminated

primarilyviathekidneyswithahalf-lifeofabout16hours.Followingi.v.administration,excretionofthe 14

C-labelled

substanceswiththeurineandfaeceswascompletedwithin7days.Noaccumulationofsubstanceormetabolitestakes

placeinthebody.

5.3Preclinicalsafetydata

Dataconcerningacutetoxicityshowthattheactiveingredientmethylprednisoloneaceponate(MPA)containedinthe

preparationcanbegradedasvirtuallynon-toxiconsingleoralingestion.Acuteintoxificationisalsounlikelyon

inadvertentadministrationofamultipleofthedosagerequiredfortherapy.

Animal-experimentalstudiesconductedtoassessthesystemictoleranceonrepeatedadministrationdidnotproduceany

findingswhichspeakagainsttheuseofthepreparationinthedosagerequiredfortherapy.

ThebasicpharmacologicaldatacharacterisedMPAasananti-inflammatoryglucocorticoid.Onthebasisofthisprofile

ofactionandtheabsenceofanyevidenceforagenotoxiceffectorthedevelopmentofreactivemetabolites,norelevant

tumorigenicpotentialcanbeassumedforMPA.Todate,epidemiologicalsurveysofmanyyearsofsystemic

glucocorticoidtherapyhavenotrevealedanyevidenceforatumorigenicactionofthissubstanceclassinman.

EmbryotoxicitystudieswithAdvantanledtoresultstypicalforglucocorticoids,i.e.embryolethaland/orteratogenic

effectsareinducedintheappropriatetestsystem.Inviewofthesefindings,particularcareshouldbetakenwhen

prescribingAdvantanduringpregnancy.Theresultsofepidemiologicalstudiesaresummarizedundersection“4.6

Pregnancyandlactation”.

Itmustalwaysbeborneinmindonuseofthepreparationduringlactationthat,aftersystemicadministration,very

smallamountsofglucocorticoidcanenterthebreastmilk.BecauseoftheminimalsystemicefficacyofMPAonuseof

therapeuticdosagesandinviewofthedermalrouteofapplication,thenewbornisexposedtoonlyaslightriskof

pharmacologicaleffectsfromthissource.

Localtolerancestudiesinanimalsandinmanhavenotproducedanyevidenceoflocalintoleranceofaseverityin

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 09/07/2008 CRN 2042218 page number: 5

InvitroandinvivotestsforagenotoxicpotentialoftheactiveingredientMPAhavenotproducedanyevidencefor

mutagenicity.

Animal-experimentalstudiestodemonstrateasensitisingeffectdidnotshowanysuchpotential.

Altogether,theresultsofthetoxicologicalstudiesdonotspeakagainsttheproperuseofMPAinman.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

DecylOleate

Glycerolmonostearate(40-55)

CetolstearylAlcohol

Hardfat

Glycerolfattyacidtri-esters(Softisan378)

Polyoxyl-40-stearate

Glycerol85%(E422)

Disodiumedetate

Benzylalcohol

Butylhydroxytoluene(E321)

Purifiedwater

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Storebelow25 o

6.5Natureandcontentsofcontainer

Tubeswith5,10,15,30,50or100g.

Tubesmadeofpurealuminium,interiorwallcoatedwithepoxyresin,andwithapolyester-basedexternalcoating,fold

sealringismadeofpolyamide-basedheatsealablematerial.Thescrewcapismadeofhighdensitypolyethylene.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 09/07/2008 CRN 2042218 page number: 6

7MARKETINGAUTHORISATIONHOLDER

IntendisGmbH

Max-Dohrn-Str.10

D-10589Berlin

Germany

8MARKETINGAUTHORISATIONNUMBER

PA1407/1/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:3 rd

April1998

Dateoflastrenewal:3 rd

April2008

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 09/07/2008 CRN 2042218 page number: 7