DOVOBET

Main information

  • Trade name:
  • DOVOBET Ointment 50/500 Micrograms/g
  • Dosage:
  • 50/500 Micrograms/g
  • Pharmaceutical form:
  • Ointment
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DOVOBET Ointment 50/500 Micrograms/g
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/213/001
  • Authorization date:
  • 10-10-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dovobet®50microgram/g+0.5mg/gointment

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Calcipotriol50microgram/g(ashydrate),betamethasone0.5mg/g(asdipropionate).

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Ointment.

ProductimportedfromtheUK:

Off-whitetoyellow,ointment.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Topicaltreatmentofstableplaquepsoriasisvulgarisamenabletotopicaltherapy.

4.2Posologyandmethodofadministration

Dovobetshouldbeappliedtotheaffectedareaoncedaily.Therecommendedtreatmentperiodis4weeks.Afterthisperiod

repeatedtreatmentwithDovobetcanbeinitiatedundermedicalsupervision.

Themaximumdailydoseshouldnotexceed15g,themaximumweeklydoseshouldnotexceed100g,andthetreatedareashould

notbemorethan30%ofthebodysurface.

Dovobetisnotrecommendedfortheuseinchildrenandadolescentsbelowtheageof18years.

4.3Contraindications

DuetothecontentofcalcipotriolDovobetiscontra-indicatedinpatientswithknowndisordersofcalciummetabolism.

Duetothecontentofcorticosteroid,Dovobetiscontraindicatedinthefollowingconditions:Viral(e.g.herpesor

varicella)lesionsoftheskin,fungalorbacterialskininfections,parasiticinfections,skinmanifestationsinrelationto

tuberculosisorsyphilis,rosacea,perioraldermatitis,acnevulgaris,atrophicskin,striaeatrophicae,fragilityofskin

veins,ichthyosis,acnerosacea,ulcers,wounds,perianalandgenitalpruritus.

Dovobetiscontraindicatedinguttate,erythrodermic,exfoliativeandpustularpsoriasis.

Dovobetiscontraindicatedinpatientswithsevererenalinsufficiencyorseverehepaticdisorders.

4.4Specialwarningsandprecautionsforuse

Applicationonlargeareasofdamagedskinandunderocclusivedressingsoronmucousmembranesorinskinfoldsshouldbe

avoidedsinceitincreasesthesystemicabsorptionofcorticosteroids.Skinofthefaceandgenitalsareverysensitiveto

corticosteroids.Long-termtreatmentofthesepartsofthebodyshouldbeavoided.Theseareasshouldonlybetreatedwiththe

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Whenlesionsbecomesecondarilyinfected,theyshouldbetreatedwithantimicrobiologicaltherapy.However,wheninfection

worsens,treatmentwithcorticosteroidsshouldbestopped.

Whentreatingpsoriasiswithtopicalcorticosteroidstheremaybeariskofgeneralisedpustularpsoriasisorofreboundeffects

whendiscontinuingtreatment.Medicalsupervisionshouldthereforecontinueinthepost-treatmentperiod.

Withlong-termusethereisanincreasedriskoflocalandsystemiccorticosteroidundesirableeffects.Thetreatmentshouldbe

discontinuedincaseofundesirableeffectsrelatedtolong-termuseofcorticosteroid,seesection4.8.

Theremaybeariskofreboundwhendiscontinuingalong-termtreatmentwithcorticosteroids.

Thereisnoexperiencefortheuseofthisproductonthescalp.Thereisnoexperiencewithconcurrentuseofotheranti-psoriatic

productsadministeredlocallyorsystemicallyorwithphototherapy.

DuringDovobettreatmentphysiciansarerecommendedtoadvisepatientstolimitoravoidexcessiveexposuretoeithernaturalor

artificialsunlight.TopicalcalcipotriolshouldbeusedwithUVradiationonlyifthephysicianandpatientconsiderthatthe

potentialbenefitsoutweighthepotentialrisks(seesection5.3).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Noneknown.

4.6Fertility,pregnancyandlactation

Pregnancy

TherearenoadequatedatafromtheuseofDovobetinpregnantwomen.Studiesinanimalswithglucocorticoidshaveshown

reproductivetoxicity(seesection5.3),butanumberofepidemiologicalstudieshavenotrevealedcongenitalanomaliesamong

infantsborntowomentreatedwithcorticosteroidsduringpregnancy.Thepotentialriskforhumansisuncertain.Therefore,during

pregnancy,Dovobetshouldonlybeusedwhenthepotentialbenefitjustifiesthepotentialrisk.

Lactation

Betamethasonepassesintobreastmilkbutriskofanadverseeffectontheinfantseemsunlikelywiththerapeuticdoses.Thereare

nodataontheexcretionofcalcipotriolinbreastmilk.CautionshouldbeexercisedwhenprescribingDovobettowomenwho

breastfeed.ThepatientshouldbeinstructednottouseDovobetonthebreastwhenbreastfeeding.

4.7Effectsonabilitytodriveandusemachines

Dovobethasnoornegligibleinfluenceontheabilitytodriveandtousemachines.

4.8Undesirableeffects

Verycommon>1/10

Common>1/100and<1/10

Uncommon>1/1,000and<1/100

Rare>1/10,000and<1/1000

Veryrare<1/10,000

ThetrialprogrammeforDovobetointmenthassofarincludedmorethan2,500patientsandhasshownthatapproximately10%of

patientscanbeexpectedtoexperienceanon-seriousundesirableeffect.

Basedondatafromclinicaltrialsandpostmarketusethecommonundesirableeffectsarepruritus,rashandburningsensationof

skin.Uncommonundesirableeffectsareskinpainorirritation,dermatitis,erythema,exacerbationofpsoriasis,folliculitisand

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TheundesirableeffectsarelistedbyMedDRASOCandtheindividualundesirableeffectsarelistedstartingwiththemost

frequentlyreported.

Skinandsubcutaneoustissuedisorders

Common:Pruritus

Common:Rash

Common:Burningsensationofskin

Uncommon:Skinpainorirritation

Uncommon:Dermatitis

Uncommon:Erythema

Uncommon:Exacerbationofpsoriasis

Uncommon:Folliculitis

Uncommon:Applicationsitepigmentationchanges

Rare:Pustularpsoriasis

Undesirableeffectsobservedforcalcipotriolandbetamethasone,respectively:

Calcipotriol

Undesirableeffectsincludeapplicationsitereactions,pruritus,skinirritation,burningandstingingsensation,dryskin,erythema,

rash,dermatitis,eczema,psoriasisaggravated,photosensitivityandhypersensitivityreactionsincludingveryrarecasesof

angioedemaandfacialoedema.

Systemiceffectsaftertopicalusemayappearveryrarelycausinghypercalcaemiaorhypercalciuria,cf.section4.4.

Betamethasone(asdipropionate)

Thisproductcontainsapotentcorticosteroid.

Localreactionscanoccuraftertopicaluse,especiallyduringprolongedapplication,includingskinatrophy,telangiectasia,striae,

folliculitis,hypertrichosis,perioraldermatitis,allergiccontactdermatitis,depigmentationandcolloidmilia.Whentreating

psoriasistheremaybeariskofgeneralisedpustularpsoriasis.

Systemiceffectsduetotopicaluseofcorticosteroidsarerareinadults,howevertheycanbesevere.Adrenocorticalsuppression,

cataract,infectionsandincreaseofintra-ocularpressurecanoccur,especiallyafterlongtermtreatment.Systemiceffectsoccur

morefrequentlywhenappliedunderocclusion(plastic,skinfolds),whenappliedonlargeareasandduringlongtermtreatment,

cf.section4.4.

4.9Overdose

Useabovetherecommendeddosemaycauseelevatedserumcalciumwhichshouldrapidlysubsidewhentreatmentis

discontinued.

Excessiveprolongeduseoftopicalcorticosteroidsmaysuppressthepituitary-adrenalfunctionsresultinginsecondaryadrenal

insufficiencywhichisusuallyreversible.Insuchcasessymptomatictreatmentisindicated.

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Ithasbeenreportedthatduetomisuseonepatientwithextensiveerythrodermicpsoriasistreatedwith240gofDovobetointment

weekly(maximumdose100gweekly,cf.section4.2and4.4)for5monthsdevelopedCushing'ssyndromeandpustularpsoriasis

afterabruptlystoppingtreatment.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

DO5AX52Calcipotriol,combinations.

CalcipotriolisavitaminDanalogue.Invitrodatasuggeststhatcalcipotriolinducesdifferentiationandsuppressesproliferationof

keratinocytes.Thisistheproposedbasisforitseffectinpsoriasis.

Likeothertopicalcorticosteroids,betamethasonedipropionatehasanti-inflammatory,antipruritic,vasoconstrictiveand

immunosuppressiveproperties,however,withoutcuringtheunderlyingcondition.Throughocclusiontheeffectcanbeenhanced

duetoincreasedpenetrationofthestratumcorneum(approximatelybyafactorof10).Theincidenceofadverseeventswill

increasebecauseofthis.Themechanismoftheanti-inflammatoryactivityofthetopicalsteroids,ingeneral,isunclear.

Asafetystudyin634psoriasispatientshasinvestigatedrepeatedcoursesofDovobetusedoncedailyasrequired,eitheraloneor

alternatingwithDovonex,forupto52weeks,comparedwithDovonexusedalonefor48weeksafteraninitialcourseofDovobet.

Adversedrugreactionswerereportedby21.7%ofthepatientsintheDovobetgroup,29.6%intheDovobet/Dovonexalternating

groupand37.9%intheDovonexgroup.Theadversedrugreactionsthatwerereportedbymorethan2%ofthepatientsinthe

Dovobetgroupwerepruritus(5.8%)andpsoriasis(5.3%).

Adverseeventsofconcernpossiblyrelatedtolong-termcorticosteroidusewerereportedby4.8%ofthepatientsintheDovobet

group,2.8%intheDovobet/Dovonexalternatinggroupand2.9%intheDovonexgroup.

5.2Pharmacokineticproperties

ClinicalstudieswithradiolabelledointmentindicatethatthesystemicabsorptionofcalcipotriolandbetamethasonefromDovobet

islessthan1%ofthedose(2.5g)whenappliedtonormalskin(625cm2)for12hours.Applicationtopsoriasisplaquesandunder

occlusivedressingsmayincreasetheabsorptionoftopicalcorticosteroids.

Absorptionthroughdamagedskinisapprox24%.Proteinbindingisapprox64%.Plasmaeliminationhalf-lifeafterintravenous

applicationis5-6hours.Duetotheformationofadepotintheskineliminationafterdermalapplicationisinorderofdays.

Betamethasoneismetabolisedespeciallyintheliver,butalsointhekidneystoglucuronideandsulphateesters.Excretiontakes

placebyurineandfaeces.

5.3Preclinicalsafetydata

Studiesofcorticosteroidsinanimalshaveshownreproductivetoxicity(cleftpalate,skeletalmalformations).Inreproduction

toxicitystudieswithlong-termoraladministrationofcorticosteroidstoratsprolongedgestationandprolongedanddifficultlabour

wasdetected.Moreoverreductioninoffspringsurvival,inbodyweightandbodyweightgainwasobserved.Therewasno

impairmentoffertility.Therelevanceforhumansisunknown.

Adermalcarcinogenicitystudyinmicerevealednospecialhazardtohumans.

Inastudywherealbinohairlessmicewererepeatedlyexposedtobothultraviolet(UV)radiationanddermallyadministered

calcipotriolfor40weeksatdoselevelscorrespondingto9,30and90µg/m2/day(equivalentto0.25,0.84,2.5timesthe

maximumrecommendeddailydosefora60kgadult,respectively),areductioninthetimerequiredforUVradiationtoinducethe

formationofskintumourswasobserved(statisticallysignificantinmalesonly),suggestingthatcalcipotriolmayenhancethe

effectofUVradiationtoinduceskintumours.Theclinicalrelevanceofthisfindingisunknown.

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Liquidparaffin

Polyoxypropylene-15-stearylether

-tocopherol

Whitesoftparaffin

6.2Incompatibilities

Nottobemixedwithothermedicinalproducts.

6.3Shelflife

Unopenedcontainer:Theshelflifeexpirydateofthisproductisthedateshownonthecontainerandoutercartonoftheproductas

marketedinthecountryoforigin.

Afterfirstopeningofcontainer:12months.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

6.5Natureandcontentsofcontainer

Aluminium/epoxyphenoltubeswithpolyethylenescrewcap.

Tubesizes:60g&120g

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

8PARALLELPRODUCTAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:10 th

October2008

10DATEOFREVISIONOFTHETEXT

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