DOVOBET

Main information

  • Trade name:
  • DOVOBET Ointment 50 + 0.5
  • Dosage:
  • 50 + 0.5
  • Pharmaceutical form:
  • Ointment
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DOVOBET Ointment 50 + 0.5
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1500/062/001
  • Authorization date:
  • 25-06-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dovobet50micrograms/0.5mg/gointment

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onegramofointmentcontains50microgramsofcalcipotriol(asmonohydrate)and0.5mgbetamethasone(as

dipropionate).

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Ointment.

ProductimportedfromtheUK:

Off-whitetoyellowointment.

ProductimportedfromItaly:

Off-whitetoyellowointment.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Topicaltreatmentofstableplaquepsoriasisvulgarisamenabletotopicaltherapyinadults.

4.2Posologyandmethodofadministration

Posology

Dovobetointmentshouldbeappliedtotheaffectedareaoncedaily.Therecommendedtreatmentperiodis4weeks.

ThereisexperiencewithrepeatedcoursesofDovobetupto52weeks.Ifitisnecessarytocontinueorrestarttreatment

after4weeks,treatmentshouldbecontinuedaftermedicalreviewandunderregularmedicalsupervision.Whenusing

calcipotriolcontainingmedicinalproducts,themaximumdailydoseshouldnotexceed

15g.Thebodysurfaceareatreatedwithcalcipotriolcontainingmedicinalproductsshouldnotexceed30%(see

section4.4).

Specialpopulations

Renalandhepaticimpairment

ThesafetyandefficacyofDovobetointmentinpatientswithsevererenalinsufficiencyorseverehepaticdisordershave

notbeenevaluated.

Paediatricpopulation

ThesafetyandefficacyofDovobetointmentinchildrenbelow18yearshavenotbeenestablished.

Nodataareavailable.

Methodofadministration

Dovobetointmentshouldbeappliedtotheaffectedarea.Inordertoachieveoptimaleffect,itisnotrecommendedto

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4.3Contraindications

Hypersensitivitytotheactivesubstancesortoanyoftheexcipients.

Dovobetointmentiscontraindicatedinerythrodermic,exfoliativeandpustularpsoriasis.

DuetothecontentofcalcipotriolDovobetointmentiscontra-indicatedinpatientswithknowndisordersofcalcium

metabolism.

DuetothecontentofcorticosteroidDovobetointmentiscontraindicatedinthefollowingconditions:Viral(e.g.herpes

orvaricella)lesionsoftheskin,fungalorbacterialskininfections,parasiticinfections,skinmanifestationsinrelationto

tuberculosisorsyphilis,perioraldermatitis,atrophicskin,striaeatrophicae,fragilityofskinveins,ichthyosis,acne

vulgaris,acnerosacea,rosacea,ulcers,wounds,perianalandgenitalpruritus.

4.4Specialwarningsandprecautionsforuse

Effectsonendocrinesystem

DovobetointmentcontainsapotentgroupIIIsteroidandconcurrenttreatmentwithothersteroidsmustbeavoided.

Adversereactionsfoundinconnectionwithsystemiccorticosteroidtreatment,suchasadrenocorticalsuppressionor

impactonthemetaboliccontrolofdiabetesmellitusmayoccuralsoduringtopicalcorticosteroidtreatmentdueto

systemicabsorption.Applicationunderocclusivedressingsshouldbeavoidedsinceitincreasesthesystemicabsorption

ofcorticosteroids.Applicationonlargeareasofdamagedskinoronmucousmembranesorinskinfoldsshouldbe

avoidedsinceitincreasesthesystemicabsorptionofcorticosteroids(seesection4.8).

Inastudyinpatientswithbothextensivescalpandextensivebodypsoriasisusingacombinationofhighdosesof

Dovobetgel(scalpapplication)andhighdosesofDovobetointment(bodyapplication),5of32patientsshoweda

borderlinedecreaseincortisolresponsetoadrenocorticotropichormone(ACTH)challengeafter4weeksoftreatment

(seesection5.1).

Effectsoncalciummetabolism

Duetothecontentofcalcipotriol,hypercalcaemiamayoccurifthemaximumdailydose(15g)isexceeded.Serum

calciumis,however,quicklynormalisedwhentreatmentisdiscontinued.Theriskofhypercalcaemiaisminimalwhen

therecommendationsrelevanttocalcipotriolarefollowed.Treatmentofmorethan30%ofthebodysurfaceshouldbe

avoided(seesection4.2).

Localadversereactions

Skinofthefaceandgenitalsareverysensitivetocorticosteroids.Themedicinalproductshouldnotbeusedinthese

areas.Thepatientmustbeinstructedincorrectuseofthemedicinalproducttoavoidapplicationandaccidentaltransfer

totheface,mouthandeyes.Handsmustbewashedaftereachapplicationtoavoidaccidentaltransfertotheseareas.

Concomitantskininfections

Whenlesionsbecomesecondarilyinfected,theyshouldbetreatedwithantimicrobiologicaltherapy.

However,ifinfectionworsens,treatmentwithcorticosteroidsshouldbestopped.

Discontinuationoftreatment

Whentreatingpsoriasiswithtopicalcorticosteroidstheremaybeariskofgeneralisedpustularpsoriasisorofrebound

effectswhendiscontinuingtreatment.Medicalsupervisionshouldthereforecontinueinthepost-treatmentperiod.

Long-termuse

Withlong-termusethereisanincreasedriskoflocalandsystemiccorticosteroidadversereactions.

Thetreatmentshouldbediscontinuedincaseofadversereactionsrelatedtolong-termuseofcorticosteroid(seesection

4.8).

Unevaluateduses

ThereisnoexperiencefortheuseofDovobetointmentinguttatepsoriasis.

ConcurrenttreatmentandUVexposure

Thereisnoexperiencefortheuseofthismedicinalproductonthescalp.Dovobetointmentforbodypsoriasislesions

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Dovobetwithothertopicalanti-psoriaticproductsatthesame

treatmentarea,otheranti-psoriaticmedicinalproductsadministeredsystemicallyorwithphototherapy.

DuringDovobetointmenttreatment,physiciansarerecommendedtoadvisepatientstolimitoravoidexcessive

exposuretoeithernaturalorartificialsunlight.TopicalcalcipotriolshouldbeusedwithUVRonlyifthephysicianand

patientconsiderthatthepotentialbenefitsoutweighthepotentialrisks(seesection5.3).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Nointeractionstudieshavebeenperformed.

4.6Fertility,pregnancyandlactation

Pregnancy

TherearenoadequatedatafromtheuseofDovobetointmentinpregnantwomen.Studiesinanimalswith

glucocorticoidshaveshownreproductivetoxicity(seesection5.3),butanumberofepidemiologicalstudieshavenot

revealedcongenitalanomaliesamonginfantsborntowomentreatedwithcorticosteroidsduringpregnancy.The

potentialriskforhumansisuncertain.Therefore,duringpregnancy,Dovobetointmentshouldonlybeusedwhenthe

potentialbenefitjustifiesthepotentialrisk.

Breast-feeding

Betamethasonepassesintobreastmilkbutriskofanadverseeffectontheinfantseemsunlikelywiththerapeuticdoses.

Therearenodataontheexcretionofcalcipotriolinbreastmilk.CautionshouldbeexercisedwhenprescribingDovobet

ointmenttowomenwhobreast-feed.ThepatientshouldbeinstructednottouseDovobetointmentonthebreastwhen

breast-feeding.

Fertility

Studiesinratswithoraldosesofcalcipotriolorbetamethasonedipropionatedemonstratednoimpairmentofmaleand

femalefertility.

4.7Effectsonabilitytodriveandusemachines

Dovobethasnoornegligibleinfluenceontheabilitytodriveandtousemachines.

4.8Undesirableeffects

ThetrialprogrammeforDovobetointmenthassofarincludedmorethan2,500patientsandhasshownthat

approximately10%ofpatientscanbeexpectedtoexperienceanon-seriousundesirableeffect.

Thesereactionsareusuallymildandcovermainlyvariousskinreactionslikerash,pruritusandburningsensation.

Pustularpsoriasishasbeenreportedrarely.Reboundeffectafterendoftreatmenthasbeenreportedbutthefrequency

ofthisisnotknown.

BasedondatafromclinicaltrialsandpostmarketusethefollowingadversereactionsarelistedforDovobetointment.

TheadversereactionsarelistedbyMedDRASystemOrganClass,andtheindividualadversereactionsarelisted

startingwiththemostfrequentlyreported.Withineachfrequencygrouping,theadversereactionsarelistedinorderof

decreasingseriousness.

Thefollowingterminologieshavebeenusedinordertoclassifythefrequenciesofadversereactions:

Verycommon1/10

Common1/100to<1/10

Uncommon1/1,000to<1/100

Rare1/10,000to<1/1,000

Veryrare<1/10,000

Notknown(cannotbeestimatedfromtheavailabledata)

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Common

Pruritus

Rash

Burningsensationofskin

Uncommon

Exacerbationofpsoriasis

Skinpainorirritation

Dermatitis

Erythema

Folliculitis

Applicationsitepigmentationchanges

Rare

Pustularpsoriasis

Generaldisordersandadministrationsiteconditions

Notknown

Reboundeffect-includedinsection4.4

Thefollowingadversereactionsareconsideredtoberelatedtothepharmacologicalclassesofcalcipotrioland

betamethasone,respectively:

Calcipotriol

Adversereactionsincludeapplicationsitereactions,pruritus,skinirritation,burningandstingingsensation,dryskin,

erythema,rash,dermatitis,eczema,psoriasisaggravated,photosensitivityandhypersensitivityreactionsincludingvery

rarecasesofangioedemaandfacialoedema.Systemiceffectsaftertopicalusemayappearveryrarelycausing

hypercalcaemiaorhypercalciuria

(seesection4.4).

Betamethasone(asdipropionate)

Localreactionscanoccuraftertopicaluse,especiallyduringprolongedapplication,includingskinatrophy,

telangiectasia,striae,folliculitis,hypertrichosis,perioraldermatitis,allergiccontactdermatitis,depigmentationand

colloidmilia.Whentreatingpsoriasistheremaybeariskof

generalisedpustularpsoriasis.

Systemicreactionsduetotopicaluseofcorticosteroidsarerareinadults,howevertheycanbesevere.

Adrenocorticalsuppression,cataract,infections,impactonthemetaboliccontrolofdiabetesmellitusandincreaseof

intra-ocularpressurecanoccur,especiallyafterlongtermtreatment.Systemicreactionsoccurmorefrequentlywhen

appliedunderocclusion(plastic,skinfolds),whenappliedonlargeareasandduringlongtermtreatment(seesection

4.4).

4.9Overdose

Useabovetherecommendeddosemaycauseelevatedserumcalciumwhichshouldrapidlysubsidewhentreatmentis

discontinued.

Excessiveprolongeduseoftopicalcorticosteroidsmaysuppressthepituitary-adrenalfunctionsresultinginsecondary

adrenalinsufficiencywhichisusuallyreversible.Insuchcasessymptomatictreatmentisindicated.

Incaseofchronictoxicitythecorticosteroidtreatmentmustbediscontinuedgradually.

Ithasbeenreportedthatduetomisuseonepatientwithextensiveerythrodermicpsoriasistreatedwith240gof

Dovobetointmentweekly(correspondingtoadailydoseofapproximately34g)for5months(maximum

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Antipsoriatics.Otherantipsoriaticsfortopicaluse,Calcipotriol,combinations.ATCCode:

D05AX52

CalcipotriolisavitaminDanalogue.Invitrodatasuggeststhatcalcipotriolinducesdifferentiationandsuppresses

proliferationofkeratinocytes.Thisistheproposedbasisforitseffectinpsoriasis.

Likeothertopicalcorticosteroids,betamethasonedipropionatehasanti-inflammatory,antipruritic,vasoconstrictiveand

immunosuppresiveproperties,however,withoutcuringtheunderlyingcondition.Throughocclusiontheeffectcanbe

enhancedduetoincreasedpenetrationofthestratumcorneum.

Theincidenceofadverseeventswillincreasebecauseofthis.Themechanismoftheanti-inflammatoryactivityofthe

topicalsteroids,ingeneral,isunclear.

Asafetystudyin634psoriasispatientshasinvestigatedrepeatedcoursesofDovobetointmentusedoncedailyas

required,eitheraloneoralternatingwithDovonex,forupto52weeks,comparedwithDovonexusedalonefor48

weeksafteraninitialcourseofDovobetointment.Adversedrugreactionswerereportedby21.7%ofthepatientsin

theDovobetointmentgroup,29.6%intheDovobetointment/Dovonexalternatinggroupand37.9%intheDovonex

group.Theadversedrugreactionsthatwerereportedbymorethan2%ofthepatientsintheDovobetointmentgroup

werepruritus(5.8%)andpsoriasis(5.3%).Adverseeventsofconcernpossiblyrelatedtolong-termcorticosteroiduse

(e.g.skinatrophy,folliculitis,depigmentation,furuncleandpurpura)werereportedby4.8%ofthepatientsinthe

Dovobetointmentgroup,2.8%intheDovobetointment/Dovonexalternatinggroupand2.9%intheDovonexgroup.

AdrenalresponsetoACTHwasdeterminedbymeasuringserumcortisollevelsinpatientswithbothextensivescalp

andbodypsoriasis,usingupto106gperweekcombinedDovobetgelandDovobetointment.Aborderlinedecreasein

cortisolresponseat30minutespostACTHchallengewasseenin5of32patients(15.6%)after4weeksoftreatment

andin2of11patients(18.2%)whocontinuedtreatmentuntil8weeks.Inallcases,theserumcortisollevelswere

normalat60minutespostACTHchallenge.Therewasnoevidenceofchangeofcalciummetabolismobservedinthese

patients.WithregardtoHPAsuppression,therefore,thisstudyshowssomeevidencethatveryhighdosesofDovobet

gelandointmentmayhaveaweakeffectontheHPAaxis.

5.2Pharmacokineticproperties

Clinicalstudieswithradiolabelledointmentindicatethatthesystemicabsorptionofcalcipotriolandbetamethasone

fromDovobetointmentislessthan1%ofthedose(2.5g)whenappliedtonormalskin(625cm2)for12hours.

Applicationtopsoriasisplaquesandunderocclusivedressingsmay

increasetheabsorptionoftopicalcorticosteroids.Absorptionthroughdamagedskinisapprox.24%.

Followingsystemicexposure,bothactiveingredients–calcipotriolandbetamethasonedipropionate–arerapidlyand

extensivelymetabolised.Proteinbindingisapprox.64%.Plasmaeliminationhalf-lifeafterintravenousapplicationis

5-6hours.Duetotheformationofadepotintheskineliminationafterdermalapplicationisinorderofdays.

Betamethasoneismetabolisedespeciallyintheliver,butalsointhekidneystoglucuronideandsulphateesters.The

mainrouteofexcretionofcalcipotriolisviafaeces(ratsandminipigs)andforbetamethasonedipropionateitisvia

urine(ratsandmice).Inrats,tissuedistributionstudieswithradiolabelledcalcipotriolandbetamethasonedipropionate,

respectively,showedthatthekidneyandliverhadthehighestlevelofradioactivity.

Calcipotriolandbetamethasonedipropionatewerebelowthelowerlimitofquantificationinallbloodsamplesof34

patientstreatedfor4or8weekswithbothDovobetgelandDovobetointmentforextensivepsoriasisinvolvingthe

bodyandscalp.Onemetaboliteofcalcipotriolandonemetaboliteofbetamethasonedipropionatewerequantifiablein

someofthepatients.

5.3Preclinicalsafetydata

Studiesofcorticosteroidsinanimalshaveshownreproductivetoxicity(cleftpalate,skeletalmalformations).In

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prolongedanddifficultlabourweredetected.Moreover,reductioninoffspringsurvival,bodyweightandbodyweight

gainwasobserved.Therewasnoimpairmentoffertility.Therelevanceforhumansisunknown.

Adermalcarcinogenicitystudywithcalcipotriolinmicerevealednospecialhazardtohumans.

Photo(co)carcinogenicitystudiesinmicesuggestthatcalcipotriolmayenhancetheeffectofUVRtoinduceskin

tumours.

Nocarcinogenicityorphotocarcinogenicitystudieshavebeenperformedwithbetamethasonedipropionate.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Liquidparaffin

Polyoxypropylene-15-stearylether

all-rac--tocopherol

Whitesoftparaffin

6.2Incompatibilities

Intheabsenceofcompatibilitystudies,thismedicinalproductmustnotbemixedwithothermedicinalproducts.

6.3Shelflife

Unopenedcontainer:Theshelflifeexpirydateofthisproductisthedateshownonthetubeandoutercartonofthe

productasmarketedinthecountryoforigin.

Afterfirstopeningofcontainer:12months.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

6.5Natureandcontentsofcontainer

ProductimportedfromtheUK:

Over-labelledcartoncontaininganAluminium/epoxyphenoltubewithpolyethylenescrewcap.

Tubesize:60g.

ProductimportedfromItaly:

CartoncontainingtwoAluminium/epoxyphenoltubewithpolyethylenescrewcap.

Tubesizes:2x30g.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7PARALLELPRODUCTAUTHORISATIONHOLDER

ProfindWholesaleLtd

Unit625,KilshaneAvenue

NorthwestBusinessPark

Dublin15

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1500/62/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:25thJune2010

10DATEOFREVISIONOFTHETEXT

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