DALACIN VAGINAL OVULE

Main information

  • Trade name:
  • DALACIN VAGINAL OVULE
  • Dosage:
  • 100 Milligram
  • Pharmaceutical form:
  • Pessary
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DALACIN VAGINAL OVULE
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0016/044/002
  • Authorization date:
  • 21-12-1998
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dalacin100mgVaginalOvule

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Clindamycinphosphateequivalentto100mgclindamycin.

‘Forexcipientssee6.1”.

3PHARMACEUTICALFORM

Pessary.

Semisolid,whitetooff-whitepessaries.

4CLINICALPARTICULARS

4.1TherapeuticIndications

DalacinVaginalOvuleisindicatedforthetreatmentofbacterialvaginosis(formerlyreferredtoasHaemophilus

vaginitis,Gardnerellavaginitis,nonspecificvaginitis,Corynebacteriumvaginitis,oranaerobicvaginosis).

4.2Posologyandmethodofadministration

Therecommendeddoseisoneovuleintravaginallyatbedtimeforthreeconsecutivedays.(Forinstructionsforusesee

Section6.6)

UseinPaediatricPatients:TheuseofDalacinVaginalOvulehasnotbeenstudiedinpatientsunder16yearsofage.

UseinElderlyPatients:TheuseofDalacinVaginalOvulehasnotbeenstudiedinpatientsover65yearsofage.

UseinPatientswithRenalImpairment:TheuseofDalacinVaginalOvulehasnotbeenstudiedinpatientswith

impairedrenalfunction.

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.3Contraindications

DalacinVaginalOvulesarecontraindicatedinpatientswithahistoryofhypersensitivitytoclindamycin,lincomycinor

thehardfat(asuppositorybaseconsistingofamixtureofglyceridesofsaturatedfattyacid).DalacinVaginalOvules

arealsocontraindicatedinindividualswithahistoryofantibiotic-associatedcolitis.

4.4Specialwarningsandprecautionsforuse

BeforeorafterinitiationoftherapywithDalacinVaginalOvule,otherinfectionsincludingTrichomonasvaginalis,

Candidaalbicans,Chlamydiatrachomatisandgonococcalinfectionsmayneedtobeinvestigatedbyadequate

laboratorytests.

TheuseofDalacinVaginalOvulemayresultintheovergrowthofnonsusceptibleorganisms,particularlyyeasts.

Onsetofsymptomssuggestiveofpseudomembranouscolitismayoccurduringorafterantimicrobialtreatment.

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inseverityfrommildtolife-threatening.Therefore,itisimportantthatthisisconsideredinpatientswhopresentwith

diarrhoeasubsequenttotheadministrationofantibacterialagents.Moderatecasesmayimprovefollowingwithdrawal

ofthedrug.

Clindamycintreatmentmustbestoppedifpseudomembranousdiarrhoeaoccurs.Anadequateantibacterialtherapy

shouldbeprescribed.Drugsinhibitingperistalsisarecontra-indicatedinthissituation.

CautionisadvisedinpatientswhenprescribingDalacin100mgVaginalOvulestoindividualswithInflammatory

BowelDiseasesuchasCrohn’sDiseaseorUlcerativeColitis.

Aswithallvaginalinfections,sexualintercourseduringtreatmentwithDalacinVaginalOvuleisnotrecommended.

LatexcondomsanddiaphragmsmaybeweakenedifexposedtothesuppositorybaseusedinDalacinVaginalOvules

(forIncompatibilitiesseeSection6.2).Theuseofsuchproductswithin72hoursfollowingtreatmentwithDalacin

VaginalOvulesisnotrecommendedassuchusecouldbeassociatedwithdiminishedcontraceptiveefficacyor

protectionagainstsexuallytransmitteddisease.

Theuseofothervaginalproducts(suchastamponsanddouches)duringthetreatmentwithDalacinVaginalOvuleis

notrecommended.

SafetyandefficacystudieshavenotbeenperformedwithDalacinVaginalOvuleinthefollowingpopulations:

pregnant,lactatingwomen,patientswithimpairedhepaticfunction,immunodeficientorcolitis.

PediatricUse

Safetyandefficacyinpediatricpatientshavenotbeenestablished.(SeeSection4.2)

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

NoinformationisavailableontheconcomitantuseofothervaginalmedicationswithDalacinVaginalOvule.

Whenadministeredsystemically,clindamycinphosphatehasbeenshowntohaveneuromuscularblockingproperties

thatmayenhancetheactionofotherneuromuscularblockingagents.Therefore,itshouldbeusedwithcautionin

patientsreceivingsuchagents

4.6Fertility,pregnancyandlactation

REGNANCY

UseofDalacinVaginalOvuleisnotrecommendedduringthefirsttrimester,astherearenoadequateandwell-

controlledstudiesinpregnantwomenoverthisperiod.

Inclinicaltrials,intravaginaluseofDalacinVaginalCreaminpregnantwomenduringsecondtrimesterandsystemic

useofclindamycinphosphateduringthesecondandthirdtrimesterhasnotbeenassociatedwithcongenital

abnormalities.

DalacinVaginalOvulemaybeusedtotreatpregnantwomenifclearlynecessaryduringthesecondandthirdtrimester

ofpregnancy.Digitalapplicationofthevaginalovuleisrecommendedduringpregnancy.

Reproductionstudiesperformedinratsandmiceusingoralandparenteraldosesofclindamycin,rangingfrom100to

600mg/kg/day,haverevealednoevidenceofharmtothefoetusduetoclindamycin.Inonemousestrain,cleftpalates

wereobservedinspeciestreatedfoetuses;thisresponsewasnotproducedinothermousestrainsorinotherspecies,

andisthereforeconsideredtobeastrainspecificeffect.Theclinicaldoseofclindamycinfromtheadministrationof

DalacinVaginalOvuleis22.5timeslessbasedonmg/m²thatthenoobservedadverseeffectlevelseeninanimal

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ACTATION

Itisnotknownifclindamycinisexcretedinbreastmilkfollowingtheuseofvaginallyadministeredclindamycin

vaginalovule.However,orallyandparenterallyadministeredclindamycinhavebeenreportedtoappearinbreast

milk.Nevertheless,afullbenefit-riskassessmentshouldbedonewhenconsideringtheuseofclindamycinvaginal

ovuleinanursingmother.

4.7Effectsonabilitytodriveandusemachines

Thereisnoevidencetosuggestthatclindamycinhasanyeffectontheabilitytodriveand/orusemachines.

4.8Undesirableeffects

Thesafetyofa3-dayregimenofDalacinVaginalOvulewasassessedinclinicaltrials,duringwhichthefollowing

eventsinTable1,consideredtobetreatment-related,werereported.Frequenciesreportedareasfollows:Common

1/100and <

1/10,Uncommon 1/1,000and<1/100.

Table1

Thefollowingtreatment-relatedadverseeventsinTable2werereportedduringthepost-marketingsurveillance.

Frequencyreported:Veryrare<1/10,000.

MedDRA

SystemOrganClass Frequency UndesirableEffects

GastrointestinalDisorders Uncommon Abdominalcramps,

diarrhoea,nausea,localised

abdominalpain,vomiting

GeneralDisordersand

AdministrationSite

Conditions Uncommon Applicationsitepain,fever,

generalisedpain,localised

edema,

InfectionsandInfestations Common Vaginalcandidiasis

Uncommon Fungalinfection,

pyelonephritis,

vaginitis/vaginalinfection,

candidias(body)

Muscoskeletaland

ConnectiveTissueDisorders Uncommon Flankpain

NervousSystemDisorders Uncommon Headache

RenalandUrinaryDisorders Uncommon Dysuria

ReproductiveSystemand

BreastDisorders Common Vulvovaginaldisorder,

vaginalpain,

Uncommon Menstrualdisorder,vaginal

discharge

SkinandSubcutaneousTissue

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ThefollowingmedicallysignificantadverseeventsinTable3werereportedduringtherapywithsystemicformulations

ofclindamycin.Frequencyreported:Veryrare<1/10,000.

Table3

4.9Overdose

Therearenoreportsofoverdosewithclindamycinvaginalovule.

VaginallyappliedclindamycinphosphatecontainedinDalacinvaginalovulescanbeabsorbedinsufficientamountsto

producesystemiceffects.

Intheeventofoverdosage,generalsymptomaticandsupportivemeasuresareindicatedasrequired.

Accidentaloralintakecanleadtoeffectscomparablewiththoseoftherapeuticconcentrationsoforallyadministered

clindamycin.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCCode:J01FF01

MechanismifAction:Clindamycinisalincosamideantibioticwhichinhibitsbacterialproteinsynthesisatthelevelof

MedDRA

SystemOrganClass Frequency UndesirableEffects

ReproductiveSystemand

BreastDisorders Veryrare Vulvovaginalirritation,

Vaginalpain

MedDRA

SystemOrganClass Frequency UndesirableEffects

BloodandLymphaticSystem

Disorders Veryrare Transientneutropenia

(leukopenia),

agranulocytosis,

thrombocytopenia

ImmuneSystemDisorders Veryrare anaphylactoidreactions

HepatobiliaryDisorders Veryrare Jaundice

SkinandSubcutaneous

TissueDisorders Veryrare erythemamultiforme,some

resemblingStevens-Johnson

syndrome,toxicepidermal

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peptidechaininitiation.Althoughclindamycinphosphateisinactiveinvitro,rapidinvivohydrolysisconvertsthis

compoundtotheantibacteriallyactiveclindamycin.

Microbiology:Standardmethodologyforthesusceptibilitytestingofthepotentialbacterialvaginosispathogens,

Gardnerellavaginalis,Mobiluncusspp.,orMycoplasmahominis,hasnotbeendefined.

Nonetheless,clindamycinisanantimicrobialagentactiveinvitroagainstmoststrainsofthefollowingorganismsthat

havebeenreportedtobeassociatedwithbacterialvaginosis:

Bacteroidesspp.

Gardnerellavaginalis

Mobiluncusspp.

Mycoplasmahominis

Peptostreptococcusspp.

AlltheseorganismsaresensitivetoClindamycin,asassessedbytheirMIC90s(MinimallyInhibitoryConcentrationto

inhibit90%ofthestrains).Nogeographicalortemporalvariationshavebeenreported.

SusceptibilityofVaginalBacteriaassociatedwithBacterialVaginosisto

Clindamycin

Crossresistancehasbeendemonstratedbetweenclindamycinandlincomycin.

Antagonismhasbeendemonstratedbetweenclindamycinanderythromycininvitro.Theclinicalsignificanceof

thisinteractionisunknown.

5.2Pharmacokineticproperties

Systemicabsorptionofclindamycinwasestimatedfollowingaonce-a-dayintravaginaldoseofoneclindamycin

phosphatevaginalsuppository(equivalentto100mgclindamycin)administeredto11healthyfemalevolunteersfor3

days.Approximately30%(range6%to70%)oftheadministereddosewasabsorbedsystemicallyonday3ofdosing

basedonareaundertheconcentration-timecurve(AUC).Systemicabsorptionwasestimatedusingasubtherapeutic

100mgintravenousdoseofclindamycinphosphateasacomparatorinthesamevolunteersaswellasa100mgdoseof

clindamycinphosphatevaginalcream.ThemeanAUCfollowingday3ofdosingwiththesuppositorywas3.2

µghr/mL(range0.42to11µghr/mL).TheC

observedonday3ofdosingwiththesuppositoryaveraged0.27

µg/mL(range0.03to0.67µg/mL)andwasobservedabout5hoursafterdosing(range1to10hours).Incontrast,the

AUCandC

afterthesingleintravenousdoseaveraged11µghr/mL(range5.1to26µghr/mL)and3.7µg/mL

(range2.4to5.0µg/mL),respectively.Themeanapparenteliminationhalf-lifeafterdosingwiththesuppositorywas

Mircoorganism MIC

50 MIC

90 %

Susceptible

Bacteroidesbivius

Bacteroidesdisiens

Bacteroidesmelaninogenicus

Bacteroidesasaccharolyticus

Peptostreptococcusanaerobius

Peptostreptotoccus

asaccharolyticus

Mobiluncuscurtisii

Mobiluncusmulieris

<0.015

<0.015

<0.015

0.03

<0.015

0.125

0.03

0.031

0.031

<0.015

0.25

0.25

0.125

0.06

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Theresultsfromthisstudyshowedthatsystemicexposuretoclindamycin(basedonAUC)fromthesuppositorywas,

onaverage,three-foldlowerthanthatfromasinglesubtherapeutic100mgintravenousdoseofclindamycin.Relative

toacomparabledoseofclindamycinvaginalcream,systemicabsorptionoftheovulewasapproximately7-foldgreater

thanthatfollowingdosingofthevaginalcreamwithaveragevaluesofAUCandCmaxof0.4µg.hr/mL(range0.13to

1.16µg.hr/mLand0.02µg/mL(range0.01to0.07µg/mL)respectivelyfortheclindamycinvaginalcream.Inaddition,

therecommendeddailyandtotaldosesofintravaginalclindamycinsuppositoryarefarlowerthanthosetypically

administeredinoralorparenteralclindamycintherapy(100mgofclindamycinperdayfor3daysequivalenttoabout

30mgabsorbedperdayfromtheovulerelativeto600to2700mg/dayforupto10daysormore,orallyor

parenterally).Theoverallsystemicexposuretoclindamycinfromclindamycinvaginalovulesissubstantiallylower

thanthesystemicexposurefromtherapeuticdosesoforalclindamycinhydrochloride(two-foldto20-foldlower)or

parenteralclindamycinphosphate(40-foldto50-foldlower).

5.3Preclinicalsafetydata

Toxicology:Clindamycinphosphate(5mg)suspendedinahardfat(asuppositorybaseconsistingofamixtureof

glyceridesofsaturatedfattyacids)suppositorywastestedintheovariectomizedratmodel.Theresultsindicatedthat

theformulationcausedmildvaginalirritationduringtreatmentthatquicklyreversedaftertreatmentwasstopped.

Carcinogenicity/Mutagenicity:Long-termstudieshavenotbeenperformedinanimalswithclindamycintoevaluate

carcinogenic potential. Micronucleus and <?xml:namespace prefix = st1 ns = "urn:schemas-microsoft-

com:office:smarttags"/><st1:Cityw:st="on"><st1:placew:st="on">Ames</st1:place></st1:City>genotoxicitytests

performedintheratwerenegative.

Reproduction:Fertilitystudiesinratstreatedorallywithupto300mg/kg/dayofclindamycin(29timesthehuman

exposurebasedonmg/m²)revealednoeffectsonfertilityormatingability.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

HardFat

6.2Incompatibilities

Noinformationisavailableonconcomitantusewithotherintravaginalproducts.Theuseoflatexcondomsisnot

recommendedduringtherapywithDalacinVaginalOvules.TherearenodataavailableregardingtheeffectofDalacin

VaginalOvuleonlatexdiaphragms.

6.3Shelflife

Threeyears

6.4Specialprecautionsforstorage

Storebelow25 o

6.5Natureandcontentsofcontainer

Threeovulesaresuppliedinindividuallysealedlaminatedfoilpouches(strip)packedinabox,withorwithouta

plasticapplicator.

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Insertionwithouttheapplicator

Removetheovulefromthefoilpouch.

Lieonyourbackwithyourkneesdrawnuptoyourchest.

Inserttheovuleintothevaginawiththetipofyourthird(middle)fingerasfaraspossiblewithoutcausing

discomfort.

Whereanapplicatorissuppliedthepatientmaychoosetousethistoassistwithovuleinsertion:-

Insertionwiththeapplicator

AplasticapplicatorisprovidedwitheachpackageofDalacinVaginalOvules.Itisdesignedtoallowproper

vaginaladministrationofthe

ovule.

Removetheovulefromthefoilpouch.

Placetheflatendoftheovuleintotheopenendoftheapplicator.

Lieonyourbackwithyourkneesdrawnuptowardyourchest.

Holdtheapplicatorbytheribbedendofthebarrelandgentlyinsertitintothevaginaasfaraspossible

withoutcausingdiscomfort.

Slowlypresstheplungertoreleasetheovuleintothevagina.

Withdrawtheapplicatorfromthevagina.

Aftereachuse,washtheapplicatorwithlukewarm,soapywateranddrythoroughly.

7MARKETINGAUTHORISATIONHOLDER

PharmaciaLtd

RamsgateRoad

Sandwich

Kent

CT139NJ

8MARKETINGAUTHORISATIONNUMBER

PA16/44/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:21stDecember1998

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10DATEOFREVISIONOFTHETEXT

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