DALACIN C PHOSPHATE 4ML

Main information

  • Trade name:
  • DALACIN C PHOSPHATE 4ML
  • Dosage:
  • 150
  • Pharmaceutical form:
  • Concentrate for Soln for Inf
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DALACIN C PHOSPHATE 4ML
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0936/074/002
  • Authorization date:
  • 22-05-2001
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DalacinCPhosphate150mg/mlConcentrateforSolutionforInfusionorSolutionforInjection,4ml

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachmlofsolutioncontainsclindamycinphosphateequivalentto150mgclindamycingiving600mgclindamycinper

ampoule.

Excipient:

Benzylalcohol 9mg/ml

Forfulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Concentrateforsolutionforinfusionorsolutionforinjection

Clear,colourless,sterilesolutionwithapHof5.5-7.0

4CLINICALPARTICULARS

4.1TherapeuticIndications

Forthemanagementofseriousinfectionsduetoorganismssusceptibletothisanti-infective.

4.2Posologyandmethodofadministration

Parenteral(IMorIVAdministration).DalacinCPhosphatemustbedilutedpriortoIVadministrationandshouldbe

infusedoveratleast10-60minutes.

Adultsincludingtheelderly:

TheusualdailyadultdosageofDalacinCPhosphateforinfectionsoftheintra-abdomialarea,femalepelvis,andother

complicatedorseriousinfectionsis1800-2700mggivenin2,3,or4equaldoses.Lesscomplicatedinfectionsdueto

moresusceptiblemicroorganismsmayrespondtolowerdosessuchas1200-1800mg/dayadministeredin3or4equal

doses.Dosesofupto4800mgdailyhavebeenusedsuccessfully.

SingleIMinjectionsofgreaterthan600mgarenotrecommendednorisadministrationofmorethan1.2ginasingle

one-hourinfusion.

Alternatively,thedrugmaybeadministeredintheformofasinglerapidinfusionofthefirstdosefollowedby

continuousIVInfusion.

Children(over1monthofage):Seriousinfections:15-25mg/kg/dayinthreeorfourequaldoses.

Moresevereinfections:25-40mg/kg/dayinthreeorfourequaldoses.Insevereinfectionsitisrecommendedthat

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4.3Contraindications

Useinpatientshypersensitivetolincomycinorclindamycin.

Useinpatientswithdiarrhoeaorintestinalinflammatorydisease.

Useconcurrentlywitherythromycin.

4.4Specialwarningsandprecautionsforuse

DalacinCPhosphateshouldonlybeusedinthetreatmentofseriousinfections.Inconsideringtheuseofclindamycin,

thepractitionershouldbearinmindthetypeofinfectionandthepotentialhazardofthediarrhoeawhichmaydevelop,

sincecasesofcolitishavebeenreportedduring,oreventwoorthreeweeksfollowing,theadministrationof

clindamycin.

Studiesindicateatoxin(s)producedbyclostridia(especiallyClostridiumdifficile)istheprincipaldirectcauseofantibiotic-

associatedcolitis.

Colitisisadiseasewhichhasaclinicalspectrumfrommild,waterydiarrhoeatosevere,persistentdiarrhoea,leucocytosis,

fever,severeabdominalcramps,whichmaybeassociatedwiththepassageofbloodandmucus.Ifallowedtoprogress,it

mayproduceperitonitis,shockandtoxicmegacolon.Thismaybefatal.

Theappearanceofmarkeddiarrhoeashouldberegardedasanindicationthattheproductshouldbediscontinued

immediately.Thediseaseislikelytofollowamoreseverecourseinolderpatientsorpatientswhoaredebilitated.

Diagnosisisusuallymadebyrecognitionoftheclinicalsymptoms,butcanbesubstantiatedbyendoscopicdemonstration

ofpseudomembranouscolitis.ThepresenceofthediseasemaybefurtherconfirmedbycultureofthestoolforClostridia

difficileonselectivemediaandassayofthestoolspecimenforthetoxin(s)ofC.difficile.

Clostridiumdifficileassociateddiarrhoea(CDAD)hasbeenreportedwiththeuseofnearlyallantibacterialagents,

includingclindamycin,andmayrangeinseverityfrommilddiarrhoeatofatalcolitis.Treatmentwithantibacterial

agentsaltersthenormalfloraofthecolonleadingtoovergrowthofCdifficile.[134-147]

C.difficileproducestoxinsAandBwhichcontributetothedevelopmentofCDAD.

HypertoxinproducingstrainsofC.difficilecauseincreasedmorbidityandmortality,astheseinfectionscanbe

refractorytoantimicrobialtherapyandmayrequirecolectomy.CDADmustbeconsideredinallpatientswhopresent

withdiarrhoeafollowingantibioticuse.CarefulmedicalhistoryisnecessarysinceCDADhasbeenreportedtooccur

overtwomonthsaftertheadministrationofantibacterialagents.[134-147]

Cautionshouldbeusedwhenprescribingclindamycintoindividualswithahistoryofgastro-intestinaldisease,

especiallycolitis.

Regularmonitoringofliverfunction,renalfunctionandhaematologyshouldbecarriedoutduringprolongeduseofthe

drug,andininfantsundertheageofoneyear.Safetyandappropriatedosageininfantslessthanonemontholdhavenot

beenestablished.

ProlongedadministrationofDalacinCPhosphate,aswithanyanti-infective,mayresultinsuper-infectiondueto

organismsresistanttoDalacinCPhosphate.TheuseofDalacinCPhosphatemayalsoresultintheovergrowthofnon-

susceptibleorganismsparticularlyyeasts.

Thedrugshouldbeusedwithcautioninpatientswiththeatopicsyndrome,particularlywithasthma.

SinceDalacinCPhosphatedoesnotdiffuseadequatelyintocerebrospinalfluid,thedrugshouldnotbeusedinthe

treatmentofmeningitis.

Thisproductcontainsbenzylalcohol.Benzylalcoholhasbeenreportedtobeassociatedwithafatal“gaspingsyndrome”

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

1.DalacinCPhosphatehasbeenshowntohaveneuromuscularblockingpropertiesthatmayenhancetheactionof

otherneuromuscularblockingagents.Itshouldthereforebeusedwithcautioninpatientsreceivingsuchagents.

2.Cross-resistancecanbedemonstratedwithlincomycinand,particularlyinthecaseofstaphylococci,with

erythromycin.

3.In-vitrocompatibilitystudiesmonitoredfor24hoursatroomtemperatureusingaconcentrationnogreaterthan6

mg/mlhavedemonstratednoinactivationorphysicalincompatibilitywiththeuseofDalacinCPhosphateinIV.

solutionscontainingsodiumchloride,glucoseorpotassiumusuallyusedclinically.

4.ThefollowingdrugsarephysicallyincompatiblewithDalacinCPhosphate:ampicillin,phenytoinsodium,

barbiturates,aminophylline,calciumgluconate,magnesiumsulphate,ceftriaxonesodium,diphenylhydantoin,

idarubicinhydrochloride,andranitidinehydrochloride.SolutionsofclindamycinsaltshavealowpHand

incompatibilitymayreasonablybeexpectedwithalkalinepreparationsorwithdrugsunstableatlowpH.

4.6Fertility,pregnancyandlactation

Assafetyforuseinpregnancyorlactationhasnotbeenestablished,DalacinCPhosphateshouldbeusedonlyif

consideredessentialbythephysician.DalacinCPhosphatecrossestheplacentainhumans.Aftermultipledoses,

amnioticfluidconcentrationswereapproximately30%ofmaternalbloodconcentrations.

CautionshouldbeexercisedwhenDalacinCPhosphateisadministeredtoanursingmother.DalacinCPhosphatehas

beenreportedtoappearinhumanbreastmilkinrangesfrom0.7to3.8µg/mLItisunlikelythatanursinginfantcan

absorbasignificantamountofDalacinCPhosphatefromitsgastro-intestinaltract.

4.7Effectsonabilitytodriveandusemachines

Noneknown.

4.8Undesirableeffects

Gastro-intestinaltract:Nausea,vomitingabdominalpainanddiarrhoea.Theappearanceofmarkeddiarrhoeashould

beregardedasanindicationthatthisdrugshouldbediscontinuedimmediately.UsuallyC.difficiletoxinhasbeen

shownasthecauseofcolitis.

Haemopoietic:Transientneutropenia(leucopenia),eosinophilia,agranulocytisisandthrombocytopeniahavebeen

reported.NodirectaetiologicrelationshiptoconcurrentDalacinCPhosphatetherapycouldbemadeinanyofthe

foregoing.

Skinandmucousmembranes:Pruritus,vaginitisandrareinstancesofexfoliativeandvesiculobullosdermatitishave

beenreported.

Hypersensitivityreactions:Maculopapularrashandurticariahavebeenobservedduringdrugtherapy.Generalised

mildtomoderatemorbilliform-likeskinrashesarethemostfrequentlyreportedreactions.Rareinstancesoferythema

multiform,someresemblingStevens-Johnsonsyndrome,havebeenassociatedwithDalacinCPhosphate.Afewcases

ofanaphylactoidreactionshavebeenreported.

Hepatic:JaundiceandabnormalitiesinliverfunctiontestshavebeenobservedduringDalacinCPhosphatetherapy.

Nervoussystem:Dysgeusia.

Cardiovascular:Rareinstancesofcardiopulmonaryarrestandhypotensionhavebeenreportedfollowingtoorapid

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Localreactions:Localirritation,pain,abscessformationhavebeenseenwithI.M.injection.Thromobophlebitishas

beenreportedwithI.V.injection.ThesereactionscanbeminimisedbydeepI.M.injectionandavoidingtheuseofan

indwellingcatheter.

4.9Overdose

Incasesofoverdosagenospecifictreatmentisindicated.

Theserumbiologicalhalf-lifeofDalacinCPhosphateis2.4hours.Clindamycincannotreadilyberemovedfromthe

bloodbyhaemodialysisorperitonealdialysis.Ifanallergicreactionoccurs,therapyshouldbewiththeusual

emergencytreatments,includingcorticosteroids,adrenalineandanti-histamines.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ClindamycinisalincosamideantibioticwithaprimarybacteriostaticactionagainstGram-positiveaerobesandawide

rangeofanaerobicbacteria.Lincosamidessuchasclindamycinbindtothe50Ssubunitofthebacterialribosome

similarlytomacrolidessuchaserythromycinandinhibittheearlystagesofproteinsynthesis.TheactionofDalacinC

Phosphateispredominantlybacteriostaticalthoughhighconcentrationsmaybeslowlybactericidalagainstsensitive

strains.

DalacinCPhosphatehasbeenshowntohaveinvitroactivityagainstisolatesofthefollowingorganisms:

Aerobicgram-positivecocci,including:

Staphylococcusaureus;

Staphylococcusepidermidis(penicillinaseandnonpenicillinaseproducingstrains);

Whentestedbyinvitromethodssomestaphylococcalstrainsoriginallyresistanttoerythromycinrapidlydevelop

resistancetoDalacinCPhosphate;Streptococci(exceptStreptococcusfaecalis);

Pneumococci

Anaerobicgram-negativebacilli,including:

Bacteroidesspecies(includingBacteroidesfragilisgroupandBacteroidesmelaninogenicusgroup)

Fusobacteriumspecies.

Anaerobicgram-positivenon-sporeformingbacilli,including:

Propionibacterium

Eubacterium

Actinomycesspecies

Anaerobicandmicroaerophilicgram-positivecocci,including:

Peptococcusspecies;

Peptostreptococcusspecies;

Microaerophilicstreptococci.

Clostridia:

Clostridiaaremostresistantthanmostanaerobestoclindamycin.MostClostridiumpefringensaresusceptible,but

otherspecies,e.g.ClostridiumsporogenesandClostridiumteriumarefrequentlyresistanttoclindamycin.

MostGram-negativeaerobicbacteria,includingtheEnterobacteriaceae,areresistanttoclindamycin.Clindamycin

demonstratescross-resistancewithlincomycin.Whentestedbyinvitromethods,somestaphylococcalstrains

originallyresistanttoerythromycinrapidlydevelopedresistancetoclindamycin.Themechanismsforresistanceare

thesameasforerythromycin,namelymethylationoftheribosomalbindingsite,chromosomalmutationofthe

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5.2Pharmacokineticproperties

Generalcharacteristicsofactivesubstance

Followingparenteraladministration,thebiologicallyinactiveclindamycinphosphateishydrolysedtoclindamycin.

Whentheequivalentof300mgofDalacinCPhosphateisinjectedintramuscularly,ameanpeakplasmaconcentration

of6microgram/mlisachievedwithinthreehours;600mggivesapeakconcentrationof9microgram/ml.Inchildren,

peakconcentrationmaybereachedwithinonehour.Whenthesamedosesareinfusedintravenously,peak

concentrationsof7and10microgramspermlrespectivelyareachievedbytheendofinfusion.

Clindamyciniswidelydistributedinbodyfluidsandtissuesincludingbone,butitdoesnotreachthecerebrospinal

fluidinsignificantconcentrations.Itdiffusesacrosstheplacentaintothefetalcirculationandappearsinbreastmilk.

Highconcentrationsoccurinbile.

Itaccumulatesinleucocytesandmacrophages.Over90%ofclindamycininthecirculationisboundtoplasma

proteins.Thehalf-lifeis2to3hours,althoughthismaybeprolongedinpre-termneonatesandpatientswithsevere

renalimpairment.

Clindamycinundergoesmetabolism,totheactiveN-demethylandsulphoxidemetabolitesandalsosomeinactive

metabolites.About10%ofthedrugisexcretedintheurineasactivedrugormetabolitesandabout4%inthefaeces;

theremainderisexcretedasinactivemetabolites.Excretionisslowandtakesplaceoverseveraldays.Itisnot

effectivelyremovedfromthebloodbydialysis.

5.3Preclinicalsafetydata

Carcinogenesis:

LongtermstudiesinanimalshavenotbeenperformedwithDalacinCPhosphatetoevaluatecarcinogenicpotential.

Mutagenesis:

GenotoxicitytestsperformedincludedaratmicronucleustestandanAmesSalmonellareversiontest.Bothtestswere

negative.

ImpairmentofFertility:

Fertilitystudiesinratstreatedorallywithupto300mg/kg/day(approximately1.1timesthehighestrecommended

adulthumandosebasedonmg/m 2

)revealednoeffectsonfertilityormatingability.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Benzylalcohol

Disodiumedetate

Sterilisedwaterforinjections

Sodiumhydroxide(forpH-adjustment)

Dilutehydrochloricacid(forpH-adjustment)

6.2Incompatibilities

SolutionsofclindamycinsaltshavealowpHandincompatibilitiesmayreasonablybeexpectedwithalkaline

preparationsordrugsunstableatlowpH.Incompatibilityhasbeenreportedwith:ampicillinsodium,aminophylline,

barbiturates,calciumgluconate,ceftriaxonesodium,ciprofloxacin,idarubicinhydrochloride,magnesiumsulphate,

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6.3Shelflife

Undiluted:2years.Usedilutedsolutionimmediately.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.Donotrefrigerateorfreeze.

6.5Natureandcontentsofcontainer

Type1flint,colourlessglassampoulecontaining4mlsterile,aqueoussolution.5ampoulespackedinacardboard

carton,togetherwithaleaflet.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

DalacinCPhosphatehasbeenknowntobephysicallyandchemicallycompatibleforatleast24hoursindextrose5%,

waterandsodiumchlorideinjectionsolutionscontainingthefollowingantibioticsinusuallyadministered

concentrations:

Amikacinsulphate,aztreonam,cefamandolenafate,cephazolinsodium,cefotaximesodium,cefoxitinsodium,

ceftazidimesodium,ceftizoximesodium,gentamicinsulphate,netilmicinsulphate,piperacillinandtobramycin.

Thecompatibilityanddurationofstabilityofdrugadmixtureswillvarydependinguponconcentrationandother

conditions.

DalacinCPhosphateisforsingledoseuseonlyandanyunusedcontentsshouldbediscarded.

7MARKETINGAUTHORISATIONHOLDER

PharmaciaIreland

9Riverwalk

NationalDigitalPark

CitywestBusinessCampus

Dublin24

8MARKETINGAUTHORISATIONNUMBER

PA0936/074/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:09September1976

Dateoflastrenewal: 22May2006

10DATEOFREVISIONOFTHETEXT

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