DALACIN C PHOSPHATE 2ML

Main information

  • Trade name:
  • DALACIN C PHOSPHATE 2ML
  • Dosage:
  • 150
  • Pharmaceutical form:
  • Concentrate for Soln for Inf
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DALACIN C PHOSPHATE 2ML
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0936/074/001
  • Authorization date:
  • 22-05-2001
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DalacinCPhosphate150mg/mlConcentrateforSolutionforInfusionorSolutionforInjection,2ml

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachmlofsolutioncontainsclindamycinphosphateequivalentto150mgclindamycingiving300mgclindamycinper

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).DalacinCPhosphatemustbedilutedpriortoIV.administrationandshouldbe

infusedoveratleast10-60minutes.

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

childrenbegivennolessthan300mg/dayregardlessofbodyweight.

Neonates(under1monthofage):DalacinCPhosphate(IMorIVadministration):15-20mg/kg/dayin3or4equal

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2106783 page number: 1

DosageinElderly:PharmacokineticstudieswithDalacinCPhosphatehaveshownnoclinicallyimportantdifferences

betweenyounganselderlysubjectswithnormalhepaticfunctionandnormal(age-adjusted)renalfunctionafteroralor

intravenousadministration.Therefore,dosageadjustmentsarenotnecessaryintheelderlywithnormalhepaticfunction

andnormal(age-adjusted)renalfunction(seeSection5.2PharmacokineticProperties).

DosageinRenalImpairment:DalacinCPhosphatedosagemodificationisnotnecessaryinpatientswithrenal

insufficiency.

DosageinHepaticImpairment:DalacinCPhosphatedosagemodificationisnotnecessaryinpatientswithhepatic

insufficiency.

4.3Contraindications

Useinpatientshypersensitivetolincomycinorclindamycin.

Useinpatientswithdiarrhoeaorintestinalinflammatorydisease.

Useconcurrentlywitherythromycin.

4.4Specialwarningsandprecautionsforuse

DalacinCPhosphateshouldonlybeusedinthetreatmentofseriousinfections.InconsideringtheuseofDalacinC

Phosphate,thepractitionershouldbearinmindthetypeofinfectionandthepotentialhazardofthediarrhoeawhichmay

develop,sincecasesofcolitishavebeenreportedduring,oreventwoorthreeweeksfollowing,theadministrationof

DalacinCPhosphate.

Studiesindicateatoxin(s)producedbyclostridia(especiallyClostridiumdifficile)istheprincipaldirectcauseofantibiotic-

associatedcolitis.Colitisisadiseasewhichhasaclinicalspectrumfrommild,waterydiarrhoeatosevere,persistent

diarrhoea,leucocytosis,fever,severeabdominalcramps,whichmaybeassociatedwiththepassageofbloodandmucus.If

allowedtoprogress,itmayproduceperitonitis,shockandtoxicmegacolon.Thismaybefatal.

Theappearanceofmarkeddiarrhoeashouldberegardedasanindicationthattheproductshouldbediscontinued

immediately.Thediseaseislikelytofollowamoreseverecourseinolderpatientsorpatientswhoaredebilitated.

Diagnosisisusuallymadebyrecognitionoftheclinicalsymptoms,butcanbesubstantiatedbyendoscopicdemonstration

ofpseudomembranouscolitis.ThepresenceofthediseasemaybefurtherconfirmedbycultureofthestoolforClostridia

difficileonselectivemediaandassayofthestoolspecimenforthetoxin(s)ofC.Difficile.

Clostridiumdifficileassociateddiarrhoea(CDAD)hasbeenreportedwiththeuseofnearlyallantibacterialagents,

includingclindamycin,andmayrangeinseverityfrommilddiarrhoeatofatalcolitis.Treatmentwithantibacterial

agentsaltersthenormalfloraofthecolonleadingtoovergrowthofC.difficile.[134-147]

C.difficileproducestoxinsAndBwhichcontributetothedevelopmentofCDAD.

HypertoxinproducingstrainsofC.difficilecauseincreasedmorbidityandmortality,astheseinfectionscanbe

refractorytoantimicrobialtherapyandmayrequirecolectomy.CDADmustbeconsideredinallpatientswhopresent

withdiarrhoeafollowingantibioticuse,CarefulmedicalhistoryisnecessarysinceCDADhasbeenreportedtooccur

overtwomonthsaftertheadministrationofantibacterialagents.[134-147]

CautionshouldbeusedwhenprescribingDalacinCPhosphatetoindividualswithahistoryofgastro-intestinaldisease,

especiallycolitis.

Regularmonitoringofliverfunction,renalfunctionandhaematologyshouldbecarriedoutduringprolongeduseofthe

drug,andininfantsundertheageofoneyear.Safetyandappropriatedosageininfantslessthanonemontholdhavenot

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2106783 page number: 2

ProlongedadministrationofDalacinCPhosphate,aswithanyanti-infective,mayresultinsuper-infectiondueto

organismsresistanttoDalacinCPhosphate.TheuseofDalacinCPhosphatemayalsoresultintheovergrowthofnon-

susceptibleorganismsparticularlyyeasts.

Thedrugshouldbeusedwithcautioninpatientswiththeatopicsyndrome,particularlywithasthma.

SinceDalacinCPhosphatedoesnotdiffuseadequatelyintocerebrospinalfluid,thedrugshouldnotbeusedinthe

treatmentofmeningitis.

Thisproductcontainsbenzylalcohol.Benzylalcoholhasbeenreportedtobeassociatedwithafatal“gaspingsyndrome”

inprematureinfants.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

1.DalacinCPhosphatehasbeenshowntohaveneuromuscularblockingpropertiesthatmayenhancetheactionof

otherneuromuscularblockingagents.Itshouldthereforebeusedwithcautioninpatientsreceivingsuchagents.

2.Cross-resistancecanbedemonstratedwithlincomycinand,particularlyinthecaseofstaphylococci,with

erythromycin.

In-vitrocompatibilitystudiesmonitoredfor24hoursatroomtemperatureusingaconcentrationnogreaterthan6

mg/mlhavedemonstratednoinactivationorphysicalincompatibilitywiththeuseofDalacinCPhosphateinIV

solutionscontainingsodiumchloride,glucoseorpotassiumusuallyusedclinically.

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/mL.Itisunlikelythatanursinginfantcan

absorbasignificantamountofDalacinCPhosphatefromitsgastro-intestinaltract.

4.7Effectsonabilitytodriveandusemachines

Noneknown.

4.8Undesirableeffects

Gastro-intestinaltract:Nausea,vomitingabdominalpainanddiarrhoea.Theappearanceofmarkeddiarrhoeashould

beregardedasanindicationthatthisdrugshouldbediscontinuedimmediately.UsuallyC.difficiletoxinhasbeen

shownasthecauseofcolitis.

Haemopoietic:Tansientneutropenia(leucopenia),eosinophilia,agranulocytisisandthrombocytopeniahavebeen

reported.NodirectaetiologicrelationshiptoconcurrentDalacinCPhosphatetherapycouldbemadeinanyofthe

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2106783 page number: 3

Skinandmucousmembranes:Pruritus,vaginitisandrareinstancesofexfoliativeandvesiculobullosdermatitishave

beenreported.

Hypersensitivityreactions:Maculopapularrashandurticariahavebeenobservedduringdrugtherapy.Generalised

mildtomoderatemorbilliform-likeskinrashesarethemostfrequentlyreportedreactions.Rareinstancesoferythema

multiform,someresemblingStevens-Johnsonsyndrome,havebeenassociatedwithDalacinCPhosphate.Afewcases

ofanaphylactoidreactionshavebeenreported.

Hepatic:JaundiceandabnormalitiesinliverfunctiontestshavebeenobservedduringDalacinCPhosphatetherapy.

Nervoussystem:Dysgeusia.

Cardiovascular:Rareinstancesofcardiopulmonaryarrestandhypotensionhavebeenreportedfollowingtoorapid

intravenousadministration.

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

beenreportedwithI.V.injection.ThesereactionscanbeminimisedbydeepI.M.injectionandavoidingtheuseofan

indwellingcatheter.

4.9Overdose

Incasesofoverdosagenospecifictreatmentisindicated.

Theserumbiologicalhalf-lifeofclindamycinis2.4hours.DalacinCPhosphatecannotreadilyberemovedfromthe

bloodbyhaemodialysisorperitonealdialysis.

Ifanallergicreactionoccurs,therapyshouldbewiththeusualemergencytreatments,includingcorticosteroids,

adrenalineandantihistamines.

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)

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2106783 page number: 4

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

ribosomalproteinandinafewstaphylococcalisolatesenzymicinactivationbyaplasmid-mediatedadenyltransferase.

5.2Pharmacokineticproperties

Generalcharacteristicsofactivesubstance

Followingparenteraladministration,thebiologicallyinactiveclindamycinphosphateishydrolysedtoclindamycin.

Whentheequivalentof300mgofDalacinCPhosphateisinjectedintramuscularly,ameanpeakplasmaconcentration

of6microgram/mlisachievedwithinthreehours;600mggivesapeakconcentrationof9microgram/ml.Inchildren,

peakconcentrationmaybereachedwithinonehour.Whenthesamedosesareinfusedintravenously,peak

concentrationsof7and10microgramspermlrespectivelyareachievedbytheendofinfusion.

Clindamyciniswidelydistributedinbodyfluidsandtissuesincludingbone,butitdoesnotreachthecerebrospinal

fluidinsignificantconcentrations.Itdiffusesacrosstheplacentaintothefetalcirculationandappearsinbreastmilk.

Highconcentrationsoccurinbile.Itaccumulatesinleucocytesandmacrophages.Over90%ofclindamycininthe

circulationisboundtoplasmaproteins.Thehalf-lifeis2to3hours,althoughthismaybeprolongedinpre-term

neonatesandpatientswithsevererenalimpairment.

Clindamycinundergoesmetabolism,totheactiveN-demethylandsulphoxidemetabolitesandalsosomeinactive

metabolites.About10%ofthedrugisexcretedintheurineasactivedrugormetabolitesandabout4%inthefaeces;

theremainderisexcretedasinactivemetabolites.Excretionisslowandtakesplaceoverseveraldays.Itisnot

effectivelyremovedfromthebloodbydialysis.

5.3Preclinicalsafetydata

Carcinogenesis:

LongtermstudiesinanimalshavenotbeenperformedwithDalacinCPhosphatetoevaluatecarcinogenicpotential.

Mutagenesis:

GenotoxicitytestsperformedincludedaratmicronucleustestandanAmesSalmonellareversiontest.Bothtestswere

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2106783 page number: 5

ImpairmentofFertility:

Fertilitystudiesinratstreatedorallywithupto300mg/kg/day(approximately1.1timesthehighestrecommended

adulthumandosebasedonmg/m2)revealednoeffectsonfertilityormatingability.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Benzylalcohol

Disodiumedetate

Sterilisedwaterforinjections

Sodiumhydroxide(forpH-adjustment)

Dilutehydrochloricacid(forpH-adjustment)

6.2Incompatibilities

SolutionsofclindamycinsaltshavealowpHandincompatibilitiesmayreasonablybeexpectedwithalkaline

preparationsordrugsunstableatlowpH.Incompatibilityhasbeenreportedwith:ampicillinsodium,aminophylline,

barbiturates,calciumgluconate,ceftriaxonesodium,idarubicinhydrochloride,magnesiumsulphate,phenytoinsodium

andranitidinehydrochloride.

6.3Shelflife

Undiluted:2years.Usedilutedsolutionimmediately.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.Donotrefrigerateorfreeze.

6.5Natureandcontentsofcontainer

Type1flintcolourlessglassampoulecontaining2mlsterile,aqueoussolution.5ampoulespackedinacardboard

carton,togetherwithaleaflet.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

DalacinCPhosphatehasbeenknowntobephysicallyandchemicallycompatibleforatleast24hoursindextrose5%,

waterandsodiumchlorideinjectionsolutionscontainingthefollowingantibioticsinusuallyadministered

concentrations:amikacinsulphate,aztreonam,cefamandolenafate,cephazolinsodium,cefotaximesodium,cefoxitin

sodium,ceftazidimesodium,ceftizoximesodium,gentamicinsulphate,netilmicinsulphate,piperacillinand

tobramycin.

Thecompatibilityanddurationofstabilityofdrugadmixtureswillvarydependinguponconcentrationandother

conditions.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2106783 page number: 6

7MARKETINGAUTHORISATIONHOLDER

PharmaciaIreland

9Riverwalk

NationalDigitalPark

CitywestBusinessCampus

Dublin24

8MARKETINGAUTHORISATIONNUMBER

PA0936/074/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 09September1976

Dateoflastrenewal: 22May2006

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2106783 page number: 7