CLINDAMYCIN

Main information

  • Trade name:
  • CLINDAMYCIN Capsule 150mg Milligram
  • Dosage:
  • 150mg Milligram
  • Pharmaceutical form:
  • Capsule
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CLINDAMYCIN Capsule 150mg Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0408/060/001
  • Authorization date:
  • 03-03-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Clindamycin150mgCapsules

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachcapsulecontainsclindamycinhydrochlorideequivalentto150mgclindamycin.

Forexcipients,see6.1.

3PHARMACEUTICALFORM

Capsule,hard

Turquoiseblueopaque/green,hardgelatincapsuleprintedwith‘R/CLM150’inblackonbothcapandbody.

Thecapsulecontainswhitetooffwhitepowder.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Clindamycinisindicatedwheninfectionscausedbysusceptiblemicro-organismsaresevereandrecurrentandnot

respondingtofirstlineantibioticsandasanalternativetreatmentinthecaseofpenicillin-allergicpatientswith

infectionscausedbyGram-positiveaerobicbacteria.Theinfectionsinclude:

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.2Posologyandmethodofadministration

Oral.

Capsulesshouldbeswallowedwithaglassofwater.

Adults,adolescentsover12yearsofageandtheelderly:

Theusualdoseis150–450mgeverysixhours.

Children:Theusualdoseis3-6mg/kgeverysixhours.Thedosecanbeincreasedordecreaseddependingonthe

severityofinfections(nottoexceedtheadultdose).Doserange8-20mg/kg/dayin3or4divideddoses.

Thedoseandmethodofadministrationisdeterminedbytheseverityandsensitivityofthecausativeorganism(s)and

theconditionofthepatientlikeforallantibiotics,insevereinfections,invitrosensitivitytestsshouldbeconducted.

Alternativeformulationsofclindamycinareavailablefortreatingchildrenforwhomthecapsulesareunsuitableorfor

dosesthatcannotbereachedbythispharmaceuticalform.IncaseofsevereclinicalstatusIVtherapyispreferredto

-Infectionsofrespiratorytract.

-Skinandsofttissueinfections.

-Boneandjointinfections.

-Femalepelvicandgenitalinfections.

-Intra-abdominalinfections.

-Severeinfections(exceptcerebrospinalinfections)causedbyGram-positivemicroorganisms(except

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 31/08/2006 CRN 2027387 page number: 1

IncasesofBeta-Haemolyticstreptococcalinfections,treatmentwithclindamycincapsulesshouldcontinueforatleast

10daystodiminishthelikelihoodofsubsequentrheumaticfeverorglomerulonephritis.

Thedurationoftreatmentdependsontheclinicalresponseofthepatient.However,duetotheriskofseveredisruption

ofthefaecalfloraanditsconsequences(seesections4.4),treatmentshouldbekepttotheminimum.Ifprolonged

therapyisconsideredtobeunavoidable,thepatientshouldbecarefullymonitoredforadverseeffects(seesection4.4).

4.3Contraindications

Knownhypersensitivitytoclindamycinorlincomycinortoanyoftheexcipients.

4.4Specialwarningsandprecautionsforuse

Colitis:Clindamycintherapyhasbeenassociatedwithseverecolitiswhichmaybefatalalsosomesevereandpersistent

casesofdiarrhoeahavebeenreportedduringclindamycintreatmentorafterit.Sometimebloodandmucushavebeen

foundinthefaecesinconnectionwiththediarrhoea,andacutecolitishassometimesresultedfromthediarrhoea.Care

shouldbetakenwhenprescribingclindamycintoapatientwhohasatendencytowardsgastrointestinalillnesses,in

particularcolitis.Drugswhichcauseintestinalblockshouldbeavoided.

ThemostcommonlyimplicatedcauseisanovergrowthoftoxinproducingClostridiumdifficileasaresultofdisruption

ofthebowelflorabyclindamycin.Ifmarkeddiarrhoeaoccursduringtherapy,clindamycinshouldbediscontinued

immediatelyandappropriatediagnosticandtherapeuticmeasuresshouldbeinstituted.

Lactoseintolerance:Clindamycincapsulescontaininactiveingredientsincludinglactose.Patientswithrarehereditary

problemsofgalactoseintolerance,theLappLactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethis

medicine.

Hepaticandrenalinsufficiency:Insevererenalimpairment,peakplasmalevelsofclindamycinmaybeuptothree

timesnormalandtheeliminationhalf-lifeisprolonged.Dosereductionand/oranincreaseddoseintervalshouldbe

considered.Inmoderateandseveredegreesofhepaticimpairment,peakplasmalevelsofclindamycinarehigherthan

normalandtheeliminationhalf-lifeisprolonged.Dosereductionand/oranincreaseddoseintervalshouldbe

considered.

Serumclindamycinlevelsshouldbeestimated.Laboratorytestsforrenalandhepaticfunctionshouldbecarriedout

duringprolongedtherapy.

SuperinfectionparticularlywithCandidaispossible.Therefore,itisimportanttoconsiderthisdiagnosisinpatients

whopresentwithdiarrhoeasubsequenttotheadministrationofantibacterialagents.

Clindamycinisnotusedforthetreatmentofsusceptiblestrainscausingmeningealinfectionsasitisnotsufficiently

secretedintothecerebrospinalfluid.

Clindamycinshouldnotbegiveninpatientswithacuteviralinfectionsoftherespiratorytract.

Clindamycinshouldbereservedforseriousinfections,wherelesstoxicantibioticsareconsideredinappropriate.

Hypersensitivity:Clindamycinshouldbeusedwithcautioninpatientssensitivetootherantibiotics.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Antagonismhasbeendemonstratedbetweenclindamycinanderythromycininvitro.Becausethereisapossibilityofa

clinicallysignificantinteraction,clindamycinshouldnotbegivenincombinationwithmacrolidesorstreptogramin

antibacterialagents.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 31/08/2006 CRN 2027387 page number: 2

othersubstancescausingneuromuscularblock.Thereforethedrugshouldbeusedwithcautioninpatientsreceiving

thiskindofmedicationasunexpectedlife-threateningeventsmayoccurinthecourseofsurgery.

Theinfectiousandinflammatorycontext,ageandthegeneralstatusofthepatientappearasriskfactors.Inthese

circumstances,itisdifficulttoknowtherelationshipbetweentheinfectiousdiseaseanditstreatmentintheoccurrence

ofINRdisorders.However,someclassesofantibioticsaremoreimplicated,notablyfluoroquinolones,macrolides,

cyclines,cotrimoxazoleandsomecephalosporins.

4.6Pregnancyandlactation

Pregnancy:

Thedrugcrossestheplacenta.Thesafetyofuseduringpregnancyandfortheneonatehasnotbeenestablished.

Alarger-scalestudywithpregnantwomeninwhichapproximately650neonatesexposedtoclindamycinduringthe

firsttrimesterofpregnancywereexamined,didnotrevealanelevatedabnormalityrate.Inanimalstudiesclindamycin

wasnotteratogenic(seealso5.3preclinicaldata).

Theconcentrationofclindamycininthecordbloodwasfoundtobeapproximately50%ofthematernalserum

concentration.Itisassumedthataconcentrationwithatherapeuticeffectcanbereachedinthefoetus.During

pregnancyClindamycinshouldonlybeusedafterarisk/benefitassessment.

Lactation:

DuringlactationClindamycinshouldonlybeusedafterarisk/benefitassessment.Passageintothebreastmilkhasbeen

demonstrated.Apartfromonesinglecasestudytherehavebeennoreportsofanyundesirableeffectsonbreast-fed

infants.

Diarrhoea,fungusinfectionofthemucousmembranesorotherseriousadverseeventscouldoccurinthebreast-fed

infant,sothatnursingmighthavetobediscontinued.Thepossibilityofsensitisationshouldbeborneinmind.

4.7Effectsonabilitytodriveandusemachines

Thereisnoevidencetosuggestthatclindamycinhasanyeffectontheabilitytodriveand/orusemachines.

4.8Undesirableeffects

Thefollowingundesirableeffectshavebeenobservedduringtreatmentwithclindamycinandothermacrolide

antibioticswiththefollowingfrequencies:verycommon(10%),common(1.0%-<10%),uncommon(0.1%-<

1%),rare(0.01–<0.1%)andveryrare(<0.01%)includingisolatedreports.

Immunesystemdisorders

Uncommon(0.1%-<1%):skinrashandurticaria.Inwiderareasslightormoderateskinrashresemblingmeaslesor

symptomsresemblingStevens-Johnsonsyndromecanoccur.

Rare(0.01–<0.1%):anaphylacticreactions.

Nervoussystemdisorders

Uncommon(0.1%-<1%):Neuromuscularblockingactivity.

Bloodandlymphaticsystemdisorders

Rare(0.01–<0.1%):transientneutropenia(leucopenia)andagranulocytosis,andthrombocytopeniahavebeen

reported.

Gastrointestinaldisorders

Common(1.0%-<10%)(>1%):stomachaches,nausea,vomitinganddiarrhoea(seeSpecialwarningandprecautions

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 31/08/2006 CRN 2027387 page number: 3

Rare(0.01–<0.1%):oesophagitisoccur.

Hepato-biliarydisorders

Rare(0.01–<0.1%):jaundiceandchangesintheliverfunctions(alsoinlevelsofserumtransaminases)testshave

beenobserved.

Skinandsubcutaneoustissuedisorders

Uncommon(0.1%-<1%)pruritus,skinrash,urticariashaveoccurred.

Rare(0.01–<0.1%)exfoliativedermatitisandvesiculobullouseruptionscanoccur.

Musculoskeletal

Rare(0.01–<0.1%):Polyarthritis.

Reproductivesystemandbreastdisorders

Common(1.0%-<10%):observedsideeffectisvaginitis.

Generaldisordersandadministrationsiteconditions.

4.9Overdose

Incasesofoverdosage,nospecifictreatmentisindicated.

Theserumbiologicalhalf-lifeofclindamycinis2.4hours.Clindamycincannotreadilyberemovedfromthebloodby

dialysisorperitonealdialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCCode:JO1FF01.

Pharmacotherapeuticgroup:Macrolidesandlincosamides.

Modeofaction

TheantibacterialspectrumofClindamycinHydrochlorideincludesawiderangeofanaerobicbacteriaandgram-

positiveaerobicbacteria.Clindamycinisasemi-syntheticantibioticwhichisobtainedfromlincomycinbyreplacing7

(R)-hydroxylgroupwith7(S)-chlorosubstituent.Lincosamidessuchasclindamycinbindtothe50Ssubunitofthe

bacterialribosomesimilarlytomacrolidessuchaserythromycinandinhibittheearlystagesofproteinsynthesis.The

actionofclindamycinispredominantlybacteriostaticalthoughhighconcentrationsmaybeslowlybactericidalagainst

sensitivestrains.

Breakpoints

ThefollowingMICbreakpoints,separatingsusceptiblefromintermediatelysusceptibleandintermediatelysusceptible

fromresistantorganismsaresuggestedforotherthanstreptococci(NCCLS,1993):

Susceptible(S)0.5mg/L.

Resistant(R) 4.0mg/L.

Forstreptococcithebreakpointsare:

Susceptible(S) 0.25mg/L.

Resistant(R) 1.0mg/L.

Susceptibility

Theprevalenceofacquiredresistancemayvarygeographicallyandwithtimeforselectedspecies.Localinformationof

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 31/08/2006 CRN 2027387 page number: 4

onprobabilitieswhethermicroorganismswillbesusceptibletothisantibiotic.Whereresistancepatternsforparticular

speciesareknowntovarywithintheEuropeanUnion,thisisshownbelowas(*):

OS:Oxacillinsusceptible.

MR:methicillinresistant.

MS:methicillinsusceptible.

ES:erythromycinsusceptible.

ER:erythromycinresistant.

MLSR:macrolide-lincosamide-streptogramintypeBresistant.

cMLSR:constitutivemacrolide-lincosamide-streptogramintypeBresistant.

SP:slimeproducing.

NSP:non-slimeproducing.

Clindamycinhasanin-vitroandin-vivoactivityonToxoplasmagondii.

AllisolatesofEnterococcusfaecalisareresistanttoclindamycin.

Upto50%ofmethicillin-susceptibleS.aureushavebeenreportedtoberesistanttoclindamycininsomeareas.More

AntibacterialSpectrum Percentagerangeof

resistance

Thefollowingbacteriaaresusceptibleorintermediately

susceptible:

Bacteroidesfragilisgroup <10

Clostridiumperfringens 0.06

Chlamydiatrachomatis 1-2

Coryneforms,aerobic 0

Legionellaspecies <50

Staphylococcusaureus(OS) <10

S.aureus 0–29.2

S.aureus(MR) 26-28.21

Staphylococcusepidermidis 10

S.epidermidis(OS) <10

S.epidermidis(MRSP) 12

S.epidermidis(NSP) 12

Staphylococcussaprophyticus <10

Staphylococci(MR) 40.8

(70-80%) *

Streptococcusagalactiae 0-<10

Streptococcusbovis >10,<50

Streptococcuspneumoniae 0-1.4

(35-70%) *

Streptococcuspyogenes 0

Streptococci,-haemolytic(GpC,F,G) 0-<10

Streptococci,viridansGp 0-<10

Thefollowingareresistant:

clostridiumdifficile 80.3

Corynebacteriumurealyticum >50

Coryneforms,aerobic(MLSR) 100

Enterococcusfaecium >50

Enterococcusfaecalis >50

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 31/08/2006 CRN 2027387 page number: 5

whileawaitingsusceptibilitytestresultsifthereisanysuspicionofMRSA.

Completecrossresistanceamonglincosamides,erythromycin,azithromycinandothermacrolidesforS.pneumoniae,

beta-haemolyticstreptococcusofgroupA,E.faecalisandS.aureus,includingmethicillinresistantS.aureus(MRSA).

MechanismofResistance

Whentestedbyinvitromethods,somestaphylococcalstrainsoriginallyresistanttoerythromycinrapidlydeveloped

resistancetoclindamycin.Themechanismsforresistancearethesameasforerythromycin,namelymethylationofthe

ribosomalbindingsite,chromosomalmutationoftheribosomalproteinandinafewstaphylococcalisolatesenzymatic

inactivationbyaplasmid-mediatedadenyltransferase.

5.2Pharmacokineticproperties

About90%ofadoseofclindamycinhydrochlorideisabsorbedfromthegastro-intestinaltract.Plasmaconcentrations

of2to3mg/Loccurwithinonehouraftera150mgdoseofclindamycin.Absorptionisnotsignificantlydiminishedby

foodinthestomach,buttherateofabsorptionmaybereduced.

Clindamyciniswidelydistributedinbodyfluidsandtissuesincludingbone,butitdoesnotreachthecerebrospinal

fluidinsignificantconcentrations,themeanvolumeofdistributionis1.1L/kg.Itdiffusesacrosstheplacentaintothe

fetalcirculationandappearsinbreastmilk.Highconcentrationsoccurinbile.Itaccumulatesinleucocytesand

macrophages.About40–90%ofclindamycininthecirculationisboundtoplasmaproteins.

Clindamycinundergoesmetabolism,presumablyintheliver,totheactiveN-demethylandsulphoxidemetabolitesand

alsosomeinactivemetabolites.Theplasmaeliminationhalf-lifeis2to3hours,althoughthismaybeprolongedin

neonates,especiallywhenpremature,andinpatientswithmoderateorseveredegreesofrenalorhepaticimpairment.

About10%ofthedrugisexcretedintheurineasactivedrugormetabolitesandabout4%inthefaeces;theremainder

isexcretedasinactivemetabolites.Clindamycinisnoteffectivelyremovedfromthebloodbyhaemodialysisor

peritonealdialysis.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonstudiesofrepeatdosetoxicity,reproductivetoxicityor

genotoxicity.Carcinogenicitystudieshavenotbeenconducted.Indogs,repeatedhighoraldosesproducedulceration

ofthemucosaofthestomachandgallbladder.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Capsulecontents:

Lactosemonohydrate

Maizestarch

Talc

Magnesiumstearate

Capsuleshell:

QuinolineYellow(E104)

BrilliantBlue(E133)

Titaniumdioxide(E171)

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 31/08/2006 CRN 2027387 page number: 6

Printingink:

ShellacPh.Eur.

Propyleneglycol

Blackironoxide(E172)

Potassiumhydroxide

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Nospecialprecautionsforstorage.

6.5Natureandcontentsofcontainer

4,12,16,20,24,30,32,40,60,or100capsulesinaluminium/PVC/PVDCblisterpack.

100capsulesinHDPEplasticbottleswithapolypropylenesafetycap.

100capsulesinHDPEplasticbottleswithapolypropylenescrewcap

Notallpacksizeswillbemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirement.

7MARKETINGAUTHORISATIONHOLDER

RanbaxyIrelandLimited

Spafield

CorkRoad

Cashel

CountyTipperary

8MARKETINGAUTHORISATIONNUMBER

PA408/60/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:03March2006

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 31/08/2006 CRN 2027387 page number: 7