CLINDAMYCIN

Main information

  • Trade name:
  • CLINDAMYCIN Capsule 300 Milligram
  • Dosage:
  • 300 Milligram
  • Pharmaceutical form:
  • Capsule
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CLINDAMYCIN Capsule 300 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1334/001/002
  • Authorization date:
  • 15-05-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Clindamycin300mgCapsules

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachcapsulecontainsclindamycinhydrochlorideequivalentto300mgclindamycin.

Eachcapsulecontainslactosemonohydrate228.57mg(approximately).

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Capsule,hard.

Powderbluecapsule.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Clindamycinisindicatedinthetreatmentofpatientswithseriousinfectionscausedbysusceptiblemicro-organisms,

particularlyinrecurrentinfections,andnotrespondingtofirstlineantibiotics,andasanalternativetreatmentinthe

caseofpenicillin-allergicpatientswithinfectionscausedbyGram-positiveaerobicbacteria.Itisalsoindicatedin

seriousinfectionscausedbysusceptibleanaerobicpathogens.

(seesection5.1).

Pneumonia.

Chronicsinusitisduetoanaerobicbacteria.

Tonsillitis.

Skinandsofttissueinfections.

Boneandjointinfectionse.g.osteomyelitisandsepticarthritis.

Femalepelvicandgenitalinfectionssuchasendometritis,pelviccellulitis,paravaginalinfections,tuboovarian

abscessesandsalpingitis.ShouldbetreatedincombinationwithanantibioticeffectiveagainstGram-negative

aerobicbacteria.

Intra-abdominalinfectionsincludingperitonitisandabdominalabscess.Shouldbetreatedincombinationwithan

antibioticeffectiveagainstGram-negativeaerobicbacteria.

Asforallantibiotic,invitrosensitivitytestsmustbeperformedinseriousinfections.

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.2Posologyandmethodofadministration

OralCapsulesshouldnotbedividedandshouldbeswallowedwithaglassofwaterandinanuprightposition.

Adults,adolescentsover12yearsofageandtheelderly:

Theusualdoseis150–450mgeverysixhoursdependingontheseverityoftheinfection.Fordosingbelow300mg

otherpresentationsofclindamycinareavailable.

Thedosageofclindamycinmayrequirereductioninpatientswithseverrenalorhepaticimpairmentdueto

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2100014 page number: 1

Thedoseandmethodofadministrationisdeterminedbytheseverityandsensitivityofthecausativeorganism(s)and

theconditionofthepatient.Asforallantibiotics,insevereinfections,invitrosensitivitytestsshouldbeconducted.

Alternativeformulationsofclindamycinareavailablefortreatingchildrenforwhomthecapsulesareunsuitableorfor

dosesthatcannotbereachedbythispharmaceuticalform.Incaseofsevereclinicalstatusparenteraltherapyis

preferredtooraltherapy.

Incasesofbeta-haemolyticstreptococcalinfections,treatmentwithClindamycinCapsulesshouldcontinueforatleast

10daystodiminishthelikelihoodofsubsequentrheumaticfeverorglomerulonephritis.

Thedurationoftreatmentdependsontheclinicalresponseofthepatient.However,duetotheriskofseveredisruption

ofthefaecalfloraanditsconsequences(seesections4.4),treatmentshouldbekepttotheminimum.Ifprolonged

therapyisconsideredtobeunavoidable,thepatientshouldbecarefullymonitoredforadverseeffects(seesection4.4).

AbsorptionofClindamycinCapsulesisnotappreciablymodifiedbythepresenceoffood.

4.3Contraindications

Clindamyciniscontraindicatedinpatientspreviouslyfoundtobehypersensitivetothisantibioticortolincomycin

(parallergyexists)ortotheexcipientspresentinthisproduct.

4.4Specialwarningsandprecautionsforuse

Clindamycinshouldonlybeusedinthetreatmentofseriousinfectionsandwhenthepossiblebenefitofusing

clindamycinisconsideredtooutweightheriskofantibiotic-associateddiarrhoeaorcolitis,whichmayprogressto

pseudomembraneouscolitis,peritonitis,shock,toxicmegacolonanddeath.Pseudomembranouscolitiscandevelop

during,ortwoorthreeweeksfollowingtheadministrationofclindamycin.Theseintestinalcomplicationsaremore

likelytobesevereandtobecomelife-threateninginolderpatientsorpatientswhoaredebilitated.Diagnosisisusually

madebytherecognitionoftheclinicalsymptoms,butcanbesubstantiatedbyendoscopicdemonstrationof

pseudomembraneouscolitis.StoolcultureforClostridiumdifficileand/orassayforClostridiumdifficiletoxinmaybe

helpfultodiagnosis.

Cautionshouldalsobeusedwhenprescribingclindamycinforindividualswithahistoryofgastro-intestinaldisease

especiallycolitis.Ifdiarrhoeaorcolitisoccursduringtherapy,clindamycinshouldbediscontinuedimmediatelyand

appropriatediagnosticandtherapeuticmeasuresshouldbeinstituted.Itshouldbenotedthattheonsetoftheseintestina

complicationsofclindamycintreatmentmaybedelayeduntilseveralweeksfollowingthecessationoftherapy.The

mostcommonlyimplicatedcauseisanovergrowthoftoxin-producingClostridiumdifficileasaresultofdisruptionof

thebowelflorabyclindamycin.

Clindamycindoesnotcrosstheblood-brainbarrier.Therefore,clindamycinshouldnotbeusedincomplications

includingmeningealinfections.

Lactoseintolerance:ClindamycinCapsulescontainlactose;Patientswithrarehereditaryproblemsofgalactose

intolerance,theLapplactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

Hepaticandrenalinsufficiency:Insevererenalimpairment,peakplasmalevelsofclindamycinmaybeuptothree

timesnormalandtheeliminationhalf-lifeisprolonged.Dosereductionand/oranincreaseddoseintervalshouldbe

considered.Inmoderateandseveredegreesofhepaticimpairment,peakplasmalevelsofclindamycinarehigherthan

normalandtheeliminationhalf-lifeisprolonged.Dosereductionand/oranincreaseddoseintervalshouldbe

considered.

Serumclindamycinlevelsshouldbeestimated.Periodicliver,kidneyfunctionandhaematologicaltestsshouldbe

carriedoutduringprolongedtherapy.

Prolongedadministrationofclindamycin,aswithanyanti-infective,mayresultinsuper-infectionduetoorganisms

resistanttoclindamycin.SuperinfectionparticularlywithCandida,ispossible.Therefore,itisimportanttoconsider

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2100014 page number: 2

Clindamycinshouldnotbegiveninpatientswithacuteviralinfectionsoftherespiratorytract.Clindamycinshouldbe

reservedforseriousinfections,wherelesstoxicantibioticsareconsideredinappropriate.

Hypersensitivity:Clindamycinshouldbeusedwithcautioninindividualsallergictootherantibiotics,andcareshould

beobservedintheuseofClindamycinCapsulesinatopicindividuals,e.g.asthmaandallergy.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Clindamycinhasbeenshowntohaveneuromuscularblockingpropertiesthatmayenhancetheactionofother

neuromuscularblockingagents.Therefore,itshouldbeusedwithcautioninpatientsreceivingsuchagents.

Antagonismhasbeendemonstratedbetweenclindamycinanderythromycinanditschemically-relatedmacrolidesin

vitro.Becauseofpossibleclinicalsignificance,thetwodrugsshouldnotbeadministeredconcurrently.

Insomecases,antibioticsmayreducetheefficacyoforalcontraceptivesbyinterferingwiththebacterialhydrolysisof

steroidconjugatesintheintestineaffectingthereabsorptionofnon-conjugatedsteroids.Theplasmaconcentrationsof

activesteroidsmaythusbereduced.Thus,whenusedincombinationwithcontraceptivepills,adoseadjustmentmight

berequired.

4.6Fertility,pregnancyandlactation

Thisdrugshouldonlybeusedinpregnancyorlactationifconsideredessentialbythephysician.Itcrossestheplacenta

andisexcretedinbreastmilk.Thereisnoevidenceofteratogeniceffectinanimalsnortodateinman.

4.7Effectsonabilitytodriveandusemachines

Theeffectofclindamycinontheabilitytodriveandtousemachineshasnotbeenstudied.

4.8Undesirableeffects

Gastrointestinaladverseeffectsareexperiencedbyapproximately8%ofthepatients,mainlyasdiarrhoea.

Thefollowingundesirableeffectshavebeenobservedduringtreatmentwithclindamycinandothermacrolide

antibioticswiththefollowingfrequencies:verycommon(1/10);common(1/100to<1/10);uncommon(1/1,000to

<1/100);rare(1/10,000to<1/1,000),veryrare(<1/10,000)andnotknown(cannotbeestimatedfromtheavailable

data).

Bloodandlymphaticsystemdisorders

Rare: Transientneutropenia/leucopeniaandeosinophilia.Agranulocytosis,andthrombocytopeniahavebeenreported.

Immunesystemdisorders

Uncommon:Skinrashandurticaria.Inwiderareasslightormoderateskinrashresemblingmeasles,symptoms

resemblingStevens-Johnsonsyndromecanoccur.

Rare:Anaphylacticreactions.

Nervoussystemdisorders

Uncommon:Theneuromuscularblockingactivity.

Tastedisorderhasalsobeenreported.

Gastrointestinaldisorders

Common:Abdominalpain,nausea,vomiting,loosestoolsanddiarrhoea(asaresultofdisruptionofthebowelfloraby

clindamycin)andirritationofthegastrictractcanoccur.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2100014 page number: 3

Rare:Oesophagitisandcolitisassociatedwithantibiotictreatment(Pseudomembranouscolitis).

Oesophagealulcershavealsobeenreported.

Hepato-biliarydisorders

Rare:Jaundiceandchangesintheliverfunctions(alsoinlevelsofserumtransaminases)testshavebeenobserved.

Skinandsubcutaneoustissuedisorders

Uncommon:Pruritus,skinrashandurticariashaveoccurred.

Rare:Vaginitis,erythemamultiforme,(someresemblingSteven-Johnsonsyndrome)andrarecasesofexfolitativeand

vesiculobullousdermatitis.Rarecasesoftoxicepidermalnecrolysishavebeenreported.

Musculoskeletal,connectivetissueandbonedisorders

Rare:Polyarthritis

4.9Overdose

Symptomsfromoverdosingarenausea,vomitinganddiarrhoea.

Incasesofoverdosagethatmayhaveledtoadversereactions,therapyshouldbediscontinuedandtheusualemergency

treatment,includingcorticosteroids,adrenalineandantihistamines,instituted.

Theserumbiologicalhalf-lifeofclindamycinis2.4hours.Clindamycincannotreadilyberemovedfromthebloodby

dialysisorperitonealdialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Lincosamides,ATCcode:J01FF01.

Modeofaction:

Clindamycinbindtothe50Ssubunitofthebacterialribosomeandinhibittheearlystagesofproteinsynthesis.

Clindamycinhaspredominantlybacteriostaticaction.

PK/PDrelationship:

Theefficacyisbasicallydependentonthetimeperiodinwhichtheagentlevelisabovetheminimuminhibitory

concentration(MIC)ofthepathogen.

Mechanismsofresistance:

Resistancetoclindamycincanbeduetothefollowingmechanisms:

Resistancetostaphylococciandstreptococciisoftenbasedonmethylgroupsincreasinglybindingtothe23SrRNA

(so-calledconstitutiveMLS

-resistance),wherebythebindingaffinityofclindamycintotheribosomeishighly

reduced.

Themajorityofmethicillin-resistantS.Aureus(MRSA)showstheconstitutiveMLS

typeofresistanceandis

thereforeresistanttoclindamycin.Infectionscausedbymacrolide-resistantstaphylococcishouldnotbetreatedwith

clindamycin,alsowhenin-vitrosusceptibilitywasproven,becausetherapymayleadtoselectionofmutantswith

constitutiveMLS

resistance.

StrainswithconstitutiveMLS

resistanceshowcompletecross-resistanceofclindamycinwithlincomycin,macrolides

(e.g.azithromycin,clarithromycin,erythromycin,roxithromycin,spiramycin)aswellasstreptograminB.Thereis

cross-resistanceofpathogenstowardsclindamycinandlincomycin.

Breakpoints:

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2100014 page number: 4

Staphylococci:sensitive 0.25resistant>0.5

StreptococciABCGandpneumoniae:sensitive 0.5resistant>0.5

Grampositiveanaerobes:sensitive 4resistant>4

Gramnegativeanaerobes:sensitive 4resistant>4

Theprevalenceofacquiredresistancemayvarygeographicallyandwithtimeforselectedspeciesandlocalinformation

onresistanceisdesirable,particularlywhentreatingsevereinfections.Asnecessary,expertadviceshouldbesought

whenthelocalprevalenceofresistanceissuchthattheutilityoftheagentinatleastsometypesofinfectionsis

questionable.

Commonlysusceptiblespecies

Aerobicgram-positivemicro-organisms

Actinomycesisraelli °

Gardnerellavaginalis °

Staphylococcusaureus(Methicillin-sensitive)

Streptococcusagalactiae

Streptococcuspyogenes

Streptococciofthe“viridans”-group^

Anaerobicmicro-organisms

Bacteroidesspp. °

(excl.B.fragilis)

Clostridiumperfringens °

Fusobacteriumspp °

Peptococcusspp. °

Peptostreptococcusspp. °

Prevotellaspp.

Propionibacteriumspp. °

Veillonellaspp. °

Othermicro-organisms

Chlamydiatrachomatis °

Chlamydophilapneumonia °

Gardnerellavaginalis °

Mycoplasmahominis °

Speciesforwhichacquiredresistancemaybea

problem

Aerobicgram-positivemicro-organisms

Staphylococcusaureus

Staphylococcusaureus(Methicillin-resistant) +

(veryhighresistancerates(60-90%)ineach<?

xml:namespaceprefix=st1ns="urn:schemas-

microsoft-com:office:smarttags"/><st1:stockticker

w:st="on">CMS</st1:stockticker>)

Staphylococcusepidermis +

Staphylococcushaemolyticus

Staphylococcushominis

Streptococcuspneumonia

Aerobicgram-negativemicro-organisms

Moraxellacaterrhalis $

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2100014 page number: 5

Noupdateddatawereavailableatreleaseoftables.Primaryliterature,scientificstandardliteratureandtherapeutic

recommendationsassumesusceptibility.

Inherentsusceptibilityofmostoftheisolatesshowsintermediateresistance.

Atleastoneregionshowsresistancerateshigherthan50%.

^Collectivenameforaheterogenousgroupofstreptococcispecies.Resistanceratemayvaryaccordingtothe

streptococcispeciespresent.”

5.2Pharmacokineticproperties

Absorption:About90%ofadoseofclindamycinhydrochlorideisabsorbedfromthegastro-intestinaltract.Plasma

concentrationsof2to3mg/Loccurwithinonehouraftera150mgdoseofclindamycin.Absorptionisnot

significantlydiminishedbyfoodinthestomach,buttherateofabsorptionmaybereduced.

Distribution:Clindamyciniswidelydistributedinbodyfluidsandtissuesincludingbone,butitdoesnotreachthe

cerebrospinalfluidinsignificantconcentrations.Themeanvolumeofdistributionis1.1L/kg.Itdiffusesacrossthe

placentaintothefoetalcirculationandappearsinbreastmilk.Highconcentrationsoccurinbile.Itaccumulatesin

leucocytesandmacrophages.About40-90%ofclindamycininthecirculationisboundtoplasmaproteins.

Elimination:Clindamycinundergoesmetabolism,presumablyintheliver,totheactiveN-demethylandsulphoxide

metabolitesandalsosomeinactivemetabolites.Theplasmaeliminationhalf-lifeis2–3hours,althoughthismaybe

prolongedinneonates,especiallywhenpremature,andinpatientswithmoderateorseveredegreesofrenalorhepatic

impairment.About10%ofthedrugisexcretedintheurineasactivedrugormetaboliteandabout4%inthefaeces;the

remainderisexcretedasinactivemetabolites.Clindamycinisnoteffectivelyremovedfromthebloodbyhaemodialysis

orperitonealdialysis.

Characteristicsinpatients

Elderly:Thehalf-life,volumeofdistributionandclearance,andextentofabsorptionafteradministrationof

clindamycinarenotalteredbyincreasedage.

Inpatientswithreducedrenalfunction:Inthepresenceofkidneydiseases,eliminationhalf-lifeisprolonged;however,

adosagereductionisunnecessaryintheeventofmildtomoderateimpairmentofrenalfunction.

Inpatientswithreducedliverfunction:Inpatientswithmoderatetoseverereducedliverfunctionthehalf-lifeis

prolonged,butwhengivingthedoseevery8houraccumulationisrarelyseen.Dosereductionisnormallynot

Bacteroidesfragilis

Inherentlyresistantorganisms

Aerobicgram-positivemicro-organisms

Enterococcusspp.

Listeriamonocytogenes

Aerobicgram-negativemicro-organisms

Escherichiacoli

Haemophilusinfluenzae

Klebsiellaspp.

Pseudomonasaeruginosa

Anaerobicmicro-organisms

Clostridiumdifficile

Othermicro-organisms

Mycoplasmapneumoniae

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2100014 page number: 6

5.3Preclinicalsafetydata

Thereisnoevidenceofteratogeniceffectinanimalsnortodateinman.

Carcinogenesis:

Longtermstudiesinanimalshavenotbeenperformedwithclindamycintoevaluatecarcinogenicpotential.

Mutagenesis:

GenotoxicitytestsperformedincludedaratmicronucleustestandanAmesSalmonellareversiontest.Bothtestswere

negative.

ImpairmentofFertility:

Fertilitystudiesinratstreatedorallywithupto300mg/kg/day(approximately1.1timesthehighestrecommended

adulthumandosebasedonmg/m2)revealednoeffectsonfertilityormatingability.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

CapsuleContents

Lactosemonohydrate

MaizeStarch

Magnesiumstearate

Talc

CapsuleBody&Cap

Gelatin

PatentBlueV(E131)

Titaniumdioxide(E171)

6.2Incompatibilities

Notapplicable

6.3Shelflife

4years

6.4Specialprecautionsforstorage

Nospecialprecautionsforstorage.

6.5Natureandcontentsofcontainer

BlisterpackscomposedofPVC/PE/PVdCaluminiumfoil;packsizes:4,8,16,20,24,30,32,40and100.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2100014 page number: 7

7MARKETINGAUTHORISATIONHOLDER

ChanelleHealthcareLtd.,

Loughrea,

Co.Galway,

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA1334/1/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:15thMay2009

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/10/2011 CRN 2100014 page number: 8