GENTAMICIN INJECTION BP

Main information

  • Trade name:
  • GENTAMICIN INJECTION BP
  • Dosage:
  • 40 Mg/ Ml
  • Pharmaceutical form:
  • Solution for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • GENTAMICIN INJECTION BP
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0437/016/008
  • Authorization date:
  • 20-04-2004
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0437/016/008

CaseNo:2045348

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

HOSPIRAUKLtd

Queensway,RoyalLeamingtonSpa,WarwickshireCV313RW,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

GENTAMICIN40mg/mlInjection

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom20/02/2008until19/04/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Gentamicin40mg/mlInjection

2QUALITATIVEANDQUANTITATIVECOMPOSITION

GentamicinSulphateequivalenttogentamicinbase40.0mg/ml.

Forexcipients,see6.1.

3PHARMACEUTICALFORM

SolutionforInjection

4CLINICALPARTICULARS

4.1TherapeuticIndications

Gentamicinisindicatedinthetreatmentofserioussystemicinfections,includingthoseofthecentralnervoussystem,

duetoorganismssensitivetothisanti-infective.

4.2Posologyandmethodofadministration

Gentamicinisnormallygivenbytheintramuscularroute,butcanbegivenintravenouslywhenintramuscular

administrationisnotfeasible,e.g.inshockedorseverelyburnedpatients.Whengivenintravenously,theprescribed

doseshouldbeadministeredslowlyover2to3minutesdirectlyintoaveinorintotherubbertubingofgivingset.

Rapid,directintravenousadministrationmaygiverise,initially,topotentiallyneurotoxicconcentrationsanditis

essentialthattheprescribeddoseisadministeredovertherecommendedperiodoftime.

Adults:

Theusualtotaldailydoseis180-240mginthreedivideddoses(3mg/kg/day).

Dosagemaybeincreasedasrequireduptoamaximumof5mg/kg/24hoursandthefrequencyincreasedto6hourly.

Intheabsenceofrenaldysfunction,asingledailydoseof160mgmaybeusedinsomecases.

Childrenaged1yearto12years:

Theusualtotaldailydoseis4.5mg/kginthreedivideddoses.

Childrenaged0to7days:

Theusualtotaldailydoseis5mg/kgintwodivideddoses.

Childrenaged7daysto1year:

Theusualtotaldailydoseis6mg/kgintwodivideddoses.

DosesinPatientswithImpairedRenalFunction:

Dosageisadjustedforpatientswithrenalimpairmenttominimisetheriskoftoxicity.Thefirstdoseshouldbeas

normal–afterthis,dosesshouldbegivenlessfrequently,theintervalbeingdeterminedbyresultsofrenalfunction

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RenalFunctionTests:

Serumlevelsshouldbemonitoreddaily.

Peaklevelsininfantsandyoungchildren:

Peakserumlevelsarereachedin1houranddosageshouldbeadjustedtoachievelevelsofmorethan4

micrograms/ml,butnotexceed10micrograms/ml.

4.3Contraindications

Useinpatientshypersensitivetogentamicin.

Useconcurrentlywithotherpotentiallynephrotoxicorototoxicdrugsubstances.

Gentamicinshouldbeusedwithcautioninprematureinfantsbecauseoftheirrenalimmaturity,inelderlypeopleand

generallyinpatientswithimpairedrenalfunction.

Diabetes,auditoryvestibulardysfunctions,otitismedia,ahistoryofotitismedia,previoususeofototoxicdrugsanda

geneticallydeterminedhighsensitivitytoaminoglycosideinducedototoxicity,areothermainfactorswhichmaypre-

disposethepatientstotoxicity.

4.4Specialwarningsandprecautionsforuse

PatientsbeingtreatedwithGentamicinshouldbeundercloseclinicalobservationbecauseofitspotentialtoxicity.

Aswithotheraminoglycosidestoxicityisrelatedtoserumconcentration.With6-8hourlydosing,serumlevelsmore

than10micrograms/mlmaybeassociatedwitheffectsonthevestibularmechanism.Toxicitycanbeminimisedby

monitoringserumconcentrationsanditisadvisabletocheckserumlevelstoconfirmthatpeaklevels(onehour)do

notexceed10micrograms/mlandthattroughlevels(onehourbeforenextinjection)donotexceed2micrograms/ml.

Evidenceoftoxicityrequiresadjustmentofdosageorwithdrawalofthedrug.

Concurrentuseofotherneurotoxicand/ornephrotoxicdrugscanincreasethepossibilityofGentamicintoxicity.Co-

administrationwiththefollowingagentsshouldbeavoided.

Neuromuscularblockingagentssuchassuccinylcholineandtubocurarine.

Otherpotentiallynephrotoxicorototoxicdrugssuchascephalosporinsandmethicillin.

Potentdiureticssuchasethacrynicacidandfrusemide.

Otheraminoglycosides.

Dose CreatinineClearance

(ml/min) BUN

mg/ml Intervalbetween

doses

80mg 30-70 40-100 12hrs

10-30 100-200 24hrs

5-10 >200 48hrs

Antibacterials:increasedriskofnephrotoxicitywithcephalosporinsnotablycephalothin.

(ii) Gentamicinhasbeenknowntopotentiateanticoagulantssuchaswarfarinandphenindione.

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4.6Pregnancyandlactation

UseinPregnancy

Gentamicinshouldonlybeusedduringpregnancyorlactationifconsideredessentialbythephysician.

UseinLactation

Thedrugcrossestheplacentaanditisexcretedinsmallamountsinbreastmilk.

4.7Effectsonabilitytodriveandusemachines

Notapplicable.

4.8Undesirableeffects

OtotoxicityandnephrotoxicityarethemostcommonsideeffectsassociatedwithGentamicintherapy.Botheffectsare

relatedtorenalimpairmentandhencethedosageinsuchpatientsshouldbealteredassuggested.

OtheradversereactionsassociatedwithGentamicintherapyincludenausea,vomiting,urticaria,reversible

granulocytopenia,allergiccontactsensitizationandneuromuscularblockade.

4.9Overdose

Asinthecaseofotheraminoglycosides,toxicityisassociatedwithserumlevelsaboveacriticalvalue.Inpatientswith

normalrenalfunctionitisunlikelythattoxicserumlevels(inexcessof10micrograms/ml)willbereachedafter

administrationofrecommendeddoses.Wherehigherlevelsoccurbecauseofrenalimpairment,dosageshouldbe

reduced.Intheeventofanoverdoseortoxicreaction,peritonealdialysisorhaemodialysiswilllowerserum

Gentamicinlevels.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Gentamicinisusuallybactericidalinaction.Althoughtheexactmechanismofactionhasnotbeenfullyelucidated,the

drugappearstoinhibitproteinsynthesisinsusceptiblebacteriabyirreversiblybindingto30Sribosomalsubunits.

Ingeneral,Gentamicinisactiveagainstmanyaerobicgram-negativebacteriaandsomeaerobicgram-positivebacteria.

Gentamicinisinactiveagainstfungi,viruses,andmostanaerobicbacteria.

Invitro,Gentamicinconcentrationsof1-8micrograms/mlinhibitmostsusceptiblestrainsofEscherichiacoli,

Haemophilusinfluenzae,Moraxellalacunata,Neisseria,indolepositiveandindolenegativeProteus,Pseudomonas

(includingmoststrainsofPs.aeruginosa),Staphylococcusaureus,S.epidermidis,andSerratia.However,different

speciesanddifferentstrainsofthesamespeciesmayexhibitwidevariationsinsusceptibilityinvitro.Inaddition,in

vitrosusceptibilitydoesnotalwayscorrelatewithinvivoactivity.Gentamicinisonlyminimallyactiveagainst

(iv) Cholinergics:antagonismofeffectofneostigmineandpyridostigmine.

Cyclosporin:increasedriskofnephrotoxicity.

(vi) Cytotoxics:increasedriskofnephrotoxicityandpossibleriskofototoxicitywithcisplatin.

(vii) Diuretics:increasedriskofototoxicitywithloopdiuretics.

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NaturalandacquiredresistancetoGentamicinhasbeendemonstratedinbothgram-negativeandgram-positive

bacteria.Gentamicinresistancemaybeduetodecreasedpermeabilityofthebacterialcellwall,alterationinthe

ribosomalbindingsite,orthepresenceofaplasmid-mediatedresistancefactorwhichisacquiredbyconjugation.

Plasmid-mediatedresistanceenablestheresistantbacteriatoenzymaticallymodifythedrugbyacetylation,

phosphorylation,oradenylationandcanbetransferredbetweenorganismsofthesameordifferentspecies.

Resistancetootheraminoglycosidesandseveralotheranti-infectives(e.g.chloramphenicol,sulphonamides,

tetracycline)maybetransferredonthesameplasmid.

Thereisapartialcross-resistancebetweenGentamicinandotheraminoglycosides.

5.2Pharmacokineticproperties

Gentamicinandotheraminoglycosidesarepoorlyabsorbedfromthegastro-intestinaltractbutarerapidlyabsorbed

afterintramuscularinjection.Averagepeakplasmaconcentrationsofabout4microgramspermlhavebeenobtained30

to60minutesafterintramuscularadministrationofadoseequivalentto1mgofGentamicinperkgbody-weight

althoughtheremaybeconsiderableindividualvariationandhigherconcentrationsinpatientswithrenalfailure.Similar

concentrationsareobtainedafterintravenousadministration.Severaldosesarerequiredbeforeequilibrium

concentrationsareobtainedintheplasmaandthismayrepresentthesaturationofbindingsitesinbodytissuessuchas

thekidney.BindingofGentamicintoplasmaproteinsisusuallylow.

FollowingparenteraladministrationGentamicinandotheraminoglycosidesdiffusemainlyintoextracellularfluidsand

factorswhichaffectthevolumeofdistributionwillalsoaffectplasmaconcentrations.

However,thereislittlediffusionintothecerebrospinalfluidandevenwhenthemeningesareinflamedeffective

concentrationsmaynotbeachieved;diffusionintotheeyeisalsopoor.Aminoglycosidesdiffusereadilyintothe

perilymphoftheinnerear.Gentamicincrossestheplacentabutonlysmallamountshavebeenreportedinbreastmilk.

SystemicabsorptionofGentamicinandotheraminoglycosideshasbeenreportedaftertopicaluseondenudedskinand

burnsandfollowinginstillationintoandirrigationofwounds,body-cavities,andjoints.

Theplasmaeliminationhalf-lifeforGentamicinhasbeenreportedtobe2to3hoursthoughitmaybeconsiderably

longerinneonatesandpatientswithrenalimpairment.Gentamicinandotheraminoglycosidesdonotappeartobe

metabolisedandareexcretedvirtuallyunchangedintheurinebyglomerularfiltration.Atsteady-stateatleast70%ofa

dosemayberecoveredintheurinein24hoursandurineconcentrationsinexcessof100microgramspermlmaybe

obtained.However,Gentamicinandtheotheraminoglycosidesappeartoaccumulateinbodytissuestosomeextent,

mainlyinthekidney,althoughtherelativedegreetowhichthisoccursmayvarywithdifferentaminoglycosides.

Releasefromthesesitesisslowandaminoglycosidesmaybedetectedintheurineforupto20daysormoreafter

administrationceases.SmallamountsofGentamicinappearinthebile.

5.3Preclinicalsafetydata

Thereisnopreclinicaldataofrelevancetotheprescriberwhichareadditionaltothatalreadyincludedinothersections

oftheSPC.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiummetabisulphite

Disodiumedetate

WaterforInjections

Sulphuricacid(2.5N)

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6.2Incompatibilities

Gentamicininjectionshouldnotbemixedwithotherdrugsbeforeinjectionandwhereco-administrationofpenicilins,

cephalosporins,erythromycin,lipiphysansulphadiazine,frusemideandbetalactamantibioticsandheparinisnecessary,

thedrugsshouldbeadministeredseparately,eitherasbolusinjectionintothetubingofthegivingsetoratseparate

sites.Gentamicinshouldnotbeaddedtosolutionscontainingbicarbonateasthismayleadtothereleaseofcarbon

dioxide.

6.3ShelfLife

6.4Specialprecautionsforstorage

Priortofirstuse:Donotstoreabove25°C.

Inuse:Followingdilutionineithernormalsalineor5%dextroseinPVCinfusionbags,chemicalandphysicalin-use

stabilityhasbeendemonstratedfor7daysat2-8 °

However,fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotusedimmediately,in-

usestoragetimesandconditionspriortousearetheresponsibilityoftheuserandwouldnormallynotbelongerthat24

hoursat2-8 °

C,unlessdilutionhastakenplaceincontrolledandvalidatedasepticconditions.

6.5Natureandcontentsofcontainer

AclearTypeIglassvialcontaining6mlwitha20mmrubberclosure(S63W4432/50),aluminiumsealandplasticflip

offcap.Availableinsinglepacksandpacksof5.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Singleuseonly.Discardanyunusedcontents.

Foradministrationbyintravenousinfusiontheprescribeddoseshouldbedissolvedinupto100mlofnormalsalineor

5%glucoseinwater,butnotsolutionscontainingbicarbonate.

Syringes,vialsthatareeitheremptyorhaveremainingsolutionshouldbecarefullydiscardedinathickplasticbagor

imperviouscontainer,andincinerated.

7MARKETINGAUTHORISATIONHOLDER

HospiraUKLimited

Queensway

RoyalLeamingtonSpa

Warwickshire

CV313RW

8MARKETINGAUTHORISATIONNUMBER

PA437/16/8

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Priortofirstuse: 36months.

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10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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