2014 07 24 19 55 33 Drugdosingatextremesofbod 45662

September2013
DrugDosinginExtremesof
BodyWeight
incriticallyillpatients
1stEdition
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UKCPA: DrugDosinginExtremesofBodyWeightincriticallyillpatients 1 Edition(v1.0)September2013
Contents
Contents 1
Introduction 2
Acknowledgements 3
Background 4
DrugDosingInformation 7
Aciclovir 7
Ambisome 8
Anidulafungin 10
Benzylpenicllin 11
Ceftriaxone/Cefalosporins 13
Ciprofloxacin 15
Clarithromycin 17
Clindamycin 18
CoTrimoxazole 20
Daptomycin 22
Dexmedetomidine 24
Ertapenem 25
Flucloxacillin 27
Fluconazole 28
Immunoglobulin 29
Levofloxacin 31
Linezolid 33
Meropenem 35
Metronidazole 37
Phenytoin 39
Piperacillin/Tazobactam 41
Rifampicin 43
Sugammadex 44
Tigecycline 45
Voriconazole 46
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Introductionto1stedition(2013)
Obesity is becoming increasingly prevalent in the western world and consequently more
common in critically ill patients. However, the dosing information for most drugs is generally
obtained from studies carried out on average weight patients so may not be relevant to
patients at the extremes of bodyweight. Yet for critically ill patients, it may be especially
importanttoadministeranoptimaldoseofadrugtoensuretherapeuticlevelsareobtained.
Thisdocumentwhichrepresentsinformationandexperienceofdosingofdrugsincriticallyill
patients in extremes of body weight, has been produced by the Scottish Adult Critical Care
PharmacistsNetwork(SACCPN)inanattempttomakethenecessaryinformationmorereadily
available.
The information provided is supported by collation of the limited literature available in this
area,andbyanecdotalexperienceofpharmacistsworkingwithincriticalcareinScotland.This
documentisintendedtoprovideinformationondosingin extremesofbodyweight,toallow
practitioners to make informed decisions. The document does not provide a substitute for
clinicaljudgement,andtheauthorstrustthattheinformationprovidedwillonlybeusedaspart
of the clinical decision making process. Every effort has been made to ensure that the
informationcontainedinthisdocumentisaccurateanduptodate,howevernoliabilitycanbe
acceptedforanyinaccuraciesormisstatementsoffactcontainedherein,norforanypatientor
clinical outcomeswhichmayoccuras aresultofreferringtoinformation containedwithinthis
document. It is expected that this document will continue to evolve but as a start we have
includedsomeofthecommonlyusedmedicinesusedwithincriticalcareareas.Itishopedto
includemoremonographsinfutureeditions.
Wehopethatyouwillfindthedocumentusefulandfeedbackiswelcome.Pleasesendanynew
information or experiences for inclusion in future editions to either Keith Addie
(keith.addie@ggc.scot.nhs.uk)orAlanTimmins(alan.timmins@nhs.net)sothattheinformation
containedinthedocumentcanbekeptuptodateandrelevanttoclinicalpractice.
ManyThanks
KeithAddie
SeniorClinicalPharmacist
VictoriaInfirmary,Glasgow
OnbehalfoftheScottishAdultCriticalCarePharmacistsNetwork
N.B.Informationprovideddoesnotprovideasubstituteforclinicaljudgement.
Noliabilitycanbeacceptedforanyinaccuraciesormisstatementsoffactcontainedherein,norforanypatientorclinical
outcomeswhichmayoccurasaresultofreferringtoinformationcontainedwithinthisdocument.
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Acknowledgments
WorkingGroup
KeithAddie,SeniorPharmacist,VictoriaInfirmary,Glasgow
AlisonBell,SeniorPharmacist,DumfriesandGallowayRoyalInfirmary
MartynGall,SeniorPharmacistSouthernGeneralHospital,Glasgow
MoragNaysmith,SeniorPharmacistWesternGeneralHospitalEdinburgh
AlanTimmins,PrincipalPharmacist,VictoriaHospitalKirkcaldy
Wewouldliketoacknowledgethecontributionofthefollowingpharmaciststotheproductionofthis
document:
MornaBallofGlasgowRoyalInfirmary
JoanneBerrichofInverclydeRoyalHospital,Greenock
PeterBucknerofForthValleyRoyalHospital,Larbert
AlisonCarruthersofBordersGeneralHospital,Melrose
RuthForrestoftheWesternInfirmary,Glasgow
SusanHughesofCrosshouseHospital,Kilmarnock
DianeKennedyofAyrHospital
RakeshKishoreofGlasgowRoyalInfirmary
PamelaMacTavishofGlasgowRoyalInfirmary
ClaireMcMasteroftheGoldenJubileeNationalHospital,Clydebank
FionaMacGregoroftheRoyalAlexandraHospital,Paisley
JenniferMurphyofWishawGeneralHospital
FionaMcIntyreofNinewellsHospital,Dundee
PatriciaNicholasoftheGoldenJubileeNationalHospital,Clydebank
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Background
Thereislittleinformationaboutdosingadjustmentsinsignificantlyunderweightpatients.There
are some pieces of information in the guidance document. Some guidance may be obtained
fromconsideringdosinginchildren,howeveritisimportanttorememberthatmetabolismis
likely to be considerably different in children. Obesity may have no effect on morbidity and
mortalityinICU1ormayincreaseit2Thelatterpaperprovidesareviewoftheeffectsofobesity
onmetabolismandondrughandling,asdoestheonebyJansonandThursky3.
WeightsusedinDosing
Thefollowingmethodshavebeenusedtoadjustdosinginobesity
Descriptor Abbreviation Formula
TotalBodyWeight TBW Weight(Wt)
ActualBodyWeight ABW Weight(Wt)
BodyMassIndex BMI Wt/height(m)2
IdealBodyWeight IBW =45.4+[0.89x(height{cm}152.4)](+4.5ifmale)
ExcessBodyWeight EBW =TBWIBW
MaximumBodyWeight MBW =IBW+20%
AdjustedBodyWeight AdjBW =IBW+[DWCF*xEBW]
LeanBodyWeight LBW Male=[9270xTBW]/[6680+(216xBMI)]
Female=[9270xTBW]/8780+(244xBMI)]
FatFreeMass FFM Male=[TBWx0.285]+[12.1xheight(m)2]
Female=[TBWx0.287]+[9.74xheight(m)2]
PredictedNormalWeight PNW Male=[TBWx1.57][TBWxBMIx0.0183]10.5
Female=[TBWx1.75][TBWxBMIx0.0242]12.6
BodySurfaceArea BSA =[(height{cm}xTBW)/3600]
*DWCF=DoseWeightCorrectionFactor(seebelow)
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TotalBodyWeight(TBW)istheweightasmeasured.ThisissometimesreferredtoastheActual
BodyWeight(ABW),whichcancauseconfusionwiththeAdjustedBodyWeight(AdjBW).Body
MassIndex(BMI)israrelyusedfordosing,butgivesanindicationofthepatientsstature.The
Ideal Body Weight (IBW) is obtained from statistical tables relating to life expectancy, and so
has little direct connection to pharmacokinetic parameters, but it is commonly used in dose
adjustment.MaximumBodyWeight(MBW)isarelatedtermthatissimilarlyapproximate.
WhenusingIBW,thereisanassumptionthattheExcessBodyWeight(EBW)hasnoinfluence
ondrughandling.Howevertheadiposetissuedoeshavesomevasculatureandsomefluid,and
in fact will usually have some influence. This can be accounted for by the Dose Weight
CorrectionFactor.Accuratevaluesforthefactorarenoteasilyobtained, butavalueof0.4is
often assumed. This value has been found to be useful with watersoluble drugs, particularly
aminoglycosides.
Lean Body Weight (LBW), Fat Free Mass and Predicted Normal Weight take into account the
gender,heightandweight(e.g.tallthinpeopleormuscularpeople)toestimatethefractional
fatmass,soareintheoryaregoodmodelsfordrugsthatarehighlyhydrophilic.Howeverthey
are not widely used in practice, and are more often seen in a research context with specific
drugs.BodySurfaceAreaismainlyusedincancerchemotherapy.
Much of the work relating to the above equations was carried out on previous generations,
when there were fewer subjects in the upper extremities of the weight range than in the
presentday,andthereisverylittlevalidationfortheuseofanyofthesedescriptorsfordrug
dosing. Modified weights used in altering drug doses may not be applicable for assessing
ventilatoryparameters,haemofiltrationornutritionalrequirements,andviceversa.
Pharmacology/kinetics
Duetovariablealterationsinthevolumeofdistribution,clearanceandeliminationhalflifein
obesity dosing adjustments can be complex. In obese patients, the glomerular filtration rate
(GFR) may be increased relative to a normal patient, so in theory drug clearance may be
increased.Howevercomplicationsofobesity,includingdiabetesandhypertension,mayreduce
clearance,somaynegatethis.CalculationofcreatinineclearanceusingtheCockcroft&Gault
method in obese patients should use lean body weight (or maximum body weight), since
musclemassisproportionatelymuchlessinobesepatients.
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An increased proportion of adipose tissue compared with lean tissue alters the volume of
distribution of lipophilic drugs, TBW should generally therefore be used for dosing. For
hydrophilic drugs dosing relates better to lean body mass (i.e. IBW), though as noted above
thereissomeextrawater/bloodsupplytoexcesstissue,soanadjustmentfactorissometimes
addedtogiveadjustedbodyweight.
As there remains a lack of good information, careful monitoring of effect and side effects is
mandatoryinanypatientswhereitissuspectednormalparametersmaynotapply.
References
1. AkinnusiME,PinedaLA,ElSohlAA.Effectofobesityoncriticalcaremorbidityandmortality:a
metaanalysis.CriticalCareMedicine,2008;36:p151158
2. PieracciFM,BariePS,PompACriticalcareofthebariatricpatient.CriticalCareMedicine.2006
;34:p17961804
3. JansonB,ThurskyK.Dosingofantibioticsinobesity.CurrentOpinionsinInfectiousDiseases,25;
(6)p634649
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DrugDosingInformation

Aciclovir
Summaryofproductcharacteristics(SPC)1
Dosageinadults:5mg/kgevery8hoursor10mg/kginimmunocompromisedpatientsor
herpesencephalitis.1
Halflifeisdependentonrenalfunction.
DoseadjustmentsforrenalimpairmentasperSPCorrefertorenaldrughandbook.2

SummaryofSACCPNliteraturereviewandliteraturefrommanufacturer
Underweightpatients
Nodataavailableonanydoseadjustmentrequiredinlowbodyweight
Obesepatients
Literaturedescribesacutekidneyinjuryinobesepatientswhereaciclovirdosewasbasedonactualbody
weight.3
Summary/Comments
Underweightpatients
Noinformationavailable
Obesepatients
CalculatedoseusingIdealBodyWeightinobesepatientstakingrenalfunctionintoaccount.2,4
References
1. Zovirax(Aciclovir)GlaxoSmithKlineLtd.SummaryofProductCharacteristics,Accessedat
www.medicines.org.uk,23rdNovember2012
2. AshleyC(Ed)&Currie,A(Ed).Therenaldrughandbook.3rdedition.Radcliffepublishing,Oxford.
2009.
3. Personalcommunication.GlaxoSmithKlineMedicinesInformationdepartment.Emailreceived
2ndJanuary2013
4. Antimicrobialdosinginobesepatients.ClinicalInfectiousDiseases.1997;25:1;112118.
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Ambisome
Therapyisusuallyinstitutedatadailydoseof1.0mg/kgofbodyweight,andincreasedstepwise
to3.0mg/kg,asrequired.
Nodoseadjustmentrecommendedforrenalimpairment.1

Underweightpatients
DoseasperSPConmg/kgbasis.
Obesepatients
Gilead are about to commence a pharmacokinetic study in the obese population but until data is
availablefromthisthemanufacturerrecommendsthatallpatientsaredosedonamg/kgbasis.Patients
intheclinicalstudiesrangedfromverylowbirthweightneonatestoadults80kg+butthereiscurrently
nodataavailablefrommanufacturerinobesepatients.2
Thereisasinglecasereportofanobesepatientwithnonmeningealcryptococcalinfectionsuccessfully
treated with amphotericin B plus flucytosine, followed by oral fluconazole. The dose of amphotericin
was based on actual body weight; levels were not determined, the dose of flucytosine was based on
IBW, and serum levels were maintained within the desired therapeutic range, without haematologic
toxicity.3,4
Summary/Comments
Underweightpatients
DoseasperSPConamg/kgbasis.
Obesepatients
Manufacturerrecommendsdosingonactualbodyweight,suggestmonitoringfortoxicityin
obesepatients.
References
1. Ambisome(Amphotericin)GileadSciencesLtd.SummaryofProductCharacteristics.Accessed
atwww.medicines.org.uk19thJuly2013
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2. PersonalcorrespondencewithGileadMedicalInformation11thJuly2013
3. WurtzR,ItozakuG,RodvoldK.AntimicrobialDosinginObesepatients.ClinicalInfectious
Diseases1997;25:1128.
4. GillumJG,JohnsonM,LavoieSetal.Pharmacotherapy1995;15:2513.
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Anidulafungin
Asingle200mgloadingdoseshouldbeadministeredonDay1,followedby100mgdailythereafter.1
Pfizerdoesnotrecommendadjustingthedoseofanidulafunginbasedonbodyweightinadultpatients.
Phase3datashowedweightinanidulafungingrouprangedfrom35kgto196.5kg.2
Underweightpatients
Nospecificinformationavailable.
Obesepatients
Luietalconductedaposthocpharmacokineticanalysisofaphase3studyconductedinICUpatients.All
patientsreceiveda200mgloadingdoseonDay1followedby100mgmaintenancedosedaily,withthe
exceptionofone240kgpatientwhowasgivena150mgdailymaintenancedose.Thehigherdosewasat
thediscretionoftheprincipalinvestigatorinordertoensuresufficientlyhighexposuretoanidulafungin.
Thepatienthadglobaltreatmentsuccess.Thispatientwasexcludedfromthesummarystatistics.2`
Summary/Comments
Underweightpatients
Nochangetomanufacturersrecommendeddosage
Obesepatients
Nochangetomanufacturersrecommendeddosage
References
1. Ecalta(Anidulafungin)Pfizer.SummaryofProductCharacteristicsAccessedat
www.medicines.org.uk12thJuly2013
2. LuiPetalPharmacokineticsofanidulafungininadultintensivecarepatients.Mycoses54
(SupplS2):75/121.

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Benzylpenicillin
600mgto3600mgdaily,dividedinto46dosesdependingontheindication
HigherdosesasperSPCdependingonindication.
HighdosageofbenzylpenicllinsodiumBPmayresultinhypernatraemiaandhypokalaemia
unlessthesodiumcontentistakenintoaccount.1
Underweightpatients
Nospecificinformationavailable
Obesepatients
One review recommends that for penicillins dosing should be at the higher end of the recommended
treatmentranges,particularlyformorbidlyobesepatientswithmoresevereinfections.3
Wurz et al suggested the use of a correction formula 0.30(actual body weightideal body weight) +
idealbodyweightwheredosewasincreasedinproportiontotheexcessinbodyweight4.
Hitesetalattemptedtovalidatetheuseoftheformulabycarryingoutatherapeuticdrugmonitoring
study in both obese and non obese patients to evaluate the effect of obesity on attainment of
therapeuticconcentrationsofbetalactamantibiotics5.
Intheobesepopulationuseofstandarddosagesofbetalactamantibioticsresultedininsufficientserum
concentrationsin32%ofpatientsandoverdosedserumconcentrationsin25%.
Continuous renal replacement therapy (CRRT) was identified as a risk factor for higher serum
concentrations.Dosageregimensbasedonthecorrectionformulaonlyslightlyincreasedserumdrug
concentrationsbuthadnoimpactonadequacyoftreatment.5
Robertsetalassessedtherapeuticdrugmonitoringofbetalactamantibiotics,assessedagainstatarget
concentrationoftroughconcentrationsof45xMIC,apharmacodynamictargetof100%.6
74% of patients initial doses of beta lactam doses did not achieve steady state pharmacodynamic
endpointswhicharebelievedtobeassociatedwithmaximalbetalactamactivity.
In50%ofpatientsadoseincreasewasrequiredtoattainconcentrationtargetswhilstin24%ofpatients
adosagedecreasewasrequired.
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Theaggressivepharmacodynamictargetschosenforthisstudyappearedtohavegoodclinicalresults
andlittleobservedtoxicity,howeverlackedthestatisticallysignificantdataonoutcomeswhichcould
onlybeproducedbyarandomisedclinicaltrial.6
Noinformationavailablefrommanufacturer.7
Summary/Comments
Underweightpatients
Obesepatients
Dosingforpenicillins,dosingshouldbeattheupperendofthehigherendoftherecommended
treatmentranges,particularlyinmorbidlyobesepatientswithmoresevereinfections.
Suggestdosingatupperendofrangewhereappropriate,takingintoaccountpatientsrenal
function.Suggestdiscussingwithlocalmicrobiologyorinfectiousdiseases.
References
1. Crystapen(Benzylpenicillin)GenusPharmaceuticals.SummaryofProductCharacteristicsAccessed
atwww.medicines.org.uk8thFebruary2013
2. AshleyC(Ed),CurrieA(Ed),TheRenalDrugHandbook.3rdedition.RadcliffePublishing,Oxford2009
3. ErstadB.Dosingofmedicationsinmorbidlyobesepatientsintheintensivecareunitsetting.
IntensiveCareMedicine2004;30:1832.
4. WurzR,ItokazuG,RodvoldK.AntimicrobialDosinginObesePatients.ClinicalInfectiousDiseases.
ClinicalInfectiousDiseases1997;25:1128.
5. HitesM,TacconeFS,WolffFetal.CaseControlstudyofDrugMonitoringofLactamsinObese
CriticallyillPatients.AntimicrobialAgentsandChemotherapy2013;57(2):708
6. RobertsJA,UlldemolinsM,RobertsMSetal.TherapeuticdrugmonitoringofLactamsincritically
illpatients:proofofconcept.InternationalJournalofAntimicrobialAgents2010;36:33239.
7. GenusPharmaceuticals.Personalcommunicationwithmedicalinformationdepartment.7th
February2013

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Ceftriaxone/Cefalosporins
SummaryofproductcharacteristicsCeftriaxone(SPC)1
Standardtherapeuticdosage:1goncedaily
SevereInfections:24gdaily,normallyasaoncedailydose.
DoseadjustmentsforrenalimpairmentorhepaticimpairmentasperSPCorrefertorenal
drughandbook.2

SummaryofSACCPNliteraturereviewandliteraturefrommanufacturer3
Underweightpatients
Noinformation
Obesepatients
Ceftriaxone
Suggestdosingattopendoflicenseddoseinobesepatientsforceftriaxone/cefalosporinstakinginto
account renal and hepatic function as above. (Licensed dose of ceftriaxone in severe infections 24g
daily).
Dosereduction/cautionisnecessaryinpatientswithsevererenalimpairmentaccompaniedbyhepatic
insufficiency.1
Twoseparatestudiesassesseddistributionofcefalosporinsgiveninobesemaleandfemalesubjects.
AdditionalInformationCefalosporins
Mannetalassessedsubcutaneousadiposetissueconcentrations ofcefamandoleinadultpatientsgiven
assurgicalprophylaxisinoperationslastinggreaterthan3hours.Increaseddosesofcefamandole(2g3
hrly) necessary to maintain wound concentrations above MIC during surgery in morbidly obese
patients.4
Yostetalassessedplasmalevelsafterintravenousadministrationofcefotaximeinnormalweightand
morbidly obese male and female subjects. Analysis of plasma levels showed no statistical significant
differencebetweentheconcentrationsachievedinnormalweightandmorbidlyobesesubjects.5
The above studies appear to suggest that as hydrophilic drugs, standard dosing of cefalosporins will
achieve adequate plasma levels however higher than normal doses may be required to achieve
adequatelevelsinsubcutaneousadiposetissuewhichmayberelevantwhentheyareusedassurgical
prophylaxis.
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Summary/Comments
Underweightpatients
Noinformation
Obesepatients
Suggestdosingattopendoflicenseddoseinobesepatientsforceftriaxone/cefalosporins
takingintoaccountrenalandhepaticfunctionasabove.(Licenseddoseinsevereinfections24g
daily)
Dosereduction/cautionisnecessaryinpatientswithsevererenalimpairmentaccompaniedby
hepaticinsufficiency.1
References
1. RocephinRoche.SummaryofProductCharacteristicsAccessedatwww.medicines.org.ukaccessed
11thJanuary2013
2. AshleyC(Ed)&Currie,A(Ed).Therenaldrughandbook.3rdedition.RadcliffePublishing,Oxford.
2009.
3. PersonalcommunicationwithRocheApril2013.
4. MannHJ,BuchwaldH.Cefamandoledistributioninserum,adiposetissueandwounddrainagein
morbidlyobesepatients.DrugIntelligenceandClinicalPharmacy1986;20:869873.
5. YorstRL,DerendorfH.DispositionofCefotaximeanditsDesacetylMetaboliteinMorbidlyObese
MaleandFemaleSubjects.TherapeuticDrugMonitoring1986;8:189194.
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Ciprofloxacin
Byintravenousinfusion400mgevery812hours
Noadviceonunderweightorobesepatients
DoseadjustmentsforrenalimpairmentorhepaticimpairmentasperSPC/renaldrughandbook
asrelevant.2
Underweightpatients
Noinformationonunderweightpatientshowever,mg/kgdosingcanbeused.
Obesepatients
Informationfrommanufacturer:
Themanufacturerprovidesnospecificadvice.However,theyprovideanumberofreferences
Allardetalsuggestusingaweightadjusteddosebasedon
Idealbodyweight+0.45(totalbodyweightIBW)
Theyalsonotedanincreasedtotalclearanceinobesepatients.4
VanZantenet alsuggestthathigherdosesofciprofloxacinshouldalwaysbeusedeither600mgbdor
400mg tds. Slight preference to 600mg bd as this achieves higher Cmax/MIC ratio.5Hollenstein et al
suggest that in obese patients, ciprofloxacin doses should be weight adjusted based on actual body
weightin ordertoachievethesametissueconcentrationsasthoseachievedinleansubjectsalthough
acceptthatthismayleadtoanincreasedriskofadverseeffect.6
Summary/Comments
Underweightpatients
Obesepatients
Obesepatientsmaybenefitfromincreaseddosingandweightbaseddoseshavebeensuggested
usingIBW+(0.45xexcessbodyweight)and45mg/kg/dose.Itisalsosuggestedthat600mg
bdisbetterthan400mgtdsasthisimproves(Cmax):MICratio.
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References
1. CiproxinBayer.SummaryofProductCharacteristicsAccessedatwww.medicines.org.uk11th
January2013
2009.
3. PersonalcommunicationwithBayer10thJanuary2013.
4. AllardSetal.Intravenousciprofloxacindispositioninobesity.ClinPharmacolTher1993;54(4):
368373
5. VanZantenARH,etal.Ciprofloxacinpharmacokineticsincriticallyillpatients:Aprospective
cohortstudy.Jcritcare2008;23,422430
6. HollensteinUMetal.Softtissueconcentrationsofciprofloxacininobeseandleansubjects
followingweightadjusteddosing.IntJObes2001;25(3):354358
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Clarithromycin
Byintravenousinfusion500mgevery12hours

Dosesof500mgtwicedaily,1000mgtwicedailyand2000mgtwicedailywerefoundtohavecomparable
overalleffecthowever,thehigherdosesresultedinincreasedgastrointestinalsideeffects.3
Underweightpatients
Noinformationondosinginunderweightpatients.
Obesepatients
Noinformationondosinginobesepatients
Summary/Comments
Underweightpatients
Obesepatients
Noinformationondosinginobesepatients.
References
1. Klaricid(Clarithromycin)AbbottHealthcareProductsPLtd.SummaryofProductCharacteristics
Accessedatwww.medicines.org.uk29thMay2013
2. PersonalcorrespondencewithAbbott,29thMay2013
3. AbbottLaboratories(July2012)BiaxinTMUSProductInformation,NorthChicago,IL.
http://www.rxabbott.com/pdf/biapi.pdf.Accessed7thJune2013
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Clindamycin
Seriousinfections:600mg1.2gintwo,threeorfourdivideddoses
Formoreseriousinfectionsthesedosesmayhavetobeincreased.Inlifethreatening
situationsdosesashighas4.8gdailyhavebeenused.
Clindamycindosagemodificationnotusuallynecessaryinpatientswithrenal/hepatic
insufficiency.
Underweightpatients
Noinformationavailablefordosinginunderweightpatients
Obesepatients
Halovic et al demonstrated that in patients hospitalised with cellulitis and cutaneous abscess weight
>100kgandBMI>40wereriskfactorsfortreatmentfailureinpatientstreatedwithcotrimoxazoleand
clindamycin (the two most common antibiotics prescribed to patients for this indication in this study)
Further subgroup analysis demonstrated that morbidly obese patients were at a higher risk of clinical
failureiftheyweredischargedonaloworaldoseofclindamycinorcotrimoxazole(P=0.002).2
Inadequate oral doses of <10mg/kg per 24 hours in divided doses had worse outcomes in morbidly
obesepatients.3
Summary/Comments
Underweightpatients
Noinformationavailableindosinginunderweightpatients
Obesepatients
Forserious/lifethreateninginfectionsdosesofupto4.8gdailydivideddoses
Dosesof<10mg/24hourshavedemonstratedworseoutcomesinobesepatients.
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References
1. DalacinCPhosphate(Clindamycin)PharmaciaLtd.SummaryofProductCharacteristics
Accessedatwww.medicines.org.uk,14thJune2013
2. HalilovicJ,Heintz,BrownJ.Riskfactorsforclinicalfailureinpatientshospitalisedwithcellulitis
andcutaneousabscess.JournalofInfection2012;65:128134.3
3. JansonBandThurskyK.DosingofAntibioticsinObesity.CurrentOpinionInfectiousDisease
2012;25:634649
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CoTrimoxazole
Acuteinfections960mgevery12hours(treatment)
PneumocystisJiroveciPneumonitisPCPinfections:treatmentdose20mgoftrimethoprim
and100mgofsulfamethoxazoleperkgofbodyweightperdayintwoormoredivided
doses.1
Underweightpatients
Noinformationavailableondosinginunderweightpatients.
Obesepatients
For treatment of pneumocystis pneumonia doses of up to 20mg/kg per 24 hours trimethoprim and
100mg/kgper24hourssulfamethoxazolehavebeenused.
Inadequate oral doses (<5mg/kg per 24 hours trimethoprim) had worse outcomes in morbidly obese
patients.3
Halovic et al demonstrated that in patients hospitalised with cellulitis and cutaneous abscess weight
>100kgandBMI>40wereriskfactorsfortreatmentfailureinpatientstreatedwithcotrimoxazoleand
clindamycin(thetwomostcommonantibioticsprescribedtopatientsforthisindicationinthisstudy).
Further subgroup analysis demonstrated that morbidly obese patients were at a higher risk of clinical
failureiftheyweredischargedonaloworaldoseofclindamycinorcotrimoxazole(P=0.002).4
Summary/Comments
Underweightpatients
Obesepatients
Asabovetakingrenalfunctionintoaccount
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References
1. Septrin(CoTrimoxazole)AspenGlobal.SummaryofProductCharacteristicsAccessedat
www.medicines.org.uk,14thJune2013
2009.
3. JansonBandThurskyK.DosingofAntibioticsinObesity.CurrentOpinionInfectiousDisease
2012;25:634649.
4. HalilovicJ,Heintz,BrownJ.Riskfactorsforclinicalfailureinpatientshospitalised
withcellulitisandcutaneousabscess.JournalofInfection2012;65:128134.
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Daptomycin
Indicationsforuse Dosagerecommendation
cSSTI*withoutS.aureusbacteraemia 4mg/kgoncedaily
RIE**orcSSTIassociatedwithS.aureus
6mg/kgoncedaily
bacteraemia
*cSSTI=complicatedskinandsoftskininfection**RIE=rightsidedinfectiveendocarditis
asrelevant.2
Underweightpatients
Noinformationbeyondstandardmg/kgdosing.
Obesepatients
Dvorchicketalsuggestuseoftotalbodyweightforcalculationofdosesisappropriatebasedontotal
bodyweight.3PaietalalsonotedthatuseoftotalbodyweighttocalculateresultedinhigherCmaxand
AUCvaluesinmorbidlyobesesubjectsthaninnormalweightsubjectswithsimilarcreatinineclearance
values.4As daptomycin displays a concentration dependent pharmacodynamic effect, the authors
arguedthatdosingbasedontotalbodyweightisappropriateasdosingbasedonIBWmayfailtoreach
adequateconcentrations.
Summary/Comments
Underweightpatients
Noinformationbeyondmg/kgdosing.
Obesepatients
Appropriatetodoseontotalbodyweightensuringappropriatemonitoringfortoxicityanddose
adjustmentforrenalimpairment.
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References
1. Cubicin(Daptomycin)NovartisPharmaceuticalUKLtd.SummaryofProductCharacteristics
Accessedatwww.medicines.org.uk,8thFebruary2013
2009.
3. DvorchickBH,DamphousseD.ThepharmacokineticsofDaptomycininmoderatelyobese,
morbidlyobeseandmatchednonobesesubjects.JournalofClinicalPharmacology,2005;45:
4856
4. PaiMP,NorenbergJP,AndersonTetal.Influenceofmorbidobesityonthesingledose
pharmacokineticsofdaptomycin.Antimicrobialagentsandchemotherapy2007;51(8):2741
2747
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Dexmedetomidine
Patientsalreadyintubatedandsedatedmayswitchtodexmedetomidinewithaninitialinfusionrateof
0.7micrograms/kg/hwhichmaythenbeadjustedstepwisewithinthedoserange0.2to1.4
micrograms/kg/hinordertoachievethedesiredlevelofsedation,dependingonthepatient'sresponse.
Underweightpatients
As above, manufacturer recommends a lower starting infusion rate should be considered for frail
patients.
Obesepatients
Orioncontacted.NoadditionalinformationsuppliedfromtheSPC.Advisetotitratedoseaccordingto
effectinallpatients.Meanbodymassinclinicaltrials=80.6kg.
Summary/Comments
Underweightpatients
Titratedoseaccordingtoresponse.
Obesepatients
Titratedoseaccordingtoresponse
References
1. Dexdor(Dexmedetomidine)OrionPharm(UK)LtdSummaryofProductCharacteristicsAccessed
atwww.medicines.org.uk,4thDecember2012
2. PersonalcommunicationwithJulieBooth,OrionPharm(UK)Ltd4thDecember2012
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Ertapenem
Adultsandadolescents(1317yearsofage)1gram(g)givenoncedailybytheintravenous
route.1
Underweightpatients
Noinformationavailablerelatingtodosingofertapeneminunderweightpatients.
Obesepatients
Paper by Chen et al discussed pharmacokinetic and pharmacodynamics of a 1g dose of ertapenem

administeredtonormalweight,obese andmorbidlyobeseadults.Theareaunderthe concentration
timecurvewassignificantlyhigherinnormalweightsubjectsthaninclinicallyobesesubjects.
The authors stated that the results suggested that the standard 1g ertapenem dose may not provide
adequatedrugexposureinobesepatientsfororganismswithaminimuminhibitoryconcentration(MIC)
inexcessof0.25to0.5g/ml.InVitrostudieshavesuggestedthatthefollowingorganismsmayhave
MIC90s* which exceed 0.25g/ml: Strep pneumoniae, oxacillin susceptible coagulase negative
staphylococci,AcinebactersppandPseudomonasaeruginosa.3
MIC90S=provideminimuminhibitoryconcentrationin90%ofstrainstested
Summary/Comments
Underweightpatients
Obesepatients
Nodosageadjustmentsoutwithlicenseddosecanberecommendedineitherunderweightor
overweight patients, however the MIC90s of certain organisms should be taken into account
whenprescribingertapenem.
Suggestdiscusseachpatientwithlocalmicrobiology/infectiousdiseases.
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References
1. Invanz(Ertapenem)MerckSharpandDohmeLtdSummaryofProductCharacteristics.
Accessedatwww.medicines.org.uk5thFebruary2013
2009.
3. ChenM,NafzigerAN,DrusanoGL.Comparativepharmacokineticsandpharmacodynamictarget
attainmentofErtapeneminnormalweight,obeseandextremelyobeseadults.Antimicrobial
AgentsandChemotherapy2006;50(4):12221227.
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Flucloxacillin
Usualadultdosage250mgto1gfourtimesdaily(IV)
Dosesdoubledwherenecessary
Underweightpatients
Obesepatients
Seebenzylpenicllinmonographforgeneralinformationondosingofbetalactamsinobesity.
Summary/Comments
Underweightpatients
Obesepatients
Dosingforpenicillins,dosingshouldbeattheupperendofthehigherendoftherecommended
treatmentranges,particularlyinmorbidlyobesepatientswithmoresevereinfections.3
Suggest dosing at upper end of range where appropriate, taking into account patients renal
function.Suggestdiscussingwithlocalmicrobiologyorinfectiousdiseasesspecialist.
References
1. FlucloxacillinActivisUKLtd.SummaryofProductCharacteristics.Accessedat
www.medicines.org.uk8thFebruary2013
2009.
3. ErstadB.Dosingofmedicationsinmorbidlyobesepatientsintheintensivecareunitsetting.
IntensiveCareMedicine2004;30:1832.

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Fluconazole
Therecommendeddailydosesarebetween50800mg(800mgisequivalentto12mg/kgina
65kgpersondependingoninfection).
DoseadjustmentsforrenalimpairmentasperSPCorrefertorenaldrughandbook.1,2

Underweightpatients
Obesepatients
Theonlydocumentedcaseisofa185kgman,BMI48.3,wasgiven1200mgandshowedalowerAUCand
increasedfluconazoleclearance.Theconclusionwasthatthefluconazoledoseshouldbebasedonthe
higherendofthe6to12mg/kgdosingrangebasedontotalbodyweightbasedonthissinglestudy.3
Summary/Comments
Underweightpatients
Nospecificinformationavailable.
Obesepatients
Insufficientinformationavailabletomakearecommendation.Seeaboveforonecasereport.4
References
1. Diflucan(Fluconazole)PfizerSummaryofProductCharacteristics.Accessedat
www.medicines.org.uk1stAugust2013
2009.
3. ChenLG.,DiBaisioA.,LiscoS.J.,HurfordW.E.Fluconazoleserumconcentrationsand
pharmacokineticsinanobesepatient.Pharmacotherapy1997;.17(5I):10231026.
4. JarrettR.A,SlainD.Antifungaldosinginobesity:Areviewoftheliterature.CurrFungalInfect
rep(2011)5:8391.
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Immunoglobulin
Byintravenousinfusion,dosebasedonindication.RefertoDepartmentofHealthguidelines.2
DoseadjustmentsforrenalimpairmentorhepaticimpairmentasperSPC
SummaryofSACCPNliteraturereviewandrecommendationsfromClinicalguidelinesfor
immunoglobulinuse2
Underweightpatients
Nospecificinformationonunderweightpatientshowever,mg/kgdosingcanbeused.
Obesepatients
Informationfromguidelines:
Thereislimitedevidenceforidealbodyweightadjusteddosingandthereforenofirmrecommendation.
However, a number of specialist centres and corporations from Western Australia, United States of
AmericaandtheUKusetheequationsbelow:Notethisisdifferentfromtheequationsshownonp4
Calculateidealbodyweight(IBW)(kg):
IBWformales =50+[2.3x(heightininches60)]
IBWforfemales =45.5+[2.3x(heightininches60)]
Calculatedosedeterminingweight(DDW)(kg):
DDW =IBW+0.4[actualbodyweight(kg)IBW]
The guidelines suggest that if adjusted weight dosing for patients >30kg/m2 or if actual weight >20%
morethanIBW,adjustedbodyweightprescribingshouldbeconsidered.Itisalsorecommendedthat,
foradults,thedoseshouldberoundeddowntothenearestvial.Localdosingweighttablesmaybein
use.
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Summary/Comment
Underweightpatients
Obesepatients
Nostrongevidence,howeverspecialistconsensusadvocatestheuseoftheDDWequation
above.
References
1. Summaryofproductcharacteristicsforindividualnormalhumanimmunoglobulinproducts.
Accessedatwww.medicines.org.uk27thJune2013
2. DepartmentofHealth.Clinicalguidelinesforimmunoglobulinuse.Secondeditionupdate,
editedforScotland.DepartmentofHealth.March2013.
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Levofloxacin
Usualrecommendeddose500mgonceortwicedailydependingonindication.1
DoseadjustmentsasperSPCorrefertorenaldrughandbook.2
Underweightpatients
Obesepatients
Literaturesearchyieldedlittleresults
Cooketalcarriedoutaverysmallstudyandconcluded;aftera750mgintravenousdoseevery24hours,
obese individuals achieve a comparable peak concentration to normalweight individuals. However,
they state obese individuals with normal renal function may clear levofloxacin more effectively and
consequently have a lower AUC. No recommendations were made except to consider this variation
when dosing in obese patients, particularly individuals who have a high clearance or a pathogen
requiringmoreaggressivetherapy.3
Luque et al reported on a single case of an obese individual give levofloxacin IV every 12hours. They
found the AUC was doubled in this patient compared with those expected in nonobese health y
volunteers.4
Summary/Comments
Underweightpatients
Obesepatients
Toolittleinformationtogiveadefinitivedoserecommendationinobesepatients.
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References
1. Tavanic(Levofloxacin)Sanofi.SummaryofProductCharacteristicsAccessedat
www.medicines.org.uk7thJune2013
2009.
3. CookAM,MartinC,AdamsVRandMoreheadAR.Pharmacokineticsofintravenouslevofloxacin
administeredat750milligramsinobeseadults.Antimicrob.AgentsChemother.2012,
55(7):3240
4. LuqueS,GrauS,M,ColinoCI&FerrerA.Levofloxacinweightadjsteddosingand
pharmacokineticdispositioninamorbidlyobesepatient.JAntimicrobChemother
2011;66(7):16534

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Linezolid
Byintravenousinfusion600mgtwicedaily.1
Noadviceonunderweightorobesepatients.
DoseadjustmentsforrenalimpairmentorhepaticimpairmentasperSPC/renaldrug
handbookasrelevant.2
Underweightpatients
There have been no studies carried out on underweight adults in any clinical trials, however in a
compassionateuseprogrammeadultpatientswhoweighedmorethan40kgweretreatedatadoseof
600mg every 12 hours (both IV and oral). For adult patients 40kg a dose of 10mg/kg every 12 hours
wasused(bothIVandoral).4
Obesepatients
Base dose on total body weight however as body weight has an impact on linezolid clearance and
absorption rate constant in patients with cystic fibrosis then for this patient group lean body weight
shouldbeused.4
Dosage adjustments based on BMI alone are not required and standard doses for patients with body
weights up to approximately 150kg should provide AUC values similar to those seen in non obese
patients.4600mgtwicedailywassufficientforthetreatmentofskinandsofttissueinfectionsinobese
adults.
Summary/Comments
Underweightpatients
Nostudiescarriedoutonunderweightadultsinanyclinicaltrials
Inacompassionateuseprogrammeofadultpatients,thosewhoweighedmorethan40kgwere
treatedatadoseof600mgevery12hours(bothIVandoral).Adultpatients40kgreceiveda
doseof10mg/kgevery12hours(bothIVandoral).
Obesepatients
DosageadjustmentsbasedonBMIalonearenotrequiredandstandarddosesforpatientswith
bodyweightsuptoapproximately150kgshouldprovideAUCvaluessimilartothoseseeninnon
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obesepatients.
600mg twice daily was sufficient for the treatment of skin and soft tissue infections in obese
adults.
References
1. Zyvox(Linezolid)PfizerLtd.SummaryofProductCharacteristics,Accessedvia
www.medicines.org.uk,15thApril2013
3. 2009.DiPaolo,A.,Malacarne,P.,Guidotti,E.,Danesi,R.andDelTacca,M.Pharmacological
IssuesofLinezolid,AnUpdatedCriticalReview.ClinPharmacokinet2010:49(7);439447
4. BhalodiAA,PapasavasPK,TishierDS,NicolauDPandKutiJL,Pharmacokineticsof
intravenouslinezolidinmoderatelytomorbidlyobeseadults.AntimicrobialAgentsand
Chemotherapy;March201357(3),114449
5. PersonalCommunication,PfizerMedicalInformation.15thApril2013
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Meropenem
Byintravenousinfusion500mg2gevery8hours.
Noinformationondosinginunderweightorobesepatients.
asrelevant.2
Underweightpatients
Nodosingadvicefound.
Obesepatients
SeeBenzylpenicillinforgeneralinformationondosingofBetaLactamsinobesity
BeardenetalassessedthepharmacokineticsofMeropenemadministeredtoobesesubjects.
Meropenem1gdosedto9obesefemalepatients(BMI>40).CMax58%andAUC66%ofthosereported
inavailableliteraturefornormalBMIsubjects.
Calculatedpercentageoftimeaboveminimuminhibitoryconcentration(%T>MIC)fororganismswithan
MICof1mg/mland4mg/mlwere78.6%and49.6%ofan8hourdosingintervalrespectively.4
DuetotheshorthalflifeofMeropenem,thesechangeshadlittleeffectonT>MIC(3%),whencompared
withnormalweightpatients.Basedonthestudyfindingstheauthorsrecommendednochangeinthe
meropenemdosingregimenforobesepatients.4
Summary/Comments
Underweightpatients
Noinformationondosinginthesepatients
Obesepatients
Nochangerecommendedtostandarddosingregimen.
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References
1. Meronem.(Meropenem)AstraZenecaSummaryofProductCharacteristicsAccessedat
www.medicines.org.uk11thJanuary2013
2009.
3. PersonalcommunicationwithAstraZenecaNovember2012.
4. BeardenDT,EarleSB,McConnellDBetal.Pharmacokineticsofmeropeneminextremeobesity
(abstract).Presentedat45thInterscienceconferenceonAntimicrobialAgentsand
Chemotherapy(ICAAC);December1619,2005;WashingtonDC,USA.
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Metronidazole
Usualdosesrangefrom500mgTDStotreatestablishedanaerobicinfections(inadults)tosingle
dailydosesofupto2g,forthetreatmentoftrichomoniasis.
Cautionisadvisedintheelderly.Particularlyathighdosesalthoughthereislimitedinformation
availableonmodificationofdosage.1
Underweightpatients
Noinformationfoundondosinginunderweightpatients,althoughmg/kgdosingcouldbeused.
Obesepatients
An analysis of two separate studies assessing the effect of the BMI of 738 pregnant women with
bacterialvaginosis(whoeachreceivedadoseof2gMetronidazoleat0and48hours)ontherateofits
recurrence,concludedthatBMIhaddidnoteffecttherateofrecurrenceofandthereforeitwasthought
thattheefficacyofMetronidazolewassimilaramongdifferentBMIcategories.2
AnotherstudyalsonotedthatPharmacokineticparametersinpregnantpatientswerenotsignificantly
differentfromthoseinnonpregnantwomen3
Single doses of up to 12g have been reported to have been taken in suicide attempts/accidental
overdosageswithresultingsymptomslimitedtovomiting,ataxiaandslightdisorientation.1
Summary/Comments
Underweightpatients
Nospecificinformationavailable,mg/kgdosingcouldbeused.
Obesepatients
Usestandarddosing
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References
1. Flagyl(Metronidazole)Zentiva.SummaryofProductCharacteristicsAccessedat
2. MastrobattistaJM,KlebanoffMA,CareyJC,etal.Theeffectofbodymassindexontherapeutic
responsetobacterialvaginosisinpregnancy.AmLPerinatol2008;25:233237
3. Micromedex.Metronidazolemonograph.Obtainedfromwww.micromedexsolutions.com
Accessed15thMay2013

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Phenytoin
Loadingdose(intravenous)1015mg/kg.N.BBritishNationalFormularyrecommends
intravenousloadingdoseof20mg/kguptoamaximumdoseof2g.
Maintenancedose5mg/kgdaily
Nospecificadviceonunderweightorobesepatients
asrelevant.3
Underweightpatients
Nospecificinformationonunderweightpatientshowever,mg/kgdosingcanbeusedasabove.
Obesepatients
Phenytoin loading dose should be calculated on the basis of IBW plus the product of 1.33 times the
excessweightoverIBW.Veryobeseindividualswillrequirelargeabsoluteloadingdosesofphenytointo
rapidlyachievetherapeuticdrugconcentrations.5
Summary/Comments
Underweightpatients
Nospecificinformationonunderweightpatientshowever,mg/kgdosingcanbeusedasabove.
Obesepatients
Obesepatientsmaybenefitfromincreaseddosingfortheloadingdoseusingaweightof
Dosingweight=Idealbodyweight+[1.33x(ActualbodyweightIdealbodyweight)]
Bothgroupsofpatientwillrequiretherapeuticdrugmonitoringtoensuremaintenancedose
maintainslevelswithinthetherapeuticrange.Albuminandrenalfunctionshouldbetakeninto
accountwheninterpretingthelevelsiftotalphenytoinismeasuredasopposedtofree
phenytoinlevels.
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References
1. Epanutin.(Phenytoin)PfizerLtd.SummaryofProductCharacteristicsAccessedat
www.medicines.org.uk26thJune2013
2. BritishNationalFormulary65,March2013.PublishedjointlybyBMJGroupandPharmaceuticalPress.
3. AshleyC(Ed)&Currie,A(Ed).Therenaldrughandbook.3rdedition.RadcliffePublishing,Oxford.2009.
4. PersonalcommunicationwithPfizerJanuary2013.
5. AbernethyDR,GreenblattDJ.Phenytoindispositioninobesity,determinationofloadingdose.Arch
Neurol1985;42(5):468471.
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Piperacillin/Tazobactam
Usualrecommendeddoseis4.5gevery8hrs.
Forsevereinfectionsandinneutropenicpatientswithinfectionsthedosemaybeincreasedto
4.5gevery6hrs.1
DoseadjustmentsforrenalimpairmentasperSPCorreferrenaldrughandbook.2
Underweightpatients
Nospecificadviceavailableforunderweightpatients.
The BNF for Children3 lists the dose as Child 212 years 112.5 mg/kg (max. 4.5 g) every 8 hours for
complicated intraabdominal infections or 90mg/kg (max 4.5g) every 8 hours for other infections
includinginpatientswithneutropeniawhichwouldsuggestreducingthedoseinpatientsunder40kgor
50kgifneutropenic..
Obesepatients
Suggesthigherdosesofpiperacillin/tazobactam4.5g6hrly.Maximumreporteddoseofpiperacillin(not
piperacillin/tazobactam)reportedas24g/dayN.B.piperacillinnotlicensedinthe UnitedKingdom.3Ithas
beensuggestedthatcontinuousinfusionforisolateswithhighMICmaybebeneficial,howevera2013
Cochrane review found no evidence of improved outcomes when comparing continuous infusions of
intravenousantibioticstotraditionalintermittentinfusionsofantibiotics.4,5
Severalreferencessuggestthatbonemarrowrelatedtoxicitywaslinkedtothecumulativedose
of piperacillin/tazobactam and that the dose should be reduced in low body weight patients.
Nospecificdosingadvicehasbeenfoundandthereferencesalllinkedbacktothesamecase
report.6
There is currently a clinical trial running in Montpelier investigating the pharmacokinetics of

Piperacillin/Tazobactamincriticallyillpatientsover120kg.
Summary/Comments
Underweightpatients
Nospecificadviceavailable,suggestmg/kgdosingasabove
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Obesepatients
Suggest4.5g6hrlydependentonrenalfunction.
References
1. Tazocin(Piperacillin/Tazobactam)PfizerLtd.SummaryofproductcharacteristicsAccessedat
www.medicines.org.uk12thMarch2013
2. AshleyC(Ed)&Currie,A(Ed).Therenaldrughandbook.3rdedition.RadcliffePublishing,Oxford.2009.
3. BNFforChildrenMarch2013accessedonline9thMay2013
4. JansonBandThurskyK,Dosingofantibioticsinobesity,CurrOpinInfectDis.2012Dec;25(6):63449.
5. ShiuJ,WangE,TejaniAMetal.Continuousversusintermittentinfusionsofantibioticsforthe
treatmentofsevereacuteinfections(Review).TheCochraneLibrary2013,issue3.
www.thecochranelibrary.comaccessed7thJune2013
6. RuizIrastorzaG,BarreiroG,AguirreC,Reversiblebonemarrowdepressionbyhighdose
piperacillin/tazobactamBritishjournalofhaematology95:41996Decpg6112
7. PharmacokineticofDoripenemandPiperacillin/TazobactaminMoreThan120kgCriticallyIllPatients
http://clinicaltrials.gov/ct2/show/record/NCT01517815accessed11thApril2013.
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Rifampicin
Usualrecommendeddose600mg1200mgdailyin24divideddoses.
Adailydoseof8mg/kgshouldnotbeexceededinpatientswithimpairedliverfunction.

Underweightpatients
Noinformationavailableondosinginunderweightpatients.
Obesepatients
Dosingbasedonactualbodyweightmayleadtodrugtoxicityandsuggestusingidealbodyweight.
Essentiallythismeansupto1200mg/dayindivideddoses.4
Summary/Comments
Underweightpatients
Obesepatients
Doseusingidealbodyweight,upto1200mg/dayindivideddoses.
References
1. Rifadin(Rifmpicin)SAnofiAvensis.SummaryofproductcharacteristicsAccessedat
www.medicines.org.uk8thApril2013
2009.
3. PersonalcommunicationwithSanofiAventis2ndApril2013
4. GeiselerPJetalAmRevRespirDis1985;131(6):9446
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Sugammadex
Adoseof4mg/kgsugammadexisrecommendedifrecoveryhasreachedatleast12post
tetaniccounts(PTC)followingrocuroniumorvecuroniuminducedblockade
Adoseof2mg/kgsugammadexisrecommended,ifspontaneousrecoveryhasoccurreduptoat
leastthereappearanceofT2followingrocuroniumorvecuroniuminducedblockade.
SPCrecommendsusingABWfordosecalculation
Underweightpatients
Asabove
Obesepatients
Van Lancker et al (1) proposed that (IBW +40%) would be appropriate for obese patients. However
subsequent replies disagreed, saying that while this was true based on pharmacokinetic principles, in
realitydosingbasedonTBWismoredependable.(2,3)
Summary/Comments
Underweightpatients
Useactualbodyweight,asperSPC
Obesepatients
Usetotalbodyweight.
References
1. Bridion.(Sugammadex)MerckSharpandDohmeLtd.SummaryofProductCharacteristicsAccessedat
www.medicines.org.uk6thSeptember2013.
2. VanLanckerP,DillmansB,BogaertTetal.Idealversuscorrectedbodyweightfordosageofsugammadex
inmorbidlyobesepatients.Anaesthesia2011;66:721725
3. CarronMFreoUParottoEandOriC.Thecorrectdosingforsugammadexinmorbidlyobesepatients.
Anaesthesia2012;67:298299
4. SabateAandLlauradoS.Idealversuscorrectedbodyweightfordosageofsugammadexin
morbidlyobesepatients.Anaesthesia2012;67:682
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Tigecycline
Therecommendeddoseforadultsisaninitialdoseof100mgfollowedby50mgevery12hours
for5to14days.Thedurationoftherapyshouldbeguidedbytheseverity,siteoftheinfection,
andthepatient'sclinicalresponse.1
Tigecyclinehasnotbeensystematicallyevaluatedforsafetyorefficacyinextremesofbodyweight.In
clinicaltrials,patientweighthasrangedfrom34kgto200kg,andanalysisofAUCandclearancedidnot
appeartobedifferent,suggestingthereisnopharmacokineticjustificationfordoseadjustmentbased
onpatientweight.2
Underweightpatients
Noinformation
Obesepatients
Noinformation
Summary/Comments
Underweightpatients
Noinformation
Obesepatients
Noinformation
References
1. Tygacil(Tigecycline)PfizerLtd.SummaryofProductCharacteristicsAccessedat
2. PersonalCommunicationPfizerMedicalInformation21stJanuary2013
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Voriconazole
Intravenous Oral
Patients40kgand Patientslessthan
above 40kg*
LoadingDose 6mg/kgevery12 400mgevery12hours 200mgevery12hours

hours
(first24hours)
MaintenanceDose 4mg/kgtwicedaily 200mgtwicedaily 100mgtwicedaily
(afterfirst24hours)
*Referstopatientsaged15yearsandolder.
Noadviceonobesepatients
asrelevant.2
Underweightpatients
Dosingasabove.
Obesepatients
Fororalroutedosingasabove.
Dosingforivweightbased.
Loading dose regimen 6mg/kg every 12 hours for 24 hours then 4mg/kg every 12 hours. Phase 3 trial
datawasforpatients39to123kgactualbodyweight
Koselke et al performed a retrospective cohort study to evaluate voriconazole trough levels in obese
BMI>35kg/m2 and normal weight BMI>18.5 24.9 KG/m2. Strong association between
supratherapeutic concentrations in morbidly obese patients receiving 4mg/kg actual body weight.
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Authorsuggeststhatformorbidlyobesepatientsmaybemoreappropriatetodoseasidealoradjusted
bodyweight.
Summary/Comments
Underweightpatients
DosingasperSPC/renaldrughandbook.
Obesepatients
Strong association between supratherapeutic concentrations in morbidly obese patients

receiving4mg/kgactualbodyweight.Someevidencetosupportusingadjustedbodyweightin
patientswithBMI>35kg/m2althoughnotadefinitiverecommendation.6
References
1. Vfend(Voricoonazole)PfizerLtd.SummaryofProductCharacteristicsAccessedat
2009.
3. PersonalcommunicationwithPfizerMedicalInformationJuly2013
4. Thepharmacokineticsandsafetyofintravenousvoriconazoleanovelwidespectrum
antifungalagent.PurkinLetal.BrJClinPharmacol2003;56(Suppl1)29
5. Pharmacokineticsandsafetyofvoriconazolefollowingintravenoustooraldoseescalation
regimens.PurkinetalAntimicrobAgentsChemother2002;46(8):25462553.
6. Koselkeetal.Evaluationoftheeffectofobesityonvoriconazoleserumconcentrations.J
AntimicrobChemother2012;67:29572692.
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2014 07 24 19 55 33 Drugdosingatextremesofbod 45662

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September2013

Descriptor Abbreviation Formula

TotalBodyWeight TBW Weight(Wt)

ActualBodyWeight ABW Weight(Wt)

BodyMassIndex BMI Wt/height(m)2

IdealBodyWeight IBW =45.4+[0.89x(height{cm}152.4)](+4.5ifmale)

ExcessBodyWeight EBW =TBWIBW

MaximumBodyWeight MBW =IBW+20%

AdjustedBodyWeight AdjBW =IBW+[DWCF*xEBW]

LeanBodyWeight LBW Male=[9270xTBW]/[6680+(216xBMI)]

FatFreeMass FFM Male=[TBWx0.285]+[12.1xheight(m)2]

PredictedNormalWeight PNW Male=[TBWx1.57][TBWxBMIx0.0183]10.5

BodySurfaceArea BSA =[(height{cm}xTBW)/3600]

Paper by Chen et al discussed pharmacokinetic and pharmacodynamics of a 1g dose of ertapenem

There is currently a clinical trial running in Montpelier investigating the pharmacokinetics of

LoadingDose 6mg/kgevery12 400mgevery12hours 200mgevery12hours

MaintenanceDose 4mg/kgtwicedaily 200mgtwicedaily 100mgtwicedaily

Strong association between supratherapeutic concentrations in morbidly obese patients

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