Drug Use During Breastfeeding

8/4/2015 eTherapeutics+Complete:TherapeuticChoices:DrugUseduringBreastfeeding

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DrugUseduringBreastfeeding

Dateofrevision:December2014

M.S.BrochetBPharmMScS.ItoMDFRCPCThefollowingisanoverviewofdruguseduringbreastfeeding.Thisinformationisnotintendedtobeacomprehensivereviewthereaderisthereforeencouragedtoseekadditionalandconfirmatoryinformation.

PrinciplesofDrugUseduringBreastfeeding

Clinicianscanusethefollowinggeneralprinciplestomanagecaseswheredrugexposureinabreastfedinfantisquestioned:

Almostalldrugsareexcretedtosomedegreeinbreastmilk.Breastmilk/feedinghastangiblemedicalandotherbenefitscomparedtoformula.1,2,3Evenwhenthebreastmilk:maternalplasmaconcentrationratioapproachesorexceeds1,theamountofdrugingestedbytheinfantrarelyattainstherapeuticlevels.Briefexposuretoadrug,asmightbeexpectedinthecaseofanalgesicsgiventorelievepostpartumpain,isusuallyoflessconcernthanadruggivenforlongperiodsoftime.Theamountofdrugingestedbytheinfantcan,onoccasion,beminimizedbyfeedingtheinfantjustbeforeoratthetimeofmaternaldosing.Inthecaseofchronicdrugtherapy,theinfantisusuallyexposedtolowerconcentrationsofthedrugwhilebreastfeedingthanwhilethefetusisinutero.Nevertheless,inmostcasesthelongtermconsequencesofchronicexposuretosubtherapeuticlevelsofmedicationsarenotknown.Recommendationsaboutbreastfeedingduringdrugtherapydependonknowingifsmallamountsofthedrug(subtherapeuticamounts)takenforevenshortperiodsoftimemaybeassociatedwiththefollowing:

idiosyncraticreactions,e.g.,chloramphenicolinterferencewithgeneticallyabnormalmetabolicpathways,e.g.,nitrofurantoininpatientswithG6PDdeficienciessynergisticeffectswithdrugstheinfantreceivestherapeutically,e.g.,caffeineincoffeeandteamayenhanceeffectsoftherapeuticcaffeineoraminophyllineintheneonate

Cliniciansrequireareasonableknowledgeofpharmacologyandtherapeuticsinthenewbornaswellasaknowledgeoftheamountofdrugexcretedinbreastmilk.

TheDrugsandLactationdatabase(LactMed)isareliableandauthoritativewebbasedresourceaboutdrugexcretioninbreastmilkandrecommendationsforbreastfeedingduringmaternaltherapy.5ItisfreeofchargeandrunbytheUSNationalLibraryofMedicine.LactMedishousedwithintheTOXNETWebsite.

Considerseveralimportantquestionswhenabreastfeedingmotherstartsdrugtherapy:4

IsthedrugabsorbedfromtheGItract?Isthedrugevergivendirectlytoinfantsfortherapeuticreasons?Doestheestimateddosedeliveredthroughbreastmilkapproachatherapeuticquantity?Aretheeffectsofthedrugeasilyrecognizedintheinfant?Arethereidiosyncraticorallergicreactionstothedrugthatarenotdoserelated?Aretherelesstoxicalternativesformaternaltherapy?Isthereapotentialfordrugaccumulationduringprolongedtherapy?Couldsubtherapeuticdosesofthedrugmaskearlysignsofmedicalconditionsintheinfant?Istheriskposedbythedrugsubstantialenoughtooutweighthesignificantprovenbenefitsofbreastfeeding?

DrugsCompatiblewithBreastfeeding

Drugsconsideredcompatiblewithbreastfeedingfaroutnumberthoseconsideredcontraindicatedduringbreastfeeding.Table1discussessomeexamplesofdrugsconsideredtobecompatiblewithbreastfeeding.



Table1:DrugsCompatiblewithBreastfeedinga

TherapeuticClass

Drugs/DrugClasses

CompatiblewithBreastfeeding Comments

Analgesics Acetaminophen,morphine

Formostopioidanalgesics,theamountofdrugexcretedinbreastmilkissmall,andshorttermuseshouldbeofnomajorconcern.Ifusedforlongerthan3daysmonitorcloselyfordrowsiness/sedation,difficultybreathing,difficultybreastfeeding,decreasedtone,particularlyinprematureinfantsandneonates.6Meperidineisanexceptioninneonates,thelonghalflivesofmeperidine(13h)andnormeperidine(63h)mayresultinaccumulationinplasma,possiblyleadingtoneurobehaviouraldepression.7,8Inaddition,usecodeinewithcautionatthelowesteffectivedosefortheshortestperiodoftime.MotherswithultrarapidmetabolizerCYP2D6genotype(Chinese,Japanese,Hispanic0.51%Caucasian110%AfricanAmerican3%NorthAfrican,Ethiopian,SaudiArabian1628%)mayexperienceintensifiedeffectsfromaregulardosingregimenofcodeineduetoincreasedconversionofcodeinetomorphine,causingmorphinetoxicity.Resultanthighlevelsofmorphineinmaternalserumcouldcauserelativelyhighmorphinelevelsinbreastmilk.4Mothersexperiencingmorphinetoxicity,whetherduetothisgenotypeormorphineoverdose,shouldnotbreastfeed.Codeineuseshouldbelimitedtolessthan34daysinabreastfeedingmother.OxycodoneandhydrocodonearealsometabolizedbyCYP2D6toapotentactivemetaboliteseecodeineforinformationregardingtheultrarapidmetabolizerCYP2D6genotype.4MaternaloxycodoneusehasbeenassociatedwithasimilarincidenceofneonatalCNSdepressionascodeine9andlevelsinbreastmilkstronglycorrelatedwithplasmalevelsinonestudy.10Useofoxycodoneorhydrocodonewhilebreastfeedingshouldbeconsideredonlyinpatientswhocannottakeotheropioidsandshouldbelimitedtolessthan34days.Theamountofmorphineexcretedinbreastmilkcouldreach7.5%ofthepediatricdose.11Despitewidespreaduseofmorphinebybreastfeedingmothers,thereisonlyonecasereportofanursinginfantwiththerapeuticplasmaconcentrations.12Limiteddataindicatesthathydromorphoneisexcretedintobreastmilkinsmallamounts.4Datafortramadolarelacking.Shorttermusemaybeaconcernduetoitslonghalflife(7hfortramadoland8.5hfortheactivemetaboliteinnewborns)especiallyinprematureinfants:monitorforincreasedsleepiness.Excretionintobreastmilkislow,thereforeitisunlikelytoaffecthealthybabies.Anexclusivelybreastfedinfantwouldreceiveabout10%ofthetherapeuticdoseforachild.13Methadonelevelsinhumanmilkarelow.Anexclusivelybreastfedinfantwouldreceive



Antibiotics Aminoglycosides,cephalosporins,clindamycin,fluoroquinolones,macrolides,metronidazole,nitrofurantoin,penicillins,sulfonamides

Formanyantibiotics,theamountsingestedbyabreastfedinfantwillbebelowtherapeuticlevels(e.g.,penicillins,cephalosporins),butmightbesufficienttoresultinidiosyncraticreactions(e.g.,chloramphenicol)orcauseanemiainaninfantwithG6PDdeficiency(e.g.,nitrofurantoin,sulfonamides).OtherpotentialproblemsaremodificationstothenormalGIfloraleadingtothrushanddiarrhea.However,clinicalsignificanceoftheserisksisusuallynothighenoughtojustifydiscontinuationofbreastfeeding.AminoglycosidesareexcretedinbreastmilkwhenadministeredimorivtothemotherbecausethedrugsarepoorlyabsorbedfromtheGItract,itisunlikelythatrenaltoxicityorototoxicitywouldoccurintheinfant.Onlysmallamountsoforalclindamycinareexcretedinbreastmilk(26%oftherecommendedpediatricdosage).Itisunlikelythatthesequantitieswouldbeclinicallyrelevantbutatleastonecaseofbloodystoolshasbeenreportedinthebreastfedinfantofamotherreceivingclindamycin.Topicalclindamycin(notusedinthenipplearea)isgenerallyassociatedwithlowermaternalsystemicdruglevelsandlowerbreastmilkexcretioncomparedtosystemicuse.14Erythromycinisexcretedinbreastmilkinlowamountsandiscompatiblewithbreastfeeding.Limiteddataregardingclarithromycinandazithromycindemonstratethatthesedrugsareexcretedinbreastmilkinsmallamounts,buttheamountofdrugingestedbyabreastfedinfantislikelybelowtherapeuticpediatriclevels.16,17Nodataareavailableregardingtheexcretionoftelithromycininbreastmilk.Metronidazoleuseduringbreastfeedinghasraisedsomeconcernsbasedonreportsthatitismutagenicinbacteriaandcarcinogenicinrodentsduringlifelongingestion.Specificuntowardeffectsinanursinginfantasaresultofmetronidazoleingestionhavenotbeenreported.Withoutmoredirectevidenceoftheharmfuleffectsofshorttermuseinhumans,itseemsoverlyconservativetowithholdthedrugordiscontinuebreastfeedinginpatientswithsymptomaticinfections.Forthetreatmentoftrichomoniasiswithasingleoraldoseofmetronidazole2g,somecliniciansnowrecommendaninterruptionofbreastfeedingfor1224h,especiallywithyoungbabies.7Topicalmetronidazole(aslongasitisnotusedinthenipplearea)isconsideredcompatiblewithbreastfeedingsincebloodlevelsandexcretionintobreastmilkarelowerthanwithmaternalsystemicmetronidazoleuse.Fluoroquinoloneshavetraditionallynotbeenusedininfantsbecauseofconcernsregardingadverseeffectsonjointdevelopment.Studiesindicatelittlerisk.Shorttermuseofciprofloxacin,levofloxacin,norfloxacinorofloxacinisacceptableinnursingmothers.Thesequinolonesareexcretedinbreastmilkinsmallamountswhichdonotresultinsignificantserumconcentrationsinbreastfedinfants.Thecalciuminbreastmilkmayalsodecreasequinoloneabsorptionintheinfant.14Therearenodataavailableformoxifloxacin.Maternaluseofgatifloxacineyedropspresentsnegligibleriskforthenursinginfant.14Thesulfonamidesareexcretedinbreastmilkinsmallamounts.ThereareconcernsaboutthesedrugscausinganemiainaninfantwithG6PDdeficiencywhichismorecommoninthoseofAfrican,Greek,middleeasternandsoutheastAsianorigin.Usewithcautioninmothersbreastfeedingprematureinfantsorneonateswithhyperbilirubinemia.7Usealternativesunlesstheinfectionisnotrespondingtoothertherapy.Theuseofnitrofurantoininbreastfeedingmothersisgenerallysafe,asonlysmallamountstransferintothebreastmilk.Despitethelackofdocumentedreports,thereisapotentialriskofhemolyticanemiainallnewbornsexposedtonitrofurantoinowingtotheirglutathioneinstability,especiallyininfantswithG6PDdeficiency.Althoughsomesuggestthatnitrofurantoinbeavoided



ininfants



viabreastmilk,butacausativelinkisuncertain.29Therearealsoreportsofuneventfulbreastfeedingduringmaternalsertralineuse.30Paroxetineistransferredintobreastmilkresultinginanestimatedinfantdoseofbetween0.1%and4.3%oftheweightadjustedmaternaldoseb.Inthesestudies,paroxetinewasnotdetectedintheserumofthemajorityofinfants(inwhomitwasmeasured)andnoadverseeffectswerereported.30,31,32,33,34Theamountoffluoxetineexcretedinbreastmilkis218%oftheweightadjustedmaternaldose.b,25,26,27,28,30,31,32,33,34,35Nearlytherapeuticserumconcentrationswerereportedinsomesymptomaticinfants.36,37,38,39,40,41,42,43,44Also,infantsbreastfedbymothersonfluoxetinehadpoorerweightgain,althoughthesignificanceisunclear.40Afewcasesofcolichavebeenassociatedwithfluoxetine.37,41Becauseofthelonghalflivesoffluoxetineanditsactivemetabolites,cautionisadvised,particularlywhenbreastfeedingapreterminfantorneonate.14Excretionoffluvoxamineseemstobelowandnoadverseeffectswerereportedinthefewavailablecases.30,45Theamountofcitalopramexcretedinbreastmilkisapproximately0.79%oftheweightadjustedmaternaldoseb.Inonestudy,asingleinfantpresentedanuneasysleeppatternwhichimprovedwhenmaternaldosewasdecreased.46,47,48,49Theamountofescitalopramexcretedinbreastmilkislessthan8%oftheweightadjustedmaternaldosebandnoadverseeffectswerereportedintheavailablecases.14Venlafaxineanditsmetabolitesareexcretedinbreastmilkinapproximately59%oftheweightadjustedmaternaldose.b,50,51Inonestudyof7infantstheactivemetaboliteOdesmethylvenlafaxinewasdetectedintheplasmaof4infants.Noadverseeffectswerereportedintheinfants.52Excretionofdesvenlafaxine(Odesmethylvenlafaxine)intobreastmilkislessthan7%ofthematernalweightadjusteddosebandserumdruglevelsofbreastfedinfantsarelessthan6%ofsimultaneousmaternallevels.53Althoughbupropion,moclobemideandmirtazapinehavenotbeenstudiedextensively,foreachofthesedrugstheamountexcretedinbreastmilkislessthan2%oftheweightadjustedmaternaldose.bNoadverseeffectswerereported14,54,55,56,57,58,59exceptforbupropion(threecasereportsofpossibleseizure)althoughthesignificanceisunclear.60,61,62Limiteddataindicatethatexcretionoftrazodoneintobreastmilkislow,butdataonitsactivemetabolitesarelacking.63,64,65,66Theamountofduloxetineexcretedintobreastmilkseemstobelow,lessthan1%oftheweightadjustedmaternaldosebisexcretedintobreastmilk.67,68Overall,nosignificantshorttermeffecthasbeenreportedforthecommonlyusedantidepressantssuchastricyclicsandSSRIs.Clinicalsignificanceofreportedadverseeventsremainsunclear.Basethechoiceofantidepressantsonthematernalconditionandresponse.Nomatterwhatdrugisused,usecautionuntilmoreexperienceisgained.

Antiepileptics Carbamazepine,clonazepam,phenytoin,valproicacid

Theexcretionintomilkislow:approximately5%and2%oftheweightadjustedmaternaldosebforcarbamazepineanditsepoxidemetabolite,lessthan4%forvalproicacid,andlessthan8%forphenytoin.Noadverseeffectsduetocarbamazepine,phenytoinorvalproateexposureviabreastmilkwereobservedat



6yearsinaprospectiveobservationalmulticenterstudy.69Limiteddataforclonazepamindicatethattheweightadjustedmaternaldoseis



Antihistamines Cetirizine,desloratadine,fexofenadine,loratadine

Loratadineandfexofenadine(basedonterfenadinedata)resultininfantexposurelevelsof6months.11Theestimatedamountofdiphenhydramineababyisexposedtothroughbreastmilkislow(approximately0.3%ofapediatricdose).Occasionaluseisnotexpectedtocauseadverseeffects.Nonsedatingantihistaminesarepreferredforlongertermuseasanecdotalreportssuggestapossibledecreaseinmilkproduction.14Otherantihistaminesmaybegiven,butdataontheconcentrationsofthesedrugsinbreastmilkarelacking.Infantsshouldbemonitoredforirritabilityordrowsiness.79Antihistaminesarenotusuallycontraindicatedduringbreastfeeding.Alternativestooralantihistaminesthatmaybeconsideredduringbreastfeedingincludenasallyadministeredcorticosteroidsorcromolyn.Cromolynandnedocromileyedropsareconsideredacceptableduringbreastfeedingbecauseoftheirlowbioavailability.7

Antihypertensives Labetalol,metoprolol,propranololBenazepril,captopril,enalapril,quinapril,ramiprilMethyldopaDiltiazem,nifedipine,verapamilHydrochlorothiazide,furosemide

Betablockersthataresafetouseevenintheneonatalperiodarelabetalol,metoprololandpropranolol.70,80,81Acebutolol,atenololandsotalol(althoughthelatterisnotindicatedasanantihypertensiveagent)maycauserelativelyhighexposurelevels,10%,25%and20%,respectively,ofthoseexpectedwhenthedrugisgivendirectlytoaninfantinatherapeuticdose.Thismaynotbeaprobleminpostneonatalinfants.However,exercisecautionintheearlyneonatalperiodbecausenewbornsmayhavelowclearanceofatenololandsotalolasaresultofimmaturerenalfunction(lowGFR).Signsofbetablockadehavebeenreportedinabreastfedinfantofawomantakingatenolol(bradycardia,cyanosis,hypotension,hypothermia)andacebutolol(hypotension,bradycardia,tachypnea,drowsiness).82,83,84MethyldopaandsomeACEinhibitors(benazepril,captopril,enalapril,quinaprilandramipril)arenotexcretedintobreastmilkinclinicallysignificantamountsandareconsideredcompatiblewithbreastfeeding.11,14,85,86DataconcerningtheuseofangiotensinIIreceptorantagonistsduringlactationarelacking.Usewithcautioninbreastfeedingmothers.7Nifedipineisexcretedintobreastmilkinlowamountsandnoadverseeffectshavebeenreportedininfants.Itisconsideredcompatiblewithbreastfeeding.Verylimiteddataindicatesamountsofdiltiazemandverapamilinbreastmilkarelowandwouldnotbeexpectedtohaveanyadverseeffectsinbreastfedinfants.14Dataondiureticsarelacking.Intensediuresismaydecreasebreastmilkproduction.Hydrochlorothiazide50mgdailyisconsideredacceptableduringbreastfeedingbasedonacasereportwhereanexclusivelybreastfedinfantreceived



(prophylactic)

proguanil nursinginfant.7ThereisnoinformationontheamountofprimaquinethatentersintohumanbreastmilkbutthedrugmaycauseseverehemolysisinG6PDdeficientindividuals.Becausedataarenotyetavailableonthesafetyandefficacyofatovaquone/proguanilininfantsweighing



Antivirals Acyclovir,valacyclovir

Acyclovirandvalacyclovir(whichisalmostentirelytransformedtoacyclovir)excretionintomilkarelow(lessthan1%ofthemaximaldailypediatricdosage).Noadverseeffectswerereportedinbreastfedinfants.102Nostudieshavebeenreportedontheexcretionofamantadineinhumanmilk.However,amantadineisadopamineagonist.Clinicalstudiesusingamantadineconcurrentlywithneurolepticmedicationshavedemonstratedadecreaseofprolactinandgalactorrheainducedbyneurolepticdrugs.Thematernalprolactinlevelinamotherwithestablishedlactationmaynotaffectherabilitytobreastfeed.103,104Dataonfamciclovirinbreastfeedingandpediatricsarelacking.Acyclovirandvalacyclovirarepreferred.14

Oseltamivir Sincetheamountofoseltamivirexcretedinbreastmilkseemstobelow(lessthan1%oftheusualpediatricdosageand0.5%oftheweightadjustedmaternaldosebafter75mgtwicedailyfor5daysina9monthspostpartumnursingmother),itwouldnotbeexpectedtocauseanyadverseeffectsinbreastfedinfants,especiallyiftheinfantisolderthan2months.105,106Nodataareavailableregardingtheexcretionofzanamivirinbreastmilk,butduetothepoorinhaledabsorptionandverylowplasmalevels,itwouldnotbeexpectedtocauseanyadverseeffectsinbreastfedinfants.106

Anxiolyticsandsedatives

Lorazepam,oxazepam

Ifusedoccasionallyasasedative,benzodiazepinesarenotcontraindicatedduringbreastfeeding.107Benzodiazepineswithshorterhalflives,lowerlipophilicityandnoactivemetabolitesarepreferredinbreastfeedingmothers(e.g.,oxazepam,lorazepam).Benzodiazepinestakenoveralongerperiodoftimetotreatchronicmaternalconditionsmaybeofconcern.Thebenzodiazepinesandtheirmetabolitesareexcretedinbreastmilk,arepoorlymetabolizedbytheneonate,andhavebeenassociatedwithdrowsinessinnursinginfants.Consequently,discouragethechronicuseofabenzodiazepineinbreastfeedingmothersunlesstheinfant'sconditioniscloselymonitored.

Asthmatherapy Inhaledbronchodilators,inhaledcorticosteroids

Inhaledbronchodilatorsandinhaledcorticosteroidsareacceptableduringbreastfeedingasbioavailabilityandmaternalserumlevelsarelow.108Theaverageamountofterbutalineanexclusivelybreastfedinfantwouldreceiverangesfrom0.20.7%oftheweightadjustedmaternaldose.bSerumlevelswereundetectableintheinfantinonecase.109,110Theamountofinhaledbudesonideinbreastmilkislow(0.3%oftheweightadjustedmaternaldoseb).111Nodataareavailableregardingtheexcretionofomalizumabintobreastmilk.Dataonexcretionoftheleukotrienereceptorinhibitormontelukastintomilkarelacking.However,itdoesnotpenetratetheCNSormanyothertissuesandishighlyproteinbound,makingtheprobabilityofthebabybeingexposedviabreastmilklikelyverylow.7Themanufacturerofzafirlukastindicatesthatitisexcretedintomilkinlowconcentrations(0.5%oftheweightadjustedmaternaldoseb).112Ithasbeenusedinchildrenas



youngas12months.113

Contraceptives Progestinonlyformulations

Progestinonlycontraceptivesshouldbeconsideredforpostpartumwomenandmaybeintroducedimmediatelyafterdelivery(or46weekspostpartuminthecaseoflevonorgestrelintrauterinedevicetoallowtimeforuterineinvolution).Estrogencontainingcontraceptives(includingpills,patch,vaginalring)shouldnotbestarteduntilbreastfeedingisfullyestablished(approximately6weeks)asevenlowdoseformulationscandecreasemilkyield.114

Corticosteroids Prednisolone,prednisone

Prednisoneandprednisoloneareexcretedinbreastmilkinlowamountsandarenotexpectedtocauseadverseeffectsinthebaby.Dependingonmaternaldoseadministered,babywillbeexposedto110%ofaneonataldose.11,115Theoretically,highdosemethylprednisoloneintravenouspulsetherapymayresultinbreastmilklevelsthatcouldapproachtherapeuticdosesforthenursinginfant.Recommendationsforthetimeperiodduringwhichtoavoidbreastfeedingaftertheinfusionrangefrom448hours.14

Decongestants,oral

Pseudoephedrine 5.5%oftheweightadjustedmaternaldosagebisexcretedinbreastmilkafterasingleoraldoseof60mgofpseudoephedrine.Decreasedmilkproductionwasreportedatthesamedosage.Irritabilitywasreportedininfantsexposedtopseudoephedrineinonestudyofbreastfeedingmothers.79,116Useshouldbelimitedtoafewdaysanddiscontinuedifadecreaseinmilkproductionisobserved.Nodataareavailableontheuseofphenylephrineduringbreastfeeding,thereforeanalternatedrugmaybepreferred,especiallywhilenursinganewbornorpreterminfant.Intranasalisotonicsalinesolutionsortopicaldecongestants(oxymetazoline,xylometazoline)arepreferredoveroraldecongestants.

Diabetestherapy Insulin,metformin Humaninsulinisnormallyfoundinbreastmilk.Amountofsyntheticinsulinsecretedintobreastmilkisunknownbut,ifsecreted,thispeptidewouldbedestroyedintheinfant'sGItractwithnosignificantabsorption.7Metforminlevelsinmilkarelowandinfantswouldreceivelessthan0.5%oftheirmother'sweightadjusteddosage.Itissometimesdetectableinlowlevelsintheserumofbreastfedinfantsbutnoadverseeffectsinbreastfedinfantswerereportedinonestudy.Metforminshouldbeusedwithcautionwhilenursingnewbornandprematureinfantsandthosewithrenalimpairment.14Theamountofglyburideexcretedinbreastmilkseemstobelow(lessthan1%oftheweightadjustedmaternaldoseb):noadverseeffectsonbreastfedinfant'sbloodglucosehavebeenreportedbutdataarelimited.117Nodataareavailableregardingtheexcretionofacarboseintobreastmilk.However,lessthan2%ofadoseofacarboseisabsorbedfromthemother'sGItractmakingitunlikelythatanydrugreachestheinfantthroughbreastmilk.118Nodataareavailableregardingtheexcretionofgliclazide,glimepiride,nateglinide,pioglitazone,repaglinideandrosiglitazoneinbreastmilk.Analternatedrugmaybepreferred,especiallywhilenursinganewbornorpreterminfant.Some



expertsrecommendmonitoringthebreastfedinfant'sbloodglucoseduringmaternaltherapywithhypoglycemicagents.118

Gastrointestinaldrugs

Antacids,sucralfate Aluminum,calciumandmagnesiumantacidsandsucralfatearepartiallyorpoorlyabsorbedorallyandareconsideredsafetouse.7

Antidiarrheals Useofloperamideduringbreastfeedingisunlikelytoaffecttheinfantasitisminimallyabsorbedorally.Basedonitschemicalandpharmacologicalsimilaritytonarcotics,occasionalsmalldosesofdiphenoxylatemaybeacceptablewhilebreastfeedinganolderinfant,butalternativesarepreferred,especiallywhilenursinganewborn.7,14

GImotilityagents Theexcretionintomilkofdomperidoneandmetoclopramidearelessthan0.05%and6%respectivelyofadailypediatricdose.Noadverseeventsarereportedfordomperidonebutintestinaldiscomfortwasreportedin2breastfedinfantsofmotherstakingmetoclopramide.119,120,121Domperidoneisusedtoincreasemilkproductioninsomewomenwhodonotrespondtoanonpharmacologicapproach.

H2antagonists Thoughconsideredsafeforusebybreastfeedingmothers,cimetidineandranitidinemayconcentrateinmilkwhereasfamotidineandnizatidinehavethelowestconcentrations,makingthempreferablechoices.7,23Ranitidinehasbeenwidelyusedinpediatricsprimarilyforgastroesophagealreflux.Adverseeffectshavenotbeenreportedinnursinginfants.

Laxatives PsylliumisacceptabletouseduringbreastfeedingbecauseitisnotabsorbedfromtheGItract.Therehavebeennocasesofloosestoolsreportedinbreastfedinfants.14Docusate,bisacodylandmagnesiumhydroxidearenotappreciablyabsorbedfromtheGItractandthereforethesedrugsareunlikelytobefoundinthematernalserumorbreastmilk.7,14Onepostpartumpatientreceivingalaxativecontainingdocusateinadoseof120mgdailyinadditiontodanthron100mgdailystatedthatdiarrheaoccurredinherbreastfedinfant.14Usualdosesofsennaareacceptabletouseduringbreastfeeding.However,alaxativeeffectwasobservedinafewcasereports.Cascaraisnotafirstlinechoiceduetocasereportsofalaxativeeffectinbreastfedinfantsandunknownoralabsorption.7,14Nodataareavailableregardingtheexcretionoflactuloseintobreastmilkhoweverlessthan3%ofadoseoflactuloseisabsorbedfromthemother'sGItract,makingitunlikelythatanydrugreachestheinfantthroughbreastmilk.11Oralpolyethyleneglycol(e.g.,PEG3350)andrectalglycerinarenegligiblyabsorbedfromtheGItractandunlikelytohavesignificantlevelsinbreastmilk.11

Misoprostol Misoprostollevelsinbreastmilkarelowamountingestedbythe



nursinginfantwouldnotbeexpectedtocauseadverseeffects.14

Protonpumpinhibitors

Protonpumpinhibitorsareunstableinanacidmilieuand,wheningestedviamilk,wouldprobablybedestroyedintheinfant'sstomachpriortoabsorption.7Pantoprazoleandomeprazoleareexcretedinmilkinsmallquantities.122,123Lansoprazoleandomeprazoleareusedforthetreatmentofgastroesophagealrefluxinneonatesandpediatrics.Esomeprazoleisthesenantiomerofomeprazoleandthereforewouldalsonotbeexpectedtocauseanyadverseeffectsinbreastfedinfants.123

Migrainetherapy Eletriptan,sumatriptan

Occasionaluseofsumatriptanandeletriptanseemstobeacceptablebecausetheamountofthesedrugsexcretedintomilkislow(3.5%and0.02%oftheweightadjustedmaternaldosage,brespectively).Dataonalmotriptan,frovatriptan,naratriptan,rizatriptanandzolmitriptanarelacking.7Becausethereislimitedpublishedexperiencewithergotamine,dihydroergotamineandmethysergideduringbreastfeeding,andadverseeffectsintheinfantcannotberuledout,mostauthoritiesconsiderthesedrugstobeundesirabletousewhilenursing.7,14

Musclerelaxants Cyclobenzaprine,methocarbamol

Theexcretionofcyclobenzaprine,methocarbamolandorphenadrineintomilkhasnotbeenreported.However,occasionalcyclobenzaprineandmethocarbamolexposuresareacceptablebecauseofcyclobenzaprine'sstructuralsimilaritiestoamitriptyline(seeAntidepressants)andtheveryshorthalflifeofmethocarbamol.Noadverseeventshavebeenpublished,butinfants(especiallythosethatarenewbornorpremature)shouldbemonitoredforsedationwhilenursing.7

NSAIDs Diclofenac,flurbiprofen,ibuprofen,indomethacin,naproxen

MostNSAIDshavebeenshowntobepresentinbreastmilkinsmallamountsandareconsideredsafetouse.Theuseofshortactingdrugs,suchasibuprofenandflurbiprofen,maybepreferredoverthosewithalongerhalflifesuchasnaproxen.7Lessthan1%ofthepediatricdoseofdiclofenacisexcretedintobreastmilk.Diclofenacalsohasashorthalflife.14,126Theamountofindomethacinexcretedinbreastmilkislessthan4%ofatypicalneonataldoseanditisconsideredsafetousewhilebreastfeeding.However,otheragentswithmorepublishedinformationonuseduringbreastfeedingmaybepreferableespeciallywhilenursinganewbornorpreterminfant.11Dataoncelecoxibarelimitedtoafewinfantsbutmilklevelswerelowandadverseeffectswerenotnotedwhentakenshortterm.7Moredataareneededtodeterminerisksincethedrughasalonghalflifeandhighoralabsorption.

Scabicides,pediculicides

Permethrin Permethrin5%creamisthetreatmentofchoiceforscabies.Permethrin1%orpyrethrins/piperonylbutoxidemaybeusedforthetreatmentofheadlicewhilebreastfeeding.124Topicalabsorptionofpermethrinandpyrethrinsislow.Permethrinisrapidlymetabolizedtoinactivemetabolitesandexcretedinurine.Overttoxicityisunlikely.Avoidapplicationonnipples.Percutaneousabsorptionofpiperonylbutoxideisunknown.7,125



Lindaneisnotrecommendedbecauseitisabsorbedthroughthemother'sskinandexcretedintomilkfat.Directcontactoflindanewithneonatalskinresultsinsignificantabsorption.Directexposureispotentiallytoxicininfantswithreportsofelevatedliverenzymes,seizuredisordersandhypersensitivity.Itmayalsohaveestrogeniceffectsthatcouldinhibitlactation.14,125LindaneisnotcurrentlyavailableinCanada.

Smokingcessation

Nicotinereplacementtherapy

Dataonnicotinepatchesarelimitedbuttheamountofnicotineandcotinineexcretedinbreastmilkseemtobelessthan8%oftheweightadjustedmaternaldoseb.Witha21mgtransdermalpatch,nicotinepassesintobreastmilkinamountsequivalenttosmoking17cigarettesdaily.Lowerpatchstrengthsof7and14mgprovideproportionatelyloweramountsofnicotinetothebreastfedinfant.Nostudiesonnicotinesprayornicotinegumuseinnursingmothershavebeenreported.Nicotinegummayproducelargevariationsinpeaklevelswhengumischewedrapidly:fluctuationssimilartosmokingitself.Somecliniciansrecommendtowait23hafterusingthegumbeforebreastfeeding.127DataonvareniclinearelackingbuttransferispossibleandeffectonCNSisaconcern.7Forinformationontheuseofbupropionduringbreastfeeding,seeAntidepressants.

Thyroidagents Antithyroidagents Theestimatedlevelofexposuretopropylthiouracilinbreastfeedinginfantsislessthan1%ofthetherapeuticdosestandardizedbyweight,andthethyroidfunctionoftheinfantisnotaffected.128Methimazoleindosesupto20mg/dayhasbeendocumentednottoaffecttheinfant'sthyroidfunction.129,130,131Foreitherdrug,noadverseeffectsinbreastfedinfantshavebeenreportedsofarandmonitoringofinfants'thyroidfunctionisnotnecessaryifdevelopmentisprogressingnormally.131

Thyroidhormones Levothyroxineiscompatiblewithbreastfeeding.Thyroidhormonescrossintobreastmilkinlowamounts.Theirpresenceisnotlikelytoaffecttheinfant'sthyroid.23

Vaccines WomenwhoarebreastfeedingcanbevaccinatedwithTd,Tdap,pneumococcal,meningococcal,hepatitisA,hepatitisB,HPV,rabies,typhoid,MMR,varicella,HPVandcholeravaccinesifindicated.SafetyoftheJapaneseencephalitisvaccineinbreastfeedingisunknownanditshouldbeadministeredonlyiftheriskofdiseaseoutweighstheunknownriskofvaccination.YellowfevervaccineisnotrecommendedforbreastfeedingwomenandBCGvaccineshouldbeusedwithcaution.Womenwhoreceivesmallpoxvaccineaspostexposureprophylaxisshouldavoidbreastfeedingandotherclosecontactwiththeirbabyuntilthescabhasseparatedfromthevaccinationsite.132

a.Thislistisnotexhaustiveordefinitive.Drugsnotlistedinthetablearenotnecessarilycontraindicated.Individualizedriskassessmentisrequiredwhenprescribinganymedicationtoabreastfeedingwoman.b.Weightadjustedmaternaldoseisamother'sdosebasedonbodyweight(e.g.,mg/kg).Expertsrecommendthatanamountof



drugreceivedbytheinfantviabreastmilkwhichis>10%oftheweightadjustedmaternaldoseshouldbeatheoreticallevelofconcernwhenconsideringtheacceptabilityofdrugexposure.Theestimatedamountofdrugreceivedbytheinfantviabreastmilkiscalculatedbymultiplyingthestandardmilkintake(150mL/kg/day)bythedrugconcentrationinbreastmilk.

Abbreviations:G6PD=glucose6phosphatedehydrogenaseGFR=glomerularfiltrationrate

DrugsforNonmedicalUse

TobaccosmokingandalcoholingestionarethemostcommonsourcesofnonmedicinaldrugexposureinbreastfedinfantsinCanada.Becausetheysooftenoccurinthesameindividual,itisdifficulttostudytheirindependenteffects.Increasingly,thesedrugsareusedtogetherwithillicitdrugssuchasmarijuanaandcocaine.

Table2:BreastfeedingandNonmedicalUseofDrugs

Drug Comments

Alcohol Notcompatiblewithbreastfeeding.Thealcoholmetabolizingcapacity(alcoholandaldehydedehydrogenase)isprematurethroughouttheneonatalandinfantileperiod.Overall,motordevelopmentisslightlyslowerininfantsbreastfedbymotherswhoregularlydrinkalcohol.Chronicorheavyconsumersofalcoholshouldnotbreastfeed.7Shorttermalcoholconsumptionbynursingmothersreportedlyhasanimmediateeffectontheodourcharacteristicsofthemilkandthefeedingbehaviouroftheirinfants,resultinginlessconsumptionofmilk.133Toavoidexposureoftheinfanttoalcohol,breastfeedingmothersshouldnotconsumealcoholorshouldconsumenomorethanonedrink23hbeforebreastfeeding.7

Caffeine Hypothetically,anursinginfantingests0.11%ofthematernaldoseafterthemotherdrinks12cupsofcoffee.Thisisaninsignificantamountofthedrug,butitmustberememberedthatthehalflifeofcaffeineis80hinthetermnewbornand97.5hinaprematureinfant(2030timesthatofanadult).Therefore,repeatedingestionmightleadtoaccumulationofcaffeineintheinfantduringthefirst2weeksofpostnatallife.Thishasyettobestudied.

Recreationalorstreetdrugs

Nosystematicstudiesofrecreationalorstreetdrug(ordrugmetabolite)excretionexist.

Tobacco Discourageduringbreastfeedingbecausetherearewelldocumentedhealthriskstothemotherandinfantfromsecondhandsmoke.Infantexposuretonicotineislargelythroughinhalationofsecondhandsmoke.Inmothersunwillingtostopsmokingduringbreastfeeding,itshouldbenotedthatbreastfedbabiesofmotherswhocontinuetosmokehavebetterimmunityandlessrespiratoryinfectionsthanbottlefedbabiesofmotherswhocontinuetosmoke.134

Nicotineisconcentratedinhumanbreastmilk.135,136Onestudysuggeststhatcigarettesmokingsignificantlyreducesbreastmilkproduction.137Encouragenursingmotherstospeaktotheirhealthcareprovidersregardingoptionsforsmokingcessation.

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Drug Use During Breastfeeding