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Medications and Lactation: Principles 
for Safe Practice for the Clinician 
Evelyn Fulmore, Pharm.D. 
McLeod Regional Medical 
Center 
Florence, SC
Disclosures 
 No financial relationships or duality of 
interest to disclose 
 I will be discussing use of agents to improve 
milk supply (galactagogues)
Learning Objectives 
 Basic physiology of lactation and 
mechanisms of medication entry into 
mother’s breast milk 
 Factors to consider when selecting 
medications during lactation 
 Role of galactagogues in lactation induction 
 Tips in utilizing and interpreting available 
lactation drug information resources
PPhhyyssiioollooggyy ooff LLaaccttaattiioonn 
 SSuucckklliinngg ssttiimmuullaatteess 
nniippppllee ® ppiittuuiittaarryy ggllaanndd 
sseeccrreetteess ooxxyyttoocciinn ® lleett 
ddoowwnn rreefflleexx rreessuullttss iinn 
mmiillkk eejjeeccttiinngg cceellllss 
ccoonnttrraacctt ffoorrcciinngg mmiillkk 
ffrroomm mmiillkk cceellllss iinnttoo mmiillkk 
dduuccttss..
PPhhyyssiioollooggyy ooff LLaaccttaattiioonn 
 MMiillkk ppoooollss iinn llaacciiffeerroouuss 
ssiinnuusseess uunnddeerr tthhee 
aarreeoollaa.. SSuucckklliinngg 
ssttiimmuullaatteess mmiillkk ttoo ccoommee 
ffrroomm tthhee nniippppllee..
CCoommppoossiittiioonn ooff BBrreeaassttmmiillkk 
 CCoolloossttrruumm ((DDaayyss ##33--55)) 
hhiigghh pprrootteeiinn, iimmmmuunnoogglloobbuulliinnss, mmiinneerraallss, llooww iinn 
llaaccttoossee aanndd ffaatt 
 TTrraannssiittiioonnaall mmiillkk ((DDaayyss ##66--1100)) 
hhiigghh iinn ffaatt, llaaccttoossee;; lloowweerr iinn pprrootteeiinn aanndd mmiinneerraallss 
 MMaattuurree mmiillkk ((DDaayy ##1144)) 
6600--8800%% wwhheeyy pprrootteeiinn, 5500%% ffaatt, 4400%% llaaccttoossee, ggrroowwtthh 
ffaaccttoorr, llooww iinn VViittaammiinn DD
Factors Affecting Amount of Drug 
Received by the Infant 
 Milk yield 
 Colostrum versus Mature milk 
 Concentration of drug in the milk 
 How well the breast was emptied during the 
previous feeding 
 Infants ability to absorb, detoxify, and excrete 
the drug
TTrraannssffeerr ooff MMeeddiiccaattiioonnss iinnttoo 
BBrreeaasstt MMiillkk 
 CCoonncceennttrraattiioonn ggrraaddiieenntt 
– PPaassssiivvee ddiiffffuussiioonn ooff nnoonn--iioonniizzeedd aanndd ffrreeee ((nnoonn-- 
pprrootteeiinn bboouunndd)) mmeeddss 
– MMaatteerrnnaall sseerruumm ddrruugg ccoonncceennttrraattiioonn 
vvoolluummee ooff ddiissttrriibbuuttiioonn ((VVdd)) aanndd hhaallff--lliiffee 
- RReettrrooggrraaddee ddiiffffuussiioonn ooff ddrruugg ffrroomm bbrreeaasstt mmiillkk ttoo 
ppllaassmmaa 
SSppeenncceerr JJPP eett..aall.. MMeeddiiccaattiioonnss iinn tthhee BBrreeaasstt--FFeeeeddiinngg MMootthheerr.. AAFFPP 22000011;; 
6644::111199
TTrraannssffeerr ooff MMeeddiiccaattiioonnss iinnttoo 
BBrreeaasstt MMiillkk 
11.. LLiippiidd ssoolluubbiilliittyy 
22.. MMoolleeccuullaarr wweeiigghhtt 
33.. MMaatteerrnnaall ppllaassmmaa lleevveellss 
44.. MMaatteerrnnaall pprrootteeiinn bbiinnddiinngg 
55.. OOrraall bbiiooaavvaaiillaabbiilliittyy, hhaallff lliiffee 
66.. IIoonn ttrraappppiinngg ((ppKKaa))
LLiippiidd SSoolluubbiilliittyy 
 DDrruuggss tthhaatt aarree hhiigghhllyy lliippiidd ssoolluubbllee ppeenneettrraattee 
mmiillkk iinn hhiigghheerr ccoonncceennttrraattiioonnss 
 AAvvooiidd eexxttrreemmeellyy lliippiidd ssoolluubbllee ddrruuggss.. 
 EExxaammpplleess:: DDiiaazzeeppaamm, pphheennoobbaarrbbiittaall
MMoolleeccuullaarr WWeeiigghhtt 
 TThhee lloowweerr tthhee mmoolleeccuullaarr wweeiigghhtt ((<<220000 DD)), tthhee 
ggrreeaatteerr ppeenneettrraattiioonn iinnttoo mmiillkk 
 MMoolleeccuullaarr wweeiigghhttss <<330000 DD :: ((eegg.. AAllccoohhooll, 
aammpphheettaammiinneess, ddiieett ppiillllss)) 
 MMoolleeccuullaarr wweeiigghhttss ≥≥ 660000 DD :: ((eegg.. HHeeppaarriinn, 
EEnnooxxaappaarriinn, IInnssuulliinn, RReemmiiccaaddee)) 
 LLaarrggeerr tthhee mmoolleeccuullaarr wweeiigghhtt//ssiizzee ((pprreeffeerrrreedd))
MMaatteerrnnaall PPllaassmmaa lleevveell 
 TThhee mmoosstt iimmppoorrttaanntt ddeetteerrmmiinnaanntt ooff ddrruugg 
ppeenneettrraattiioonn iinnttoo mmiillkk 
 AAss mmaatteerrnnaall ppllaassmmaa lleevveellss rriissee, tthhee 
ccoonncceennttrraattiioonn iinn mmiillkk rriisseess 
 DDrruugg ddeelliivveerryy ssyysstteemmss tthhaatt rreessuulltt iinn llooww 
mmaatteerrnnaall ppllaassmmaa lleevveellss aarree pprreeffeerrrreedd iinn 
bbrreeaasstt ffeeeeddiinngg mmootthheerr ((eegg.. IInnhhaalleerr mmeedd, 
ttooppiiccaallss))
MMaatteerrnnaall PPrrootteeiinn BBiinnddiinngg 
 MMoosstt iimmppoorrttaanntt ppaarraammeetteerr iinn cchhoooossiinngg aa 
ssaaffee ddrruugg ffoorr aa nnuurrssiinngg mmootthheerr 
 MMoosstt ddrruuggss cciirrccuullaattee iinn tthhee mmaatteerrnnaall 
ppllaassmmaa bboouunndd ttoo aallbbuummiinn 
 ““FFrreeee”” oorr ““UUnnbboouunndd”” ddrruugg ttrraannssffeerrss iinnttoo 
mmiillkk 
 DDrruuggss tthhaatt aarree hhiigghhllyy pprrootteeiinn bboouunndd 
rreemmaaiinn iinn tthhee mmaatteerrnnaall ppllaassmmaa aanndd ddoonn’’tt 
ppeenneettrraattee ttiissssuueess oorr bbrreeaasstt mmiillkk
OOrraall BBiiooaavvaaiillaabbiilliittyy 
 TThhee aammoouunntt ooff ddrruugg tthhaatt iiss aabbssoorrbbeedd bbyy tthhee 
iinnffaanntt’’ss GGII ttrraacctt aanndd rreeaacchheess tthhee cciirrccuullaattiioonn 
 LLooww oorraall bbiiooaavvaaiillaabbiilliittyy:: aammiinnooggllyyccoossiiddeess, 
hheeppaarriinn, iinnssuulliinn, oommeepprraazzoollee 
 AAccttiioonn ooff aa ddrruugg iinn tthhee GGII ttrraacctt mmaayy pprroodduuccee 
SSEE:: ddiiaarrrrhheeaa, ccoonnssttiippaattiioonn, PPMMCC
IIoonn TTrraappppiinngg ((ppKKaa)) 
 IIoonn ttrraappppiinngg –– ddrruugg bbeeccoommeess ttrraappppeedd iinn mmiillkk 
ccoommppaarrttmmeenntt ((dduuee ttoo llooww ppHH mmiillkk)) 
 ppKKaa iiss tthhee ppHH wwhheerree aa ddrruugg iiss eeqquuaallllyy iioonniicc oorr 
nnoonniioonniicc ((tthhee mmoorree iioonniicc, lleessss ttrraannssffeerr ffrroomm 
mmiillkk ttoo ppllaassmmaa)) 
 DDrruuggss wwiitthh hhiigghh ppKKaa ((>>77..22)), hhaavvee hhiigghheerr 
MMiillkk//PPllaassmmaa rraattiioo ((eegg..PPhheennoobbaarrbbiittaall, 
iiooddiinnaatteedd ddrruuggss)) 
 CChhoooossee ddrruuggss wwiitthh aa llooww ppKKaa
DDrruuggss TThhaatt DDeeccrreeaassee MMiillkk SSuuppppllyy 
 NNiiccoottiinnee 
 AAllccoohhooll 
 SSeeddaattiinngg AAnnttiihhiissttaammiinneess ((eegg.. DDiipphheennhhyyddrraammiinnee)) 
 EEssttrrooggeenn ccoonnttaaiinniinngg oorraall ccoonnttrraacceeppttiivveess 
 PPrrooggeesstteerroonnee ccoonnttrraacceeppttiivveess ((iiff ssttaarrtteedd eeaarrllyy 
ppoossttppaarrttuumm bbeeffoorree mmiillkk ssuuppppllyy eessttaabblliisshheedd)) 
 BBrroommooccrriippttiinnee ((PPaarrllooddeell))
Drugs That Aid in Milk Production: 
Galactagogues 
 Herbals: Fenugreek 
 Metoclopramide (Reglan) 
 Domperidone (Motillium) 
 Synthetic Oxytocin nasal spray
Galactagogues 
 Used to increase breast milk supply 
 Need to determine the etiology of low milk 
supply 
 Ensure proper breastfeeding technique 
 Only use with adequate milk removal 
 Must evaluate for medical co-morbidities 
(e.g. hypothyroidism, retained placenta)
Herbal: Fenugreek 
 Trigonella foenum graecum 
 MOA: stimulate sweat production; 
Phytoestrogen and Diosgenin - increase 
milk flow 
 Tea (bitter taste), capsule or tablet 
 Sweat and urine (maple syrup smell) 
 Caution use in Asthma or diabetes 
 Contains coumarin (interact with 
NSAIDS) 
 No scientific data
Domperidone (Motillium) 
 Not approved for use in the US 
 MOA: increase prolactin ® milk production 
 Maternal safety has not been established 
 FDA warning concerning reports of QT 
interval prolongation, cardiac arrest, sudden 
death (IV formulation) 
 Clinical trial showed increase breastmilk 
volume without affecting nutrient composition 
Campbell-Yeo M. Effect of Domperidone on Compositiono of Preterm Human 
Breast Milk. Pediatrics 2010; 125 (1):e107-e114
Metoclopramide (Reglan) 
 Most commonly used 
 MOA: increase prolactin 
 Caution: clearance of metoclopramide in the 
neonate is prolonged can result in side 
effects (methemoglobinemia) 
 Short term use recommended (1-3 weeks) 
 Common dosing: 1st day – 10 mg, 2nd day – 10 
mg bid, thereafter 10 mg tid
Synthetic Oxytocin Nasal Spray 
 Hormone (synthetically derived) 
 MOA: causes release of milk from milk 
glands to the ducts (helps empty the breast) 
 Prepared by compounding Rx (10 unit/ml) 
 Dose: 1-2 sprays each nostril before breast 
feeding or pumping
Synthetic Oxytocin Nasal Spray: 
Mean Daily Milk Production 
Fewtrell MS. Arch Dis Child Fetal Neonatal Ed. 2006 May; 91(3): F169–F174.
SSaaffeettyy DDaattaa aanndd BBrreeaasstt FFeeeeddiinngg 
 BBrreeaasstt ffeeeeddiinngg llaacckkss ssttaannddaarrddiizzeedd rriisskk 
ccaatteeggoorriieess 
 MMoosstt ooff tthhee ddaattaa oonn mmeeddss aanndd bbrreeaasstt ffeeeeddiinngg 
aarree ffrroomm sscciieennttiiffiicc lliitteerraattuurree 
 GGiivveenn tthhee llaacckk ooff ssttaannddaarrddiizzaattiioonn, ootthheerr 
rreeccoommmmeennddaattiioonnss ffoorr uussiinngg mmeeddss wwhhiillee 
bbrreeaasstt ffeeeeddiinngg hhaavvee bbeeeenn uusseedd bbyy hheeaalltthh 
ccaarree pprroovviiddeerrss 
MMaasstteerr KKPP eett..aall.. BBrreeaasstt FFeeeeddiinngg aanndd OOTTCC mmeeddiiccaattiioonnss.. UUSS PPhhaarrmm 22000077;; 3322 ((77)):: 88--1122
LLaaccttaattiioonn RReessoouurrcceess 
 BBooookkss 
– GGeerraalldd GG.. BBrriiggggss.. ““DDrruuggss 
iinn PPrreeggnnaannccyy aanndd 
LLaaccttaattiioonn:: AA rreeffeerreennccee 
GGuuiiddee ttoo FFeettaall aanndd 
NNeeoonnaattaall RRiisskk””,, 99tthh 
eeddiittiioonn;; 22001122
Definitions of Breast Feeding 
Recommendations 
 Compatible 
 Hold Breast Feeding 
 No (limited) Human Data – Probably Compatible 
 No (limited) Human Data – Potential Toxicity 
 No (limited) Human Data – Potential Toxicity 
(Mother) 
 Contraindicated 
Briggs GG et. al. Drugs iinn PPrreeggnnaannccyy aanndd 
LLaaccttaattiioonn,, 22000088;; 88tthh eeddiittiioonn
LLaaccttaattiioonn RReessoouurrcceess 
 BBooookkss 
– TThhoommaass WW.. HHaallee.. 
““MMeeddiiccaattiioonnss aanndd 
MMootthheerrss’’ MMiillkk”” 22001122,, 1155tthh 
eeddiittiioonn
Dr. Hale’s Lactation Risk Category 
 L1 Safest 
 L2 Safer 
 L3 Moderately Safe 
 L4 Potentially Hazardous 
 L5 Contraindicated 
Hale TW. Medications and MMootthheerrss'' MMiillkk,, 22001100;; 
1144tthh eeddiittiioonn..
DDrr.. HHaallee’’ss LLaaccttaattiioonn RRiisskk CCaatteeggoorryy 
 LL11 SSaaffeesstt:: DDrruugg ttaakkeenn bbyy llaarrggeerr ## ooff bbrreeaasstt 
ffeeeeddiinngg wwoommeenn wwiitthhoouutt aannyy oobbsseerrvveedd 
aaddvveerrssee eeffffeeccttss iinn iinnffaanntt 
 LL22 SSaaffeerr:: DDrruugg ssttuuddiieedd iinn aa lliimmiitteedd ## ooff 
bbrreeaasstt ffeeeeddiinngg wwoommeenn wwiitthhoouutt aannyy oobbsseerrvveedd 
aaddvveerrssee eevveennttss iinn iinnffaannttss 
 LL33 MMooddeerraatteellyy SSaaffee:: NNoo ccoonnttrroolllleedd ttrriiaallss iinn 
bbrreeaasstt ffeeeeddiinngg wwoommeenn, bbuutt rriisskk ooff uunnttoowwaarrdd 
eeffffeeccttss iiss ppoossssiibbllee
DDrr.. HHaallee’’ss LLaaccttaattiioonn RRiisskk CCaatteeggoorryy 
 LL33 MMooddeerraatteellyy SSaaffee:: NNoo ccoonnttrroolllleedd ttrriiaallss iinn 
bbrreeaasstt ffeeeeddiinngg wwoommeenn,, bbuutt rriisskk ooff uunnttoowwaarrdd 
eeffffeeccttss iiss ppoossssiibbllee OORR ccoonnttrroolllleedd ssttuuddiieess 
sshhooww oonnllyy mmiinniimmaall nnoonn--tthhrreeaatteenniinngg aaddvveerrssee 
eeffffeeccttss 
 LL44 PPootteennttiiaallllyy HHaazzaarrddoouuss:: PPoossiittiivvee 
eevviiddeennccee ooff rriisskk ttoo tthhee bbrreeaassttffeedd iinnffaanntt OORR ttoo 
tthhee bbrreeaasstt mmiillkk pprroodduuccttiioonn bbuutt bbeenneeffiitt 
oouuttwweeiigghhss tthhee rriisskk
DDrr.. HHaallee’’ss LLaaccttaattiioonn RRiisskk CCaatteeggoorryy 
 LL55 CCoonnttrraaiinnddiiccaatteedd:: SSttuuddiieess iinn 
bbrreeaassttffeeeeddiinngg wwoommeenn hhaavvee ddeemmoonnssttrraatteedd 
ssiiggnniiffiiccaanntt aanndd ddooccuummeenntteedd rriisskk ttoo tthhee iinnffaanntt.. 
RRiisskk cclleeaarrllyy oouuttwweeiigghhss bbeenneeffiittss ooff bbrreeaasstt 
ffeeeeddiinngg..
Values Used to Estimate Infant Drug 
Exposure 
 Milk to Plasma Ratio (M/P) 
– Ratio of the concentration of drug in mother’s milk divided by the 
concentration in the mother’s plasma 
– M/P <1 is preferred 
 Theoretical Infant Dose (TID) 
– Multiply the milk concentration x daily milk intake of the infant 
– Compared to the usual maintenance pediatric dose 
 Relative Infant Dose (RID) 
– Divide the infant’s dose via milk (mg/kg/day) by the mother’s dose 
(mg/kg/day) 
– Assumes daily milk intake of 150 ml/kg/day 
– RID<10% is considered safe 
– Exception: fluconazole, metronidazole (have a high RID but are 
non toxic)
LLaaccttaattiioonn RReessoouurrcceess 
 IInntteerrnneett 
– DDrr.. HHaallee’’ss BBrreeaassttffeeeeddiinngg 
PPhhaarrmmaaccoollooggyy ppaaggee (( 
hhttttpp::////wwwwww..nneeoonnaattaall..ttttuuhhsscc..eedduu//ffaacctt))
LLaaccttaattiioonn RReessoouurrcceess 
 IInntteerrnneett 
– UU..SS.. NNaattiioonnaall LLiibbrraarryy ooff 
MMeeddiicciinnee.. LLaaccttMMeedd 
((hhttttpp::////ttooxxnneett..nnllmm..nniihh..ggoovv//ccggii-- 
bbiinn//ssiiss//hhttmmllggeenn??))//LLAACCTT))
LactMed
LactMed
Linezolid (Zyvox)
The Transfer of Drugs and Other Chemicals Into Human Milk 
Committee on Drugs 
Pediatrics 2001;108;776 
CLINICAL REPORT 
The Transfer of Drugs and Therapeutics Into Human 
Breast Milk: An Update on Selected Topics 
Hari Cheryl Sachs, MD, FAAP* and COMMITTEE ON DRUGS 
Pediatrics; originally published online August 26, 2013; 
DOI: 10.1542/peds.2013-1985
BBeeffoorree PPrreessccrriibbiinngg DDrruugg TThheerraappyy iinn tthhee 
LLaaccttaattiinngg WWoommaann 
11.. IIss ddrruugg tthheerraappyy rreeaallllyy nneecceessssaarryy?? 
22.. TThhee ssaaffeesstt ddrruugg sshhoouulldd bbee cchhoosseenn.. 
33.. IIff tthheerree iiss aa ppoossssiibbiilliittyy tthhaatt aa ddrruugg mmaayy 
pprreesseenntt aa rriisskk ttoo tthhee iinnffaanntt,, tthheenn ccoonnssiiddeerr 
mmeeaassuurriinngg bblloooodd lleevveellss 
44.. DDrruugg eexxppoossuurree iinn tthhee iinnffaanntt mmaayy bbee lliimmiitteedd 
bbyy ttiimmiinngg ooff mmeedd aanndd bbrreeaassttffeeeeddiinngg 
AAAAPP CCoommmmiitttteeee oonn DDrruuggss.. TThhee ttrraannssffeerr ooff ddrruuggss aanndd ootthheerr cchheemmiiccaallss 
iinnttoo hhuummaann mmiillkk.. PPeeddiiaattrriiccss 22000011;;110088 ((33))::777777
AAnnaallggeessiiccss 
 AAcceettaammiinnoopphheenn ((TTyylleennooll)) iiss ccoommppaattiibbllee wwiitthh bbrreeaasstt 
ffeeeeddiinngg 
 NNoonnsstteerrooiiddaall aannttiiiinnffllaammmmaattoorryy ddrruuggss ((NNSSAAIIDDSS)) –– 
iibbuupprrooffeenn iiss pprreeffeerrrreedd 
– NNaapprroossyynn,, ssuulliinnddaacc,, ppiirrooxxiiccaamm sshhoouulldd bbee aavvooiiddeedd 
 NNaarrccoottiicc//OOppiiaatteess –– mmoorrpphhiinnee,, ccooddeeiinnee,, ooxxyyccooddoonnee,, 
aanndd hhyyddrrooccooddoonnee aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg 
– MMeeppeerriiddiinnee ((DDeemmeerrooll)) sshhoouulldd bbee aavvooiiddeedd
Narcotics/Opiates 
 Case controlled studies evaluating long term 
developmental outcomes are needed 
 Breastfeeding should be supported if: 
– “stable” and compliant with methadone or 
buprenorphine +/- naloxone (Subutex®, Suboxone®) 
– negative maternal urine toxicology test at delivery 
except for prescribed medications 
– plan to continue substance abuse treatment in the 
postpartum period 
– do not have medical contraindication to breastfeeding 
Breastfeeding Medicine 2009; 4(4):225-228
AAnnttiibbiioottiiccss 
 PPeenniicciilllliinnss aanndd cceepphhaalloossppoorriinnss aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt 
ffeeeeddiinngg 
– MMoonniittoorr iinnffaanntt ffoorr ddiiaarrrrhheeaa ((cchhaannggee iinn gguutt fflloorraa)) 
 TTeettrraaccyycclliinnee iiss ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg 
– CCaallcciiuumm iinn bbrreeaasstt mmiillkk lliimmiittss aabbssoorrppttiioonn ;; aavvooiidd ddooxxyyccyylliinnee aanndd 
mmiinnooccyycclliinnee 
 QQuuiinnoolloonneess hhaavvee nnoott bbeeeenn rraatteedd bbyy AAAAPP 
– LLeevvaaqquuiinn iiss ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg 
 TTrriimmeetthhoopprriimm--ssuullffaammeetthhooxxaazzoollee ((BBaaccttrriimm)) iiss ccoommppaattiibbllee wwiitthh 
bbrreeaasstt ffeeeeddiinngg 
– NNoott rreeccoommmmeennddeedd iinn iinnffaannttss << 22 mmoonntthh ((ddeeppllaacceemmeenntt ooff bbiilliirruubbiinn))
AAnnttiiddeepprreessssaannttss 
 TTrriiccyycclliicc aannttiiddeepprreessssaannttss –– lliittttllee oorr nnoo eeffffeecctt oonn bbrreeaasstt ffeeeeddiinngg 
iinnffaanntt 
– AAAAPP lliissttss aass ppoossssiibbllee ccoonncceerrnn wwiitthh eexxppoossuurree lloonngg--tteerrmm 
 SSeelleeccttiivvee sseerroottoonniinn rreeuuppttaakkee iinnhhiibbiittoorrss ((SSSSRRIIss)) –– ggeenneerraallllyy 11sstt 
cchhooiiccee 
– PPaarrooxxeettiinnee ((PPaaxxiill)) oorr SSeerrttrraalliinnee ((ZZoolloofftt)) pprreeffeerrrreedd ttoo 
FFlluuooxxeettiinnee ((PPrroozzaacc)) 
 SSeerroottoonniinn NNoorreeppiinneepphhrriinnee RReeuuppttaakkee IInnhhiibbiittoorrss ((SSNNRRIIss)) 
– VVeennllaaffaaxxiinnee ((EEffffeexxoorr)) 
 TTaakkee ddoossee aatt bbeeddttiimmee ttoo lliimmiitt eexxppoossuurree ttoo iinnffaanntt
Antidepressants: 
SSRIs and SNRIs 
 Limited to small case studies 
 Paroxetine and sertraline produced low RID 0.5-3% 
 Fluoxetine, citalopram, venlafaxine have variable 
RID near to equal 10% 
 Preference hierarchy: sertraline, paroxetine, 
citalopram, venlafaxine, fluoxetine 
 Watch for uneasy sleep, colic, irritability, poor 
feeding, drowsiness 
Breastfeeding Medicine 2008; 3 (1): 44-52
Relative Infant Dose (RID) of Commonly 
Prescribed Antidepressants 
Antidepressant Relative Infant Dose (%) 
Buproprion (Wellbutrin) 2 
Citalopram (Celexa) 3-10 
Desvenlafaxine (Khedezla) 5.5-8.1 
Duloxetine (Cymbalta) <1 
Escitalopram (Lexapro) 3-6 
Fluoxetine (Prozac) <12 
Fluvoxamine (Luvox) <2 
Mirtazapine (Remeron) 0.5-3 
Paroxetine (Paxil) 0.5-3 
Sertraline (Zoloft) 0.5-3 
Venlafaxine (Effexor) 6-9 
Chad L et.al. Update on antidepressant use during breastfeeding. Canadian Fam Physician 2013; 59: 633-634.
AAnnttiieeppiilleeppttiicc MMeeddss 
 PPhheennyyttooiinn,, CCaarrbbaammaazzeeppiinnee,, aanndd VVaallpprrooiicc aacciidd aarree 
ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg 
– CCaauuttiioonn iinn uussee dduuee ttoo rriisskk ffoorr hheeppaattoottooxxiicciittyy 
((VVaallpprrooaattee)) 
 LLaammoottrriiggiinnee ((LLaammiiccttaall)),, PPrriimmaaddoonnee ((MMyyssoolliinnee)),, 
PPhheennoobbaarrbbiittaall aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg 
– nnoott pprreeffeerrrreedd dduuee ttoo ssllooww mmeettaabboolliissmm iinn tthhee iinnffaanntt 
rreessuullttiinngg iinn sseeddaattiioonn 
 LLeevveettiirraacceettaamm ((KKeepppprraa)) aanndd TTooppiirraammaattee ((TTooppaammaaxx)) 
aappppeeaarr ccoommppaattiibbllee wwiitthh bbrreeaassttffeeeeddiinngg
Antiepileptic meds: 
Topiramate and Levetiracetam 
 5 mother child pairs on Topiramate 
– mean milk:plasma ratio 0.86 
– Topiramate concentrations in infant were low 
– 4 of 5 mothers also taking carbamazepine (inducer) 
 8 women on Levetiracetam 
– Milk and plasma concentration equal 
– Levetiracetam concentrations in infants were low 
Ohman I et.al. Topiramate kinetics during delivery and lactation. Epilepsia 2002; 43: 
1157-1160 
Johannasen SI et.al. Levetiracetam concentrations in serum and breast milk at birth and 
during lactaction. Epilepsia 2005; 46: 775-777
AAnnttiihhiissttaammiinneess 
 AAllll sseeddaattiinngg aannttiihhiissttaammiinneess hhaavvee tthhee 
ppoossssiibbiilliittyy ooff ccaauussiinngg sseeddaattiioonn iinn tthhee iinnffaanntt 
 SSeeddaattiinngg aannttiihhiissttaammiinneess ((eesspp.. wwiitthh 
ddeeccoonnggeessttaanntt)) ccaann ddeeccrreeaassee mmiillkk ssuuppppllyy 
 NNoonnsseeddaattiinngg aannttiihhiissttaammiinneess aarree ccoommppaattiibbllee 
wwiitthh bbrreeaasstt ffeeeeddiinngg 
– LLoorraattaaddiinnee ((CCllaarriittiinn)) pprreeffeerrrreedd
BBlloooodd PPrreessssuurree MMeeddss 
 DDiiuurreettiiccss aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg 
– AAvvooiidd hhiigghh ddoosseess 
 BBeettaa bblloocckkeerrss aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg 
– PPrroopprraannoollooll,, mmeettoopprroollooll,, aanndd llaabbeettaallooll pprreeffeerrrreedd 
– AAtteennoollooll,, nnaaddoollooll,, aanndd ssoottaallooll ccaann lleeaadd ttoo SSEE ((hhyyppootteennssiioonn,, 
bbrraaddyyccaarrddiiaa,, ttaacchhyyppnneeaa)) 
 CCaallcciiuumm cchhaannnneell bblloocckkeerrss ((CCCCBBss)) aarree ccoommppaattiibbllee 
wwiitthh bbrreeaasstt ffeeeeddiinngg 
– NNiiffeeddiippiinnee ((PPrrooccaarrddiiaa)) iiss pprreeffeerrrreedd 
 AACCEE iinnhhiibbiittoorrss aanndd AARRBBss mmuusstt uussee wwiitthh ccaauuttiioonn
DDiiaabbeetteess MMeeddss 
 IInnssuulliinn iiss ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg 
 22nndd GGeenneerraattiioonn ssuullffoonnyylluurreeaass ((eegg.. ggllyybbuurriiddee,, 
gglliippiizziiddee,, gglliimmeeppeerriiddee)) aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt 
ffeeeeddiinngg 
 MMeettffoorrmmiinn iiss ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg 
 LLiimmiitteedd ddaattaa wwiitthh uussee ooff tthhiioogglliittaazzoonneess ((eegg.. 
AAvvaannddiiaa®,, AAccttooss®)) 
 MMoonniittoorr iinnffaannttss ffoorr ssyymmppttoommss ooff hhyyppooggllyycceemmiiaa
Diabetes Meds: 
Glyburide and Glipizide 
 Nonrandomized controlled study 
 Single dose of glyburide (5 or 10 mg, n=8) 
 Daily dose of glyburide or glipizide (5 mg; n=5) 
 No glyburide was found in milk 
 Mean infant exposure < 1.5% 
 Blood glucose levels were normal 
 Glyburide and glipizide compatible with 
breastfeeding 
Feig DS et.al. Transfer of glyburide and glipizide into 
breast milk. Diabetes Care 2005; 28:1851-5
DDiiaabbeetteess MMeeddss:: MMeettffoorrmmiinn 
 PPrroossppeeccttiivvee ssttuuddyy 
 6611 bbrreeaasstt ffeedd,, 5500 ffoorrmmuullaa ffeedd iinnffaannttss 
 EEvvaalluuaattee ggrroowwtthh,, mmoottoorr--ssoocciiaall ddeevveellooppmmeenntt oorr 
iillllnneessss 
 MMeeddiiaann mmeettffoorrmmiinn ddoossee 22..5555 ggrraammss ppeerr ddaayy 
 66 mmoonntthhss ooff lliiffee -- nnoo ddiiffffeerreennccee iinn wweeiigghhtt,, hhtt,, mmoottoorr-- 
ssoocciiaall ddeevveellooppmmeenntt,, iillllnneessss ((pp ≥≥ 00..0066)) 
 MMeeaann iinnffaanntt eexxppoossuurree 00..2288--11..0088%% 
 MMeettffoorrmmiinn ssaaffee iinn 11sstt 66 mmoonntthhss ooff lliiffee 
Glueck CJ et.al. J Pediatrics 2006; 148 (5): 628-632
MMeeddiiccaattiioonnss CCoonnttrraaiinnddiiccaatteedd iinn 
BBrreeaasstt FFeeeeddiinngg 
 AAnnttiinneeooppllaassttiiccss 
 IImmmmuunnee ssuupppprreessssaannttss 
 EErrggoott aallkkaallooiiddss 
 GGoolldd 
 IIooddiinnee//RRaaddiiooccoonnttrraasstt mmeeddiiaa 
 LLiitthhiiuumm ccaarrbboonnaattee 
 CCeerrttaaiinn aannttiibbiioottiiccss 
 SSoocciiaall ddrruuggss aanndd ddrruuggss ooff aabbuussee
Minimizing PPootteennttiiaall RRiisskk ttoo NNuurrssiinngg 
IInnffaannttss ffrroomm MMaatteerrnnaall MMeeddiiccaattiioonnss 
 GGeenneerraall CCoonnssiiddeerraattiioonnss 
– AAvvooiidd ddrruugg tthheerraappyy wwhheenn ppoossssiibbllee 
– UUssee ttooppiiccaall tthheerraappyy wwhheenn ppoossssiibbllee 
– MMeeddss tthhaatt aarree ssaaffee ffoorr uussee iinn tthhee iinnffaanntt AARREE ggeenneerraallllyy ssaaffee 
ffoorr tthhee bbrreeaasstt--ffeedd mmootthheerr 
– MMeeddss tthhaatt aarree ssaaffee iinn pprreeggnnaannccyy aarree NNOOTT aallwwaayyss ssaaffee iinn 
bbrreeaasstt--ffeeeeddiinngg 
– UUssee rreelliiaabbllee rreeffeerreenncceess ffoorr oobbttaaiinniinngg iinnffoo oonn mmeeddss iinn bbrreeaasstt 
mmiillkk 
SSppeenncceerr JJPP eett.. aall.. MMeeddiiccaattiioonnss iinn tthhee BBrreeaasstt--FFeeeeddiinngg MMootthheerr.. AAFFPP 
22000011,,6644::112200
MMiinniimmiizziinngg PPootteennttiiaall RRiisskk ttoo NNuurrssiinngg 
IInnffaannttss ffrroomm MMaatteerrnnaall MMeeddiiccaattiioonnss 
 MMeeddiiccaattiioonn ddoossiinngg 
– AAddmmiinniisstteerr ssiinnggllee ddaaiillyy ddoossee mmeeddss jjuusstt bbeeffoorree tthhee 
lloonnggeesstt sslleeeepp iinntteerrvvaall ffoorr tthhee iinnffaanntt,, uussuuaallllyy aafftteerr 
tthhee bbeeddttiimmee ffeeeeddiinngg 
– BBrreeaassttffeeeedd iinnffaanntt iimmmmeeddiiaatteellyy bbeeffoorree mmeedd ddoossee 
wwhheenn mmuullttiippllee ddaaiillyy ddoosseess aarree nneeeeddeedd 
SSppeenncceerr JJPP.. MMeeddiiccaattiioonnss iinn tthhee BBrreeaasstt--FFeeeeddiinngg MMootthheerr..AAFFPP,, 22000011:: 
6644::112200
CCoonncclluussiioonn 
 HHeeaalltthhccaarree pprroovviiddeerrss sshhoouulldd eennccoouurraaggee 
mmootthheerrss ttoo bbrreeaasstt ffeeeedd 
 EEvviiddeennccee ssuuppppoorrttss mmoosstt ccoommmmoonnllyy 
pprreessccrriibbeedd mmeeddss iinn bbrreeaasstt ffeeeeddiinngg mmootthheerrss 
ccaann bbee ttaakkeenn ssaaffeellyy 
 UUttiilliizzee aavvaaiillaabbllee llaaccttaattiioonn rreeffeerreenncceess 
 FFuurrtthheerr hheellpp ccaann bbee pprroovviiddeedd bbyy yyoouurr 
llaaccttaattiioonn ccoonnssuullttaanntt aanndd cclliinniiccaall pphhaarrmmaacciisstt
References 
1. Buck, ML. Drugs in Pregnancy and Lactation: Literature an Resource Update. Pediatric 
Pharm., 2010;16 (1): 1-5. 
2. Burkey BW. Evaluating Medication Use in Pregnancy and Lactation: What Every 
Pharmacist Should Know. J Pediatric Pharmacol Ther 2013; 18(3):247-258. 
3. Chad L et.al. Update on Antidepressant Use During Breastfeeding. Canadian Family 
Physician, 2013; 59: 633-634. 
4. Feig DS et. al. Oral Antidiabetic Agents in Pregnancy and Lactation: A Paradigm Shift? 
The Annals of Pharmacotherapy, 2007:41(7): 1174-1180. 
5. Glatstein MM et. al. Use of Hypoglycemic Drugs During Lactation. Canadian Family 
Physician, 2009; 55: 371-373. 
6. Glueck CJ et.al. Growth, Motor, and Social Development in Breast and Formula-fed 
Infants of Metformin-treated Women with Polycystic Ovarian Syndrome. J Pediatrics, 
2006; 148(5):628-32. 
7. Sachs et.al. AAP Committee on Drugs: The Transfer of Drugs and Therapeutics Into 
Human Breast Milk: An Update on Selected Topics. Pediatrics, 2013; 132 (3): e796- 
e809. 
8. Mathhew JL. Effect of Maternal Antibiotics on Breast feeding Infants. Postgrad Med 
Journal, 2004; 80:196-200.
References 
9. Mortel M and Mehta SD. Systematic Review of the Efficacy of Herbal Galactogogues. 
Journal of Human Lactation,2013;29(2):154-162. 
10. Pack AM. Therapy Insight: Clinical Management of Pregnant Women with Epilepsy. Nat 
Clin Pract Neurol, 2006; 2(4):190-200. 
11. Wagner CL. Human Milk and Lactation. Medscape, 2012. 
12. The Academy of Breastfeeding Medicine (ABM) Protocol Committee. ABM Clinical 
Protocol #18: Use of Antidepressants in Nursing Mothers. Breast Feeding Medicine, 
2008;3(1):44-52. 
13. The Academy of Breastfeeding Medicine (ABM) Protocol Committee. ABM Clinical 
Protocol #21: Guidelines for Breastfeeding and the Drug-Dependent Woman. Breast 
Feeding Medicine, 2009;4(4):225-228. 
14. The Academy of Breastfeeding Medicine (ABM) Protocol Committee. ABM Clinical 
Protocol #9. Use of Galactogogues in Initiating or Augmenting the Rate of Maternal Milk 
Secretion. Breast Feeding Medicine, 2011;6(1):41-49.
Medications and Lactation: Principles 
for Safe Practice for the Clinician 
Evelyn Fulmore, Pharm.D. 
McLeod Regional Medical 
Center 
Florence, SC

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Medications and Lactation: Principles for Safe Practice for the Clinician – Evelyn Fulmore, Pharm.D., McLeod Regional Medical Center

  • 1. Medications and Lactation: Principles for Safe Practice for the Clinician Evelyn Fulmore, Pharm.D. McLeod Regional Medical Center Florence, SC
  • 2. Disclosures  No financial relationships or duality of interest to disclose  I will be discussing use of agents to improve milk supply (galactagogues)
  • 3. Learning Objectives  Basic physiology of lactation and mechanisms of medication entry into mother’s breast milk  Factors to consider when selecting medications during lactation  Role of galactagogues in lactation induction  Tips in utilizing and interpreting available lactation drug information resources
  • 4. PPhhyyssiioollooggyy ooff LLaaccttaattiioonn  SSuucckklliinngg ssttiimmuullaatteess nniippppllee ® ppiittuuiittaarryy ggllaanndd sseeccrreetteess ooxxyyttoocciinn ® lleett ddoowwnn rreefflleexx rreessuullttss iinn mmiillkk eejjeeccttiinngg cceellllss ccoonnttrraacctt ffoorrcciinngg mmiillkk ffrroomm mmiillkk cceellllss iinnttoo mmiillkk dduuccttss..
  • 5. PPhhyyssiioollooggyy ooff LLaaccttaattiioonn  MMiillkk ppoooollss iinn llaacciiffeerroouuss ssiinnuusseess uunnddeerr tthhee aarreeoollaa.. SSuucckklliinngg ssttiimmuullaatteess mmiillkk ttoo ccoommee ffrroomm tthhee nniippppllee..
  • 6. CCoommppoossiittiioonn ooff BBrreeaassttmmiillkk  CCoolloossttrruumm ((DDaayyss ##33--55)) hhiigghh pprrootteeiinn, iimmmmuunnoogglloobbuulliinnss, mmiinneerraallss, llooww iinn llaaccttoossee aanndd ffaatt  TTrraannssiittiioonnaall mmiillkk ((DDaayyss ##66--1100)) hhiigghh iinn ffaatt, llaaccttoossee;; lloowweerr iinn pprrootteeiinn aanndd mmiinneerraallss  MMaattuurree mmiillkk ((DDaayy ##1144)) 6600--8800%% wwhheeyy pprrootteeiinn, 5500%% ffaatt, 4400%% llaaccttoossee, ggrroowwtthh ffaaccttoorr, llooww iinn VViittaammiinn DD
  • 7. Factors Affecting Amount of Drug Received by the Infant  Milk yield  Colostrum versus Mature milk  Concentration of drug in the milk  How well the breast was emptied during the previous feeding  Infants ability to absorb, detoxify, and excrete the drug
  • 8. TTrraannssffeerr ooff MMeeddiiccaattiioonnss iinnttoo BBrreeaasstt MMiillkk  CCoonncceennttrraattiioonn ggrraaddiieenntt – PPaassssiivvee ddiiffffuussiioonn ooff nnoonn--iioonniizzeedd aanndd ffrreeee ((nnoonn-- pprrootteeiinn bboouunndd)) mmeeddss – MMaatteerrnnaall sseerruumm ddrruugg ccoonncceennttrraattiioonn vvoolluummee ooff ddiissttrriibbuuttiioonn ((VVdd)) aanndd hhaallff--lliiffee - RReettrrooggrraaddee ddiiffffuussiioonn ooff ddrruugg ffrroomm bbrreeaasstt mmiillkk ttoo ppllaassmmaa SSppeenncceerr JJPP eett..aall.. MMeeddiiccaattiioonnss iinn tthhee BBrreeaasstt--FFeeeeddiinngg MMootthheerr.. AAFFPP 22000011;; 6644::111199
  • 9. TTrraannssffeerr ooff MMeeddiiccaattiioonnss iinnttoo BBrreeaasstt MMiillkk 11.. LLiippiidd ssoolluubbiilliittyy 22.. MMoolleeccuullaarr wweeiigghhtt 33.. MMaatteerrnnaall ppllaassmmaa lleevveellss 44.. MMaatteerrnnaall pprrootteeiinn bbiinnddiinngg 55.. OOrraall bbiiooaavvaaiillaabbiilliittyy, hhaallff lliiffee 66.. IIoonn ttrraappppiinngg ((ppKKaa))
  • 10. LLiippiidd SSoolluubbiilliittyy  DDrruuggss tthhaatt aarree hhiigghhllyy lliippiidd ssoolluubbllee ppeenneettrraattee mmiillkk iinn hhiigghheerr ccoonncceennttrraattiioonnss  AAvvooiidd eexxttrreemmeellyy lliippiidd ssoolluubbllee ddrruuggss..  EExxaammpplleess:: DDiiaazzeeppaamm, pphheennoobbaarrbbiittaall
  • 11. MMoolleeccuullaarr WWeeiigghhtt  TThhee lloowweerr tthhee mmoolleeccuullaarr wweeiigghhtt ((<<220000 DD)), tthhee ggrreeaatteerr ppeenneettrraattiioonn iinnttoo mmiillkk  MMoolleeccuullaarr wweeiigghhttss <<330000 DD :: ((eegg.. AAllccoohhooll, aammpphheettaammiinneess, ddiieett ppiillllss))  MMoolleeccuullaarr wweeiigghhttss ≥≥ 660000 DD :: ((eegg.. HHeeppaarriinn, EEnnooxxaappaarriinn, IInnssuulliinn, RReemmiiccaaddee))  LLaarrggeerr tthhee mmoolleeccuullaarr wweeiigghhtt//ssiizzee ((pprreeffeerrrreedd))
  • 12. MMaatteerrnnaall PPllaassmmaa lleevveell  TThhee mmoosstt iimmppoorrttaanntt ddeetteerrmmiinnaanntt ooff ddrruugg ppeenneettrraattiioonn iinnttoo mmiillkk  AAss mmaatteerrnnaall ppllaassmmaa lleevveellss rriissee, tthhee ccoonncceennttrraattiioonn iinn mmiillkk rriisseess  DDrruugg ddeelliivveerryy ssyysstteemmss tthhaatt rreessuulltt iinn llooww mmaatteerrnnaall ppllaassmmaa lleevveellss aarree pprreeffeerrrreedd iinn bbrreeaasstt ffeeeeddiinngg mmootthheerr ((eegg.. IInnhhaalleerr mmeedd, ttooppiiccaallss))
  • 13. MMaatteerrnnaall PPrrootteeiinn BBiinnddiinngg  MMoosstt iimmppoorrttaanntt ppaarraammeetteerr iinn cchhoooossiinngg aa ssaaffee ddrruugg ffoorr aa nnuurrssiinngg mmootthheerr  MMoosstt ddrruuggss cciirrccuullaattee iinn tthhee mmaatteerrnnaall ppllaassmmaa bboouunndd ttoo aallbbuummiinn  ““FFrreeee”” oorr ““UUnnbboouunndd”” ddrruugg ttrraannssffeerrss iinnttoo mmiillkk  DDrruuggss tthhaatt aarree hhiigghhllyy pprrootteeiinn bboouunndd rreemmaaiinn iinn tthhee mmaatteerrnnaall ppllaassmmaa aanndd ddoonn’’tt ppeenneettrraattee ttiissssuueess oorr bbrreeaasstt mmiillkk
  • 14. OOrraall BBiiooaavvaaiillaabbiilliittyy  TThhee aammoouunntt ooff ddrruugg tthhaatt iiss aabbssoorrbbeedd bbyy tthhee iinnffaanntt’’ss GGII ttrraacctt aanndd rreeaacchheess tthhee cciirrccuullaattiioonn  LLooww oorraall bbiiooaavvaaiillaabbiilliittyy:: aammiinnooggllyyccoossiiddeess, hheeppaarriinn, iinnssuulliinn, oommeepprraazzoollee  AAccttiioonn ooff aa ddrruugg iinn tthhee GGII ttrraacctt mmaayy pprroodduuccee SSEE:: ddiiaarrrrhheeaa, ccoonnssttiippaattiioonn, PPMMCC
  • 15. IIoonn TTrraappppiinngg ((ppKKaa))  IIoonn ttrraappppiinngg –– ddrruugg bbeeccoommeess ttrraappppeedd iinn mmiillkk ccoommppaarrttmmeenntt ((dduuee ttoo llooww ppHH mmiillkk))  ppKKaa iiss tthhee ppHH wwhheerree aa ddrruugg iiss eeqquuaallllyy iioonniicc oorr nnoonniioonniicc ((tthhee mmoorree iioonniicc, lleessss ttrraannssffeerr ffrroomm mmiillkk ttoo ppllaassmmaa))  DDrruuggss wwiitthh hhiigghh ppKKaa ((>>77..22)), hhaavvee hhiigghheerr MMiillkk//PPllaassmmaa rraattiioo ((eegg..PPhheennoobbaarrbbiittaall, iiooddiinnaatteedd ddrruuggss))  CChhoooossee ddrruuggss wwiitthh aa llooww ppKKaa
  • 16. DDrruuggss TThhaatt DDeeccrreeaassee MMiillkk SSuuppppllyy  NNiiccoottiinnee  AAllccoohhooll  SSeeddaattiinngg AAnnttiihhiissttaammiinneess ((eegg.. DDiipphheennhhyyddrraammiinnee))  EEssttrrooggeenn ccoonnttaaiinniinngg oorraall ccoonnttrraacceeppttiivveess  PPrrooggeesstteerroonnee ccoonnttrraacceeppttiivveess ((iiff ssttaarrtteedd eeaarrllyy ppoossttppaarrttuumm bbeeffoorree mmiillkk ssuuppppllyy eessttaabblliisshheedd))  BBrroommooccrriippttiinnee ((PPaarrllooddeell))
  • 17. Drugs That Aid in Milk Production: Galactagogues  Herbals: Fenugreek  Metoclopramide (Reglan)  Domperidone (Motillium)  Synthetic Oxytocin nasal spray
  • 18. Galactagogues  Used to increase breast milk supply  Need to determine the etiology of low milk supply  Ensure proper breastfeeding technique  Only use with adequate milk removal  Must evaluate for medical co-morbidities (e.g. hypothyroidism, retained placenta)
  • 19. Herbal: Fenugreek  Trigonella foenum graecum  MOA: stimulate sweat production; Phytoestrogen and Diosgenin - increase milk flow  Tea (bitter taste), capsule or tablet  Sweat and urine (maple syrup smell)  Caution use in Asthma or diabetes  Contains coumarin (interact with NSAIDS)  No scientific data
  • 20. Domperidone (Motillium)  Not approved for use in the US  MOA: increase prolactin ® milk production  Maternal safety has not been established  FDA warning concerning reports of QT interval prolongation, cardiac arrest, sudden death (IV formulation)  Clinical trial showed increase breastmilk volume without affecting nutrient composition Campbell-Yeo M. Effect of Domperidone on Compositiono of Preterm Human Breast Milk. Pediatrics 2010; 125 (1):e107-e114
  • 21. Metoclopramide (Reglan)  Most commonly used  MOA: increase prolactin  Caution: clearance of metoclopramide in the neonate is prolonged can result in side effects (methemoglobinemia)  Short term use recommended (1-3 weeks)  Common dosing: 1st day – 10 mg, 2nd day – 10 mg bid, thereafter 10 mg tid
  • 22. Synthetic Oxytocin Nasal Spray  Hormone (synthetically derived)  MOA: causes release of milk from milk glands to the ducts (helps empty the breast)  Prepared by compounding Rx (10 unit/ml)  Dose: 1-2 sprays each nostril before breast feeding or pumping
  • 23. Synthetic Oxytocin Nasal Spray: Mean Daily Milk Production Fewtrell MS. Arch Dis Child Fetal Neonatal Ed. 2006 May; 91(3): F169–F174.
  • 24.
  • 25. SSaaffeettyy DDaattaa aanndd BBrreeaasstt FFeeeeddiinngg  BBrreeaasstt ffeeeeddiinngg llaacckkss ssttaannddaarrddiizzeedd rriisskk ccaatteeggoorriieess  MMoosstt ooff tthhee ddaattaa oonn mmeeddss aanndd bbrreeaasstt ffeeeeddiinngg aarree ffrroomm sscciieennttiiffiicc lliitteerraattuurree  GGiivveenn tthhee llaacckk ooff ssttaannddaarrddiizzaattiioonn, ootthheerr rreeccoommmmeennddaattiioonnss ffoorr uussiinngg mmeeddss wwhhiillee bbrreeaasstt ffeeeeddiinngg hhaavvee bbeeeenn uusseedd bbyy hheeaalltthh ccaarree pprroovviiddeerrss MMaasstteerr KKPP eett..aall.. BBrreeaasstt FFeeeeddiinngg aanndd OOTTCC mmeeddiiccaattiioonnss.. UUSS PPhhaarrmm 22000077;; 3322 ((77)):: 88--1122
  • 26. LLaaccttaattiioonn RReessoouurrcceess  BBooookkss – GGeerraalldd GG.. BBrriiggggss.. ““DDrruuggss iinn PPrreeggnnaannccyy aanndd LLaaccttaattiioonn:: AA rreeffeerreennccee GGuuiiddee ttoo FFeettaall aanndd NNeeoonnaattaall RRiisskk””,, 99tthh eeddiittiioonn;; 22001122
  • 27. Definitions of Breast Feeding Recommendations  Compatible  Hold Breast Feeding  No (limited) Human Data – Probably Compatible  No (limited) Human Data – Potential Toxicity  No (limited) Human Data – Potential Toxicity (Mother)  Contraindicated Briggs GG et. al. Drugs iinn PPrreeggnnaannccyy aanndd LLaaccttaattiioonn,, 22000088;; 88tthh eeddiittiioonn
  • 28. LLaaccttaattiioonn RReessoouurrcceess  BBooookkss – TThhoommaass WW.. HHaallee.. ““MMeeddiiccaattiioonnss aanndd MMootthheerrss’’ MMiillkk”” 22001122,, 1155tthh eeddiittiioonn
  • 29. Dr. Hale’s Lactation Risk Category  L1 Safest  L2 Safer  L3 Moderately Safe  L4 Potentially Hazardous  L5 Contraindicated Hale TW. Medications and MMootthheerrss'' MMiillkk,, 22001100;; 1144tthh eeddiittiioonn..
  • 30. DDrr.. HHaallee’’ss LLaaccttaattiioonn RRiisskk CCaatteeggoorryy  LL11 SSaaffeesstt:: DDrruugg ttaakkeenn bbyy llaarrggeerr ## ooff bbrreeaasstt ffeeeeddiinngg wwoommeenn wwiitthhoouutt aannyy oobbsseerrvveedd aaddvveerrssee eeffffeeccttss iinn iinnffaanntt  LL22 SSaaffeerr:: DDrruugg ssttuuddiieedd iinn aa lliimmiitteedd ## ooff bbrreeaasstt ffeeeeddiinngg wwoommeenn wwiitthhoouutt aannyy oobbsseerrvveedd aaddvveerrssee eevveennttss iinn iinnffaannttss  LL33 MMooddeerraatteellyy SSaaffee:: NNoo ccoonnttrroolllleedd ttrriiaallss iinn bbrreeaasstt ffeeeeddiinngg wwoommeenn, bbuutt rriisskk ooff uunnttoowwaarrdd eeffffeeccttss iiss ppoossssiibbllee
  • 31. DDrr.. HHaallee’’ss LLaaccttaattiioonn RRiisskk CCaatteeggoorryy  LL33 MMooddeerraatteellyy SSaaffee:: NNoo ccoonnttrroolllleedd ttrriiaallss iinn bbrreeaasstt ffeeeeddiinngg wwoommeenn,, bbuutt rriisskk ooff uunnttoowwaarrdd eeffffeeccttss iiss ppoossssiibbllee OORR ccoonnttrroolllleedd ssttuuddiieess sshhooww oonnllyy mmiinniimmaall nnoonn--tthhrreeaatteenniinngg aaddvveerrssee eeffffeeccttss  LL44 PPootteennttiiaallllyy HHaazzaarrddoouuss:: PPoossiittiivvee eevviiddeennccee ooff rriisskk ttoo tthhee bbrreeaassttffeedd iinnffaanntt OORR ttoo tthhee bbrreeaasstt mmiillkk pprroodduuccttiioonn bbuutt bbeenneeffiitt oouuttwweeiigghhss tthhee rriisskk
  • 32. DDrr.. HHaallee’’ss LLaaccttaattiioonn RRiisskk CCaatteeggoorryy  LL55 CCoonnttrraaiinnddiiccaatteedd:: SSttuuddiieess iinn bbrreeaassttffeeeeddiinngg wwoommeenn hhaavvee ddeemmoonnssttrraatteedd ssiiggnniiffiiccaanntt aanndd ddooccuummeenntteedd rriisskk ttoo tthhee iinnffaanntt.. RRiisskk cclleeaarrllyy oouuttwweeiigghhss bbeenneeffiittss ooff bbrreeaasstt ffeeeeddiinngg..
  • 33. Values Used to Estimate Infant Drug Exposure  Milk to Plasma Ratio (M/P) – Ratio of the concentration of drug in mother’s milk divided by the concentration in the mother’s plasma – M/P <1 is preferred  Theoretical Infant Dose (TID) – Multiply the milk concentration x daily milk intake of the infant – Compared to the usual maintenance pediatric dose  Relative Infant Dose (RID) – Divide the infant’s dose via milk (mg/kg/day) by the mother’s dose (mg/kg/day) – Assumes daily milk intake of 150 ml/kg/day – RID<10% is considered safe – Exception: fluconazole, metronidazole (have a high RID but are non toxic)
  • 34. LLaaccttaattiioonn RReessoouurrcceess  IInntteerrnneett – DDrr.. HHaallee’’ss BBrreeaassttffeeeeddiinngg PPhhaarrmmaaccoollooggyy ppaaggee (( hhttttpp::////wwwwww..nneeoonnaattaall..ttttuuhhsscc..eedduu//ffaacctt))
  • 35. LLaaccttaattiioonn RReessoouurrcceess  IInntteerrnneett – UU..SS.. NNaattiioonnaall LLiibbrraarryy ooff MMeeddiicciinnee.. LLaaccttMMeedd ((hhttttpp::////ttooxxnneett..nnllmm..nniihh..ggoovv//ccggii-- bbiinn//ssiiss//hhttmmllggeenn??))//LLAACCTT))
  • 39. The Transfer of Drugs and Other Chemicals Into Human Milk Committee on Drugs Pediatrics 2001;108;776 CLINICAL REPORT The Transfer of Drugs and Therapeutics Into Human Breast Milk: An Update on Selected Topics Hari Cheryl Sachs, MD, FAAP* and COMMITTEE ON DRUGS Pediatrics; originally published online August 26, 2013; DOI: 10.1542/peds.2013-1985
  • 40. BBeeffoorree PPrreessccrriibbiinngg DDrruugg TThheerraappyy iinn tthhee LLaaccttaattiinngg WWoommaann 11.. IIss ddrruugg tthheerraappyy rreeaallllyy nneecceessssaarryy?? 22.. TThhee ssaaffeesstt ddrruugg sshhoouulldd bbee cchhoosseenn.. 33.. IIff tthheerree iiss aa ppoossssiibbiilliittyy tthhaatt aa ddrruugg mmaayy pprreesseenntt aa rriisskk ttoo tthhee iinnffaanntt,, tthheenn ccoonnssiiddeerr mmeeaassuurriinngg bblloooodd lleevveellss 44.. DDrruugg eexxppoossuurree iinn tthhee iinnffaanntt mmaayy bbee lliimmiitteedd bbyy ttiimmiinngg ooff mmeedd aanndd bbrreeaassttffeeeeddiinngg AAAAPP CCoommmmiitttteeee oonn DDrruuggss.. TThhee ttrraannssffeerr ooff ddrruuggss aanndd ootthheerr cchheemmiiccaallss iinnttoo hhuummaann mmiillkk.. PPeeddiiaattrriiccss 22000011;;110088 ((33))::777777
  • 41. AAnnaallggeessiiccss  AAcceettaammiinnoopphheenn ((TTyylleennooll)) iiss ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg  NNoonnsstteerrooiiddaall aannttiiiinnffllaammmmaattoorryy ddrruuggss ((NNSSAAIIDDSS)) –– iibbuupprrooffeenn iiss pprreeffeerrrreedd – NNaapprroossyynn,, ssuulliinnddaacc,, ppiirrooxxiiccaamm sshhoouulldd bbee aavvooiiddeedd  NNaarrccoottiicc//OOppiiaatteess –– mmoorrpphhiinnee,, ccooddeeiinnee,, ooxxyyccooddoonnee,, aanndd hhyyddrrooccooddoonnee aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg – MMeeppeerriiddiinnee ((DDeemmeerrooll)) sshhoouulldd bbee aavvooiiddeedd
  • 42. Narcotics/Opiates  Case controlled studies evaluating long term developmental outcomes are needed  Breastfeeding should be supported if: – “stable” and compliant with methadone or buprenorphine +/- naloxone (Subutex®, Suboxone®) – negative maternal urine toxicology test at delivery except for prescribed medications – plan to continue substance abuse treatment in the postpartum period – do not have medical contraindication to breastfeeding Breastfeeding Medicine 2009; 4(4):225-228
  • 43. AAnnttiibbiioottiiccss  PPeenniicciilllliinnss aanndd cceepphhaalloossppoorriinnss aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg – MMoonniittoorr iinnffaanntt ffoorr ddiiaarrrrhheeaa ((cchhaannggee iinn gguutt fflloorraa))  TTeettrraaccyycclliinnee iiss ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg – CCaallcciiuumm iinn bbrreeaasstt mmiillkk lliimmiittss aabbssoorrppttiioonn ;; aavvooiidd ddooxxyyccyylliinnee aanndd mmiinnooccyycclliinnee  QQuuiinnoolloonneess hhaavvee nnoott bbeeeenn rraatteedd bbyy AAAAPP – LLeevvaaqquuiinn iiss ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg  TTrriimmeetthhoopprriimm--ssuullffaammeetthhooxxaazzoollee ((BBaaccttrriimm)) iiss ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg – NNoott rreeccoommmmeennddeedd iinn iinnffaannttss << 22 mmoonntthh ((ddeeppllaacceemmeenntt ooff bbiilliirruubbiinn))
  • 44. AAnnttiiddeepprreessssaannttss  TTrriiccyycclliicc aannttiiddeepprreessssaannttss –– lliittttllee oorr nnoo eeffffeecctt oonn bbrreeaasstt ffeeeeddiinngg iinnffaanntt – AAAAPP lliissttss aass ppoossssiibbllee ccoonncceerrnn wwiitthh eexxppoossuurree lloonngg--tteerrmm  SSeelleeccttiivvee sseerroottoonniinn rreeuuppttaakkee iinnhhiibbiittoorrss ((SSSSRRIIss)) –– ggeenneerraallllyy 11sstt cchhooiiccee – PPaarrooxxeettiinnee ((PPaaxxiill)) oorr SSeerrttrraalliinnee ((ZZoolloofftt)) pprreeffeerrrreedd ttoo FFlluuooxxeettiinnee ((PPrroozzaacc))  SSeerroottoonniinn NNoorreeppiinneepphhrriinnee RReeuuppttaakkee IInnhhiibbiittoorrss ((SSNNRRIIss)) – VVeennllaaffaaxxiinnee ((EEffffeexxoorr))  TTaakkee ddoossee aatt bbeeddttiimmee ttoo lliimmiitt eexxppoossuurree ttoo iinnffaanntt
  • 45. Antidepressants: SSRIs and SNRIs  Limited to small case studies  Paroxetine and sertraline produced low RID 0.5-3%  Fluoxetine, citalopram, venlafaxine have variable RID near to equal 10%  Preference hierarchy: sertraline, paroxetine, citalopram, venlafaxine, fluoxetine  Watch for uneasy sleep, colic, irritability, poor feeding, drowsiness Breastfeeding Medicine 2008; 3 (1): 44-52
  • 46. Relative Infant Dose (RID) of Commonly Prescribed Antidepressants Antidepressant Relative Infant Dose (%) Buproprion (Wellbutrin) 2 Citalopram (Celexa) 3-10 Desvenlafaxine (Khedezla) 5.5-8.1 Duloxetine (Cymbalta) <1 Escitalopram (Lexapro) 3-6 Fluoxetine (Prozac) <12 Fluvoxamine (Luvox) <2 Mirtazapine (Remeron) 0.5-3 Paroxetine (Paxil) 0.5-3 Sertraline (Zoloft) 0.5-3 Venlafaxine (Effexor) 6-9 Chad L et.al. Update on antidepressant use during breastfeeding. Canadian Fam Physician 2013; 59: 633-634.
  • 47. AAnnttiieeppiilleeppttiicc MMeeddss  PPhheennyyttooiinn,, CCaarrbbaammaazzeeppiinnee,, aanndd VVaallpprrooiicc aacciidd aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg – CCaauuttiioonn iinn uussee dduuee ttoo rriisskk ffoorr hheeppaattoottooxxiicciittyy ((VVaallpprrooaattee))  LLaammoottrriiggiinnee ((LLaammiiccttaall)),, PPrriimmaaddoonnee ((MMyyssoolliinnee)),, PPhheennoobbaarrbbiittaall aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg – nnoott pprreeffeerrrreedd dduuee ttoo ssllooww mmeettaabboolliissmm iinn tthhee iinnffaanntt rreessuullttiinngg iinn sseeddaattiioonn  LLeevveettiirraacceettaamm ((KKeepppprraa)) aanndd TTooppiirraammaattee ((TTooppaammaaxx)) aappppeeaarr ccoommppaattiibbllee wwiitthh bbrreeaassttffeeeeddiinngg
  • 48. Antiepileptic meds: Topiramate and Levetiracetam  5 mother child pairs on Topiramate – mean milk:plasma ratio 0.86 – Topiramate concentrations in infant were low – 4 of 5 mothers also taking carbamazepine (inducer)  8 women on Levetiracetam – Milk and plasma concentration equal – Levetiracetam concentrations in infants were low Ohman I et.al. Topiramate kinetics during delivery and lactation. Epilepsia 2002; 43: 1157-1160 Johannasen SI et.al. Levetiracetam concentrations in serum and breast milk at birth and during lactaction. Epilepsia 2005; 46: 775-777
  • 49. AAnnttiihhiissttaammiinneess  AAllll sseeddaattiinngg aannttiihhiissttaammiinneess hhaavvee tthhee ppoossssiibbiilliittyy ooff ccaauussiinngg sseeddaattiioonn iinn tthhee iinnffaanntt  SSeeddaattiinngg aannttiihhiissttaammiinneess ((eesspp.. wwiitthh ddeeccoonnggeessttaanntt)) ccaann ddeeccrreeaassee mmiillkk ssuuppppllyy  NNoonnsseeddaattiinngg aannttiihhiissttaammiinneess aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg – LLoorraattaaddiinnee ((CCllaarriittiinn)) pprreeffeerrrreedd
  • 50. BBlloooodd PPrreessssuurree MMeeddss  DDiiuurreettiiccss aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg – AAvvooiidd hhiigghh ddoosseess  BBeettaa bblloocckkeerrss aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg – PPrroopprraannoollooll,, mmeettoopprroollooll,, aanndd llaabbeettaallooll pprreeffeerrrreedd – AAtteennoollooll,, nnaaddoollooll,, aanndd ssoottaallooll ccaann lleeaadd ttoo SSEE ((hhyyppootteennssiioonn,, bbrraaddyyccaarrddiiaa,, ttaacchhyyppnneeaa))  CCaallcciiuumm cchhaannnneell bblloocckkeerrss ((CCCCBBss)) aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg – NNiiffeeddiippiinnee ((PPrrooccaarrddiiaa)) iiss pprreeffeerrrreedd  AACCEE iinnhhiibbiittoorrss aanndd AARRBBss mmuusstt uussee wwiitthh ccaauuttiioonn
  • 51. DDiiaabbeetteess MMeeddss  IInnssuulliinn iiss ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg  22nndd GGeenneerraattiioonn ssuullffoonnyylluurreeaass ((eegg.. ggllyybbuurriiddee,, gglliippiizziiddee,, gglliimmeeppeerriiddee)) aarree ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg  MMeettffoorrmmiinn iiss ccoommppaattiibbllee wwiitthh bbrreeaasstt ffeeeeddiinngg  LLiimmiitteedd ddaattaa wwiitthh uussee ooff tthhiioogglliittaazzoonneess ((eegg.. AAvvaannddiiaa®,, AAccttooss®))  MMoonniittoorr iinnffaannttss ffoorr ssyymmppttoommss ooff hhyyppooggllyycceemmiiaa
  • 52. Diabetes Meds: Glyburide and Glipizide  Nonrandomized controlled study  Single dose of glyburide (5 or 10 mg, n=8)  Daily dose of glyburide or glipizide (5 mg; n=5)  No glyburide was found in milk  Mean infant exposure < 1.5%  Blood glucose levels were normal  Glyburide and glipizide compatible with breastfeeding Feig DS et.al. Transfer of glyburide and glipizide into breast milk. Diabetes Care 2005; 28:1851-5
  • 53. DDiiaabbeetteess MMeeddss:: MMeettffoorrmmiinn  PPrroossppeeccttiivvee ssttuuddyy  6611 bbrreeaasstt ffeedd,, 5500 ffoorrmmuullaa ffeedd iinnffaannttss  EEvvaalluuaattee ggrroowwtthh,, mmoottoorr--ssoocciiaall ddeevveellooppmmeenntt oorr iillllnneessss  MMeeddiiaann mmeettffoorrmmiinn ddoossee 22..5555 ggrraammss ppeerr ddaayy  66 mmoonntthhss ooff lliiffee -- nnoo ddiiffffeerreennccee iinn wweeiigghhtt,, hhtt,, mmoottoorr-- ssoocciiaall ddeevveellooppmmeenntt,, iillllnneessss ((pp ≥≥ 00..0066))  MMeeaann iinnffaanntt eexxppoossuurree 00..2288--11..0088%%  MMeettffoorrmmiinn ssaaffee iinn 11sstt 66 mmoonntthhss ooff lliiffee Glueck CJ et.al. J Pediatrics 2006; 148 (5): 628-632
  • 54. MMeeddiiccaattiioonnss CCoonnttrraaiinnddiiccaatteedd iinn BBrreeaasstt FFeeeeddiinngg  AAnnttiinneeooppllaassttiiccss  IImmmmuunnee ssuupppprreessssaannttss  EErrggoott aallkkaallooiiddss  GGoolldd  IIooddiinnee//RRaaddiiooccoonnttrraasstt mmeeddiiaa  LLiitthhiiuumm ccaarrbboonnaattee  CCeerrttaaiinn aannttiibbiioottiiccss  SSoocciiaall ddrruuggss aanndd ddrruuggss ooff aabbuussee
  • 55. Minimizing PPootteennttiiaall RRiisskk ttoo NNuurrssiinngg IInnffaannttss ffrroomm MMaatteerrnnaall MMeeddiiccaattiioonnss  GGeenneerraall CCoonnssiiddeerraattiioonnss – AAvvooiidd ddrruugg tthheerraappyy wwhheenn ppoossssiibbllee – UUssee ttooppiiccaall tthheerraappyy wwhheenn ppoossssiibbllee – MMeeddss tthhaatt aarree ssaaffee ffoorr uussee iinn tthhee iinnffaanntt AARREE ggeenneerraallllyy ssaaffee ffoorr tthhee bbrreeaasstt--ffeedd mmootthheerr – MMeeddss tthhaatt aarree ssaaffee iinn pprreeggnnaannccyy aarree NNOOTT aallwwaayyss ssaaffee iinn bbrreeaasstt--ffeeeeddiinngg – UUssee rreelliiaabbllee rreeffeerreenncceess ffoorr oobbttaaiinniinngg iinnffoo oonn mmeeddss iinn bbrreeaasstt mmiillkk SSppeenncceerr JJPP eett.. aall.. MMeeddiiccaattiioonnss iinn tthhee BBrreeaasstt--FFeeeeddiinngg MMootthheerr.. AAFFPP 22000011,,6644::112200
  • 56. MMiinniimmiizziinngg PPootteennttiiaall RRiisskk ttoo NNuurrssiinngg IInnffaannttss ffrroomm MMaatteerrnnaall MMeeddiiccaattiioonnss  MMeeddiiccaattiioonn ddoossiinngg – AAddmmiinniisstteerr ssiinnggllee ddaaiillyy ddoossee mmeeddss jjuusstt bbeeffoorree tthhee lloonnggeesstt sslleeeepp iinntteerrvvaall ffoorr tthhee iinnffaanntt,, uussuuaallllyy aafftteerr tthhee bbeeddttiimmee ffeeeeddiinngg – BBrreeaassttffeeeedd iinnffaanntt iimmmmeeddiiaatteellyy bbeeffoorree mmeedd ddoossee wwhheenn mmuullttiippllee ddaaiillyy ddoosseess aarree nneeeeddeedd SSppeenncceerr JJPP.. MMeeddiiccaattiioonnss iinn tthhee BBrreeaasstt--FFeeeeddiinngg MMootthheerr..AAFFPP,, 22000011:: 6644::112200
  • 57. CCoonncclluussiioonn  HHeeaalltthhccaarree pprroovviiddeerrss sshhoouulldd eennccoouurraaggee mmootthheerrss ttoo bbrreeaasstt ffeeeedd  EEvviiddeennccee ssuuppppoorrttss mmoosstt ccoommmmoonnllyy pprreessccrriibbeedd mmeeddss iinn bbrreeaasstt ffeeeeddiinngg mmootthheerrss ccaann bbee ttaakkeenn ssaaffeellyy  UUttiilliizzee aavvaaiillaabbllee llaaccttaattiioonn rreeffeerreenncceess  FFuurrtthheerr hheellpp ccaann bbee pprroovviiddeedd bbyy yyoouurr llaaccttaattiioonn ccoonnssuullttaanntt aanndd cclliinniiccaall pphhaarrmmaacciisstt
  • 58. References 1. Buck, ML. Drugs in Pregnancy and Lactation: Literature an Resource Update. Pediatric Pharm., 2010;16 (1): 1-5. 2. Burkey BW. Evaluating Medication Use in Pregnancy and Lactation: What Every Pharmacist Should Know. J Pediatric Pharmacol Ther 2013; 18(3):247-258. 3. Chad L et.al. Update on Antidepressant Use During Breastfeeding. Canadian Family Physician, 2013; 59: 633-634. 4. Feig DS et. al. Oral Antidiabetic Agents in Pregnancy and Lactation: A Paradigm Shift? The Annals of Pharmacotherapy, 2007:41(7): 1174-1180. 5. Glatstein MM et. al. Use of Hypoglycemic Drugs During Lactation. Canadian Family Physician, 2009; 55: 371-373. 6. Glueck CJ et.al. Growth, Motor, and Social Development in Breast and Formula-fed Infants of Metformin-treated Women with Polycystic Ovarian Syndrome. J Pediatrics, 2006; 148(5):628-32. 7. Sachs et.al. AAP Committee on Drugs: The Transfer of Drugs and Therapeutics Into Human Breast Milk: An Update on Selected Topics. Pediatrics, 2013; 132 (3): e796- e809. 8. Mathhew JL. Effect of Maternal Antibiotics on Breast feeding Infants. Postgrad Med Journal, 2004; 80:196-200.
  • 59. References 9. Mortel M and Mehta SD. Systematic Review of the Efficacy of Herbal Galactogogues. Journal of Human Lactation,2013;29(2):154-162. 10. Pack AM. Therapy Insight: Clinical Management of Pregnant Women with Epilepsy. Nat Clin Pract Neurol, 2006; 2(4):190-200. 11. Wagner CL. Human Milk and Lactation. Medscape, 2012. 12. The Academy of Breastfeeding Medicine (ABM) Protocol Committee. ABM Clinical Protocol #18: Use of Antidepressants in Nursing Mothers. Breast Feeding Medicine, 2008;3(1):44-52. 13. The Academy of Breastfeeding Medicine (ABM) Protocol Committee. ABM Clinical Protocol #21: Guidelines for Breastfeeding and the Drug-Dependent Woman. Breast Feeding Medicine, 2009;4(4):225-228. 14. The Academy of Breastfeeding Medicine (ABM) Protocol Committee. ABM Clinical Protocol #9. Use of Galactogogues in Initiating or Augmenting the Rate of Maternal Milk Secretion. Breast Feeding Medicine, 2011;6(1):41-49.
  • 60. Medications and Lactation: Principles for Safe Practice for the Clinician Evelyn Fulmore, Pharm.D. McLeod Regional Medical Center Florence, SC

Editor's Notes

  1. During the 1st 10-14 days, large gaps exist between alveolar cells which enhance drug absorption. This will be important in considering breastfeeding the preterm infant.
  2. The most important factor in infant exposure through breast milk is the amount of medication in the mother’s serum.Pass from the maternal plasma compartment through capillary wall into the alveolar cells to penetrate the breast milk.
  3. We will spend a few moments to review each of these factors that determine penetration into medications into breast milk.
  4. Drugs that are very lipid soluble penetrate in milk in higher concentrations almost without exception. Of particular interest are the drugs that are active in the CNS. CNS active drugs invariably have the unique characteristics required to enter milk. Therefore, if a drug is active in the CNS, higher levels in milk are expected; although the amounts still are often subclinical. Examples include drugs like Diazepam and Phenobarbital.
  5. The molecular weight of a medication is a significant determinant as to the entry of that medication into human milk. Medications with small MWs (&amp;lt;200 daltons) can easily pass into milk traversing small pores in the cell walls of the mammary epithelium. Examples of low MW drugs include: alcohol, amphetemines, diet pills. Drugs with higher molecular weights must traverse the membrane by dissolving in the cell’s lipid membranes, which may significantly reduce milk levels. Examples include Heparin, Enoxaparin, Insulin, Remicade. Larger molecular weight or size agents are preferred due to the reduced amounts that enter into the milk compartment.
  6. Protein binding also plays an important role. Drugs circulate in the maternal plasma, either bound to albumin or freely soluble in the plasma. It is the free component “unbound fraction” that transfers into milk, while the bound fraction stays in the maternal circulation. Examples: warfarin and many NSAIDs. Levels are reduced in milk simply because they are excluded from the milk compartment. This is one of the single most important physiologic parameters to consider when choosing a safe medication for a nursing mother.
  7. Once a drug has entered the mother’s milk and has been ingested by the infant, it must traverse or pass through the infant’s GI tract prior to absorption. Some drugs are poorly stable in this environment due to the proteolytic enzymes and acids present in the infant’s stomach. Examples of drugs with low oral bioavailability in the infant include. Aminoglycosides, heparin, insulin, omeprazole, and other large peptide drugs. Other drugs are poorly absorbed by the infant’s gastrointestinal tract and do not enter the infant’s blood stream. Thus oral bioavailability is a useful tool to estimate just how much of the drug will be absorbed by the infant. Realize also that some drugs that exert their action in the GI tract may produce local side effects in the infant causing diarrhea, constipation, or PMC.
  8. Drugs are trapped in milk (ion trapping) due to the low pH of human milk (7-7.2). With drugs with a high pKa, the ionic state of the drug changes and stops its exit back into the maternal circulation. This is important for weak basic drugs, such as barbiturates (like phenobarbital with high pKa).
  9. In the US it is estimated that 15% of breast feediing mothers use herbal galactagogues. Four herbs (shatavari, tobangun, fenugreek, milk thistle) with potential use as galactagogues have been studied. Currently the Academy of Breast feeding Medicine does not recommend use of herbals as galactagogues.
  10. Fenugreek seeds contain hormone precursors that increase milk supply. Scientists do not know for sure how this happens. Some believe it is possible because breasts are modified sweat glands, and fenugreek stimulates sweat production. It has been found that fenugreek can increase a nursing mother&amp;apos;s milk supply within 24 to 72 hours after first taking the herb. Once an adequate level of milk production is reached, most women can discontinue the fenugreek and maintain the milk supply with adequate breast stimulation. Many women today take fenugreek in a pill form (ground seeds placed in capsules). The pills can be found at most vitamin and nutrition stores and at many supermarkets and natural foods stores. Fenugreek can also be taken in tea form, although tea is believed to be less potent than the pills and the tea comes with a bitter taste that can be hard to stomach. Fenugreek is not right for everyone. The herb has caused aggravated asthma symptoms in some women and has lowered blood glucose levels in some women with diabetes.
  11. The Milk to Plasma Ratio is the ratio of the concentration of the drug in the mother’s milk divided by the concentration in the mother’s plasma. If high (&amp;gt;1-5), it is useful as an indicator of drugs that may sequester in milk in high levels. If low (&amp;lt;1), it is a good indicator that only minimal levels of the drug are transferred into milk. While it is best to choose drugs with low M/P ratios, the amount of the drug which transfers is largely determined by the level of drug in the mother’s plasma compartment. Even with high M/P ratios and low maternal plasma levels, the amount of drug that transfers can be low. The Theoretical Infant Dose is a value calculated by multiplying the milk concentration x the daily milk intake of the infant. This value is then compared to published usual maintenance pediatric doses. Lastly, the Relative Infant Dose (RID) is a value calculated by dividing the infant’s dose via milk (mg/kg/day) by the maternal dose (mg/kg/day). This weight normalizing method indicates approximately how much of the “maternal dose” the infant is receiving. In the literature, some investigators do not normalize this value by weight so be careful we making comparisons.
  12. The transfer of venlafaxine into breastmilk studied by Newport and colleagues in 13 infant-mother pairs showed a mean milk:plasma ratio of 275.3%. The highest venlafaxine and desvenlafaxine concentration in breastmilk occurred an average of 8 hours after a maternal dose. Infant plasma concentrations of venlafaxine/desvenalfaxine were 37.1% of the maternal plasma concentrations, with a theoretical infant dose of 0.208 mg/kg/day. No adverse effects were reported. The considerable transfer of drug into breastmilk suggests the need for confirmatory studies and caution when prescribing this drug in clinical practice.
  13. On the basis of small studies, including single-dose studies, case reports and short-term studies, phenytoin, carbamazepine and valproate are probably safe. These AEDs are all moderately to highly protein-bound, and are not transferred in high concentrations in breast milk. A small study of four infants indicates that lamotrigine might be transferred to the infant through breast milk in concentrations similar to those seen in the mother, as lamotrigine is extensively metabolized by glucuronidation, which is immature in infants. Given these findings, infants who are breastfed by mothers receiving lamotrigine should be monitored.
  14. In eight women receiving levetiracetam, concentrations of the drug were approximately equal in milk and plasma.[51] In their babies, however, levels of levetiracetam in the serum were very low, indicating extensive transfer in milk and rapid elimination of levetiracetam in infants. Similarly, 2-3 weeks after delivery in five mother-child pairs in which the mother was treated with topiramate, the mean milk : maternal plasma concentration ratio of topiramate was 0.86,[52] yet topiramate concentrations of the drug in the infants were very low, indicating efficient elimination by the infant. It should be noted, however, that in this small study four of the five mothers were also taking carbamazepine, which induces metabolism of topiramate, as well as inducing fetal metabolism in general (including metabolism of carbamazepine).