drug use during pregnancy and lactation.ppt

8/17/2019 Drug Use During Pregnancy and Lactation.ppt

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Drug Use DuringPregnancy and

Lactation


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Objectives

1.Recognize factors which determine

drug passage across the pacenta and

into breast mi!.".#dentify aspects of medications that

determine safety during actation.

$.Review anti%infectives and migrainemeds in pregnancy and actation


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&eratogens

' ( substance) organism) physica agentsor deficiency state capabe of inducingabnorma structure or function such as*

+ ,ross structura abnormaities

+ -unctiona deficiencies

+ #ntrauterine growth restriction

+ ehaviora aberrations

+ Demise

Dic!e) /0. 0ed in 2orth (m 134356$*786%41.


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&eratogenic -actors

' &iming of e9posure

' Deveopmenta stage during e9posure

' 0aterna dose and duration' 0aterna pharmaco!inetics

' ,enetic factors:phenotypes

' #nteractions between agents


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-D( Pregnancy ategories

' ategory not re;uired if*

+ Drug not absorbed systemicay

(2D + 2o potentia for indirect feta harm

' Otherwise) in addition to the pregnancy

category) information on teratogenicity) effectson reproduction) and when avaiabe) effectson ater growth) deveopment and functionamaturation of the chid shoud be incuded


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-D( Pregnancy ategories

' 0ajor probems e9ist

+? drug reay mean

+Difficut to assign an >(? to any drug +Does not address actation safety


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-D( Labeing hanges

' $ categories + fertiity) pregnancy) andactation

'inica considerations provides ris!sand possibe aternatives

' @ummary ris! assessment evauateshuman and anima data

' Discussion of underying data used toformuate ris!


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Drug &ransfer to the -etus

' Pacenta transfer may occur by*

+Passive diffusion

+-aciitated diffusion + (ctive transport

' Pacenta surface area

' Pacenta metaboism


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Drug Passage into reast 0i!

' Diffusion from materna pasma into

mi!

' Aigher materna pasma eves meanhigher breast mi! concentrations

'


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Drug &ransfer

' (cross Pacenta

+ 0oecuar weight

+ Lipid soubiity + #onization

+ Protein binding

+ hemica@tructure

' #nto reast 0i!

+ 0oecuar weight

+ Lipid soubiity + #onization

+ Protein binding

+ Drugconcentration

+ Drug e;uiibrium


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Other -actors

' (cross Pacenta

+ @ize B C

datons

+ Aigh bood

concentration

+ @imiar

configuration

' #nto reast 0i!

+ @ize B "

datons + Drug pEa

+


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-eta Drug Disposition

' 8 + 4F passes through iver) the rest

traves through ductus venosus to heart

and brain' Aepatic drug metaboism

' (drena gand metaboism

' Recircuation through amniotic fuid


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Drug oncentration in reast 0i!

' Lower pA than serum

' Garying degrees of fat

concentrations

+-oremi!

+Aindmi!' 0i!:Pasma ratio


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acuating Drug


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2eonata -actors

' Goume of mi! consumed

' Aigher gastric pA

' Differences in ,# fora

' ,# transit time

' Aigher concentrations of free drug

' Aigher percentage of body water' Lower rates of metaboism and e9cretion


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#nfant (dverse


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(nti%infectives

' Peniciins

' ephaosporins

' arbapenems' -uoro;uinoones

' 0acroides

' (minogycosides

' @ufonamides

' 0isceaneous

(ntibiotics

' (ntiviras

' (ntiretroviras

' (ntifungas


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Peniciins

' ategory in pregnancy

+ ross the pacenta easiy and rapidy

+oncentrations e;ua materna eves

' Lactation + rosses in ow concentrations

+ ompatibe with breastfeeding


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ephaosporins

' ategory in pregnancy + ross the pacenta during pregnancy + @ome reports of increased anomaies with

specific cephaosporins Hcefacor)cephae9in) cephradrineI

+ Primariy cardiac and ora ceft defects

' Lactation +


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arbapenemsHertapenem) imipenem) meropenemI

' ategory :: in pregnancy

+ Li!ey cross the pacenta

+ Gery itte human data

' Lactation

+


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-uoro;uinoonesHfo9insI

' Pregnancy ategory

+ 2ot recommended in pregnancy

+ artiage damage in animas

+ @afer aternatives usuay e9ist

' Lactation

+


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0acroidesHazithromycin) carithromycin) erythromycinI

' Pregnancy ategories ::

+ ross the pacenta in ow amounts

+ Limited data with azithromycin andcarithromycin

' Lactation +


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(minogycosidesHami!acin) gentamicin) tobramycinI

' Pregnancy ategory

+ Rapidy cross pacenta

+


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@ufonamides

' Pregnancy ategory

+ Readiy cross the pacenta

+ oncerns of use at term

' Lactation

+


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&etracycines Hdo9ycycine) minocycine) tetracycineI

' Pregnancy ategory D

+ an cause probems with teeth and bone

and other defects:effects

+ Aave been in!ed to materna iver to9icity

' Lactation + ompatibe with breastfeeding

+ @erum eves in infants undetectabe


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0isceaneous (ntibiotics

' (ztreonam

+ Pregnancy ategory ) i!ey safe in

pregnancy) itte human data

+ Lactation + ompatibe per ((P

' indamycin

+ Pregnancy ategory ) commony used + Lactation + ompatibe per ((P


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' Linezoid

+ Pregnancy ategory ) no human dataavaiabe

+ Lactation + un!nown) myeosuppression inanimas

' 0etronidazoe

+ Pregnancy ategory ) carcinogenic inanimas) avoid in 1st trimester if possibe

+ Lactation + hod feeds for 1"%"Chrs afterward


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' 2itrofurantoin

+ Pregnancy ategory ) possibe hemoyticanemia with use at term

+ Lactation + ompatibe) avoid with ,%8%PDdeficiency

' &rimethoprim

+ Pregnancy ategory ) potentiayprobematic eary in pregnancy

+ Lactation + ompatibe as combination drug


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' Gancomycin

+ Pregnancy ategory ) compatibe

+ Lactation + i!ey compatibe) notabsorbed


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(ntivirasHacycovir) famcicovir) vaacycovirI

' Pregnancy ategory

+ (cycovir and vaacycovir readiy cross

the pacenta

+ an be used for A@G treatment and

suppression

'Lactation + (cycovir and vaacycovir are compatibe

+ -amcicovir shoud be avoided

(ntiretroviras:2R


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(ntiretroviras:2RHabacavir) didanosine Hdd#I) emtricitabine

H-&II

' Pregnancy ategories ::

+ 0aterna benefit usuay outweighs feta ris!

+ ross the pacenta

+ Limited data with each do not show

increased ris! of anomaies

+ Didanosine has been associated with

severe actic acidosis w: or w:o pancreatitis


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(ntiretroviras:2RHamuvidine H$&I) stavudine HdC&II

' Pregnancy ategory


+ ross the pacenta by simpe diffusion

+ Data with amivudine show no increased ris! of

anomaies

+ @tavudine has been associated with severe

actic acidosis w: or w:o pancreatitis + ( 2Rs have been possiby in!ed to

mitochondria dysfunction postnatay

( ti t i :2R


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(ntiretroviras:2RHtenofivir) zacitabine HddI) zidovudine

H(J&II' Pregnancy ategory ::


+ross the pacenta by simpe diffusion

+ Limited data with zacitabine do not show

increased ris! of anomaies

+ Jidovudine is commony used) but may cause

neonata anemia

+ Limited data with tenofivir show ow ris! of

teratogenicity


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(ntiretroviras:22RHdeavirdine) efavirenz) nevirapineI

' Pregnancy ategory

+ 0aterna ris! usuay outweighs feta ris!

+ Li!ey cross into fetus Hnevirapine readiyI

+ Deavirdine has possibe G@D ris!) but imitedhuman data

+


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(ntiretroviras:P#

' Pregnancy ategory :

+ 0aterna benefit usuay outweighs feta

ris!

+ Li!ey cross the pacenta

+ ( P#s can cause hypergycemia H

,D0KI

+ (tazanavir can cause hyperbiirubinemia

+ #ndinavir can cause nephroithiasis


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(ntiretroviras:-usion #nhibitor HenfuvirtideI

' Pregnancy ategory

+ 0aterna benefit usuay outweighs feta

ris!

+ Gery arge moecue HCC3" datonsI)

i!ey does not cross pacenta

+ (nima data does not show ris!

+ 2o human data avaiabe

+ Aod during first trimester if possibe


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(ntiretrovira ombinations

' (tripa H1 tab daiyI

+


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(ntifungas:(zoesHfuconazoe) itraconazoe) !etoconazoe)

posaconazoe) voriconazoeI' Pregnancy ategories :::D

+ Li!ey cross pacenta

+ -uconazoe Cmg:day seems to be

associated with cranio%facia abnormaities

+ #traconazoe appears to have ow ris!

+ Eetoconazoe can impair testosterone and

cortiso synthesis + 2o data in humans is avaiabe for

voriconazoe) increased ris! in animas

(ntifungas:(zoes


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(ntifungas:(zoesHfuconazoe) itraconazoe) !etoconazoe)

posaconazoe) voriconazoeI' Lactation

+ -uconazoe is compatibe per ((P

+ #traconazoe coud concentrate in mi!and body tissues) not recommended

+ Eetoconazoe is compatibe per ((P

+ 2o data with voriconazoe) notrecommended


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(ntifungas:


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(ntifungas:Poyenes

' (mphotericin

+ Pregnancy ategory ) compatibe) ipid

compe9es aso compatibe

+ Lactation + no data avaiabe


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0igraine Aeadache &herapy

' &riptans

'


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&riptans H7%A&1 agonistsI

' Pregnancy ategory

+ Limited human data e9ists) sumatriptan has

been associated with G@Ds in severa cases

+ 2o data avaiabe in humans for amotriptan)

eetriptan) frovatriptan) or zomitriptan

+ Limited human data e9ists with naratriptan

and rizatriptan) athough anima dataindicates moderate ris!s

+ Pregnancy registry avaiabe for e9posures


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&riptans H7%A&1 agonistsI

' Lactation

+ ross into breastmi! and may concentrate

+ 2o reports of human actation with

amotriptan) frovotriptan) naratriptan)

rizatriptan) or zomitriptan

+ @umatriptan is compatibe per ((P

+


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utabita and affeine' utabita

+ Pregnancy ategory ) can see neonata

withdrawa symptoms with ong%term use

+ Lactation + not recommended

' affeine

+ Pregnancy ategory ) doses generayower than that in coffee

+ Lactation + compatibe

Di h h d


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Dichoraphenazone and

#sometheptene H0idrinI' Dichoraphenazone

+ Pregnancy ategory

+Lactation + simiar agent consideredcompatibe

' #sometheptene

+ Pregnancy ategory ) e9tremey imiteddata

+ Lactation + potentiay compatibe


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Nuestions to (s!

' (re there aternative therapiesK

' an treatment wait unti postpartumK

'#s the disease worse than the therapyK

' =hat does the avaiabe iterature sayK


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Nuestions to (s!

' #s this drug used in neonatesK

' Aow od is the infantK

' =hat is the duration of therapyK' =hat are the pharmaco!inetics of the

agentK

' =hat is the ris!:benefit for the motherK

' Does this medicine cause probems in ,8PD

deficiencyK


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onsiderations in reastfeeding

' =ithhod or deay therapy if possibe

' Use a drug with poor penetration into mi!

' Use an aternate route of administration' (void nursing at pea! drug concentrations

' ,ive drug before infants ongest seep

' Pump and dump mi!' Discontinue breastfeeding

drug use during pregnancy and lactation.ppt

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