Breastfeeding and Maternal Medications Tarah Colaizy, MD, MPH

Breastfeeding and Maternal
Medications
Psst.. Weaning is almost never the right answer
Tarah Colaizy, MD, MPH
Assistant Professor of Pediatrics/Neonatology
Carver College of Medicine, University of Iowa
Medical Director, Mother’s Milk Bank of Iowa
AAP Breastfeeding Statement
http://pediatrics.aappublications.org/content/earl
y/2012/02/22/peds.2011-3552
•“Breastfeeding and human milk are the
normative standards for infant feeding”
•“breastfeeding should be considered a public
health issue and not only a lifestyle choice”
•Recommends 6 months exclusive
breastfeeding with continued breastfeeding for
1 year or longer
Other Breastfeeding Statements
• WHO: exclusive breastfeeding for 6 months,
followed by continued breastfeeding for two years or
longer
• ACOG: “American College of Obstetricians and
Gynecologists recommends that exclusive
breastfeeding be continued until the infant is
approximately 6 months old. A longer breastfeeding
experience is, of course, beneficial.
• AAFP: “infants shoulb be breastfed and/or receive
expressed human milk exclusively for the first six
months of life. Breastfeeding should continue with the
addition of complementary foods throughout the
second half of the first year. “
American Academy of Family Physicians
Breastfeeding Policy Statement
Breastfeeding is the physiological norm for both mothers and
their children. Breastmilk offers medical and psychological
benefits not available from human milk substitutes. The AAFP
recommends that all babies, with rare exceptions, be
breastfed and/or receive expressed human milk
exclusively for the first six months of life. Breastfeeding
should continue with the addition of complementary foods
throughout the second half of the first year. Breastfeeding
beyond the first year offers considerable benefits to both
mother and child, and should continue as long as mutually
desired. Family physicians should have the knowledge to
promote, protect, and support breastfeeding.
Breastfeeding: Infant Benefits
• Infection prevention
– Lower risk of otitis, lower respiratory
infections, infectious diarrhea
• Decreases infant mortality
– 720 infant deaths in the US annually
are preventable by breastfeeding
• Cardiovascular protection
– Lower adult blood pressure
• Endocrine protection
– Lower risk of diabetes
– Lower risk of obesity, child and adult
• Developmental optimization
– IQ scores in adulthood higher in
formerly breastfed
Mary Cassat
Breastfeeding: Maternal Benefits
• Osteoporosis prevention
• Cancer prevention
– Uterine, breast, ovarian
• Reduced post partum blood loss,
quicker uterine involution
• Longer inter-pregnancy interval,
LAM
• Lower risk of Type II diabetes
among women without
gestational diabetes
• Lower rates of post-partum
depression
• Portable, cheap, clean and green
Maria Pretti
US Breastfeeding Rates
• Initiation in the US is between 70 and 75%
• Rates at 6mo are about 25%, at 12mo 12%
– Fall far below Healthy People 2020 goals
• Many women stop breastfeeding due to
medication use
– Major reason given for weaning early
• 90-99% of women will take some medication
post-partum
But if mom is taking medicine,
then so is the baby!
• Yep.
• Not all drugs enter milk equally, some don’t
enter at all
• Generally, if you’d prescribe it for a baby, its
safe for the mom
– Weaning for keflex or amoxicillin?
• Babies are exposed to MUCH HIGHER levels
of medications when administered during
pregnancy, due to placental transfer
– If mom was on a psych med all during pregnancy,
baby is already exposed.
Mom takes medication: that medication needs to be…
Maternal Dose
Orally available to mom
Absorbed into mom’s bloodstream
Able to cross into milk
Orally available to baby
Absorbed by baby’s GI tract
Absorbed into baby’s bloodstream
Infant Dose
Drug Entry into Milk
• Most medications
penetrate into the milk
compartment to some
extent, typically
delivering sub-clinical
doses to infants
• Almost always options
for other medications if
there is truly a concern
Drug Transfer into Milk
• Drugs get into milk if they:
– Are highly lipid soluble
– Attain high concentrations in maternal
plasma
– Have low molecular weight, <200kd passes
easily, >500 does not
– Have low protein binding (<90%)
– Pass into the CNS (indicates lipophilicity)
Modes of Drug Transfer
• Direct Diffusion:
– Mother’s plasma level most important
determinent, milk level rises as maternal
level rises
– Milk level falls as maternal level falls, due
to equilibrium
– Ionic drugs can get “trapped” in milk
– Human milk pH 7.0-7.2
– Drugs with pKa of <7.2 are less
sequestered (pKa is the pH at which a drug is equally
ionic and nonionic)
Modes of Drug Transfer
• Paracellular Pathway:
– Big gaps between alveolar cells in first
days of lactation - stuff leaks between
– Larger things can get into milk, like white
blood cells, larger proteins
– Drugs will enter milk more during colostral
phase, but overall intake is low by infant
– By end of 1st week, breast starts getting
smarter and junctions start to close
Modes of Drug Transfer
• Protein Binding:
– Drugs bound to albumin are soluable in
plasma
– Free portion enters the milk, protein-bound
stays with mom
– Drugs that are highly protein bound
(Coumadin), have low milk levels
– Good protein binding >90%
Relative Infant Dose
• RID = infant’s dose via milk
/
(ml/kg/d)
mother’s dose
• Gives general idea of how
much drug the infant is
exposed to
• RID <10% is considered
safe, but even higher RID
can be fine, depending on
infant safety profile of
medication
– ie, fluconazole,
metronidazole RID>20%
Auguste Renoir
Theoretic Infant Dose
• Maximum likely dose per kg per day infant
would ingest based on the peak milk level
(Cmax)
(if baby was getting peak conc all the time)
• Based on intake of 150ml/kg/d X conc in milk
• Most often, dose to infant is much lower as
levels wax and wane in milk throughout the
day
Half Life (T 1/2)
• Shorter is better
• If T 1/2 is 1-3 hours,
milk levels will be
declining when infant
feeds again
• Longer T 1/2 (12-24
hrs) is less desirable,
stay in plasma longer,
more exposure to infant
and Tmax
• Shorter is better
• Time from
administration to
maternal plasma peak
• Try not to nurse during
Tmax
Milk/Plasma Ratio
Concentration of drug in mother’s milk
/
Concentration in mother’s plasma
• If high, 1-5, sequestered in milk
• Less than 1 is preferable
– However, drugs can have a higher milk/plasma
ratio but a very low maternal plasma level and be
completely OK
Lactation Risk Scores
Pregnancy risk categories not helpful
L1:
Safest, drug taken by large #s of nursing
mothers without any increase in side
effects in infants
L2:
Safer, drug studied in limited #s of nursing
mothers without an increase in side effects in
their infants
L3:
Moderately safe, no controlled studies in nursing
mothers, risk of side effects unknown but likely
minor, or studies with minor side effects. Drug
should be used if maternal benefit > potential
infant risk
Lactation Risk Scores
L4:
Possibly hazardous, evidence of risk to infant or
milk production, benefits to mother may be
acceptable despite risk to infant (quinolones in
septic mother)
L5:
Contraindicated, studies with significant
documented risk to infant based on human
experience or medication has a high risk of
causing damage to infant. Risk of using drug
outweighs any benefit of breastfeeding
General Recommendations
• Topical drugs or those ingested but not
absorbed (oral vanco, etc) are not going to
get to the infant
• Beware of drugs with long PEDIATRIC half
lives as they can build up in infants
(benzodiazepines, fluoxetine, barbiturates)
• Drugs that can get into milk and that cause
sedation in the mom can cause sedation in
the baby, increases the risk of SIDS
• Pediatric approved drugs are usually a safe
bet
General Recommendations
• Beware of drugs that
affect milk supply, esp
in early postpartum
period (combination
OCPS, mini-pill, Depo,
NuvaRing, etc)
– If maintenance of milk
supply is very important
to the mother, avoidance
of all hormonal
contraception is the best
bet
Pablo Picasso
General Recommendations
• Remember that if M/P is
high, but Cmax low,
drug is probably OK
• Choose drugs with
shorter half-lives
• Avoid nursing at Tmax if
possible
• Choose drugs with
higher protein binding
• Choose drugs that are
less lipid soluble
Examples of good choices
follow….
Not an exhaustive list!
Safe Bets
• Analgesics
– Acetaminophen, codeine, fentanyl, ibuprofen,
ketorolac, meperidine, methadone, morphine,
propoxyphene
• Antibiotics
– Amox, aztreonam, cefadroxil, cefazolin,
cefotaxime, cefoxitin, cefprozil, ceftazadime,
ceftriaxone, clinda, erythro, gent, moxalactam,
nitrofurantoin, ofloxacin, sulbactam, sulfisoxazole,
tetracycline, ticarcillin, TMP/SMX
Safe Bets
• Anticoagulants
– Warfarin, heparin
• Anticonvulsants
– Barbiturates, carbamazepine, ethosuximide, mg
sulfate, phenytoin, valproic acid
• Antihistamines
– Dexbrompheniramine, fexofenadine, loratadine,
terfenadine, triprolidine
• Anti-thyroid
– Carbimazole, methimazole, propylthiouracil
Safe Bets
• Anti-tubercular
– Ethambutol, isoniazid, pyrimethamine, rifampin,
streptomycin
• Anti-viral
– Acyclovir, valacyclovir
• Antihistamines
– Dexbrompheniramine, fexofenadine, loratadine,
terfenadine, triprolidine
• Anesthetics
– Halothane, lidocaine, scopolamine, thiopental
(moms can nurse after general as soon as they
are awake and able, that means its worn off!)
Safe Bets
• Asthma meds
– Albuterol, ipratropium bromide, montelukast,
prednisone, terbutaline, theophylline, zafirlukast
• Decongestants
– Pseudoephedrine, ipratropium bromide
• GI agents
– Famotidine, omeprazole, ranitine,
• Migraine
– Sumatriptan, propranolol
• Anti-hypertensives
– Propranolol, hydrocholorothiazide, captopril,
enalapril
Safe Bets
• Antidepressants
– Amitriptyline, buproprion,
paroxetine, fluvoxamine
• Anti-anxiety
– Alprazolam, diazepam,
lorazepam
• Anti-psychotic
– Olanzepine, Haldol,
clozapine, risperdone
Mary Cassat
Chemotherapy drugs
•
•
•
•
Cyclophosphamide - immune supression
Cyclosporine - immune supression
Doxorubicin - concentrated in milk
Methotrexate - immune supression
Many Chemo drugs are not safe, esp taken for
long periods. Hale has an excellent section
on chemotherapy and breastfeeding
Radioactive stuff and radiology
• Maternal X rays, CT, MRI themselves don’t get to
the milk
• Oral contrast agents and non-radioactive IV contrast
are safe
• Radioactive isotopes often require pumping for
periods between 0 and 24 hours, but milk can be kept
for 8-10 half-lives then fed (Hale has a great section!)
• Radioactive iodines are very dangerous, esp I-131,
I-125, less so I-123.
Cold Medicines
Pseudoephedrine can significantly
decrease milk supply!
Guaifenesin, phenylephrine,
diphenhydramine, dextromethorphan
are safe
Alcohol and Breastfeeding
• Alcohol can inhibit the let-down reflex
• Alcohol passively diffuses into the milk
• Studies not convincing for harmful effects of
occasional drink
• Tell moms don’t nurse if you feel the effects
• AAP lists it as “usually compatible,” with
comment on reported effects of large
amounts, e.g. drowsiness, diaphoresis, deep
sleep, weakness, decrease in linear growth,
abnormal weight gain
Nicotine and Breastfeeding
• Nicotine passes through the milk
• Case reports of irritability and poor growth
• Study reported increased respiratory illnesses among
bottle fed infants of smoking mothers cf breastfed
infants of women who continue to smoke
• AAP has taken nicotine (and hence smoking) off the
list of “Drugs of abuse for which adverse effects have
been reported”
• Advice to moms: quit or cut down, smoke
outside only, have ‘smoking jacket’
Useful References
• Medications and Mother’s Milk, 13th ed,
Thomas W. Hale, 2008
– Best, most concise reference available, and
cheap! $31 at Amazon
• LactMed, http://toxnet.nlm.nih.gov/cgi-
bin/sis/htmlgen?LACT
– National Library of Medicine Database, excellent
and well-maintained.
• AAP Committee on Drugs Policy Statement,
“Transfer of Drugs and Other Chemicals in
Human Milk”. Pediatrics 108:3, 2001
Less Useful References
• PDR - Terrible!
• Drugs in Pregnancy
and Lactation, Briggs.
– Complicated, more
focused on
pregnancy, costs
over $100
Take Home Message
• Evaluate all the risks of the drug in
relationship to the actual dose received by
the infant, and the infant’s ability to handle it,
before making a decision.
“keep in mind the risks of formula feeding are
significant and should not be trivialized” Thomas Hale
Take Home Message
• Interruption of breastfeeding for medication
administration due to lack of proper
knowledge is not acceptable. Its not trivial to
the families. In most cases, breastfeeding
can continue.
You owe it to your patients: make an
informed decision