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Using Medications in
Breastfeeding Mothers
Thomas W. Hale, Ph.D.
Professor
Department of Pediatrics
Texas Tech University
School of Medicine
Copyright T.W. Hale, 2013
Disclosure
l 
l 
Clinical Trial with Ferring Laboratories
Consultant for UCB Pharmaceuticals
Alveolus
Copyright T.W.Hale, 2013
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Colostral Phase (Day 1-2)
From Day 3 to Day 4 Postpartum
Serum
Sodium
134-146
meq
Chloride
95-108
Milk
Sodium
8-15
Chloride
10-20
Lactose
180
Albumin
35-50 g/L
Copyright T.W.Hale, 2013
Albumin
0.3 g/L
2
Milk Volumes during first week postpartum
Risk to Infant
l 
Depends on 3 major factors
l  Choice of Drug
l  Age of the infant
l  Premature…some
l  Older
l  Volume
risk
infant…minimal risk
of milk
l  Colostrum….minimal
risk
breastfeeding… some risk
l  Late stage lactation…minimal risk
l  Full
l  Exposure
l  Prior
in utero?
Dependence or Tolerance
Pharmacokinetics and Drug
Levels in Milk
l 
Size really matters
Drugs > 800 daltons enter milk poorly
l 
Protein Binding:
l 
pKa
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Drugs < 300 daltons enter milk easily
Higher the binding the poorer the levels in milk
Higher the pKa the more drug is trapped in milk.
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“Ion trapping”
Vd
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Higher the Vd, the lower the levels in milk
They’re all in the periphery, not in plasma
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Pharmacokinetics and Drug
Levels in Milk
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Lipid Solubility
l 
Plasma levels
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More lipid soluble, the higher drug levels in milk
The Higher, the more drug enters milk
The Lower, the less enters milk (fluticasone)
Transport processes are poorly understood
At least 5 drugs are thought to be transported but 4 do not
attain clinical levels
l  Ranitidine, Cimetidine, Iodine, Nitrofurantoin, Acyclovir
l 
Other Kinetic Factors
l 
Oral bioavailability
l  Drug exposure via milk depends on the bioavailability
of the drug in the infant.
l  Morphine
(26%)
proteins unabsorbed (heparin, etanercept, etc)
l  Sumatriptan (14%)
l  Domperidone (13%)
l  Tetracyclines (most poorly absorbed in milk)
l  Large
l 
Stability in GI tract of infant is important
l  Proton pump inhibitors are unstable at low pH.
Anesthetic Drugs
l 
Induction:
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Propofol, midazolam, etc
l 
Rapidly redistribute to peripheral sites. Levels in milk are negligible
within an hour or so.
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Epidural Opiates:
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Meperidine:
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Transfer to fetus to some degree, but limited in milk.
Poor choice, high fetal levels, moderate milk levels, sedation documented…
AVOID
Anesthetic Gases:
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Nitrous oxide, halogenated gases, etc
Almost instantly dissipated via expiration. None will enter milk.
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Simple Diffusion of Drugs into Human
Milk
Nucleus
Capillary
Drugs with Apparent Transporters (Influx Transporters)
Iodine
Acyclovir
Cimetidine
Nucleus
Nitrofurantoin
Ranitidine
???
Capillary
Extracellular
Proteins
Transported
Protein
Transporters
IgA
IgM, IgG (minimally)
Nucleus
Prolactin
IGF-1
????
Capillary
Plasma
Cell
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Large drugs and proteins are generally excluded
Birth Control Preparations
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Avoid estrogen-containing products
Progestin-only mini pills preferred.
l  Progestin receptors not present in ‘lactating tissues’
l  If suppression occurs, you can stop immediately.
l  Lots of calls on Merena IUD ???
Depo-Provera
l  Some controversy about lowering production (early
postnatally), but not proven.
l  Do not use early postpartum, use BCP first, then Depo
Antibiotics
l 
Penicillins, Cephalosporins are generally safe
l 
Erythromycin, Zithromax
l 
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Dicloxacillin, Flucloxacillin, Cloxacillin good for mastitis.
are safe except early postpartum.
Increase risk of hypertropic pyloric stenosis with erythromycin
l 
Clindamycin: safe… RID = 0.8% - 1.8%
l 
Fluoroquinolones
l 
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Grood for most MRSA
Ciprofloxacin - use cautiously. Now AAP approved.
Ofloxacin, Norfloxacin, Levofloxacin may be preferred.
l 
Metronidazole
l 
l  Levels moderate but are considered safe. Commonly used in neonates.
All may induce changes in intestinal Flora…diarrhea, candida overgrowth.
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Anticonvulsants
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Lamotrigine (Lamictal):
l  RID= 9.2-18%; probably safe; safest after 1 month
Valproic acid( Depakene, Depakote):
l  RID= 1.4-1.7%; probably safe; avoid in moms at risk
for pregnancy.
Levetiracetam (Keppra):
l  RID= 3.3 – 7.8%; probably safe; levels fall quickly in
infants postpartum.
Topiramate (Topamax):
l  RID= 3-24%; probably safe, but monitor infant levels.
Vaccinations
MMR
Safe
Yellow Fever
Safer than getting disease
Hepatitis B
Safe
Hepatitis A
Safe
DPT
Safe
Flumist
Probably safe
Influenza
Safe
Varicella
Safe
Inactivated Polio
Safe
Gardasil (HPV)
Safe
Viral Diseases
Influenza
Infant exposed for 2-3 days prior to maternal symptoms
Hepatitis A
Safe to Breastfeed
Hepatitis B
Safe ONLY after HBIG and Vaccination
Hepatitis C
Safe
Cytomegalovirus
Depends on timing but is relatively low risk
HIV
Do not breastfeed in this country
Varicella Zoster
Hazardous, cover lesions.
Herpes Simplex
Cover lesions on breast, AAP approved.
West Nile Virus
In milk, but infants seem largely unaffected.
Lyme Disease
DNA of spirochete present in milk, possibly infectious
HPV
Present in milk, but not apparently ‘very’ infectious
Remember that in most instances, infant has been exposed for days to weeks
prior to diagnosis.
Copyright T.W.Hale, 2013
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Antihypertensives
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Preferred Beta Blockers
l  Preferred: Metoprolol, Labetalol, Propranolol
l  AVOID: Acebutolol, Atenolol (poor choice)
Preferred Calcium Channel blockers
l  Nifedipine, Nimodipine, Verapamil, Nitrendipine
ACE inhibitors
l  Avoid in very premature infants
l  Captopril, Enalapril, Benazepril are preferred in
breastfeeding mothers.
Aldomet, hydralazine are fine.
Analgesics
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Hydrocodone, morphine are generally safe in
breastfeeding mothers.
Avoid codeine due to “rapid metabolizers”.
Avoid High doses of Oxycodone (apnea).
Fentanyl levels in milk are low.
Ibuprofen, Ketorolac, and acetaminophen are Ok
Naproxen is not preferred but can be used briefly.
Meperidine is poor choice due to neonatal sedation,
neurobehavioral delay.
Buprenorphine is a potent, long-acting narcotic agonist
and antagonist. RID = 2 %
Vitamin D
l 
Vitamin D levels in milk are low
l 
Infants need supplementation
l 
Vitamin D doses need re-evaluated in our population.
l 
Newborns need 400 IU/day
l 
Other Vitamins: be careful, use modest amounts, such as in
prenatal vitamins.
Copyright T.W.Hale, 2013
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Antidepressants
Post-Partum Depression
l 
Untreated depression produces major sequelae in
breastfed or formula fed infants.
l 
Past hesitancy in using antidepressants is lessening due to
studies that show that postpartum depression interferes
with optimal parenting and neurobehavioral
development of children at one year.
In mothers who were depressed first 6 months, infants
developed depressed style of interacting, and had inferior
Bayley scores at 1 year.
l 
l 
Prematurity, low birth weight, IUGR.
Tricyclic Antidepressants
l 
l 
Most are safe but much less popular due to:
l  more anticholinergic side effects
l  Extraordinarily dangerous in overdose
Effective for:
l  patients who have used previously
l  younger patients
l  less expensive
l  Chronic pain syndromes
Copyright T.W.Hale, 2013
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Serotonin Reuptake Inhibitors
(SSRIs)
l  Fluoxetine
l  Citalopram
l  Sertraline
l  Escitalopram
l  Paroxetine
l 
Reboxetine
l  Fluvoxamine
l  Venlafaxine
l  Desvenlafaxine
Fluoxetine
l 
l 
l 
Has long half-life “active” metabolite (360 hrs)
About 14% of consuming breastfeeding mothers use
fluoxetine
Many studies in the literature
concentration in milk levels varies from 28.8 to 181 µg/Liter of
milk for fluoxetine
l  41.6 to 199 µg/Liter for norfluoxetine
l 
l 
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l 
11 studies of 190 infants, 10 reported adverse effects in
some infants.
Relative Infant Dose = 6.9%
Caution recommended with :
l 
l 
Infants exposed in-utero….discontinuation syndrome
Incidence slightly lower with fluoxetine (T1/2 longer)
Fluoxetine Suggestions
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In naïve patients, use Sertraline or Escitalopram. But use
the one that works best on the patient.
In older infants ( > 2 months) Fluoxetine should not be a
problem.
If you MUST use Fluoxetine always opt to breastfeed; risk
is still probably low.
Burch KJ, Wells BG. Fluoxetine/norfluoxetine concentrations in human milk. Pediatrics 1992; 89(4 Pt 1):676-677.
Taddio A, Ito S, Koren G. Excretion of fluoxetine and its metabolite, norfluoxetine, in human breast milk. J Clin Pharmacol
1996; 36(1):42-47.
Lester BM, Cucca J, Andreozzi L, Flanagan P, Oh W. Possible association between fluoxetine hydrochloride and colic in an
infant. J Am Acad Child Adolesc Psychiatry 1993; 32(6):1253-1255.
Brent NB, Wisner KL. Fluoxetine and carbamazepine concentrations in a nursing mother/infant pair. Clin Pediatr (Phila)
1998; 37(1):41-44.
Kristensen JH, Ilett KF, Hackett LP, Yapp P, Paech M, Begg EJ. Distribution and excretion of fluoxetine and norfluoxetine in
human milk. Br J Clin Pharmacol 1999; 48(4):521-527.
Copyright T.W.Hale, 2013
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Sertraline
l 
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Studies available for more than 49 mother/infant pairs, 2 adverse
effect reported
In mothers taking antidepressants, 48 % used Sertraline.
Milk concentrations are very low: 18.4 to 95.8 µg/liter
In most infants, plasma levels of sertraline were below limit of
detection (< 2 ng/mL)
Stowe study 7 of 11 plasma levels were undetectable.
Ilett (1998)
4 of 8 plasma levels undetectable.
l 
l 
l 
• 
May be poorly absorbed orally in infants ???
RID = 0.4 - 2.2 %
Preferred SSRI at this time, but again use the one that works !
Mammen OK, Perel JM, Rudolph G, Foglia JP, Wheeler SB. Sertraline and norsertraline levels in three breastfed infants. J Clin Psychiatry 1997;
58(3):100-103.
Stowe ZN, Owens MJ, Landry JC, Kilts CD, Ely T, Llewellyn A, Nemeroff CB. Sertraline and desmethylsertraline in human breast milk and
nursing infants. Am J Psychiatry 1997; 154(9):1255-1260.
Kristensen JH, Ilett KF, Dusci LJ, Hackett LP, Yapp P, Wojnar-Horton RE, Roberts MJ, Paech M. Distribution and excretion of sertraline and Ndesmethylsertraline in human milk. Br J Clin Pharmacol 1998; 45(5):453-457.
Wisner KL, Perel JM, Findling RL. Antidepressant treatment during breast-feeding. Am J Psychiatry 1996; 153(9):1132-1137.
Stowe ZN, Hostetter AL, Owens MJ, Ritchie JC, Sternberg K, Cohen LS, Nemeroff CB. The pharmacokinetics of sertraline excretion into human breast
• 
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milk: determinants of infant serum concentrations. J Clin Psychiatry 2003; 64(1):73-80.
Paroxetine
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Half-life = 21 hours, no active metabolite
One case study of breast milk
l  milk levels 7.6 µg/Liter of milk( dose=20 mg/d)
l  Dose > 0.34% of maternal dose
RID = 1.25% The drug was not detected in the plasma of 7 of the
8 infants.
Stowe… 16 mother/infants. Milk levels varied from 17-101 µg/mL
with doses of 10-50 mg/day. Plasma levels in infants were below
level of detection.
Highest risk of Neonatal withdrawal
Highest rate of adolescent suicide. Try not to use in adolescents.
1. Stowe ZN, Cohen LS, Hostetter A, Ritchie JC, Owens MJ, Nemeroff CB. Paroxetine in human breast milk and nursing infants. Am J
Psychiatry 2000; 157(2):185-189.
2. Ohman R, Hagg S, Carleborg L, Spigset O. Excretion of paroxetine into breast milk. J Clin Psychiatry 1999; 60(8):519-523.
3. Misri S, Kim J, Riggs KW, Kostaras X. Paroxetine levels in postpartum depressed women, breast milk, and infant serum. J Clin Psychiatry
2000; 61(11):828-832.
Citalopram
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M:P ratio is 3
Relative Infant Dose = 0.7-5.9 %
At three weeks
l  Maternal serum = 185 nM … Infant serum = 7 nM
Mean M/P ratio is 1.6 .
Manufacturer reports two cases of somnolence in breastfed
babies.
I’ve had 2 case reports of somnolence as well.
Spigset O, Carieborg L, Ohman R, Norstrom A. Excretion of citalopram in breast milk. Br J Clin Pharmacol 1997; 44(3):295-298.
Rampono J, Kristensen JH, Hackett LP, Paech M, Kohan R, Ilett KF. Citalopram and demethylcitalopram in human milk; distribution, excretion and
effects in breast fed infants. Br J Clin Pharmacol 2000; 50(3):263-268.
Schmidt K, Olesen OV, Jensen PN. Citalopram and breast-feeding: serum concentration and side effects in the infant. Biol Psychiatry 2000; 47(2):
164-165.
Lee A, Woo J, Ito S. Frequency of infant adverse events that are associated with citalopram use during breast-feeding. Am J Obstet Gynecol 2004
Jan; 190(1):218-21.
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Escitalopram
l 
l 
Active metabolite of citalopram
Following 10 mg/day dose
l  M/P ratio = 2.2
l  Absolute infant dose = 7.6 ug/kg/day for escitalopram
and 3.0 ug/kg/day for metabolite.
l  RID = 5.3%
l  Infant plasma studies were below limit of detection
(< 3 µg/Liter)
l  Appears safe. Preferred over Citalopram
Rampono et al. Transfer of escitalopram and its metabolite demethylescitalopram into breastmilk. Br.
J. Clin. Pharmacol. 62(3):316, 2006.
Bupropion
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Bupropion levels in milk = 6.75 µg/kg/day
l  Not overly effective.
l  Fall back drug for patients with sexual side effects.
l  Lowers seizure threshold in patients WITH seizure
disorders, not seizure-free patients.
RID (all metabolites) = 0.2% - 2 %
Observe closely for reduced milk supply.
l  Anecdotal data from author !!!
Do not use in patients with history of seizure.
Baab SW, Peindl KS, Piontek CM, Wisner KL. Serum bupropion levels in 2 breastfeeding mother-infant pairs. J Clin Psychiatry. 2002;63:910-911.
Chaudron LH and Schoenecker CJ. Bupropion and breastfeeding: a case of possible infant seizure.(Letter) J.Clin. Psychiatry 2004:64(6):881-882
Haas JS, Kaplan CP, Barenboim D, Jacob P, III, Benowitz NL. Bupropion in breast milk: an exposure assessment for potential treatment to prevent post-partum
tobacco use. Tob Control 2004 Mar; 13(1):52-6.
Davis MF, Miller HS, Nolan PE, Jr. Bupropion levels in breast milk for 4 mother-infant pairs: more answers to lingering questions. J Clin Psychiatry. Feb
2009;70(2):297-298.
Using Antidepressants in
Breastfeeding Mothers ?
l 
l 
l 
Depressed women and their infants are at high risk.
l  Infantile neurobehavioral delay is well known.
l  Try your best to support them.
Most antidepressants are safe for breastfed infants.
From numerous studies, there are no data to date that
antidepressants alter long-term neurobehavioral outcome
in infants.
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Bipolar/Mood Disorders
Bipolar Disorders/Mania
l  Bipolar
disorder is a diagnosis describing low (clinically
depressed) and high (manic or hypomanic) mood swings
l  Symptoms
of Mania include:
l  Inflated
self-esteem or grandiosity
l  Elevated, expansive, irritable mood
l  Decreased need for sleep
l  More talkativeness
l  Reckless, foolish activities
Bipolar Disorders/Mania
l 
Drugs for Mania
l  Lithium
l  Olanzapine
(Zyprexa)
acid (Depakote) (avoid if possible)
l  Lamotrigine (Lamictal)
l  Carbamazepine (Tegretol)
l  Aripiprazole (Abilify)
l  Seldom if ever SSRIs
l  Valproic
Copyright T.W.Hale, 2013
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Therapy With Lithium
l 
l 
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Lithium transfers readily into human milk.
l  Slow….Takes 2-3 weeks for activation.
l  Infant levels approach 30-40% of maternal levels
l  Relative Infant dose = 12 - 30%
Clinicians must keep mom in normal range
l  < 1.1 mEq
l  Occasional monitoring of infant recommended
l  Monitor infant thyroid function.
New therapies include: Valproic acid, carbamazepine,
Lamotrigine.
Bipolar Therapy in Breastfeeding Mothers
l 
l 
l 
Lithium is hazardous.
l  HCP must follow infant closely and monitor levels
routinely.
Preferred Agents
l  Lamotrigine (Lamictal)
l  Aripiprazole (Abilify)
l  Carbamazepine (Tegretol) (pregnancy caution)
l  Other atypical antipsychotic agents
For psychotic symptoms
l  Aripiprazole, Quetiapine, Risperidone (weight gain
problems)
Treatment of Psychosis
l 
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l 
Breastfeeding research in this area is poor.
Older Drugs studied thus far:
l  Chlorpromazine (Thorazine) (RID= 0.25%)
l  Chlorprothixene (Taractan) (RID= 0.15%)
There is concern that phenothiazine family may increase
risk of SIDs and sleep apnea.
l  Promethazine (Phenergan)
l  If you need an antiemetic use ondansetron (Zofran)
Avoid them, use atypical antipsychotics instead.
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Antipsychotics
l 
Haloperidol (Haldol)
l 
Risperidone (Risperdal)*
l 
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Good choice. Low milk levels…even after weeks of therapy.
RID = 0.2-2.1% (20 mg/day) and 9.6% (30 mg/d)
Less likely to induce extrapyramidal symptoms
Milk level is low…130 ug/L
RID = <3.5% of maternal dose.
l 
Olanzapine (Zyprexa)**
l 
Quetiapine (Seroquel)
l 
l 
RID = 1.05% of the maternal dose.
RID = < 0.4%
*Hill
RC, McIvor RJ, Wojnar-Horton RE, Hackett LP, Ilett KF: J. Clin. Psychopharmacol. J.Clin. Psychopharmacol 20(2):
285-6,2000.
**Croke S, Buist A, Hackett LP, Ilett KF, Norman TR, Burrows GD. Int J Neuropsychopharmacol. 2002 Sep;5(3):243-7.
Brief Facts about Neuroleptic Drugs
l 
l 
l 
Withdrawal from SSRIs is normal and occurs in 10-30% of infants
postnatally (gestation use only).
No data yet suggests that neurobehavioral outcome in the infant is
affected following gestational or breastfeeding exposure.
Following Gestational use, data is mixed.
l  Slight increase in pulmonary hypertension (but fleeting).
l  Slight increase in Premature birth (but no different from
untreated moms)
l  Slight increase in Lower birth weight
l  However, risk of untreated depression and psychosis is
MAJOR, so lack of treatment is actually more dangerous than
drug.
Radioisotopes
Radiocontrast Agents
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X Rays
l 
l 
l 
l 
X-rays are high energy electromagnetic waves that can
pass through many materials including human tissue.
X-rays ionize matter with which they interact, by
ejecting electrons from their atoms.
Important: X rays PASS through body. While they may
damage tissues, they leave no radioactive residue that
would harm an infant.
Thus …no hazard to breastmilk or infant.
Half-lives of Radioisotopes
Radioisotope
Half-Life
Mo-99
2.75 Days
TI-201
3.05 Days
Ga-67
3.26 Days
Ga-67
78.3 Hours
I-131
8.02 Days
Xe-133
5.24 Days
In-111
2.80 Days
Cr-51
27.7 Days
I-125
60.1 Days
Sr-89
50.5 Days
Tc-99m
6.02 Hours
I-123
13.2 Hours
Sm-153
47.0 Hours
131- Iodides
l 
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Rapidly absorbed from GI tract
Distributed to extracellular body water
Largely trapped in thyroid
l  ≈ 27% goes to Thyroid
l  ≈ 27% goes to Lactating Breast
Most Excreted by kidneys:
l  Excretion:
l 
l 
30% of dose has T1/2 of 0.3 days
60% of dose has T1/2 of 7.61 days
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131
Radioactive
Iodine in Breastmilk
Recommendations
l 
Use Technetium-99 whenever possible.
l 
Avoid any form of 131I or
l 
l 
l 
125I
l 
Long half-life, concentrates in milk – infant.
l 
If dose of
l 
Other/higher doses, then monitor milk levels in
laboratory before reinstating breastfeeding.
Use
99TcO
4
131I
or
< 14 µCi, then wait at least 20 days.
123I
for thyroid scanning.
123I
Use fresh
Sodium for scanning of thyroid followed
by wait: 11-65 hours.
Safest to wait 5 half-lives with any isotope, and
particularly with Iodine-containing isotopes.
Radiocontrast Agents
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Soluble Iodinated Radiocontrast Agents
Diatrizoate
Conray
Radiocontrast Agents and Milk Concentrations
Drug
Dose
Milk
(Cmax)
Significance
Bioavail.
Gadopentetate*
6.5 g
3.09 umol/L
Dose = 0.023%
0.8%
Iohexol
0.77 g/kg
35 mg/L
Absorption Nil;
< 0.1%
Iopanoic Acid
2.77 g
20.8 mg
0.08% of maternal
dose
Nil
Metrizamide
5.06 g
32.9 mg/L
0.02% of maternal
dose
0.4%
Metrizoate
580 mg
14mg/L
0.3% of maternal
dose
Nil
* Gadolinium ion….not iodinated.
Recommendations for Iodinated and Gadoliniumcontaining Radiocontrast agents
l 
Discontinuing breastfeeding is not necessary.
l 
Mom may opt to pump and discard several hours after the
procedure. Useful with troublesome radiologists.
l 
Dose to infant less than 1% administered dose.
l 
Less than 1% of this is orally bioavailable to the infant.
l 
Use American College of Radiology Statement on my
website: www.infantrisk.com
Copyright T.W.Hale, 2013
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In Summary:
Avoid
l 
l 
l 
l 
Drugs of abuse
Ergot alkaloids
l  Migraine preps
l  Ergotamine
l  Cabergoline
Pseudoephedrine
Anti-cancer drugs
l 
l 
l 
l 
l 
Radioactive drugs
l  Discontinue briefly
Radioactive I-131
l  Do not use.
Chronic use of sedatives
Estrogens, Antiestrogens
Progesterone within 48
hours of birth.
Some Suggestions
l 
l 
Always evaluate stage of lactation.
l  Premature…higher risk
l  First 4 days, low milk volume…..low risk
l  Late stage…low milk volume….low risk
Calculate and use the Relative Infant Dose. If less than
10% then it is probably safe.
RID =
Infant dose (milk) ( mg/kg/day)
Maternal dose
(mg/kg/day)
806-352-2519
Copyright T.W.Hale, 2013
19