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Journal of Neonatology Vol. 21, No. 1, Jan. - Mar. 2007
REVIEW ARTICLE
Maternal Medication and Breastfeeding
Arun GuptaArun Gupta
Arun GuptaArun Gupta
Arun Gupta11
11
1, JP Dadhich, JP Dadhich
, JP Dadhich, JP Dadhich
, JP Dadhich22
22
2
1Breastfeeding Promotion Network of India, BP-33 Pitampura,Delhi, 2Department of Pediatrics, SL Jain Hospital, Delhi
arun@ibfan-asiapacific.orgarun@ibfan-asiapacific.org
arun@ibfan-asiapacific.orgarun@ibfan-asiapacific.org
arun@ibfan-asiapacific.org
Although neonatologists do not prescribe drugs to the nursing
mother, their opinion about drug safety during breastfeeding is
usually sought. Therefore, it is of paramount importance that
neonatologists and health professionals be up-to-date with this
kind of information. The basic principle for the prescription of
drugs to breastfeeding mothers is underpinned by the idea of
risk and benefit. The advantages of breastfeeding are enormous
for the infant, whereas the risks of most medications are minimal.
Most drugs likely to be prescribed to the nursing mother should
have no effect on milk supply or on infant well-being. Lack of
information and misinformation often lead to physicians advising
mothers to discontinue breastfeeding because of medication use.
Considerable advances have occurred in recent years in the
scientific knowledge of the benefits of breastfeeding, the
mechanisms underlying these benefits, and in the clinical
management of breastfeeding. Scientific research during the last
three decades has clearly proved that breastfeeding provides the
most suitable nutrition to the baby, protects it against infections,
allergies and asthma, promotes physical, physiological, motor,
mental and psycho-social growth and development and gives
protection against some adult diseases such as diabetes,
hypertension, ischemic heart disease and some forms of
malignancy (1). In addition, it benefits the mother in various ways.
It saves money for the family and the nation, helps fertility control
and is eco-friendly (2). Breastfeeding has also been related to
possible enhancement of cognitive development (3). There are
advantages for the mother; breastfeeding reduces the incidence
of post-partum bleeding which leads to faster uterine involution
(4), reduces the risk of breast cancer (5) and ovarian cancer (6),
delays resumption of ovulation and increases child spacing (7),
improves bone re-mineralization (8) after birth in women with
reduction in hip fractures (9) in post menopausal period and finally,
it is likely that all the benefits of human milk are not presently
known.
Among the factors that lead to early weaning are problems
related to the risk of infant exposure to maternal medications.
Information and bibliographic references on drugs and breastmilk
have been available, but many health professionals, especially
physicians, prefer to discontinue breastfeeding, either due to lack
of information or lack of interest, to attempting to adjust it with
the treatment being received by the mother (10,11). In a study
from Lithuania, one third of nursing women discontinued
breastfeeding when infant reached three months of age.
Discontinuation of breastfeeding in 21-23% of all cases was
directly or indirectly associated with use of medications. Such
data suggest that there is a lack of information often leading
physicians to advise mothers to discontinue breastfeeding because
of medication use (12).
We are attempting to address this important issue, by
addressing following aspects.
• Main pharmacokinetic characteristics of drugs influencing drug
transfer into milk;
• The list of drugs preferred for nursing women;
• Some considerations on drug safety and possible adverse
effects of medications on breastfed infant.
Pharmacokinetic characteristics of drugs
influencing drug transfer into milk
Most drugs have been found to be excreted in human breast
milk. Usually when the mother takes the drug in therapeutic
amounts for short periods of time, the levels of the drug in breast
milk are sufficiently low to be of little hazard to the infant (13).
Administration of the drug at or immediately following the infant
nurses will result in the lowest amount of drug in the milk at the
subsequent feeding. The amount of a drug or its metabolite that
enters the breast milk is dependent upon the extent to which the
substance is ionized, lipid soluble, and bound to plasma proteins.
Generally, drugs known to be extensively protein bound are
excreted in breast milk to a lesser extent than drugs that are poorly
bound to plasma proteins (14). The lipophilicity, protein binding
and ionization properties of a drug will determine how much is
excreted into the breast milk. In an extensive literature review, it
was found that drugs that were at least 85% protein bound,
measurable concentrations of drug in the infant did not occur if
there was no placental exposure immediately prior to or during
delivery. Knowledge of the protein binding properties of a drug
can provide a quick and easy tool to estimate exposure of an
infant to medication from breastfeeding (15).
The classification of drugs used during
breastfeeding
To guide physicians on the use of drugs during breastfeeding,
the AAP has published several recommendations about the
transfer of drugs into human milk, the latest being in the year
2001 (11). A more detailed description of maternal drugs and
breastfeeding has been prepared and published by World Health
Organization (16), which may be referred as when need arise.
In the latest revision, the AAP presented a new drug
classification
• Cytotoxic drugs that may interfere with cellular metabolism of
the nursing infant;
• Drugs of abuse for which adverse effects on the infant during
breastfeeding have been reported;
• Radioactive compounds that require temporary cessation of
breastfeeding;
• Drugs for which the effect on nursing infants is unknown but
may be of concern;
• Drugs that have been associated with significant effects on
some nursing infants and should be given to nursing mothers
with caution;
• Maternal medication usually compatible with breastfeeding.
10
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Journal of Neonatology Vol. 21, No. 1, Jan. - Mar. 2007
Tables 1-4 specifies the drugs according to the AAP classification.
The table does not contain those drugs for which reports in literature
were not available. Another factor that is overlooked by the AAP
classification is concerned with infant age. In a recent review on
infants’ adverse reactions to maternal medication, 63% of the
reactions occurred in newborns, 78% in infants aged less than two
months, and only 4% in infants older than six months (17).
Table 1: Cytotoxic drugs incompatible with breastfeeding
(Adapted from reference No. 11)
Drug Reason for Concern
Cyclophosphamide • Possible immune suppression
Cyclosporine • Unknown effect on growth
Doxorubicin*• Association with carcinogenesis
Methotrexate • Neutropenia
Table 2: Radioactive Compounds That Require Temporary
Cessation of Breastfeeding (Adapted from reference
No. 11)
Compound Recommended Time for
Cessation of Breastfeeding
Copper 64 (64Cu) Radioactivity in milk present at 50 h
Gallium 67 (67Ga) Radioactivity in milk present for 2 wk
Indium 111 (111In) Very small amount present at 20 h
Iodine 123 (123I) Radioactivity in milk present up to 36 h
Iodine 125 (125I) Radioactivity in milk present for 12 d
Iodine 131 (131I) Radioactivity in milk present for 2-14 d,
depending on study
Iodine131 If used for treatment of thyroid cancer,
high radioactivity may prolong exposure
to infant
Radioactive sodium Radioactivity in milk present 96 h
Technetium99m (99mTc), Radioactivity in milk present 15 h to 3 d
99mTc macroaggregates,
99mTc O4
Table 3: Drugs for Which the Effect on Nursing Infants Is
Unknown but May Be of Concern (Adapted from
reference No. 11)
Group of Name of the Reported or Possible
Medication drug Effect
Anti-anxiety • Alprazolam
• Diazepam None
• Lorazepam
• Midazolam
Antidepressants Amitriptyline
Doxepin None
Imipramine
Sertraline
Nortriptyline None
Fluoxetine, Colic, irritability, feeding
and sleep disorders, slow
weight gain
Antipsychotic Chlorprothixene None
Trifluoperazine
Haloperidol Decline in developmental
scores
Chlorpromazine Galactorrhea in mother;
drowsiness and lethargy in
infant; decline in
developmental scores
Others Amiodarone Possible hypothyroidism
Chloramphenicol Possible idiosyncratic bone
marrow suppression
Table 4: Maternal Medication Usually Compatible with
Breastfeeding (Adapted from reference No. 11)
Acetaminophen Acetazolamide Acyclovir
Allopurinol Amoxicillin Atropine
Aztreonam B1 (thiamin) B6 (pyridoxine)
B12 Baclofen Barbiturate
Caffeine Captopril Carbamazepine
Cefadroxil Cefazolin Cefotaxime
Ceftazidime Chlorothiazide Chloroquine
Ceftriaxone Chloral hydrate Cimetidine
Ciprofloxacin Cisapride Clindamycin
Codeine Dapsone Digoxin
Diltiazem Domperidone Enalapril
Erythromycin Ethambutol Ethosuximide
Fentanyl Fluconazole Folic acid
Gentamicin Halothane Hydralazine
Hydrochlorothiazide Ibuprofen Indomethacin
Isoniazid Ivermectin K1 (vitamin)
Ketoconazole Labetalol Lidocaine
Loratadine Magnesium sulfate Medroxyprogester-
one
Mefenamic acid Meperidine Methyldopa
Mexiletine Nalidixic acid Nifedipine
(hemolysis in
infant with G-6
PD deficiency)
Ofloxacin Phenytoin Prednisolone
Progesterone Propranolol Pseudoephedrine
Pyridostigmine Pyrimethamine Quinidine
Rifampin Streptomycin Terbutaline
Tetracycline Theophylline Valproic acid
Making Breastfeeding safer during maternal
medication
The safest course for the specialist, who is treating nursing
mothers, is to consult reliable sources before advising
discontinuation of breastfeeding. Overwhelming evidence has
shown that breastfeeding is the most healthful form of nutrition
for babies and should therefore be encouraged. Following
approach helps to maximize safe maternal medication use for
both the mother and the breastfed infant (10,18):
• Determine if medication is necessary.
• Choose the safest drug available that is, safe when administered
directly to infants, has a low milk:plasma ratio, has a short
half-life, has a high molecular weight, has high protein binding
in maternal serum, is ionized in maternal plasma, is less
lipophilic.
• Advise the mother to take the medication just after she has
breastfed the infant or just before the infant’s longest sleep period.
• Prefer topical or local therapy to oral and parenteral therapy,
whenever possible and indicated.
• Prefer medications containing only one type of drug, avoiding
drug combinations. Example: use only paracetamol instead of
combinations containing paracetamol, ASA and caffeine.
• Choose medications with high molecular weight, since this
considerably reduces their transfer into the milk. e.g.: heparin
• Choose medications that are poorly permeable to the blood-
brain barrier because they often reach low levels in milk.
• Choose medications that are minimally transferred into the
milk. For example, sertraline and paroxetine reach lower milk
levels than fluoxetine.
11
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Journal of Neonatology Vol. 21, No. 1, Jan. - Mar. 2007
• If there is a possibility that a drug may risk the health of the
infant, arrange for the monitoring of serum drug levels in the
infant
• Instruct the mother to observe the infant in order to identify any
side effects, such as changes in eating behavior, in sleep patterns,
agitation, abnormal muscle tone and gastrointestinal disorders.
• Avoid long-acting drugs, since the infant excretes them with
difficulty. Example: use midazolam instead of diazepam.
• Instruct the mother to express breastmilk in advance and store
it in a freezer (for no more than 15 days) to feed her baby in
case of temporary cessation of breastfeeding, and suggest
regular milk expression in order to maintain lactation.
References
1. Breastfeeding and the Use of Human Milk. Policy Statement
by American Academy of Pediatrics - Section on Breastfeeding..
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.
Pediatrics 2005115 ( 2):496-506.
2. Phatak A. Economic and ecological effects of breastfeeding.
J Obstet Gynaecol India 1999; 49: 35-38.
3. Breastfeeding and cognitive development in the first 2 years
of life. Soc Sci Med. 1988; 26:635-639.
4. Chua S, Arul Kumaran S, Lim I, et al. Influence of breastfeeding
and nipple stimulation on postpartum uterine activity. Br. J
Obstet. Gynaecol, 1994, 101: 804-805.
5. Newcomb PA, Storer BE, Longnecker MP, et al. Lactation and
a reduced risk of premenopausal breast cancer. N Eng J Med.
1994; 330:81-87.
6. Rosenblatt KA, Thomas DB, WHO Collaborative study of
Neoplasia and Steroid contraceptives. Int J Epidemiol. 1993;
22:192-197.
7. Kennedy KI, Visness CM. Contraceptive efficacy of lactational
amenorrhea. Lancet. 1992; 339: 227-230.
8. Metton LJ, Bryant SC, Wahner HW, et al. Influence of
breastfeeding and other reproductive factors on bone mass
later in life. Osteoporosis Int. 1993; 3:76-83.
9. Cumming RG, Klineberg RJ. Breastfeeding and other
reproductive factors and the risk of hip fractures in elderly
women. Int J Epidemiol. 1993; 22:684-691.
10. Chaves RG, Lamounier JA. Breastfeeding and maternal
medications. J Pediatr (Rio J) 2004; 80(5 Suppl):S189-S198.
11. American academy of pediatrics:
Committee on Drugs..
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Transfer of Drugs and Other Chemicals Into Human Milk.
Pediatrics 2001;108:776-789.
12. Pilviniene R, Maciulaitis R, Jankunas R, Milvidaite I, Markuniene
E. Breastfeeding and medications. Medicina (Kaunas).
2006;42(12):1035-1045.
13. Bowes WA Jr. The effect of medications on the lactating
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14. Berlin CM, Briggs GG. Drugs and chemicals in human milk.
Semin Fetal Neonatal Med. 2005;10:149-159.
15. Anderson GD. Using pharmacokinetics to predict the effects
of pregnancy and maternal-infant transfer of drugs during
lactation. Expert Opin Drug Metab Toxicol. 2006;2:947-960.
16. Breastfeeding and maternal medication - Recommendations
for Drugs in the Eleventh WHO Model List of Essential Drugs.
World Health Organization 2002. www.who.int/child-
adolescent-health/New_Publications/NUTRITION/
BF_Maternal_Medication.pdf
17. Anderson PO, Pochop LS, Manoguerra AS. Adverse drug
reactions in breastfed infants: Less than imagined. Clin Pediatr.
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18. Della-Giustina K, ,Chow G. Medications in pregnancy and
lactation. Emerg Med Clin North Am. 2003; 21: 585-613.
12
Neonatology CME at AIIMS, New Delhi
Neonatal Ventilation workshop from 5th to 8th July 2007 (Thursday to Sunday) . The workshop will be conducted by
Faculty from AIIMS-PGI, KEM Mumbai , MAMC Delhi & other renowned Faculty . It will focus on practical aspects of assisted
ventilation in neonates. The format will be skill-oriented with emphasis on group work in tutorials and on problem-solving.
If interested, please send one page CV outlining your roles and responsibilities and relevance of this workshop to you by 31st
May .The selected candidates will be asked to pay the registration fee. The number of participants will be restricted to 40, on
a ‘first come, first served basis’ based on screening done on June 1 , 2007.Workbook and resource material will be mailed
four weeks prior to the workshop.
Contact:
Ramesh Agarwal
Assistant Professor, Dept. of Pediatrics
All India Institute of Medical Sciences, New Delhi – 110029
Tel- 011-26593621, 9868397531 Fax No.: 011 –26862663
Email: aranag@rediffmail.com
