Corrected 1 February 2016. View correction.
This is the corrected version of the article.
Most commonly used drugs are relatively safe for breastfed babies. The dose received via milk is generally small and much less than the known safe doses of the same drug given directly to neonates and infants.
Drugs contraindicated during breastfeeding include anticancer drugs, lithium, oral retinoids, amiodarone and gold salts.
An understanding of the principles underlying the transfer into breast milk is important, as is an awareness of the potential adverse effects on the infant.
Discussion with the mother about the possibility of either negative product information or ill-informed advice from others will reduce the confusion and anxiety that may be generated.
Good resources about medicines and breastfeeding are available and include state-based medicines information services.
Although the National Health and Medical Research Council recommends exclusive breastfeeding for around six months, continued alongside complementary food until a minimum of 12 months, current breastfeeding statistics show Australia falling well below these recommendations. While 96% of women start breastfeeding, exclusive breastfeeding rates drop off to 39% of babies at three months and 15% at five months.1 Faced with these statistics, it is important to be able to give accurate advice on the safety of drugs so that breastfeeding is promoted whenever possible.
Most drugs are not of concern in breastfeeding.2-4 In addition, most lactating women take few medicines, and then only occasionally. Further, even though virtually all drugs are transferred into breast milk to some extent, the amount of drug is usually small and unlikely to cause an adverse effect on the baby. Considering the number of drugs available, relatively few known adverse effects occur in babies and it is generally not necessary to suspend breastfeeding because of the mother’s medication. This concept is not new. It was suggested over 100 years ago that ‘… it is possible to show that drugs … when given to a mother, rarely affect the milk injuriously, and almost never the babe to a marked degree’.5
Although the number of drugs available now is much greater, the same approach can apply. If ongoing medication use is necessary, only a few drugs warrant the cessation of breastfeeding (see Table). However, given the vulnerability of infants, vigilance is required.
Table Examples of drugs contraindicated in breastfeeding
|Amiodarone||Long half-life, iodine-containing molecule, and may affect thyroid function in infant|
|Antineoplastics||Leukopenia, bone marrow suppression|
|Gold salts||Rash, nephritis, haematological abnormalities|
|Lithium||Breastfeeding only feasible with rigorous monitoring|
|Radiopharmaceuticals||Contact obstetric information service|
|Retinoids (oral)||Potential for serious adverse effects|
What affects the concentration of a drug in milk?
It is important to be aware of how drugs transfer into breast milk and what factors can influence this.
Maternal plasma concentration
Passive diffusion is the primary pathway by which drugs enter milk. There is a good concordance between the time-course of maternal plasma-drug concentration and milk-drug concentration. Maternal plasma concentration is also affected by the drug’s distribution into different tissues. A high volume of distribution (as for sertraline) will contribute to a lower maternal plasma concentration and a subsequent lower concentration in milk.
Maternal plasma protein binding
Transfer into breast milk is also influenced by the extent to which the drug is bound by maternal plasma proteins. Free unbound drug diffuses readily while highly protein-bound drugs like ibuprofen or warfarin (both 99% protein bound) are unable to diffuse in significant amounts.6 Sertraline is highly protein bound (98%) so overall it will be minimally transferred to the breastfed baby.6 By comparison, venlafaxine has much lower protein binding and so more of the drug will be present in milk.6
Size of the drug molecule
Most drug molecules, including alcohol, nicotine and caffeine, are small enough to enter milk. Exceptions are drugs with high molecular weights such as heparins and insulin.
Degree of ionisation
Drugs cross membranes in an un-ionised form. Milk is generally slightly more acidic (pH 7.2) than the mother’s plasma (pH 7.4) so it attracts weak organic bases such as oxycodone and codeine.7 Such drugs become ionised and ‘trapped’ in the milk. Conversely, weak organic acids such as penicillin tend to be ionised and held in maternal plasma.
In addition to the passive diffusion into the aqueous phase, lipid-soluble drugs such as citalopram8 may have co-secretion by dissolution in the fat droplets of milk.2 In practical terms, this may not be of concern. It would not be an indication to change therapy if citalopram has been effective, but infant drowsiness should be monitored. Although the fat content of the milk varies according to infant age and phase of the feed, this is unlikely to impact on the choice of drug therapy.
A growing understanding of the influence of pharmacogenomics is well exemplified with codeine which is variably metabolised to morphine by the cytochrome P450 (CYP) 2D6 enzyme. The ultra-rapid metaboliser phenotype occurs in up to 10% of Western Europeans and up to 30% of North Africans. Repeated codeine doses in these women produce significant amounts of morphine. Rapid transfer from maternal plasma to the milk may result in central nervous system depression and potentially infant death.9 Codeine should be avoided during breastfeeding10 and alternative analgesia is recommended, such as paracetamol or ibuprofen.
What influences the risk of adverse effects on the baby?
If the baby is exposed to a drug in milk, several factors determine if there is an effect.
Timing of the dose
Feeding the baby just before the mother takes a drug results in the baby receiving the lowest possible drug concentration. However, this principle clearly does not apply for drugs with a long half-life, such as diazepam. For these drugs, there should be an even more rigorous assessment of whether they are needed.
Premature babies and neonates have a lower capacity to metabolise and excrete drugs.2 In addition, for babies who may already have been exposed to a drug in utero just before delivery, further exposure via breast milk will augment the existing drug concentration.
The Table lists drugs that are contraindicated in breastfeeding. Some drugs are inappropriately regarded as unsafe. Metronidazole, despite unfounded fears of carcinogenicity and mutagenicity, is safe in breastfeeding for short-term use.11 However, anecdotally, its bitter taste in milk may lead to fussiness in the feeding infant. Valproate is regarded as safe, especially in monotherapy when the risk of infant sedation is low.11 Monitoring the infant for liver and platelet changes may be advisable.12
The immunosuppressant azathioprine is excreted into breast milk as an active metabolite 6-mercaptopurine. Cautious use is advised in lactating women, and monitoring of the infant for signs of immunosuppression and other toxicity is recommended.6,11,12
The drug’s presence in breast milk does not necessarily lead to significant exposure for the baby. The infant gut may degrade or destroy a drug, for example omeprazole (for which the standard formulation is enteric-coated). Gentamicin is given intravenously to the mother. As it is poorly absorbed orally by the baby, drug concentrations will not be reflected in infant plasma.
Volume of breast milk
The amount of milk a baby receives varies. The estimated intake by an exclusively breastfed baby is 150 mL/kg/day. However, if the breast is being offered only as a comfort to an older baby, for example at night, the volume ingested is likely to be small.
Relative infant dose
The relative infant dose is the dose received via breast milk (mg/kg/day) relative to the mother’s dose (mg/kg/day). It is expressed as a percentage. A relative dose of 10% or above is the notional level of concern,6 but this is rare. An example is lithium,6,12 which is generally contraindicated in breastfeeding.13
Drugs used to stimulate milk production
Domperidone and metoclopramide are galactogogues and have both been used off-label to stimulate prolactin and enhance milk supply. However, these drugs do not have high evidence of efficacy for this indication.11,16 Also, there are concerns about the overuse of domperidone given that it may be prescribed on discharge from obstetric hospitals and used long term, sometimes at high doses. Non-pharmacological approaches to boost milk supply, such as correct advice, support and more frequent breastfeeding, are preferable.
Practice points for prescribing in breastfeeding
- If a drug is needed, prescribe it at the lowest effective dose. Temporarily suspend breastfeeding (and express milk) for potentially toxic drugs, such as cytotoxics and radiopharmaceuticals (see Table). Reinstatement of a drug will be determined by its half-life. It may not be possible to continue breastfeeding if lengthy treatment with a toxic drug is needed.
- Select alternative routes or products to minimise systemic exposure in the mother. For example, choose a poorly absorbed fibre laxative over a stimulant laxative.
- Choose drugs with a relatively short half-life, such as sertraline rather than fluoxetine, to minimise drug exposure in milk.
- Advise the mother to feed the infant before taking her medicine so that the drug concentration in milk will be at its lowest. Reassure her that the drug will return to her bloodstream from the milk as her blood concentration falls and will not ‘store’ in the milk until the next feed. This advice does not apply to drugs with a long half-life. The need for these drugs should be reassessed, especially in the neonatal period.
Finding information and advice
If unsure, seek advice on the use of a drug during breastfeeding. There are a number of different information sources available.
Drug information services
State-based obstetric drug information services provide detailed advice on the use of drugs during lactation and should be able to advise about past clinical experience with the drug (see Box).
Box Obstetric drug information services in Australia
Australian Capital Territory
Medicines Information Service
Canberra Hospital and Health Service
Phone: 02 6244 3333
New South Wales
Royal Hospital for Women
Phone: 02 9382 6539
Toll free (NSW): 1800 647 848
Northern Territory Northern Territory
Drug Information Centre
Royal Darwin Hospital
Phone: 08 8922 8424
(For health professionals)
Queensland Medicines Advice and Information Service (QMAIS)
Royal Brisbane and Women’s Hospital
Phone: 07 3646 7599 or 07 3646 7098
SA Pharmacy Obstetric and Paediatric Medicines Information Service
Women’s and Children’s Hospital
Phone: 08 8161 7222
No drug information centre currently available
Medicines Information Services
Pharmacy Department, Royal Women’s Hospital
Phone: 03 8345 3190
Medicines Information Centre
Phone: 03 9594 2361
Drugs in Pregnancy and Breastfeeding
King Edward Memorial Hospital
Phone: 08 9340 2723
LactMed11 is a freely accessible, well-resourced and peer-reviewed online database that can be downloaded as an app for mobile devices. It is updated to keep pace with new information, including published studies and drug approvals. It also incorporates information on complementary treatments.
Australian Medicines Handbook
The Australian Medicines Handbook (AMH)16 also provides information on prescribing during lactation. It includes advice about drugs that may suppress lactation and those that are contraindicated or should be used with caution. However, lack of evidence of harm does not mean that a drug is safe.
The Women’s Pregnancy and Breastfeeding Medicines Guide
The Women’s Pregnancy and Breastfeeding Medicines Guide, originally published in book format, is now available as an online subscription.12 The online version is constantly updated, providing evidence-based recommendations on the use of medicines during pregnancy and breastfeeding.
Be aware that the drug’s product information sometimes contains advice that is contrary to recommended treatment.18 An example is the treatment of mastitis with cephalexin: ‘Alternative feeding arrangements for the infant should be considered.’ Explanation should be given to the mother (and, if appropriate, her partner) that, while taking any antibiotic for mastitis, it is recommended to breastfeed more frequently and perhaps also express milk, to prevent stasis in the milk ducts and to maintain supply.
Most commonly used drugs are relatively safe for breastfed babies. The dose received via milk is generally small and much less than the known safe doses of the drugs used in neonates and infants. Further, most lactating women take few medications and often only occasionally. For women on chronic medications, most can be reassured, but some drugs will be contraindicated and others not yet adequately studied. Good resources are available, including state-based drugs and medicines information services.
Veiby G, Engelsen BA, Gilhus NE. Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding: a prospective cohort study on children of women with epilepsy. JAMA Neurol 2013;70:1367-74.
Juurlink DN, Gomes T, Guttmann A, Hellings C, Sivilotti ML, Harvey MA, et al. Postpartum maternal codeine therapy and the risk of adverse neonatal outcomes: a retrospective cohort study. Clin Toxicol (Phila) 2012;50:390-5.
Rigourd V, de Villepin B, Amirouche A, Bruneau A, Seraissol P, Florent A, et al. Ibuprofen concentrations in human mature milk--first data about pharmacokinetics study in breast milk with AOR-10127 “Antalait” study. Ther Drug Monit 2014;36:590-6.
Zheng S, Easterling TR, Hays K, Umans JG, Miodovnik M, Clark S, et al. Tacrolimus placental transfer at delivery and neonatal exposure through breast milk. Br J Clin Pharmacol 2013;76:988-96.
- Australian Breastfeeding Association. Breastfeeding rates in Australia. Melbourne: ABA; 2013. www.breastfeeding.asn.au/bf-info/general-breastfeeding-information/breastfeeding-rates-australia [cited 2015 Sep 7]
- Ilett KF, Kristensen JH. Drug use and breastfeeding. Expert Opin Drug Saf 2005;4:745-68.
- Ito S. Drug therapy for breast-feeding women. N Engl J Med 2000;343:118-26.
- Nation RL, Hotham N. Drugs and breast-feeding. Med J Aust 1987;146:308-13.
- Reed CB. A study of the conditions that require the removal of the child from the breast. Surg Gynecol Obstet 1908;6:514-27.
- Hale TW, Rowe HE. Medications and mothers’ milk. 16th ed. Amarillo (TX): Hale Publishing; 2014.
- Begg EJ, Duffull SB, Hackett LP, Ilett KF. Studying drugs in human milk: time to unify the approach. J Hum Lact 2002;18:323-32.
- 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;50:263-8.
- Drugs and their categories in pregnancy and breastfeeding. In: eTG complete [Internet]. Melbourne: Therapeutic Guidelines Limited; 2014. http://www.tg.org.au/index.php?sectionid=71 [cited 2015 Sep 7]
- Iedema J. Cautions with codeine. Aust Prescr 2011;34:133-5.
- Toxicology data network (TOXNET). Drugs and Lactaction Database (LactMed). Bethesda (MD): US National Library of Medicine National Institute of Health; 2014. http://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm [cited 2015 Sep 7]
- Royal Women’s Hospital Pharmacy Department. The Women’s pregnancy and breastfeeding medicines guide [Internet]. Melbourne: Royal Women’s Hospital; 2015. https://thewomenspbmg.org.au [cited 2015 Sep 7]
- Moretti ME, Koren G, Verjee Z, Ito S. Monitoring lithium in breast milk: an individualized approach for breast-feeding mothers. Ther Drug Monit 2003;25:364-6.
- Anderson PO, Pochop SL, Manoguerra AS. Adverse drug reactions in breastfed infants: less than imagined. Clin Pediatr (Phila) 2003;42:325-40.
- Ilett KF, Kristensen JH, Wojnar-Horton RE, Begg EJ. Drug distribution in human milk. Aust Prescr 1997;20:35-40.
- Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd; 2015. .
- Astley SJ, Little RE. Maternal marijuana use during lactation and infant development at one year. Neurotoxicol Teratol 1990;12:161-8.
- Brown E, Hotham E, Hotham N. Views of obstetric practitioners and hospital pharmacists on therapeutic goods administration approved product information for pregnancy and lactation. Aust N Z J Obstet Gynaecol 2014;54:184-8.
- Haastrup MB, Pottegård A, Damkier P. Alcohol and breastfeeding. Basic Clin Pharmacol Toxicol 2014;114:168-73.