It is well known that breastfeeding offers tremendous health benefits to both the child and mother. Breast milk provides the best nutrition for a newborn and adapts to their nutritional requirements as they develop. It contains a complete range of vitamins, minerals, and fats in an easily digestible form. In addition, breast milk includes a complex array of proteins that protect against various infections and allergies. The World Health Organization (WHO) recommends that breastfeeding be initiated within the first hour of birth and that children be exclusively breastfed for the first six months of life.
It is clear that women should be supported to initiate and continue breastfeeding. However, there are some medications that may pose challenges during lactation. The benefits of breastfeeding are such that it should be encouraged unless there is substantial evidence that the drug will harm the infant and no alternative is available.
Principles of medicine transfer from mother to infant via breastmilk
Almost all medicines transfer into breastmilk to some extent. The quantity of medicine transferred is directly related to the amount in the maternal blood. The maternal blood level depends upon the maternal dosing regimen and the pharmacokinetics of the drug in question (i.e. bioavailability, volume of distribution, clearance, half-life).
Transfer mostly occurs via passive diffusion, with greater transfer occurring in the presence of low maternal plasma protein binding and high lipid solubility. However, some drugs are actively transported into breastmilk by membrane transporters, resulting in increased levels in the breastmilk. Examples of medications that are actively transported include nitrofurantoin and aciclovir.
Factors that affect the amount of medication transferred to the infant include:
- Maternal plasma protein binding – free unbound drug diffuses into the breastmilk more readily than drugs that are highly protein bound (e.g. sertraline is 98% protein bound with minimal transfer into breastmilk; venlafaxine is 27% protein bound with higher transfer);
- Size of the drug molecule – most drug molecules are small enough to enter breastmilk. Exceptions include heparins and insulin, which are too large; and
- Extent of ionisation – drugs cross membranes in the un-ionised form. Breastmilk is typically slightly more acidic than plasma (pH 7.2 versus pH 7.4). Therefore, weak organic acids (e.g. penicillins) tend to be ionised in the maternal plasma, reducing their ability to pass into the milk. Conversely, weak organic bases (e.g. oxycodone, codeine) transfer into the milk, where they become ionised and unable to pass back to the maternal plasma.
While most medications do transfer into breastmilk, the amount is usually small and unlikely to harm the infant. However, the following points should be considered:
- Could the medication be safely prescribed to an infant?
- The doses transferred via breastmilk are typically much lower than what would be administered as a therapeutic dose if given directly to the infant. Therefore, if the medication is considered safe to be prescribed to an infant, it is generally considered safe for the mother to take during lactation.
- Was the baby full-term and well?
- The risk of medication toxicity is higher in unwell and preterm infants
- What route is being used to administer the medicine?
- Topical administration could be expected to have a lower risk than systemic administration for most medicines due to lower maternal plasma levels.
Effect on infant
The relative infant dose (RID) is the weight-adjusted dose received by the infant via breastmilk compared to the mother’s dose. An RID of less than 10% is generally considered safe unless the drug has particular safety issues (e.g. cytotoxics).
If a drug is passed into the breastmilk, there are many factors that influence the effect this may have:
- Timing of the dose – e.g. feeding the baby just before the mother takes a dose may reduce infant exposure, particularly for agents with short half-lives (this strategy is often impractical for young infants who require frequent feeds);
- Oral bioavailability (e.g. gentamicin is very poorly absorbed when taken orally; therefore, gentamicin ingested via breastmilk is unlikely to be absorbed systemically);
- Half-life of the drug (longer half-life increases the risk of accumulation in the infant); and
- Infant clearance.
Infants have a lower drug clearance than adults, and this is particularly limited in premature infants. In general, adult glomerular filtration rates (adjusted for surface area) are reached by five to six months of age and adult hepatic metabolic capacity by around 12 months of age. Due to the limited rates of hepatic metabolism in young infants, the bioavailability of drugs with high first-pass metabolism may be higher in very young infants.
Studies suggest that most adverse effects related to drug exposure from breastmilk occur in newborns and babies under two months, with few occurring in infants older than six months.
Drugs affecting breastmilk production
Some medications can affect milk production or composition. This may be due to effects on prolactin, a hormone that is required for milk secretion. Dopamine can act on the pituitary gland to reduce prolactin secretion. Therefore, dopamine antagonists may increase prolactin production, and dopamine agonists can suppress lactation.
Dopaminergic drugs, such as cabergoline and bromocriptine, have been used to prevent the onset of lactation when clinically indicated. Cabergoline is generally preferred in this setting as it has fewer adverse effects. When used for this purpose, it should be given during the first day post-partum. The recommended dosage is 1mg as a single dose. Bromocriptine has rarely been associated with seizures, stroke, myocardial infarction, hypertension, and psychic disorders when used to suppress lactation.
Many medications antagonise dopamine to some extent. The dopamine antagonists, domperidone and metoclopramide, have been used to stimulate lactation. Shen et al. (2021) conducted a meta-analysis to evaluate the safety and efficacy of these agents in breastfeeding women. They found that domperidone was associated with a significant increase in daily milk volume when taken by mothers with preterm infants and low milk supply. No significant difference was seen for metoclopramide.
Drugs that are hazardous in breastfeeding
While almost all drugs are transferred into the breastmilk to some degree, the amount is generally small and unlikely to cause adverse effects in the infant. However, some medications should not be taken during breastfeeding. Some examples are shown in Table 1.
Table 1. Drugs that are hazardous in breastfeeding
| Medication |
Reason |
| Amiodarone |
May affect thyroid function in the infant. Long and variable half-life (~14-59 days) |
| Antineoplastics* |
Bone marrow suppression. Unknown effect on growth and potential for carcinogenesis. |
| Gold salts |
Rash, nephritis, haematological abnormalities |
| Iodine (>150mcg daily) |
Risk of hypothyroidism |
| Lithium |
Breastfeeding may be appropriate in conjunction with rigorous monitoring |
| Radiopharmaceuticals |
Specialist advice required |
| Retinoids (oral) |
Potential for serious adverse effects in infant |
*Low doses used for non-neoplastic indications may be appropriate for some medications (e.g. mercaptopurine, azathioprine).
If a short course or single dose of a hazardous drug is used, it may be possible for breastfeeding to resume after a suitable washout period. The serum half-life of the drug is often used as a proxy for the half-life of the drug in breastmilk. After three half-lives, the amount of the drug eliminated by the mother is 87.5%; this increases to 94% after four half-lives, 97% after five half-lives, and 99.99% after ten half-lives.
Breastmilk should continue to be expressed during the prescribed washout period to maintain supply. For drugs with long half-lives, the required washout period may not be practical.
Safety of commonly used drugs
Antibiotics
Antibiotics are some of the more commonly used medications in breastfeeding women. Most are considered safe, although they may cause loose bowel actions in the infant.
- Penicillins – considered safe. There is no published data on the excretion of clavulanic acid into breastmilk. However, combinations of amoxicillin + clavulanic acid are often used;
- Cephalosporins – considered safe. These agents are transferred into breastmilk in low quantities. No data for ceftaroline, ceftolozane or ceftazidime + avibactam;
- Quinolones – generally considered safe. Theoretical risk of arthropathies, although this has only been reported in infants taking these agents directly. The calcium present in breastmilk may prevent or reduce infant absorption of quinolones found in breastmilk;
- Gentamicin – considered safe. Low transfer and low oral bioavailability;
- Macrolides – considered safe;
- Rifamycins – may be used. Patients should be warned that rifampicin and rifabutin can discolour breast milk. Rifaximin has very low absorption from the gastrointestinal tract;
- Tetracyclines – short courses are generally considered safe. Prolonged therapy should be avoided due to the potential risk of adverse effects on teeth and bone development; and
- Vancomycin – considered safe to use (low levels found in breastmilk and poor oral absorption).
Analgesics
Paracetamol is considered safe to use and is the analgesic of choice. Non-steroidal anti-inflammatory drugs (NSAIDs) may also be used. Ibuprofen is often the preferred NSAID as the amount transferred into breast milk is very low, it has a short half-life, and it is safely used in infants. Agents with longer half-lives (e.g. piroxicam) are typically avoided.
The use of opioids carries concerns of sedation and central nervous system depression. Most opioids are only excreted into breastmilk in small amounts following a single dose. However, accumulation can occur in the infant following repeated doses. This may be of particular concern in babies less than six months due to their reduced ability to clear opioids.
Considerations for opioids:
- Avoid if the infant has experienced apnoea, bradycardia or cyanosis;
- Avoid repeat doses (particularly in newborns or preterm infants);
- Codeine is contraindicated in breastfeeding due to concerns that ultra-rapid metabolisers may transfer higher amounts of morphine to the infant; and
- Monitor infant for sedation, feeding difficulties, and other adverse effects.
Antidepressants
If a mother has taken an antidepressant during the pregnancy without issue, the same agent can be continued during breastfeeding. The Therapeutic Guidelines make this recommendation as the exposure to antidepressants in utero is much higher than what occurs from breastmilk exposure.
If an antidepressant must be initiated during breastfeeding, it would be preferable to choose an agent with the greatest evidence of safety:
- Selective serotonin reuptake inhibitors (SSRIs) and venlafaxine have not been associated with adverse neurological or developmental outcomes in infants. Fluoxetine would not be the first choice SSRI as it has a longer half-life and passes into the breastmilk to a greater extent than other SSRIs.
- Tricyclic antidepressants (TCAs) are generally considered safe, although data is lacking on neurodevelopmental effects. Doxepin should be avoided as it is associated with isolated case reports of sedation and respiratory depression in breastfed infants.
- Moclobemide may be used with caution – it has very low transfer into breastmilk.
Antiepileptic medications:
Breastfeeding is encouraged in women who are taking antiepileptic medications. A recent systematic review suggests that exposure to these medications via breastmilk is not a concern in the majority of cases. Lamotrigine, levetiracetam, carbamazepine, topiramate, valproic acid, and gabapentin were not associated with clinically significant side effects among the breastfed infants in this study. These agents did not appear to affect growth, development, or verbal abilities of the breastfed infant.
Sedation and poor sucking were noted for infants exposed to phenobarbital and primidone.
The Therapeutic Guidelines provide the following recommendations:
- Sodium valproate and carbamazepine – considered safe during breastfeeding. Infant alertness and weight gain should be monitored.
- Lamotrigine – passage into breastmilk is variable but generally higher than that of carbamazepine and valproate. No significant adverse effects noted. Close monitoring of the infant is recommended. If a rash occurs, breastfeeding should be stopped until the cause is known.
- Pregabalin – limited data on use in breastfeeding. An alternative may be preferable, particularly when considering newborns or preterm infants.
Complementary medicines
It is often difficult to provide advice on the use of herbal and complementary medicines during breastfeeding due to a lack of published data on individual ingredients. In addition, there is a potential for contamination with undeclared conventional medicines, pesticides, or heavy metals.
Practice points
It is important to remember that breastfeeding offers many benefits to the infant and mother. Therefore, ceasing breastfeeding due to concerns about medication transfer should not be thought of as a no-risk strategy. When considering the safety of breastfeeding in a mother who is taking medication, a thorough risk assessment should be undertaken.
Points to consider include:
- Avoid unnecessary medications;
- Consider the dose and route of administration used by the mother;
- Where possible, use the lowest effective dose for the shortest period possible;
- The use of multiple medications may pose higher risks, particularly when adverse effects are additive (e.g. sedation with central nervous system depressants);
- An alternative medication or even the same medicine via a different route or formulation may be safer or have more evidence to support its use. Any changes to the medication regime must also be clinically appropriate for the mother’s condition;
- Medicines with shorter half-lives, high maternal protein binding, and low oral bioavailability are generally preferred;
- Avoid medicines known to cause serious toxicity in children;
- Consider the age of the infant; and
- Medicines registered for use in infants typically do not pose a safety hazard.
While the manufacturer’s product information can be consulted, these documents typically do not contain detailed information on medication use during lactation. They are also unlikely to contain the most current data. Product information documents are often considered to be overly conservative and may not always align with clinical practice.
Other sources of information include:
- Pregnancy and Breastfeeding Medicines Guide (published by the Royal Women’s Hospital);
- Australian Medicines Handbook;
- Therapeutic Guidelines; and
- LactMed database (maintained by the US National Library of Medicine).
