It is now well known that human milk is the best nutrition for infants. The benefits are simply enormous and supported by a world of excellent literature. However, the use of medications in breastfeeding mothers is often controversial and is steeped with misinformation in the healthcare field. This book has, for many years, been the primary source for drug information for breastfeeding mothers. The truth is, most drugs simply don’t enter milk in levels that are hazardous to a breastfed infant. The problem, however, is determining which drugs are safe and which are hazardous.
Because so few clinicians understand lactational pharmacology, the number of women who are advised to discontinue breastfeeding in order to take a medication is still far too high. Fortunately, many mothers are now becoming aware of the enormous benefits of breastfeeding and simply refuse to follow some of the advice given by their healthcare professionals. They seek out the information on their own and invariably find this book or my websites.
Because almost all mothers ingest medications during the early neonatal period, it is not surprising that one of the most common questions encountered in pediatrics concerns the use of various drugs in the breastfeeding mother. Unfortunately, most healthcare professionals simply review the package insert or advise the mother not to breastfeed without having done a thorough study of the literature to find the true answer. Discontinuing breastfeeding is often the wrong decision, and most mothers could easily continue to breastfeed and take the medication without risk to the infant. Even the FDA has recognized this and now recommends that drug manufacturers carry out studies to determine milk levels of their drug.
It is generally accepted that all medications transfer into human milk to some degree, although it is almost always quite low. Only rarely does the amount transferred into milk produce clinically relevant doses in the infant. Ultimately, it is the clinician’s responsibility to review the research I have on the drugs in this book and make a clear decision as to whether the mother should continue to breastfeed.
| Drugs may transfer into human milk if they: |
| Attain high concentrations in maternal plasma |
| Are low in molecular weight (< 800) |
| Are low in protein binding |
| Pass into the brain easily |
However, once medications transfer into human milk, other kinetic factors are involved. One of the most important is the oral bioavailability of the medication to the infant. Numerous medications are either destroyed in the infant’s gut, fail to be absorbed through the gut wall, or are rapidly picked up by the liver. Once in the liver, they are either metabolized or stored, but often never reach the mother’s plasma.
Drugs normally enter milk by passive diffusion, driven by equilibrium forces between the maternal plasma compartment and the maternal milk compartment. They pass from the maternal plasma through capillaries into the lactocytes lining the alveolus. Medications must generally pass through both bilayer lipid membranes of the alveolar cell to penetrate milk; although early on, they may pass between the alveolar cells (first 72 hours postpartum). During the first 3 days postpartum, large gaps between the alveolar cells exist. These gaps permit enhanced access into the milk for most drugs, many immunoglobulins, maternal living cells (lymphocytes, leukocytes, macrophages), and other maternal proteins. By the end of the first week, the alveolar cells swell under the influence of prolactin and subsequently close the intracellular gaps, thus reducing the transcellular entry of most maternal drugs, proteins, and other substances into the milk compartment. While it is generally agreed that medications penetrate into milk at higher levels during the colostral period, nevertheless, the absolute dose transferred during the colostrum period is still low due to the minimal volume of colostrum (30-100 mL/day) for the first few days postpartum.
In most instances, the most important determinant of drug penetration into milk is the mother’s plasma level. Almost without exception, as the level of the medication in the mother’s plasma rises, the concentration in milk increases as well. Drugs enter and exit milk as a function of the mother’s plasma level. As soon as the maternal plasma level of a medication begins to fall, equilibrium forces drive the medication out of the milk compartment back into the maternal plasma for elimination. In some instances, drugs may be trapped in milk (ion trapping) due to the lower pH of human milk (7.2). Drugs with a high pKa may become trapped in the milk compartment due to ion trapping. This is important in weakly basic drugs, such as the barbiturates (drugs with high pKa). There are some known cellular pumping systems that actively pump drugs into milk. The most important is iodine. The iodine pump is the same as found in everyone’s thyroid gland. Its purpose is to make sure the infant receives iodine to maintain thyroxine production.
The iodides, such as 131I or any “ionic” form of iodine, concentrate in milk due to this pump. Thus iodides, particularly radioactive ones, should be avoided as their milk concentrations are exceedingly high. Two other physicochemical factors are important in evaluating drugs in breastfeeding mothers—the degree of protein binding and lipid solubility. Drugs that are very lipid soluble penetrate into milk in higher concentrations almost without exception. Of particular interest are the drugs that are active in the central nervous system (CNS). CNS-active drugs invariably have the unique characteristics required to enter milk. Therefore, if a drug is active in the CNS, significant levels in milk can be expected; although the amounts still are often subclinical. Many of the neuroactive drugs produce Relative Infant Doses (RIDs) of >5%. Protein binding also plays an important role. Drugs circulate in the maternal plasma, either bound to albumin or freely soluble in the plasma. It is the free component (unbound fraction) that transfers into milk, while the bound fraction stays in the maternal circulation. Therefore, drugs that have high maternal protein binding (warfarin, most NSAIDs) have low milk levels simply because they are bound in the plasma compartment and cannot get out.
Once a drug has entered the mother’s milk and has been ingested by the infant, it must traverse through the infant’s GI tract prior to absorption. Some drugs are poorly stable in this environment due to the proteolytic enzymes and acids present in the infant’s stomach. This includes the aminoglycoside family, omeprazole, and large peptide drugs, such as heparin, and most of the new monoclonal antibodies. Other drugs are poorly absorbed by the infant’s GI tract and do not enter the infant’s bloodstream. Thus, oral bioavailability is a useful tool to estimate just how much of the drug will be absorbed by the infant. Many drugs are sequestered in the liver (first pass) and may never actually reach the plasma compartment. Absorption characteristics such as these ultimately tend to reduce the overall effect of many drugs in breastfed infants. There are certainly exceptions to this rule, and one must always be aware that the action of a drug in the GI tract can be profound, producing diarrhea, constipation, and occasionally syndromes such as pseudomembranous colitis. One of the more popular methods for estimating risk to the infant is the RID. The RID is calculated by dividing the infant’s dose via milk (mg/kg/day) by the mother’s dose in mg/kg/day. The RID gives the clinician a feeling for just how much medication the infant is exposed to on a weight-normalized basis. However, many authors calculate the infant dose without normalizing for maternal and infant weight, so be cautious.
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Key Points About Breastfeeding and Medications |
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Lastly, it is very important to always evaluate the infant’s ability to handle small amounts of medications. Some infants, such as premature or unstable infants, may not be suitable candidates for certain medications. But remember that in early postpartum (and in late stage lactation), the amount of milk produced (30-100 mL/day) is so low that the clinical dose of drug transferred is often low, so even premature neonates would receive only a limited amount from the milk.
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Evaluation of the Infant |
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