How do medications get into human milk?
The vast majority of medications passively diffuse from the individual’s plasma through the mammary gland epithelium and into the milk space.
During the first few days postpartum, large molecules, (e.g., immunoglobulins) can pass from the mother to the infant by passing between the mammary epithelial cells through the paracellular spaces. However, with the onset of secretory activation (milk ‘coming in’) the paracellular spaces between the cells (tight junctions) close, and then only small, water-soluble nonelectrolytes (e.g., alcohol, urea) pass into and out of human milk via simple diffusion through the paracellular spaces. Equilibration between maternal plasma and human milk is rapid, and human milk levels of these types of drugs approximate maternal plasma levels at all times.
After the paracellular spaces close, the majority of medications and substances cross into human milk through the mammary epithelium (the cells that make milk). For larger molecules, only the unbound, nonionized forms cross the mammary epithelium via passive diffusion driven by the concentration gradient between maternal plasma and human milk. Because this is a passive process for most drugs, they can diffuse in both directions across the epithelium. As the drug concentration in the mother’s blood decreases below the concentration in the milk because of maternal metabolism and excretion, the drug can pass from the milk back into the mother’s plasma.
What characteristics of medication influence how much of the medication will be in human milk?
Many attributes of medications can influence how much of the medication is present in human milk. These include:
- Size of molecule (molecular weight)
- Protein binding
- Lipid solubility
- Volume of distribution
Some physical and chemical factors of drugs, such as low molecular weight, low protein binding, weak bases, and high lipid solubility, favor greater passage of the drug into the mother’s milk. However, none of these factors can always be applied in isolation to predict drug passage, because they interact with each other. For example, higher lipid solubility also results in higher plasma protein binding among β-blockers, so the water-soluble β-blockers attain higher concentrations in human milk than the lipid-soluble β-blockers.
Extensive protein binding (> 85%) and high molecular weight (> about 800 Daltons) are fairly reliable predictors of poor passage into human milk. For example, monoclonal antibodies are usually not detectable in milk. However, some large molecules that are analogues of endogenous substances normally found in human milk (e.g., synthetic insulins and interferons) have been found in the milk of mothers receiving them, possibly because of active or facilitated transport. A few small molecules (e.g., acyclovir, cimetidine, nitrofurantoin) are actively transported into milk.
If the medication is known to be in human milk, how do I know if the infant will not be significantly affected?
The ratio of concentrations of a drug in milk and in plasma (the milk/plasma, or M/P, ratio) can be used as a measure of a drug’s passage into human milk. However, the M/P ratio has shortcomings that render it meaningless as a measure of drug safety. A better method of assessing drug safety during breastfeeding is to compare the dosage the infant receives in milk to the known infant dosage. But because so many adult drugs have no established infant dosage, a different method of assessment is required. The currently accepted method is the “weight-adjusted percentage of maternal dosage” or “relative infant dose” (RID), defined as follows:
RID = Daily infant dosage from breast milk [mg/kg] / Daily maternal dosage [mg/kg] × 100
The RID has much greater usefulness than the M/P ratio in determining the safety of medication use during breastfeeding. An RID less than 10% of the mother’s dosage is usually considered acceptable for breastfeeding, and an RID higher than 25% is considered unacceptable. Almost 90% of drugs fall below the 10% level, and only about 3% of drugs are passed to the infant in doses higher than 25%. Although this system works well for most drugs, a few exceptions occur for drugs with long half-lives (e.g., diazepam, fluoxetine), which can accumulate in the infant. Conversely, a few drugs with high RIDs (e.g., lamotrigine) have reassuring safety information. In addition, special consideration should apply to potentially toxic drugs with low RIDs (e.g., cancer chemotherapy, some radiopharmaceuticals) and in some cases in infants who have unusual genetic susceptibility.
Can lactating individuals be pregnant?
Lactating individuals can become pregnant. This app DOES NOT discuss the use of medications in pregnancy. Some medications, such as ACE inhibitors (such as lisinopril and enalapril) or ARBs (such as losartan) among other classes of medications, may not require pumping and dumping but do pose serious risks during pregnancy.
During lactation infant serum concentrations are nearly always lower than maternal levels because most medications have limited transfer into human milk, and there may be limited absorption by the infant (e.g. intravenous medications). During pregnancy, however, transplacental passage may result in similar serum concentrations of a drug in the fetus and the mother.
Please note that the trashthepumpanddump app does not address medication safety during pregnancy. Lactating individuals can become pregnant, in which case medication safety during pregnancy must be reviewed. A reliable resource for information on medication safety during pregnancy is MotherToBaby.org, which is from the Organization of Teratology Information Specialists.