Lactation Risk Categories

  • Posted by Cheryl Taylor, CBE

There are times when a nursing mom needs to take certain medications.  Many physicians are simply not well educated on medications and the safety of taking them while breastfeeding.  They may give information that is inaccurate and/or recommend that a mom wean to take a medication.  Breastfeeding is so very vital to an infant’s health and development and should be guarded more vigilantly by our medical community.  There truly is a small number of medications that are contraindicated for breastfeeding.

Dr. Thomas Hale is the leading expert on breastfeeding and medications.  If you have been prescribed a medication and been instructed to wean to take it, take the time to get the accurate information on that medication and how it pertains to nursing.  Your proactive manner of handling this could be what saves your breastfeeding relationship!

Drug which has been taken by a large number of breastfeeding mothers without any observed increase in adverse effects in the infant. Controlled studies in breastfeeding women fail to demonstrate a risk to the infant and the possibility of harm to the breastfeeding infant is remote; or the product is not orally bioavailable in an infant.
Drug which has been studied in a limited number of breastfeeding women without an increase in adverse effects in the infant.  And/or, the evidence of a demonstrated risk which is likely to follow use of this medication in a breastfeeding woman is remote.
There are no controlled studies in breastfeeding women, however the risk of untoward effects to a breastfed infant is possible; or, controlled studies show only minimal non-threatening adverse effects. Drugs should be given only if the potential benefit justifies the potential risk to the infant.
There is positive evidence of risk to a breastfed infant or to breastmilk production, but the benefits of use in breastfeeding mothers may be acceptable despite the risk to the infant (e.g. if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Studies in breastfeeding mothers have demonstrated that there is significant and documented risk to the infant based on human experience, or it is a medication that has a high risk of causing significant damage to an infant. The risk of using the drug in breastfeeding women clearly outweighs any possible benefit from breastfeeding. The drug is contraindicated in women who are breastfeeding an infant.

There are other categories listed in the “How to Use this Book” section of Dr. Hale’s book.  They include:

Theoretic Infant Dose:

This is an estimate of the maximum likely dose per kilogram per day that an infant would ingest via milk.  Because the literature is highly variable, I used several methods to calculate this estimate.  First, if the authors provided milk AUC information, I used this data to estimate the dose to the infant as it is much more accurate.  But more commonly, the only data provided was the peak milk level, also called Cmax.  In these cases I used this data to derive the theoretic infant dose.  For determining dose I used the standard milk intake of 150 mL/kg/day multiplied times the concentration of medication in milk (Cmax/Liter X 0.150 mL/kg/day = TID).  Please remember, this is generally the maximum concentration that would be transferred.  Most often the actual dose to the infant would be much lower.  If you know the maternal dose, calculate the Relative Infant Dose using the formula on page 12.  It may prove very useful.

Adult Concerns:

This section lists the most prevalent undesired or bothersome side effects listed for adults.  As with most medications, the occurrence of these if often quite rare, generally less than 1 – 10% of the time.  Side effects vary from one patient to another and should not be overemphasized, since most patients do not experience untoward effects.

Pediatric Concerns:

This section lists the side effects noted in the published literature as associated with medications transferred via human milk.  Pediatric concerns are those effects that were noted by investigators as being associated with drug transfer via milk.  They are not the effects that would result from direct administration to the infant.  In some sections, I have added comments that may not have been reported in the literature, but are well known attributes of this medication and are useful information to provide the mother so that she can better care for her infant (“Observe for weakness, apnea”).

Drug Interactions:

Drug interactions generally indicate which medications, when taken together, may produce higher or lower plasma levels of other medications, or they may decrease or increase the effect of another medication.  These effects may vary widely from minimal to dangerous.  Because some medications have hundreds of interactions, and because I had limited room to provide this information, I have listed only those that may be significant.  Therefore please be advised that this section may not be complete.  In several references, I have suggested that due to the large number of interactions the reader consult a more complete drug interactions reference.  Please remember that the drugs administered to a mother could interact with those being administered concurrently to an infant.  Example:  Maternal fluconazole and pediatric cisapride.


Drugs listed in this section may be suitable alternate choices for the medication listed above.  In many instances, if the patient cannot take the medication, or it is a poor choice due to high milk concentrations, these alternates may be suitable candidates.  WARNING: The alternates listed are only suggestions and may not be at all proper for the syndrome in question.  Only the clinician can make this judgment.  For instance, nifedipine is a calcium channel blocker with good anti-hypertensive qualities, but poor anti-arrhythmic qualities.  In this case, verapamil would be a better choice.

Adult Dosage:

This is the usual adult oral dose provided in the package insert.  While these are highly variable, I chose the dose for the most common use of the medication.

T 1/2 =

This lists the most commonly recorded adult half-life of the medication.  It is very important to remember that short half-life drugs are preferred.  Use this parameter to determine if the mother can successfully breastfeed around the medication, by nursing the infant…then taking the medication.  If the half-life is short enough (1 – 3 hrs), then the drug level in the maternal plasma will be declining when the infant feeds again.  This is ideal.  If the half-life is significantly long (12 – 24 hrs), and if your physician is open to suggestions, then find a similar medication with a shorter half-life (compare ibuprofen with Naproxen).  I have provided “Family” tables in the back of this text, so you can compare family members for half-lives and other kinetic parameters.


This lists the most commonly recorded pediatric half-life of the medication.  Medications with extremely long half-lives in pediatric patients may accumulate to high levels in the infant’s plasma if the half-life is exceeding long (>12 hrs.).  Pediatric half-lives are difficult to find due to the paucity of studies.

M/P =

This lists the Milk/plasma ratio.  This is the ratio of the concentration of drug in the mother’s milk divided by the concentration in the mother’s plasma.  If high (>1 – 5) it is useful as an indicator of drugs that may sequester in milk in high levels.  If low (<1) it is a good indicator that only minimal levels of the drug are transferred into milk (this is preferred).  While it is best to try to choose drugs with LOW milk/plasma ratios, the amount of drug which transfers into human milk is largely determined by the level of drug in the mother’s plasma compartment.  even with high M/P ratios and LOW maternal plasma levels the amount of drug that transfers is still low.  Therefore, the high M/P ratios often provide an erroneous impression that large amounts of drug are going to transfer into milk.  This simply may not be true.

PK =

This lists the time interval from administration of the drug, until it reaches the highest level in the mother’s plasma, which we call the Peak.  In pharmacology literature it is most commonly abbreviated Cmax.  The peak is when you do not want the mother to breastfeed her infant, rather, wait until the peak is subsiding or has at least dropped significantly.  Remember, drugs enter breastmilk as a function of the maternal plasma concentration.  The higher the mom’s plasma level, the greater the entry of the drug into her milk.  If possible, choose drugs that have short peak intervals, and don’t let mom breastfeed when it peaks.

PB =

This lists the percentage of maternal protein binding.  Most drugs circulate in the blood bound to plasma albumin.  if a drug is highly protein bound ti cannot exit the plasma compartment as well.  The higher the percentage of binding the less likely the drug is to enter the maternal milk.  Try to choose drugs that have high protein binding, in order to reduce the infants exposure to the medication.  Good protein binding is typically greater than 90%.

Oral =

Oral bioavailability refers to the ability of a drug to reach the systemic circulation after oral administration.  it is generally a good indication of the amount of medication that is absorbed into the blood stream of the patient.  Drugs with low oral bioavailability are generally either poorly absorbed in the gastrointestinal tract, or they are sequestered by the liver prior to entering the plasma compartment.  The oral bioavailability listed in this text is the adult value; almost none have been published for children or neonates.  Recognizing this, these values are still useful in estimating if a mother or perhaps an infant will actually absorb enough drug to provide clinically significant levels in the plasma compartment of the individual.  The value listed estimates the percent of an oral dose that would be found in the plasma compartment of the individual after oral administration.  In many cases, the oral bioavailability of some medications is not listed by manufacturers, but instead terms such as “Complete”, “Nil”, or “Poor” are used.  For lack of better data, I have included these terms when no data is available on the exact amount (percentage) absorbed.

Vd =

The volume of distribution is a useful kinetic term that describes how widely the medication is distributed in the body.  Drugs with high volumes of distribution (Vd) are distributed in higher concentrations in remote compartments of the body, and may not stay in the blood.  For instance, digoxin enters the blood compartment and then rapidly leaves to enter the heart and skeletal muscle.  Most of the drug is sequestered in these remote compartments (100 fold).  Therefore, drugs with high volumes of distribution (1 – 20 liter/kg) generally require much longer to clear from the body than drugs with smaller volumes (0.1 liter/kg).  For isntance, whereas it may only require a few hours to totally clear gentamycin (Vd = 0.28 l/kg) it may require weeks to clear amitriptyline (Vd = 10 l/kg) which has a huge volume of distribution.  In addition, some drugs may have one half-life for the plasma compartment, but may have a totally different half-life for the peripheral compartment, as half-life is a function of volume of distribution.  For a complete description of Vd, please consult a good pharmacology reference.  In this text, the units of measure for Vd are liters/kg.

pKa =

The pKa of a drug is the pH at which the drug is equally ionic and nonionic.  The more ionic a drug is, the less capable it is of transferring from the milk compartment to the maternal plasma compartment.  Hence, they become trapped in milk (ion-trapping).  This term is useful, because drugs that have a pKa higher than 7.2 may be sequestered to a slightly higher degree than one with a lower pKa.  Drugs with higher pKa generally have higher milk/plasma ratios.  hence, choose drugs with a lower pKa.

MW =

The molecular weight of a medication is a significant determinant as to the entry of that medication into human milk.  Medications with small molecular weights (<200) can easily pass into milk by traversing small pores in the cell walls of the mammary epithelium (see ethanol).  Drugs with higher molecular weights must traverse the membrane by dissolving in the lipid bi-layers, which may significantly reduce milk levels.  As such, the smaller the molecular weight the higher the relative transfer of that drug into milk.  Protein medication (e.g. Heparin, Insulin), which have enormous molecular weights, transfer at much lower concentrations and are virtually excluded from human breastmilk.  Therefore, when possible, choose drugs with higher molecular weights to reduce their entry into milk.

Note:  If you have a chronic disease or condition for which regular medications have been necessary, I would suggest purchasing a copy of Dr. Hale’s book to take with you to all doctor appointments.  Many doctors and specialists simply aren’t aware of how compatible most medications are with breastfeeding because it just isn’t their specialty.  Take the responsibility upon yourself to arrive with the information in hand that may be needed for your appointment and you will save yourself many headaches.

From:  Medications and Mothers’ Milk (2002) by Thomas W. Hale, PhD