Adult Dosage:
This is the usual adult oral dose provided in the package insert. While these are highly variable, we chose the dose for the most common use of the medication.
Alternatives:
Drugs listed in this section may be suitable alternate choices for the medication listed. 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 alternatives listed are only suggestions and may not be at all appropriate for the syndrome in question. Only the clinician can make this judgment. For instance, nifedipine is a calcium channel blocker with good antihypertensive qualities, but poor antiarrhythmic qualities. In this case, verapamil would be a better choice.
T½=
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 hours), 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 hours) and if your physician is open to suggestions, then find a similar medication with a shorter half-life (compare ibuprofen with naproxen). However, in today’s world, longer half-life drugs are preferred and we simply have to accommodate these and rely on published data.
Vd=
The Volume of Distribution (Vd) is a useful kinetic term that describes how widely the medication is distributed in the body. Drugs with high Vd are distributed in higher concentrations in remote compartments of the body and may not stay in the blood. Marijuana is a classic example.
Another such drug, digoxin enters the blood compartment and then rapidly leaves to enter the heart and skeletal muscles. Most of the drug is sequestered in these remote compartments (100-fold). Therefore, drugs with high Vd (1-20 L/kg) generally require much longer to clear from the body than drugs with smaller volumes (<1 L /kg). For instance, 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). Further, 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. We have found that drugs with high Vd generally produce lower milk levels. For a complete description of Vd, please consult a good pharmacology reference. In this text, the units of measure for Vd are L /kg.
Tmax=
This lists the time interval from administration of the drug until it reaches the highest level in the mother’s plasma (Cmax), which we call the peak or “time to max,” hence Tmax. Occasionally, you may be able to avoid nursing the baby when the medication is at the peak. Rather, wait until the peak is subsiding or has at least dropped significantly. Remember, drugs enter breast milk as a function of the maternal plasma concentration. In general, the higher the mother’s plasma level, the greater the entry of the drug into her milk. If possible, choose drugs that have short peak intervals, and suggest that mom not breastfeed when the drug is at Cmax.
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 Da) 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 cells’ lipid membranes, which may significantly reduce milk levels. As such, the smaller the molecular weight, the higher the relative transfer of that drug into milk. Protein medications (e.g., heparin), which have enormous molecular weights, transfer at much lower concentrations and are virtually excluded from human breast milk. Therefore, when possible, choose drugs with higher molecular weights to reduce their entry into milk. A new class of drugs has risen in popularity in the last decade. These are the monoclonal antibodies. These very selective antibodies, mostly derived from human IgG1-4, are used to treat a number of severe diseases, such as Crohn’s disease, multiple sclerosis, rheumatoid conditions, migraine headache, etc. Interesly, IgG molecules are enormous in molecular weight (around 160,000 Da) and thus enter the milk compartment poorly. Further, they are largely destroyed by proteases in the GI tract of the infant if presented in milk. At this point, we do not think much, if any, of these monoclonals enter milk or survive the GI tract of the infant. Thus far, all studies of these antibodies in human milk suggest levels in milk are far less than 1.0%, and virtually none of this would survive the GI tract of the infant. However, the use of these drugs in pregnant women in the last trimester may produce significant plasma levels in the fetus, and thus the newborn infant. Thus, some infants could be susceptible to problems associated with the fetal exposure to these drugs (immunosuppressed). Current data thus far do not suggest significant transfer of these products into human milk.
M/P=
This lists the milk/plasma (M/P) 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 higher 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.
PB=
This lists the percentage of maternal protein binding. Most drugs circulate in the blood bound to plasma albumin and other proteins. If a drug is highly protein bound, it cannot enter the milk compartment as easily. 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 infant’s 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 bloodstream of the patient. Drugs with low oral bioavailability are generally either poorly absorbed in the GI tract, are destroyed in the gut, or 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, we have included these terms when no data are available on the exact amount (percentage) absorbed.
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, the drug becomes 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.
With many drugs, the pharmacokinetics have not been described or published. In this case we leave this entry blank.