How Medications Affect Breastmilk January 20, 2013 21:26
At the pharmacy, I get a lot of questions about medications while breastfeeding. While it is always safest to avoid medications while breastfeeding, sometimes mothers are left without a choice if their condition puts their own health at risk. Although many medications are safe to use when you're breastfeeding, most drugs will get into your milk to some degree and may even affect your milk supply. To be safe, check with your child's doctor before taking any kind of medication, even over-the-counter drugs. The mechanism of how drugs enter breast milk is described below in addition to some general guidelines that I follow when counseling my patients.
Transfer of drugs into breast milk is influenced by protein binding, lipid solubility and ionization
This sounds pretty scientific but basically this means that nearly all drugs transfer into breast milk to some extent.
Notable exceptions are heparin and insulin which are too large to cross biological membranes. The infant almost invariably receives no benefit from this form of exposure and is considered to be an 'innocent bystander'.
Drug transfer from maternal plasma to milk is, with rare exceptions, by passive diffusion across biological membranes. Transfer is greatest in the presence of low maternal plasma protein binding and high lipid solubility.
In addition, milk is slightly more acidic than plasma (pH of milk is approximately 7.2 and plasma is 7.4) allowing weakly basic drugs to transfer more readily into breast milk and become trapped secondary to ionization.
What you should know is that milk composition varies within and between feeds and this may also affect transfer of drugs into breast milk. For example, milk at the end of a feed (hindmilk) contains considerably more fat than foremilk and may concentrate fat-soluble drugs.
As a general rule, maternal use of topical preparations such as creams, nasal sprays or inhalers would be expected to carry less risk to a breastfed infant than systemically administered drugs.
This is due to lower maternal concentrations and therefore lower transfer into breast milk.
However, the risk to the infant must be considered in relation to the toxicity of the drug used, the dosage regimen and the area of application. For example, use of corticosteroids nasal sprays or inhalers in standard doses would be considered compatible with breastfeeding.
Infants have lower drug clearance (elimination) than adults
Drug clearance in the infant is a particularly important consideration and premature infants have a severely limited ability to clear drugs.
Within a few days of delivery, term infants have kidney filtration rates approximately one-third of adult values after adjusting for difference in body surface area, and premature infants have even more impaired clearance.
Generally, adult kidney filtration rates (adjusted for the difference in surface area) are attained by five to six months of age.
Minimize risk to the breastfed infant by reducing drug exposure
The overall risk of a drug to a breastfed infant depends on the concentration in the infant's blood and the effects of the drug in the infant. If, after assessment of the risks and benefits, the decision is made to breastfeed while the mother is using a drug, the infant should be monitored for adverse effects such as failure to thrive, irritability and sedation.
However, it is difficult to identify adverse reactions occurring in neonates.
Feeding immediately prior to a dose may help to minimize infant exposure as concentrations in milk are likely to be lowest towards the end of a dosing interval. Or,it may be reasonable to reduce infant exposure by alternating breast and bottle-feeding. For drugs that are not considered safe in breastfeeding, breast milk may be expressed and discarded for the treatment duration. Breastfeeding may be resumed after the drug has been eliminated from the maternal blood stream. A period of approximately four half-lives (the time it takes for half of the drug to clear the body) will reduce maternal concentrations to around 10% of steady-state (full) concentrations.
Atkinson HC, Begg EJ, Darlow BA. Drugs in human milk. Clinical pharmacokinetic considerations. Clinical Pharmacokinetics 1988;14:217-40.
Bennett PN and the WHO Working Group, editors. Drugs and human lactation. 2nd edition. Amsterdam: Elsevier, 1997.
Over-the-Counter Medication Use While Breastfeeding December 20, 2012 22:20
Working as a pharmacist, it is not uncommon for me to get several questions throughout the day from breastfeeding women about the use of over-the-counter medications. Most medications can be detected in breast milk in small amounts (about 1% to 2% of maternal intake), but very few are contraindicated while breastfeeding. Adverse reactions from drug passage into breast milk is more likely in nursing infants <2 months old.
In general, the safest thing to do when an over-the-counter medication may be needed is to try nonpharmacologic symptom management first. If all else fails, then medications can definitely be considered to use, it’s just important to know which ones are safest while breastfeeding. As always, nursing mothers should consult a health care professional before starting any medication.
A drug’s characteristics determine how much of it will be transferred into the breast milk. These include the molecular weight of the drug, the proportion of drug that is bound to plasma and milk proteins, the solubility of the drug in lipids and in water, the proportion of the drug that is ionized or nonionized, the pH of the drug, and the half-life of the drug. The lower the molecular weight, the easier the drug passes into the milk. Low protein binding drugs will more readily pass through to breast milk. Lipid soluble drugs rapidly accumulate in the breast milk. Drugs that are weak bases would be more likely to cross the membranes from plasma into breast milk. The longer the half-life of the drug, the greater the accumulation will be in the mother, in the breast milk, and in the infant. Aside from potential adverse effects in the infant, some drugs may decrease milk production.
According to the American Academy of Pediatrics Committee on Drugs, to minimize a nursing infant’s exposure to maternal drug, breastfeeding women take oral medications immediately after nursing or just before the infant’s longest sleep period. As a pharmacist, I recommend single ingredient products at the lowest dose possible. Try to avoid using extra strength, maximum strength, or long-acting formulations. In addition, avoid alcohol-containing formulations when possible or avoid frequent or high doses of alcohol-containing formulations. Breastfeeding women should also be sure to watch for any possible side effects that may occur. As a last resort, breastfeeding may be withheld during the period of drug therapy if the drug is contraindicated.
Many OTC options for analgesics are available. Acetaminophen is routinely used for fever and pain in infants, and levels excreted into breast milk are expected to be less than the dose given to infants. Of the NSAIDs, ibuprofen is considered the drug of choice for breast-feeding women and is used routinely in infants. While ibuprofen is excreted into breast milk, the concentration and subsequent transfer to the infant are very low.Naproxen should be used cautiously in breast-feeding women due to its long half-life. Alternative therapeutic options are recommended; if aspirin is taken, the mother should avoid breast-feeding for one to two hours after the dose.
Allergy, Cold, and Cough Preparations
Antihistamines: All OTC antihistamines are known to be excreted in breast milk, and their sedating effects may also be seen in infants. While it is known that diphenhydramine is excreted into breast milk, the concentration and infant transfer are unknown. Clemastine is a long-acting antihistamine that should be used cautiously due to its association with significant effects on infants, including irritability, refusal to feed, and neck stiffness. All of the sedating antihistamines have the possibility of causing sedation in the infant and/or decreasing milk supply, especially when taken in conjunction with a decongestant, and should be used with caution.
Currently, the only nonsedating OTC antihistamine that is available is loratadine, which is excreted in breast milk. However, concentrations in the infant are low and considered safe. Due to its nonsedating effect, loratadine is the preferred antihistamine.
Decongestants: The two OTC oral decongestants available are pseudoephedrine and phenylephrine. Due to new regulations regarding the sale of pseudoephedrine, many cough and cold preparations have reformulated their products to contain phenylephrine. Phenylephrine, an ingredient in pediatric cough and cold preparations, is considered safe. While excretion into breast milk is unknown, it is unlikely to be excreted into breast milk in large quantities due to its poor bioavailability. The effect of phenyl ephrine on milk production and supply is also unknown; therefore, this medication should be used with caution in women with limited milk production. Pseudoephedrine is excreted in breast milk and has been shown to decrease milk production and possibly cause irritability in infants. Nasal decongestants are an alternative to systemic decongestants. Most OTC products contain either oxymetazoline or phenylephrine. Excretion in breast milk of oxymetazoline is unknown. However, due to their local activity and minimal systemic absorption, nasal decongestants may have a low concentration in breast milk and are preferred over systemic oral decongestants.
Cough Medications:Dextromethorphan is a common cough suppressant used in cough and cold preparations. Although dextromethorphan has not been studied in breast-feeding, expected concentrations in breast milk would be low. Guaifenesin is used as an expectorant in many formulations of cough and cold products. Cough preparations may also contain alcohol. While alcohol is considered compatible with breastfeeding by the AAP, lactating mothers should choose alcohol-free or low-content alcohol products.
Gastrointestinal medications include agents used for the treatment of diarrhea, constipation, and flatulence. Loperamide, which is used for the treatment of diarrhea, is generally considered compatible with breast-feeding due to minimal oral absorption. Docusate is a common OTC stool softener. It is minimally absorbed orally, and minimal transfer to breast milk would be expected. As a precaution, mothers who take docusate should watch for loose stools in the infant. Other OTC medications for the treatment of constipation are the stimulant laxatives bisacodyl and senna and the bulk-forming laxative psyllium. Bisacodyl has not been studied in breast-feeding; however, due to its minimal systemic absorption, it would not be expected to cause adverse effects in the breast-fed infant and is considered compatible. Senna, a strong laxative, is compatible with breast-feeding. Although older reports indicated an increased incidence of loose stools in infants who were exposed to senna, newer reports have not shown this adverse effect with current senna products. Psyllium is not absorbed systemically and, therefore, does not enter breast milk. It is considered compatible with breast-feeding. Simethicone, used for the treatment of intestinal gas, is commonly used in infants. The drug is not absorbed systemically and thus would not pass into breast milk. Simethicone is considered compatible with breast-feeding.
Below are some great online resources regarding medications and breast milk and from where the information above is referenced.
Motherisk. http://www.motherisk.org/index.jsp. Offers consumers answers to questions about morning sickness and the risk or safety of medications, disease, chemical exposure, and more. Provides teratogen information for healthcare professionals and updates on Motherisk’s continuing reproductive research.
Perinatology.com. http://www.perinatology.com/. Provides teratogen information for healthcare professionals, links to clinical guidelines, and more.
Organization of Teratology Information Specialists (OTIS). http://www.otispregnancy.org/. Provides medical consultation on prenatal exposures for consumers and healthcare professionals.
OBfocus. http://www.obfocus.com/. Provides information for healthcare professionals and consumers on pregnancy and lactation related issues, including drug exposure. Provides a list of resources on high-risk pregnancy.
LactMed. http://toxnet.nlm.nih.gov/. Drug and Lactation Database by U.S. Library of Medicine. Provides information on drugs and other chemicals that breastfeeding mothers may be exposed to.