Abstract
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The LactMed database contains information on drugs to which breastfeeding mothers may be exposed, and the possible adverse effects of those medications in the nursing infant. LactMed is written under contract with the Specialized Information Services (SIS) Division of the National Library of Medicine (NLM), National Institutes of Health. New information on medication use in nursing mothers is culled from several databases, such as PubMed, Web of Science, and Biosis Previews. The latter two databases are useful for locating data presented at meetings prior to formal publication.
The emphasis of LactMed has been on inclusion of U.S. medications for which published information exists. Some drugs available only outside the United States are included when they are widely used, and there is some published information on their use in nursing mothers. Examples are dipyrone (metamizole), domperidone, dothiepin, moclobemide, and sulpiride. Medications that have no published information have been de-emphasized. However, they are included whenever physicochemical or toxicological properties or analogy with similar medications can provide relatively clear guidance to the safety of use during breastfeeding. Sometimes, well-informed opinions on the safety of medications with no published information that are not in LactMed can be found in other sources, such as Hale and Rowe's Medication and Mother's Milk 2 and Briggs and Freeman's Drugs in Pregnancy and Lactation. 3
Information in LactMed is displayed in a standard format that was developed by the author, reviewers, SIS staff, and a multidisciplinary focus group prior to NLM release in 2006. Along with a general review by SIS, new LactMed records are reviewed by pediatric clinical pharmacologists Cheston Berlin, MD, and Shinya Ito, MD, both of whom have published extensively in the area of drug use during breastfeeding. Additional clinical experts have also assisted with the review of specialized areas such as herbals, nutraceuticals, and radiopharmaceuticals.
One recommendation of the focus group was to begin LactMed records with “Summary of Use during Lactation,” so that a busy clinician can readily scan the overview summation about the drug without having to read the entire record if time is limited. The “Summary of Use during Lactation” section also employs lay language that can be understood nursing mothers who are frequent users of the database. Users of LactMed should read further details in the LactMed record before making final judgements on safety when mothers are using new or unfamiliar drugs, or dosage regimens that may not have been studied.
Somewhat different from typical abstracting services, information from published articles is divided up among the various subsections of the LactMed record. For example, information in an article that reports a pharmacokinetic study of a drug in nursing mothers may have data on the amounts of drug in breastmilk placed in the “Drug Levels” section, data about infant outcomes in the “Effects in Breastfed Infants” section, and lactation effects in the “Effects on Lactation and Breastmilk” section. This latter section was recently renamed from the original name of “Effects on Lactation” because it contains information on topics such as drugs effects on the milk microbiome from antibiotics and effects on mineral content of breastmilk from chelating agents, and so on. The “Effects on Lactation and Breastmilk” section also contains information on the effects of drugs on lactational hormones, especially serum prolactin, regardless of any demonstrated clinical effects. Although data on serum prolactin may be of use when trying to assess lactation abnormalities, LactMed includes the standard admonition that “The prolactin level in a mother with established lactation may not affect her ability to breastfeed.” This statement is based on physiological studies and studies on drugs that raise serum prolactin.4,5
Other standardized phrases such as the one above are included in many LactMed records. These phrases are meant to provide consistency among records, as much as possible, so that nothing can be “read between the lines” when there are LactMed records on similar drugs. Examples include, “If drug x is required by the mother, it is not a reason to discontinue breastfeeding”; “Because there is no published experience with drug x during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant”; and “Drug x would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months.” The 1–2-month time period referred to in these statement is based on the literature on adverse drug reactions in breastfed infants6,7 and published pharmacovigilance reports. 8 These sources are very consistent in showing that about 75% of adverse reactions in breastfed infants from maternal medications occur during the first 2 months of life, predominantly (about 65% of all reactions) in the first month. The strong age dependence of adverse reactions is a major reason that LactMed does not provide lactation risk categories for individual drugs. A drug that might be risky for a newborn might have a very low risk for a 6-month old. Therefore, the user should take factors such as infant age, infant illness, drug dosage, and concomitant maternal medications into account when evaluating the safety of a maternal medication during breastfeeding.
The issue of polydrug therapy by nursing mothers has not been rigorously studied. In most systematic studies of medication use during breastfeeding, mothers are taking only one medication. Some data suggest that the use of multiple drugs that act on the central nervous system are a risk factor for adverse reactions in nursing infants. 7 The LactMed user should realize that two or three medications that appear to be relatively safe when used alone might be of concern when they are used together in the mother simultaneously. The dosage of each drug is also a factor to consider in the safety of combination therapy. The “Effects in Breastfed Infants” section of LactMed details any reports in which multiple drugs were used.
Unlike some information sources, the position of LactMed authors and editors is that breastfeeding has well-demonstrated benefits for the infant and mother,9,10 whereas documented harm to breastfed infants from maternal medications is uncommon. 7 Avoidance of breastfeeding because of a maternal medication should be the exception rather than the rule. New medications introduced into the market rarely have information on their use during breastfeeding. It is usually best to avoid using the latest drug on the market (e.g., free samples) for breastfeeding mothers. In many cases, similar medications are available that have published information, and they are listed in the “Alternate Drugs to Consider” section of LactMed. These records are easily accessed by clicking on the alternate drug names in this section.
In addition to editorial assistance, NLM provides sophisticated computer support, chemical structures from their ChemIDPlus database, hyperlinks of LactMed references to PubMed citations, and extensive cross-referencing of drug names using their RxNorm database. The cross-referencing allows users to search by proprietary name, chemical name, and some foreign drug names. Other NLM databases such as DailyMed and pages within TOXNET also have links to LactMed. SIS created and maintains the free LactMed applications (apps) for iPhone and Android operating systems that can be downloaded from LactMed's home page. New information is uploaded once monthly to the online version of LactMed and about every 6 months to the apps. For this reason, the online version might occasionally have information that is not in the apps, especially with regard to new drugs.