David J Woods
Drug Information Consultant and Senior Teaching Fellow
School of Pharmacy
University of Otago
This article, looking at the collection of drug information relating to breastfeeding, is the first in a series of articles that covers literature searching and appraisal of information on specific subject areas. They are intended to be used as a training and reference resource. For more detailed information and hyperlinks to relevant websites please visit www.pharminfotech.co.nz/adept.htm
Each article will follow a similar format. Important background questions and issues are considered first. These help to clarify the question and identify important factors to assist in finding and applying the information. A list of resources is followed by suggested search strategies. Finally, case examples are provided to demonstrate important principles.
Background questions and issues
Important background questions include:
- The maternal dose.
- The age of the infant.
- Whether the infant was born term or premature.
- The health of the infant.
- Other maternal drug therapy.
Infant exposure to the drug via breast milk is influenced by the maternal dose and the infant’s ability to eliminate the drug. Drug clearance is reduced in the newborn, especially in premature babies and organ dysfunction. It is important to realise data on drug excretion into human milk usually applies to full-term healthy infants. Drugs with similar pharmacological actions may have additive effects on the infant.
The practitioner should also consider the inherent toxicity of the drug: for example, even small amounts of antineoplastic drug in breast milk would be unacceptable. If the drug is used therapeutically in infants it is useful to relate the dose to the estimated exposure from breast milk. The drug’s pharmacokinetics are important – for example, when considering the extent of infant absorption or elimination. Finally, critical appraisal skills are required to judge of the quality of the available data.
Briggs GG, Freeman RK, Yaffe SJ.
Drugs in pregnancy and lactation. 6th ed.
Baltimore (MD): Williams & Wilkins; 2001.
A comprehensive text with updates available, this book provides a detailed description of most of the relevant published studies. The text provides good guidance and often refers to the American Academy of Pediatrics guidelines for drug use in breastfeeding
Readers should have a good understanding of the principles and be able to interpret and apply the information. The book is an evidential resource rather than a quick reference guide. As with all books it dates rapidly, especially if an update subscription is not taken.
Medications in Mother’s Milk. 10th ed.
Amarillo (TX): Pharmasoft Medical Publishing; 2002.
A useful portable reference text.
British National Formulary.
London: British Medical Association and
Royal Pharmaceutical Society of Great Britain.
The British National Formulary describes drug safety in breastfeeding according to trimester of risk. The information is not very detailed but may be useful as a first screen or to supplement or verify another resource.
Prescribing drugs in lactation
Prescriber Update, Ministry of Health, New Zealand.
This website is an excellent resource that explains both theory and calculations. Tables of commonly used drugs with M:P ratio and estimated infant exposure are provided.
Giving a description of drugs that are contraindicated in breastfeeding, this website also has an extensive
UK Drugs in Lactation Advisory Service
A joint service provided by the West Midlands and Trent Drug Information Services
A comprehensive updated resource.
Australian Drug Foundation
A useful site if you are providing information to mothers who take recreational drugs whilst breastfeeding. The risks and concerns are explained in plain language.
Recommended MeSH are “milk” or “milk, human”, “lactation” and “breastfeeding”. Textwords should also be included in the search strategy. PubMed will do this by default. For example, in PubMed use:
(milk OR lactation OR breastfeeding) AND drug
This example demonstrates the importance of using the correct search strategy. Consider the question “Is nimodipine safe in breastfeeding?” and the following Medline (PubMed) searches.
Search 1: “nimodipine AND breastfeeding” gives no results. This emphasises the importance of selecting the most appropriate terms and avoiding “literal searching”.
Search 2: “nimodipine AND lactation” gives two results, but only one of these is relevant.
Search 3: “nimodipine AND milk, human” gives two results, and both of these are relevant.
The MeSH “milk, human” is the best term to use in this context. The retrieval of the relevant citation in Search 1 is fortunate.
Search 3 gives us two citations, but the results appear to conflict. One of the studies, by Carcas et al,(1) indicates that infant exposure is very low following maternal administration of 46mg IV over 24 hours to a breastfeeding woman. The study by Tonks(2) suggests a much greater exposure, but this study has poor methodology.
A search of Medline using the terms described previously retrieves the study by Force published in 1995.(3) The maternal milk (M):plasma (P) ratio is approximately 0.85, and the weight-adjusted infant exposure is usually at least 10% of the maternal dose. A figure of 10% has been arbitrarily suggested as the maximum “infant dose” for any drug ingested via breast milk, thus infant exposure to fluconazole would seem to be unacceptably high. However, the exposure via breast milk is still much lower (at normal maternal doses) than when fluconazole is administered in therapeutic doses directly to infants. Knowledge and application of this information allows drug exposure to be put into perspective.
Fluconazole is renally excreted, and infant clearance will be reduced compared with that of an adult. Infant exposure will be significantly increased if renal function is further compromised (eg, if the baby is premature). Consequently, when high maternal doses of fluconazole are administered, or if infant renal function is compromised (or both), the weight- adjusted infant dose may be much higher than the 10% level and even exceed the infant therapeutic dose. The risk of adverse effects and toxicity may be increased in such situations.
- Carcas AJ, Abad-Santos F, de Rosendo JM, Frias J. Nimodipine transfer into human breast milk and cerebrospinal fluid. Ann Pharmacother 1996;30:148-50.
- Tonks AM. Nimodipine levels in breast milk. Aust N Z J Surg 1995;65:693-4.
- Force RW. Fluconazole concentrations in breast milk. Pediatr Infect Dis J 1995;14:235-6.