Drugs and the Breastfeeding Mother: A New Clinical Report

FDA on Medscape > FDA Expert Interview

Laurie Scudder, DNP, NP, Hari Cheryl Sachs, MD

Disclosures

October 29, 2013

Editor's Note:
Many breastfeeding women are advised to stop taking necessary medications or to discontinue nursing because of potential harmful effects on their infants. The reality is that few medications are contraindicated in breastfeeding mothers.

The American Academy of Pediatrics (AAP) has just released a new clinical report, The Transfer of Drugs and Therapeutics Into Human Breast Milk: An Update on Selected Topics, to provide guidance on drug exposure and reaffirm the recommendation that most medications and immunizations are safe during lactation. Medscape spoke with lead author and pediatrician Hari Cheryl Sachs, MD, the US Food and Drug Administration (FDA) liaison to the AAP Committee on Drugs, about the key recommendations from the report and resources to assist clinicians in obtaining current information on specific drugs to help guide their advice to breastfeeding women.

Medscape: The key message of this report is that although some drug classes should be avoided or at least used cautiously in lactating women after a careful risk/benefit assessment, many medications can and should be continued. When a healthy nursing mom presents to primary care with a common, mild illness -- such as bacterial sinusitis, migraine, intermittent asthma, or an allergic reaction -- that requires an anti-infective agent, a beta-agonist, an antihistamine, or a triptan, can providers feel comfortable treating this woman and encouraging her to continue nursing?

Dr. Sachs: As stated in the report, not all medications are present in breast milk in clinically significant levels or pose a risk to the nursing infant. The prescribing information (drug label) and LactMed (a drugs and lactation database, also available in a mobile app) will have the information to help a provider decide whether to use a drug in a lactating patient.

Medscape: The report points out that the age of the infant is an important factor in deciding how to treat a mother, because most adverse events associated with drug exposure through breast milk occur in infants younger than 2 months. What other infant factors should clinicians consider when deciding on treatment for a nursing mom?

Dr. Sachs: An important consideration for all drugs is related to the adverse-event profile and properties of the specific drug. Several excellent resources are available to inform clinicians about specific drugs, such as product labeling or LactMed. For example, the FDA recently approved newlabeling information for trimethoprim/sulfamethoxazole (Septra®), emphasizing the need for caution in administering this drug to nursing women, particularly if the infant is jaundiced, ill, stressed, or premature, because of the potential risk for bilirubin displacement and kernicterus.

Medscape: Depression and mood disorders are common in women of childbearing age, and the risks of not treating these women are potentially severe. Data on the long-term safety of psychoactive drugs are limited, yet the report does not recommend advising these women to stop breastfeeding.

Dr. Sachs: Caution is definitely warranted here. As stated in the report, the infant could potentially be exposed to clinically significant levels of these drugs, and the long-term effects are unknown. Decisions about breastfeeding for these patients should be evidence-based. The drug label and LactMed should be consulted for information on drugs that a clinician may be considering.

Medscape: What do you recommend for the care and monitoring of nursing infants whose mothers are being treated with an antidepressant, anxiolytic, or antipsychotic?

Dr. Sachs: Use of these products by nursing women should be discussed with the infant's healthcare provider. Adverse events as well as growth and development should be monitored in these infants. Any adverse events should be reported to the FDA's Adverse Event Reporting System.

Medscape: Treatment of pain is another subject discussed in detail in the report. What is recommended for short-term use in women whose pain is not controlled by over-the-counter analgesics?

Dr. Sachs: Caution is advised for nursing women using narcotic pain relievers because of the potential for adverse effects in nursing infants, and some are not recommended at all for use in nursing women because they are concentrated in breast milk.

Codeine has been associated with rare fatalities in nursing infants. In women with normal codeine metabolism, the amount of codeine (and its active metabolite, morphine) in breast milk is low and related to the dose. However, in ultra-rapid metabolizers, higher-than-expected concentrations of the active metabolite (morphine) may occur in breast milk, and potentially dangerous levels may be reached in breastfed infants.

Thus, the risk of infant exposure to codeine and morphine through breast milk should be weighed against the benefits of breastfeeding for both the mother and the baby. Close monitoring of mother/infant pairs is recommended when codeine is administered to a nursing woman. The lowest dose should be prescribed for the shortest period to achieve the desired clinical effect. Mothers using codeine should be informed about when to seek immediate medical care and how to identify the signs and symptoms of toxicity in their infants, such as drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone. Nursing mothers who are ultra-rapid metabolizers may also experience overdose symptoms, such as extreme sleepiness, confusion, or shallow breathing.

Of note, safety labeling changes for extended-release and long-acting opioid analgesics announced by the FDA in September will highlight the risk for neonatal opioid withdrawal syndrome (NOWS) in a boxed warning. Symptoms of NOWS may include poor feeding, rapid breathing, trembling, and excessive or high-pitched crying.

For more information on codeine and other treatment options, see the drug label and LactMed.

Medscape: The report reviewed agents that have been used to stimulate lactation, including dopamine antagonists, such as domperidone, and herbal products, such as fenugreek. What is the bottom line on these agents? Does any evidence support their use?

Dr. Sachs: The FDA issued a warning on domperidone. There is little evidence of benefit with domperidone, and safety information on many of these products is lacking. Nonpharmacologic methods of stimulating lactation are preferred. The report encourages breastfeeding mothers to discuss all products that they take, including herbal products, with their healthcare professionals.

Medscape: The report acknowledges that information in this area changes rapidly, making it impossible for written reports to keep pace with new developments. Drug labels will continue to be an essential source of information. Can you outline some of the key changes in the pregnancy and lactation sections of labeling?

Dr. Sachs: Under the proposed rule, the Pregnancy and Lactation subsections of labeling would each include 3 sections:Risk summary, Clinical considerations, and Data.

In the Pregnancy subsection, the Fetal Risk summary will provide a narrative description based on risk evaluations of human, animal, and pharmacologic data that describe the likelihood that a drug increases the risk for adverse developmental outcomes. The Fetal Risk summary replaces the current pregnancy letter categories (A, B, C, D, X). The Clinical considerations section is intended to further inform prescribing and risk/benefit counseling. Labor and delivery information, when available, will be incorporated into this section. Pregnancy registry information with contact information, when available, must be included in the pregnancy subsection. The Data section will provide a detailed overview of both the human and animal data used to inform the previous sections.

In the Lactation subsection, the Risk summary will summarize what is known and unknown about the amount of drug likely to be present in human milk and any potential effect on breastfeeding infants. The Clinical considerations section will include methods to minimize exposure when applicable, as well as information about monitoring the infant for toxicity or adverse effects. The Data section will provide a detailed overview of available human data used to inform the Risk summary and Clinical considerationssections.

Medscape: What are the best resources for a clinician who needs to access information about a particular pharmacologic agent quickly, in the middle of a busy clinical day?

Dr. Sachs: Drug labeling and LactMed, which I've noted several times, are important resources and are available online at:

• Drugs@FDA (the FDA's database of approved drugs);
• Daily Med (drug information, including FDA labels and package inserts);
• LactMed (drugs and lactation database); and
• LactMed App.

Editor's note: Medscape's Drugs, OTCs & Herbals provides rapid lookup.

Early Onset of Puberty in Girls Linked to Obesity

Medscape Medical News

Joanna Broder

November 04, 2013   Girls in the United States are entering puberty at younger ages than they have in the past, but investigators have not been able to pinpoint the cause. Now, a longitudinal study, published online November 4 in Pediatrics, suggests a higher body mass index (BMI) plays a role in earlier breast development in white, non-Hispanic girls.

"This study demonstrates earlier maturation in white non-Hispanic girls, with greater BMI linked as a major factor," write Frank Biro, MD, the study's lead author and the director of research for adolescent and transition medicine at Cincinnati Children's Hospital Medical Center in Ohio, and colleagues.

"This article adds to studies providing the unsettling findings that the age of onset of breast development, in synch with, though not entirely explained by, the 'obesity epidemic,' has continued to drop," writes Dr. Herman-Giddens, an adjunct professor with the Department of Maternal and Child Health at the Gillings School of Global Public Health, University of North Carolina, Chapel Hill.

The whole distribution of puberty timing has shifted to a younger age, note Dr. Frank and colleagues. The fact that girls are undergoing earlier maturation has important clinical ramifications. For example, girls who reach puberty earlier than their peers may be at increased risk for depression and low self-esteem and be more likely to engage in substance abuse and intercourse at an earlier age than girls who reach puberty later.

In addition, the ripple effects of early maturation extend into adulthood, the authors write, including increased risk of breast and ovarian cancers.

The researchers enrolled 1239 girls from Greater Cincinnati, New York City, and the San Francisco Bay Area. The girls were between the ages of 6 and 8 years at the time of enrollment. Trained clinicians examined the girls at regular intervals for 7 years from 2004 to 2011, assessing breast development through observation and palpitation. They then determined BMI percentiles and z scores, using the 2000 growth charts from the Centers for Disease Control and Prevention.

At baseline, 39% of the black girls had a BMI in the 85th percentile or higher, as did 44% of Hispanic girls, 26% of non-Hispanic white girls, and 12% of Asian girls.

The investigators found that the onset of breast development, as defined by reaching breast stage 2 or greater, differed by clinic site, race/ethnicity, and BMI at baseline.

The mean and median age breast development varied by race and ethnicity. Black girls started developing breasts at a median age of 8.8 years, whereas Hispanic, non-Hispanic white, and Asian girls did so at median ages of 9.3, 9.7, and 9.7 years, respectively.

When the investigators examined timing of breast development and BMI, they found that as the girls' BMI increased above the 50th percentile, the likelihood of earlier breast development increased, relative to girls with a BMI below the 50th percentile (P value for trend = .001). The researchers adjusted for race/ethnicity and site.

In addition, the authors found that the onset of breast development in white girls occurred at younger ages than reported in previous publications but that "black girls continue to experience breast development earlier than white girls." Much of the difference in timing of development in non-Hispanic white girls, between this study and previous ones, is likely a result of the higher BMIs in the current study population, the authors note.

The authors conclude that having a higher BMI is the strongest predictor of earlier onset of stage 2 breast development.

Dr. Herman-Giddens notes that our society may have to live with uncertainty as to what factor or combination of factors is causing girls to start puberty earlier than they did decades ago.

The obesity epidemic is an important factor in the decline in age of onset for puberty in girls, she writes, but she also notes that the study found that BMI accounted for 14.2% of the variance of all covariates in the researchers' model."

Although obesity is implicated as a 'prime driver,' factors involved in these secular changes are far more complex," she writes. "Extensive interacting variables are known to be associated with earlier development in addition to weight and genetics: certain intrauterine conditions and exposures, preschool high-meat diets, dairy products, low fiber intake, isoflavones, high-stress families, absent fathers, certain endocrine disruptors, the microbiome as it influences weight, epigenetics, light exposure, hormone-laced hair products, insulin resistance, activity level, geographical location, and others."

Pediatrics. Published online November 4, 2013.