Healthcare Providers’ Use of a Concise Summary to Prescribe for Lactating Patients

Background

Prescribing information (PI) included in prescription drug labeling is FDA’s primary tool for communicating a summary of the essential scientific information needed for the safe and effective use of a prescription drug to healthcare providers (HCPs), including use in pregnant and lactating individuals. Most breastfeeding individuals take at least one prescription drug despite a lack of safety data for many drugs used during lactation. Without lactation information in the drug labeling, HCPs may instead rely on other sources to inform prescribing or clinical decision-making for breastfeeding individuals.

To assist HCPs’ clinical decision-making, FDA published the Pregnancy and Lactation Labeling Rule (PLLR) in 2015 to improve how PI describes the benefits and risks of using a drug during lactation. Specifically, the PLLR replaced the former Nursing Mothers subsection of drug labeling with a new Lactation subsection (subsection 8.2) that includes a narrative of available human or animal data about using the drug while breastfeeding, such as the amount of drug in breast milk and potential effects on the breastfed infant and milk production.

In PI, there is a balance between providing relevant information necessary for clinical decision-making and being concise. This is particularly evident for lactation data, where animal data may be available, but clinical (human) lactation data are limited or absent. A previous research study, which involved a collaboration between CDER and outside researchers, assessed how HCPs have adapted to the new labeling format and revealed that the narrative summary may be too detailed to meet HCP needs for clinical decision-making.

Building upon those findings, CDER collaborated with the Center for Biologics Evaluation and Research and outside researchers and conducted a study¹ to explore if adding a concise summary of risk information would more succinctly communicate drug safety information to busy HCPs, and, in combination with the Lactation subsection narrative, support HCP clinical decision-making for lactating patients.

Methods

Twenty-five moderated, online focus groups lasting 75 minutes each were conducted with 113 HCPs, (e.g., pediatricians, family medicine physicians, specialists, pharmacists) to explore the risk communication effectiveness of adding a concise summary to the narrative information that is already included under the “Risk Summary”, “Clinical Considerations” and “Data” headings within the Lactation subsection of the PI (Figure 1). HCPs were recruited for demographic diversity, years of practice, practice location, and practice setting. 

Figure 1: A concise summary was added to the narrative information that is already included under the “Risk Summary”, “Clinical Considerations” and “Data” headings within the Lactation subsection of the PI

Fictitious examples of labeling from the Lactation subsection were created for four prescription drugs, including one vaccine (Table 1). Each example began with a concise summary followed by a narrative section describing the drug's potential risks. The concise summary consisted of a bolded and underlined “Statement of Known Risks”, bullet points summarizing available study findings and potential adverse reactions, and recommendations for risk mitigation.

Table 1. Detailed Content of Labeling Examples

Drug Name	Indication	Infographic Headline	Human Data	Animal Data
DRUGLME	Rheumatoid Arthritis	“Safety concerns have been identified”	No data on presence in human milk, effects on breastfed infants, or milk production Serious adverse reactions in treated adults (e.g., risk of serious infections)	Concentrations in animal milk 3x higher relative to maternal serum
DRUGVWX	Major Depressive Disorder	“Potential safety concerns have been identified”	Small study (N=20) of lactating mothers Guidance to monitor exposed infants for agitation, irritability, poor feeding and poor weight gain.	None reported
VACCINEIJK	Prevention of Measles, Mumps and Rubella	“Potential safety concerns have been identified”	Studies of lactating women vaccinated with live attenuated rubella vaccine Reports of viral transmission to breastfed infants Guidance to monitor breastfed infants for adverse effects	None reported
DRUGXYZ	Bile Acid Syntheses Disorders due to Single Enzyme Defects	“No safety concerns have been identified”	None reported Guidance that cholic acid is normally present in healthy mothers and infants, and that mothers who take drug are not expected to have higher levels	None reported

Table 1. Each healthcare provider was asked to review detailed content from the PI, including information about the drug’s indication, the infographic headline and information regarding human and/or animal data.

In each group, the moderator asked about the HCPs’ preferred information sources regarding prescription drug safety for lactating patients. The moderator also explored participants’ knowledge about PLLR-related changes to the Lactation subsection of the PI. Based on a predetermined schedule, each group reviewed three labeling examples during each focus group session, followed by the moderator asking the HCPs about the usefulness of the prescribing or counseling information on the drug for breastfeeding individuals.

Participants were also asked to provide additional feedback about each concise summary, the effectiveness of risk communication, and the quality and usefulness of available data.

Results

Very few participants were aware of the PLLR updates to the Lactation subsection in labeling. Most participants said they were likely unaware of the changes because they did not typically rely on or consult the PI to obtain drug safety information for lactation. Participants were more likely to review summaries and recommendations from apps, websites and databases (e.g., LactMed, UpToDate), or to consult with colleagues. Several noted that these resources are typically more accessible to them, and concisely convey relevant information and clinical recommendations, which is particularly helpful during a time-limited patient encounter. When they consulted the PI, it was usually to conduct research outside of patient encounters. 

Three different concise summary headlines were used in the fictitious examples:

• Concise summary headline 1: “Safety concerns have been identified”

Overall, participants perceived the format as user-friendly, including the bullet points summarizing the drug's risks in both animals and humans. The headline was perceived to help with fast clinical decision-making and most participants said the headline was a major reason they would not prescribe the drug. The statements of risk reinforced that a breastfeeding individual should not use this drug. 

However, some participants stated that information under the “Risk Summary” and “Data” headings was too limited regarding the drug's risks to the breastfeeding infant, and thus the concise summary was less useful for clinical decision-making. Some participants doubted the drug was as risky as the concise summary suggested.

• Concise summary headline 2: “Potential safety concerns have been identified” 

Because the concise summary warned of potential safety issues and adverse reactions for the breastfeeding infant, several participants said they would not prescribe the drug to breastfeeding individuals.

However, after reading the findings from one small human study under the “Data” heading, most participants said they would likely make an individual benefit-risk assessment rather than completely dismiss use of the drug. Many pharmacists said they would either contact the prescriber or counsel the patient to do so to learn about other treatment options. Yet a few HCPs were more willing to prescribe the drug, noting that the potential adverse effects described in the concise summary are commonly found in other drugs. 

• Concise summary headline 2 (vaccine): “Potential safety concerns have been identified”

Several participants except for pediatricians said that they would either not prescribe the vaccine or would counsel breastfeeding individuals against vaccination because the concise summary indicated reports of viral transmission to infants. However, even after reading the narrative in the “Risk Summary,” some participants still felt as if they did not have enough information to help with clinical decision-making.

• Concise summary headline 3: “No safety concerns have been identified”

Most participants said they would support using the drug based on the concise summary headline, while others said the lack of study data described in the concise summary was not reassuring. After reading the narrative, however, several participants said the justification for “no safety concerns identified,” despite the lack of study data, affirmed their decision to prescribe/counsel breastfeeding individuals to use this drug.

Discussion

These study findings reinforce that HCPs prefer and typically use easily accessible and concise summaries of lactation information. However, while many HCPs reported reaching an initial prescribing/counseling decision based solely on the concise summary, many modified that decision after reviewing the narrative details under the other headings in the labeling and gaining a better understanding of available study data. This led to HCPs being reluctant to make a clinical decision based on the concise summary without considering the information in the narrative.  

Results of the study indicate the need to improve the mechanism of communication about the safety of drugs for breastfeeding individuals to meet the needs of time-constrained HCPs. Although concise summaries of risk information may help facilitate this communication, the information could be re-phrased to encourage HCPs to read the full narrative content to understand the details of the available safety data and the clinical information that may be lacking.

In the absence of robust clinical data or clear safety findings, a more detailed benefit-risk discussion with the breastfeeding individual should be considered to discuss the limitations of what is known and to determine whether to continue a drug during lactation.

One limitation of this study is that participants did not have access to the full PI for each example, which might have provided additional context for clinical decision-making (e.g., including benefits of using the drug for the disease/condition, other risks of using the drug).  Another limitation is that the review of the PI for the study included the use of fictitious examples and may not reflect the HCP’s clinical decision-making behavior in an actual patient encounter.

This research advances CDER’s efforts to understand how HCPs interpret the Lactation subsection of the PI and how the PI can be improved to better communicate information to HCPs about the safety of prescription drugs used during lactation.

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¹ Koenig, T, Robins, C, Darby Lipman, P, Dinatale, M, Johnson, T, Sahin, L, Roca, C, Limpert, J, Baisden, K, Mulugeta, Y, Yao, L, Jennings, KA, Alimchandani, M, Everett, D, Gassman, A, Chang, C, Ellis, C, Pfuma Fletcher, E, & Samuels, S, 2024, Healthcare providers' use of a concise summary to prescribe for lactating patients. Res Social Adm Pharm, 20(5), 531–538. doi.org/10.1016/j.sapharm.2024.02.004