Upcoming Changes in Pregnancy and Lactation Product Labeling

May 2015, Vol 3, No 5 - Inside Pharmacy
Ann Johnson, PharmD
In December 2014, the US Food and Drug Administration (FDA) published the Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling, better known as the Pregnancy and Lactation Labeling Rule (PLLR).1

Since the 1970s, prescription drugs have been categorized as A, B, C, D, or X, depending on their risk of use during pregnancy.2 Effective June 30, 2015, these letter designations will be replaced with the new labeling requirements.2

Labeling Changes Coming into Effect June 30, 2015

Manufacturers of prescription drug products approved after June 30, 2001, must revise their product labeling to comply with the new PLLR sections within 3 to 5 years, whereas manufacturers of products approved before June 30, 2001, are only required to remove the pregnancy category from their product labeling by June 30, 2018.2

This means that products approved prior to June 30, 2001, will not have any information regarding safety of use in pregnancy and lactation on their labels. For products approved after June 30, 2001, data for the labeling updates are expected to come from already conducted clinical studies and pregnancy exposure registries.3

Labeling for over-the-counter drugs will not change, because the new rules only apply to prescription products. Prescription products currently available will be revised during an implementation phase, and product applications submitted to the FDA for approval on or after June 30, 2015, will need to use the new formatting for pregnancy and lactation in their labeling.3

Changes to Drug Labeling Subsections

Currently, product labeling associated with pregnancy and nursing is available in 3 subsections of the prescribing information (PI), sections 8.1 to 8.3. The new labeling will comprise the same 3 subsections, but with different information. Sections 8.1 and 8.2 (Pregnancy, and Labor and Delivery, respectively) will be combined to create the new section 8.1 (Pregnancy). The current section 8.3 (Nursing Mothers) will be incorporated into the new section 8.2 (Lactation), along with new information about how drugs affect a mother’s milk supply. The new section 8.3 (Females and Males of Reproductive Potential) will contain information not previously required in a product’s PI, including the need for pregnancy testing and recommendations for contraception.1

According to the PLLR, each of the subsections will be required to have specific subheadings, when applicable.4 The PLLR provides a much more rigid structure for presenting information concerning drugs’ effects on pregnancy, lactation, and fertility than the old PIs did, and this should better equip pharmacists to counsel patients.

When applicable, section 8.1 will now include information on the drug’s pregnancy exposure registry. The section will also include contact details and information necessary for people interested in enrolling in, or obtaining more information about, the registry.4 Pregnancy exposure registries collect information from women who receive a medication during pregnancy and compare their information with that of women who have not taken that medication during pregnancy. Because clinical trials are not done on pregnant women, this enables manufacturers to collect more in-depth data about a drug postlaunch, to improve the quality of information available for patients and healthcare practitioners.

In the past, pregnancy registry information was not required to be included in a drug’s PI. Many drugs have scientifically acceptable pregnancy registries, including those used to treat cancer, asthma, epilepsy, human immunodeficiency virus (HIV), and multiple sclerosis, to name a few.5 If a pregnancy registry is available for a particular drug, the registry should also be mentioned in the Patient Counseling Information section of the PI, along with a reference to section 8.1, where the contact information necessary for enrollment is located.6

Although a pregnancy exposure registry is not required, a Risk Summary section describing the drug’s risk of adverse outcomes on fetal development is required under the PLLR. This information will be based on human, animal, and drug pharmacology data.6 The Clinical Considerations subheading will present information to aid in prescribing and risk–benefit counseling, when applicable. Areas covered may include disease-associated maternal or fetal risk, dose adjustments during and after pregnancy, maternal and fetal adverse effects, and labor or delivery information.6 Pharmacists may find this section most helpful for obtaining counseling tips for patient discussions.

The last subheading in section 8.1 (Data) will describe what data, if any, were used to substantiate the scientific information presented in the Risk Summary and Clinical Considerations sections. The information will be divided into 2 separate sections for human and animal data.6 Although retail pharmacists may be less interested in the data and clinical studies supporting the PI, clinicians and other healthcare professionals in research fields may find these sections especially helpful.

Historically, PIs have provided little data on the risk of taking a medication while breastfeeding. Although the PI may previously have included information on whether a drug was excreted into the breast milk, the effects of the drug on the child and on the mother’s milk production were seldom included. The new labeling will change that. Section 8.2 (Lactation) will provide a risk summary on the presence of a drug and/or its metabolites in milk, the effects on the child being breastfed, and effects on milk production. If applicable, clinical considerations on minimizing exposure and monitoring for adverse effects will also be included. The Data subsection will include the scientific basis for the data presented under the Risk Summary and Clinical Considerations sections.4

Because of the current emphasis on the importance of breastfeeding, these new data will prove extremely useful for pharmacists counseling patients. New mothers are often extremely vigilant in the care of their children and the risks of drug exposure, and this is one area in which pharmacists can be subject matter experts and provide an even higher level of patient care.

Many new drug products have stipulations surrounding contraception requirements and fertility side effects. Although these data may have previously been available in a Risk Evaluation and Mitigation Strategy program, the data were not required to be in the PI. Under the PLLR, if a product requires pregnancy testing, contraception use, or has an effect on fertility, the data will be included in section 8.3 (Females and Males of Reproductive Potential).4 This creates an excellent counseling opportunity for pharmacists to speak with patients about the correct dosing of oral contraceptives, and/or the importance of over-the-counter contraceptive agents.

Updated drug PIs in regard to pregnancy, lactation, and reproductive potential have been needed for a long time. Advocates have pleaded with the FDA to make these changes for the past decade. Although the single-letter pregnancy designations may have provided a quick guide for physicians and pharmacists, this methodology oversimplified the process. The majority of women will take ≥1 medication during their pregnancy; research has shown that approximately 5% of women will take drugs to treat hypertension alone during their pregnancy.7 Most physicians and pharmacists will recommend limiting medication use while pregnant, but for many women with chronic conditions such as depression, asthma, or diabetes, prescription use is unavoidable. Although physicians and pharmacists will now need to spend more time reading the pregnancy and lactation sections to better understand the risks certain drugs pose to the mother, fetus, and child, all parties will benefit from the increased availability of information.


  1. US Food and Drug Administration. Pregnancy and lactation labeling final rule. www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm093307.htm. Updated December 4, 2014. Accessed February 6, 2015.
  2. Traynor K. Changes coming to pregnancy labeling. Am J Health Syst Pharm. 2015;72:175-176.
  3. US Food and Drug Administration. Questions and answers on the pregnancy and lactation labeling rule. www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm093311.htm. Updated December 3, 2014. Accessed February 6, 2015.
  4. US Food and Drug Administration. Outline of Section 8.1-8.3 on drug labeling. www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm425415.htm. Updated December 3, 2014. Accessed February 6, 2015.
  5. US Food and Drug Administration. List of pregnancy exposure registries. www.fda.gov/ScienceResearch/SpecialTopics/WomensHealthResearch/ucm134848.htm. Updated February 5, 2015. Accessed February 6, 2015.
  6. US Department of Health & Human Services, US Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologic Evaluation and Research. Pregnancy, lactation, and reproductive potential: labeling for human prescription drug and biological products – content and format. www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM425398.pdf. Published December 2014. Accessed February 6, 2015.
  7. American Heart Association. More pregnant women taking high blood pressure drugs, yet safety unclear. http://newsroom.heart.org/news/more-pregnant-women-taking-high-238172. Published September 10, 2012. Accessed February 6, 2015.
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