FDA Updates Labels for Pregnant and Breastfeeding Women

Stephanie Cajigal; Melissa S. Tassinari, PhD; Jeanine Best, MSN, RN, PNP


January 09, 2015

Editorial Collaboration

Medscape &

Editor's Note: Last month, the US Food and Drug Administration (FDA) announced that it would be revamping its drug labeling rules to clarify risk for pregnant and breastfeeding patients. Some of the changes will include:

The "pregnancy," "labor and delivery," and "nursing mothers" subsections will be replaced with subsections titled "pregnancy," "lactation," and a new subsection titled "females and males of reproductive potential."

The pregnancy and lactation subsections will include information from available human and animal studies, known or potential maternal or fetal adverse reactions, and dose adjustments needed during pregnancy and the postpartum period.

The subsection on females and males of reproductive potential will include information on pregnancy testing, birth control, and the drug's possible effect on fertility when needed.

The rule goes into effect on June 30, 2015, but manufacturers of drugs approved before that date will have a few years to make the changes.

In this interview, FDA experts Melissa S. Tassinari, PhD, and Jeanine Best, MSN, RN, PNP, from the Center for Drug Evaluation and Research, Division of Pediatric and Maternal Health, explain how the new labeling will help providers make more informed decisions.

Medscape: What were some of the issues with the previous labeling system that led to the decision to create a new system?

Ms Best: The original system, developed in the late 1970s, classified the risk of using a drug during pregnancy by assigning a specific letter category. Unfortunately, as time went on, we saw that people were using the A, B, C, D, X system as a grading system and assumed an increasing risk from A to X when, in actuality, the categories were always defined by a risk-benefit decision based on the available data for each category. For all of these categories, it was intended that a decision about whether or not to treat a pregnant woman would involve consideration of the benefit for treatment versus the known risks to the embryo or fetus.

For example, a pregnancy category A meant that there were human data from adequate and well-controlled studies in pregnant women that did not show a risk to the developing embryo or fetus. Pregnancy category B meant that either animal data did not show a risk to the fetus and there are no adequate and well-controlled studies in pregnant women, or that animal data showed some adverse fetal harm but data from adequate and well-controlled studies in pregnant women did not show a risk to the fetus. Pregnancy category C was confusing to many people because this category was assigned when there were either no animal or human data so the risk was unknown, or when there were animal data showing fetal risk but no adequate and well-controlled studies in pregnant women; however, there may be benefit to using the drug to treat a pregnant woman. Pregnancy category D generally meant that available human data demonstrated a fetal risk; however, there was benefit to using the drug to treat a pregnant woman. Pregnancy category X meant that either there were data showing fetal risk (human or animal data) or the drug had no benefit for use in pregnancy pregnant woman.

Dr Tassinari: When drugs were assigned a pregnancy category X, it meant that they were generally contraindicated for use in pregnancy. This did not make sense for drugs that were given an X simply because they were not used in pregnancy. Additionally, pregnancy category C was commonly assigned at the time a drug was approved because there is very little, if any, human data in pregnancy so we rely almost entirely on animal data. An advantage to the new rule is that manufacturers are now required to update their labeling when human data are available. Each drug has its own individual set of characteristics based on its data, and it's almost impossible to convey the complexity of the risk determination by just a single letter.

Ms Best: And to add to that, the drugs used in the oncology setting almost always pose a dilemma because most of the oncology products are cytotoxic agents. Mechanistically, we know that these drugs have the potential to cause fetal harm; however, these are considered potentially lifesaving drugs that may have benefit when used in a pregnant woman.

Medscape: Can you give an example of a more commonly used drug that might have been misunderstood under the previous labeling system?

Dr Tassinari: Oral contraceptives are currently given a pregnancy category X because there is no benefit to a pregnant woman for using oral contraceptives during pregnancy. Fetal risk was demonstrated in animal studies; however, a large body of human data has failed to demonstrate a fetal risk. In the past, this caused great anxiety when women who were on oral contraceptives discovered that they were pregnant, and because the label said X, they thought their pregnancy was now at risk.

Medscape: How commonly do pregnant or lactating women take medications?

Dr Tassinari: We know that the percentage of women who may use four or more medications has more than doubled in the past 30 years in terms of the percentage of use.[1]

That is why we are working to make sure that women who are pregnant have an awareness about their medications, and that they talk to their healthcare provider about the most appropriate way to manage the disease or condition that they are taking the medicine for during pregnancy.

Ms Best: Women with chronic diseases can become pregnant. In certain conditions you can have better pregnancy outcomes if you treat the disease rather than take a woman off her medications during pregnancy.

Dr Tassinari: I think that an important, evolving message here is that sometimes women need to take medications during pregnancy. When that is the case, the labeling in the new format will provide appropriate and available information to have the important benefit/risk conversations between the pregnant woman and her health care provider.

Medscape: What was the rationale for requiring the inclusion of animal data in labeling?

Dr Tassinari: When drugs are approved for the first time, it is uncommon to have human data about pregnancy, so the risk determination is made almost entirely on animal data that come from standard, well-described studies.

Going forward, when there are adequate human data—either pre-approval or post-approval from publications, observational studies, or post-marketing studies—those data will be summarized and added to the existing labeling. It is very important to make an integrated assessment based on available animal, human, and pharmacologic data.

Medscape: Could the labeling changes delay drugs from entering the market?

Ms Best: No. Labeling changes resulting from the new rule should not delay drug approvals. Labeling is negotiated during the application review process, and the negotiation of these revised subsections is no different from the negotiation of other sections and subsections of labeling.