The United States Food and Drug Administration (FDA) has changed and updated the drug labeling for pregnancy risk. This change will become effective on June 30, 2015, for drug applications submitted on or after this date. Applications for drugs approved from June 30, 2001, until the rule takes effect have 3 to 4 years to modify their labeling depending upon when the application to the FDA was approved.1 The current letter system will no longer be used.
The new labeling is based on providing information for counseling and decision making by the patient and healthcare providers and will rely less on simple categories that may be misleading to women, nurses, providers, and pharmacists. This information is important for nurses, as nurses provide much of the counseling for pregnant women in clinics, obstetrical triage settings, and labor units. Women who are pregnant or breastfeeding often look to nurses for advice and information.
The FDA initiated the original pregnancy risk categories for medications in response to the thalidomide tragedy in Europe in the early 1960s. Thalidomide was prescribed for pregnant women as a sleep aid and as a treatment of nausea and vomiting. Thalidomide caused phocomelia during fetal development, an unknown effect prior to the widespread use of the drug at the time. Phocomelia is the congenital absence or underdevelopment of the extremities. There were more than 8000 children born worldwide with phocomelia caused by the use of the drug during pregnancy.2 This tragedy alerted healthcare providers and FDA staff to the need for assessment of medications for fetal effects prior to the use of a particular drug in the United States.
After much discussion and input from physicians, pharmaceutical companies, scientists and researchers, and FDA staff, the pregnancy labeling regulations were instituted in 1979. The pregnancy labeling categories were developed as a guide for healthcare providers to assess the risks and benefits of a particular drug for a pregnant woman.2 This system uses 5 categories with labels A, B, C, D, and X (see Table 1).
During the time the category system was being developed, pregnant women were much less likely to use drugs during pregnancy. Pregnant women were younger and so thought to be healthier than the pregnant population today.3 In the United States, the average age at which women first get pregnant has risen, the number of pregnant women who have chronic illnesses has increased, and the use of both prescription drugs and over-the-counter medications by pregnant women has increased.3
As the use of prescription drugs by pregnant women has increased, it has become evident that the current classification system is oversimplistic and does not aid healthcare providers with decision making about these drugs during pregnancy. Providers, pharmacists, and patients commonly perceive the categories to be an indication of increasing risk.3 For example, category B is seen as a safer drug than category C. This is not necessarily true. The risk and benefit of the drug should still be carefully assessed and considered. More than 50% of prescription drugs available in the United States are category C, which essentially means that there is no research available on the effects of the drug on human fetuses.4 Categorizing drugs as category D or category X is based not only on the risk to the developing fetus but also on the utility of the drug to treat illness during pregnancy. Drugs in all of the categories do not present the same risk. Category X includes isotretinoin and oral contraceptives. Isotretinoin has demonstrated fetal teratogenicity; oral contraceptives have not been shown to cause fetal abnormalities early in pregnancy but simply have no therapeutic use to the pregnant woman.
Other concerns about the Pregnancy Category system include the absence of information for accidental exposure, lack of information about the timing of fetal exposures, and confusion about the use of animal studies when human studies are not available.2
The Teratology Society held an open meeting of its Public Affairs Committee in 1997 to generate public comment. The committee published an opinion that the categories are confusing and difficult for providers to use and should be immediately revised by the FDA.5 The FDA published a draft concept paper in 1999. The timeline leading to the current changes is delineated in Table 2.
The new labeling will include a summary of the risks of using a drug during pregnancy and lactation, a discussion of the data supporting this information, and relevant data to aid healthcare providers in decision making and counseling of pregnant and lactating women.1 The new labeling will eliminate the Labor and Delivery subsection and combine this information into the Pregnancy section. The labeling will also include information about prescribing drugs for males of reproductive age. The Nursing Mothers section will be renamed Lactation. Both sections will include data from studies. Human studies must precede animal studies. Studies with animals must include the species of animal and a comparison of the animal dose and the human dose equivalent.2
The format and overview of the information to be included in the revised labeling are listed in Table 3. Comparison of the 2 systems of labeling shows the utility of the new system and the lack of clarity of the previous system. The information given in the new system is not only longer and more technical but also more useful both for patient counseling and for the healthcare provider's understanding of the true risk and/or benefit of a drug. The information is streamlined in such a way that allows for ease of use and comprehension. Healthcare providers will not have to search various references and handbooks for data. The former system of letter demarcations was short but conveyed both false risk and false reassurance about drug categories and about individual drugs used during pregnancy.
Clinicians have been waiting years for the new system; it is a genuinely useful step in providing care to pregnant and breastfeeding women.
-Jackie Tillett, ND, CNM, FACNM
Clinical Professor
Department of Obstetrics and Gynecology
University of Wisconsin School of Medicine and Public Health
Madison, Wisconsin
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