In 2015, the U.S. Food and Drug Administration (FDA) proposed major revisions to prescription drug labeling — the Pregnancy and Lactation Labeling Rule or PLLR — in order to provide more accurate and helpful information on the effects of medications used during pregnancy and breastfeeding. The system used by the FDA for the last 30 years classifies the reproductive safety of medications using five risk categories (A, B, C, D and X) based on data derived from human and animal studies. While widely used to make decisions regarding the use of medications during pregnancy, many have criticized this system of classification, indicating that this type of drug labeling is often not helpful and, even worse, may be misleading.

An online survey, developed by the US Food and Drug Administration in collaboration with the American Academy of Allergy, Asthma & Immunology (AAAAI), was used to  investigate clinicians’ awareness of and use of the PLLR.

An online survey was developed by the US Food and Drug Administration in collaboration with the American Academy of Allergy, Asthma & Immunology (AAAAI) and conducted in 2018 with the hope of better understanding clinician use of the PLLR. 

This survey was sent out in 2018 to 1500 members of the AAAAI who were randomly selected to participate in the survey. Clinicians were asked whether they were aware of and if they used the PLLR; 184 (12%) completed the survey.

The findings of this study showed that only 46% of the clinicians were aware that the PLLR, which includes a narrative summary of risks, had replaced the previously used letter-based system of classification.  Although half of the clinicians were aware of the PLLR, almost all of them (95%) reported that they continued to use the previous system to guide the prescription of medications during pregnancy.  

Although this study was not carried out in psychiatric providers, I suspect that many providers in our field are not using the PLLR.  (There continue to be many patients who come in for consultations, wondering if there are any safer alternatives to the Category C medication they are currently taking.)  In this study, about half of the clinicians reported that the PLLR was too detailed and/or too unclear to use regularly.  

This is certainly understandable.  The letter-based system was brilliant in its simplicity.  If you are a busy clinician and a pregnant woman walks in with questions regarding her medications, you simply had to pop open a book or do a quick internet search to come up with some sort of roadmap.  It will be very difficult for clinicians to break away from this older system, especially when it means adopting a more time-consuming and complicated method of assessing risk.  

I would argue that any physician who treats women of child-bearing age, not just obstetricians, should consider the possibility of pregnancy when prescribing medications.  If possible, we should use medications for which there is adequate and reassuring reproductive safety information. When any new medication is prescribed, we should emphasize the importance of contraception and pregnancy planning and encourage women to discuss their plans prior to conception.  This is especially important when women are taking medications, like lithium and anticonvulsants such as valproic acid and topiramate, which carry teratogenic risk.  

The PLLR is a work in progress.  Hopefully the feedback from this survey and others to come will help the FDA to build a system of classifying the reproductive safety of medications that is accurate and clinically relevant, while at the same time being user-friendly.  

Ruta Nonacs, MD PhD

Namazy J, Chambers C, Sahin L, Johnson T, Dinatale M, Lappin B, Schatz M.  Clinicians’ Perspective of the New Pregnancy and Lactation Labeling Rule (PLLR): Results from an AAAAI/FDA Survey.  J Allergy Clin Immunol Pract. 2020 Feb 19.