FDA Pregnancy Categories – Understanding Drug Safety in Pregnancy and Nursing

1. FDA Pregnancy Categories – Understanding Drug Safety in Pregnancy and Nursing Medicines for treating even simple conditions like a common cold or using chemicals in beauty treatments, like salicylic acid or topical retinoids, frequently become complicated during pregnancy due to the potential impact on the developing baby, especially when considering FDA pregnancy categories and drug safety in pregnancy and lactation. With about 6 million pregnancies in the US each year, of which 50% is unplanned, unintentional exposure to various drugs is common. Furthermore, a study found that 64% of pregnant women observed received a prescription medication. It is important to make informed choices for you and your baby’s health. The Food & Drug Administration (FDA), thus, provides a clinical guideline for the safety of medicines in pregnancy. FDA Pregnancy Category This has been in use since 1979 and is as follows: Category Definition Clinical Application Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in later trimester), and the possibility of fetal harm appears remote. The possibility of fetal harm appears remote. Extremely few drugs exist in this category (e.g. multiple vitamins). A

2. Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters). If there is a clinical need for a drug in this category they are considered safe to use. Examples: acetaminophen, amoxicillin. B Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus. Pregnancy Category C is given to medicines that have not been studied in pregnant humans but that do appear to cause harm to the fetus in animal studies. These drugs should be given only if the potential benefit justifies the potential risk to the fetus. Examples: fluoroquinolones, gentamicin, saccharin, aspirin. C

3. There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk. They should only be used in pregnancy when the alternatives are worse. Examples: tetracyclines, ACE inhibitors, most antineoplastics. There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective.) D Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant. The risk of use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are, or may become pregnant. Examples: thalidomide, oral contraceptives, statins (e.g. Lipitor ®). X Source: – Drugs in Pregnancy and Lactation. 8th Ed. Briggs GG, Freeman RK, Yaffe SJ Editors. Wolters Kluwer Health. Philadelphia. 2008. Food and Drug Administration. Federal Register 1980;44:37434-67 Potential Pitfalls & Criticisms While seemingly simple and easy to use, this categorization by the FDA has its pitfalls and has seen some criticisms. ● Many drugs have not been studied enough to know if they are safe or not, resulting in ambiguity about their safety. ● The categorization does not consider the fetus’s gestational age and the drug’s effect at different trimesters of pregnancy.

4. ● There is a lack of information about the use of medication while lactating. ● FDA has yet to update categories as new data emerges. For example, they moved paroxetine (a medication for mental illness) to Category D because unpublished data showed a possible increase in cardiac abnormalities. When further studies showed a lack of association, they did not move paroxetine back to Category C. ● Lack of data on the effects of the drug on humans, resulting in an emphasis on animal experiment data. However, despite these pitfalls and criticism, this categorization remains a helpful tool for clinicians and patients to guide treatment while pregnant. Useful Online Tools ● FDA Medication Guide – Has over 900 pages of medications with an approved guide for each medication that details essential drug details like usage, dosage, side effects, and safety in pregnancy. – Enter the name of the medication in the search button to know more about it. ● DailyMed- National Library of Medicine – Information from medical labels of over 20,000 drugs companies submit to the FDA. ● CDC- Medicine & Pregnancy – User-friendly website from the CDC (Centers for Disease Control & Prevention) about safer medicine use in pregnancy. – Has guidelines and recommendations for the treatment of various health conditions while pregnant. ● Mothertobaby.org- Information about medication in pregnancy & lactation – Provides ‘evidence-based information about whether a prescribed treatment could affect their developing baby’. – The ‘Ask Our Experts’ free service lets you phone / text / chat / email an expert with questions about exposure during pregnancy or lactation. ● Pregnancy Exposure Registry – By sharing your experience with medicines, you can help gather data about drug safety. – You need not take any new medicine to be a part of this registry, which is interested only in the medicines you are already taking.

5. – The registry includes COVID-19 vaccines, which you can use to report adverse effects while pregnant. ● National Pregnancy Registry for Psychiatric Medicines – This registry is dedicated to and gathers information on the safety of psychiatric medicines taken during pregnancy. – Also open to individuals currently pregnant with a history of psychiatric illness but not on any medication. Warning! While it may seem easy to self-medicate based on this categorization, never do so and always consult with your healthcare provider, who is the best judge of what medication is suited for your complaints. Furthermore, your doctor will be aware of any recent changes regarding medication safety.