USA Drug Categories
- 1 USA FDA Fetal Risk Categories
- 2 Some Recent Findings
- 3 FDA History
- 4 FDA Pregnancy and Lactation Labeling Rule
- 5 Pregnancy Exposure Registry
- 6 Pregnancy Risk Summary
- 7 Females and Males of Reproductive Potential
- 8 Anesthetics
- 9 References
- 10 External Links
- 11 Terms
- 12 Glossary Links
USA FDA Fetal Risk Categories
In the United States the government Food and Drug Administration (FDA) historically (before 2015) established the drug labelling classes (A, B, C, D, and X) to define their safety. Since 2015 this drug classification has been replaced with the "FDA Pregnancy and Lactation Labeling Rule" (PLLR). As well as removing the previous letter classes it has added a new category of #Females and Males of Reproductive Potential.
A 2011 study of USA data from 1976-2008 has shown:
- 6 million pregnancies every year
- 50% of pregnant women reported taking at least one medication
- Pregnant women take an average of 2.6 medications at any time during pregnancy
- First trimester use of prescription medications has increased by more than 60%
- Use of 4 or more medications in the first trimester has tripled (9.9% to 27.6%)
- Small percentage of drugs contraindicated for use in pregnancy or while breast feeding
- contraindicated example include - isotretinoin, mycophenolates
- Drugs Links: Australian Drug Categories | USA Drug Categories | Human Abnormal Development | BGD Tutorial
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Yoel Toledano, Eran Hadar, Moshe Hod Pharmacotherapy for Hyperglycemia in Pregnancy- The New Insulins. Diabetes Res. Clin. Pract.: 2018; PubMed 29730391
Musaed Mohammed Alsebayel, Faisal Abdulrahman Abaalkhail, Faisal Mohammed Alsebayel, Dema A Alissa, Ahmed Hamdan Al-Jedai, Hussien Elsiesy Congenital Esophageal Atresia and Microtia in a Newborn Secondary to Mycophenolate Mofetil Exposure During Pregnancy: A Case Report and Review of the Literature. Am J Case Rep: 2018, 19;523-526 PubMed 29720579
Mary Regina Boland, Fernanda Polubriaginof, Nicholas P Tatonetti Development of A Machine Learning Algorithm to Classify Drugs Of Unknown Fetal Effect. Sci Rep: 2017, 7(1);12839 PubMed 28993650
Fantahun Molla, Admassu Assen, Solomon Abrha, Birhanetensay Masresha, Arega Gashaw, Abrham Wondimu, Yared Belete, Wondim Melkam Prescription drug use during pregnancy in Southern Tigray region, North Ethiopia. BMC Pregnancy Childbirth: 2017, 17(1);170 PubMed 28583106
Naichaya Chamroonkul, Teerha Piratvisuth Hepatitis B During Pregnancy in Endemic Areas: Screening, Treatment, and Prevention of Mother-to-Child Transmission. Paediatr Drugs: 2017; PubMed 28434087
Bonnie L Bermas, Melissa Tassinari, Megan Clowse, Eliza Chakravarty The new FDA labeling rule: impact on prescribing rheumatological medications during pregnancy. Rheumatology (Oxford): 2018, 57(suppl_5);v2-v8 PubMed 30137587
Mary Lindsey Hedgepeth Kennedy Medication management of bipolar disorder during the reproductive years. Ment Health Clin: 2017, 7(6);255-261 PubMed 29955531
Paul Barrow Review of embryo-fetal developmental toxicity studies performed for pharmaceuticals approved by FDA in 2016 and 2017. Reprod. Toxicol.: 2018; PubMed 29660390
Mary C Brucker, Tekoa L King The 2015 US Food and Drug Administration Pregnancy and Lactation Labeling Rule. J Midwifery Womens Health: 2017; PubMed 28556499
|US FDA Historic Background|
|1906||Food and Drugs Act is passed by Congress and prohibits interstate transportation of misbranded or adulterated foods, drinks, and drugs.|
|1927||Food and Drug Administration Agency is formed and given authority to enforce the Food and Drugs Act.|
|1938||Federal Food, Drug, and Cosmetic (FDC) Act is passed, requiring all drugs to have demonstrated safety prior to marketing.|
|1951||Durham-Humphrey Amendment established the category of prescription drugs and gave the FDA the power to determine if a drug should be prescription-only or over-the-counter.|
|1962||Kefauver-Harris Amendment passed after thalidomide was found to cause birth defects. It requires drug manufacturers to provide stronger evidence of safety and effectiveness prior to FDA approval for marketing.|
|1966||FDA issued requirement for animal studies referred to as “3-Segment Studies” to evaluate safety of drugs. The studies should be designed to address 1) fertility, 2) in utero development, and 3) perinatal and postnatal effects.|
|1970||FDA requires first package insert for women using oral contraceptives.|
|1979||As published in 1980, FDA establishes the ABCDX pregnancy risk categories and requires the packaging label to include one of these categories.|
|1993||FDA revises a policy that excluded women of childbearing potential from being participants in drug trials and requires improved assessments of medication responses specific to gender.|
|2007||New regulations are passed that require all studies of drugs that involve human participants to register with ClinicalTrials.gov.; some drugs to conduct postapproval studies or have a risk evaluation and mitigation strategy to monitor the drug once it is marketed; and package inserts to include contact information for reporting adverse reactions.|
|2008||FDA proposes changing the pregnancy labeling categories.|
|2015||Content and Format of Labeling for Human Prescription Drug and Biologic Products; Requirements for Pregnancy and Lactation Labeling (Final rule 79, FR 72064) is passed and requires the removal of the ABCDX labels from all prescription and biologic product labels and new requirements to include narrative descriptions.|
|Table historic data|
|US FDA - Historic Drug Categories (pre-2015)|
FDA Pregnancy and Lactation Labeling Rule
- "The PLLR requires changes to the content and format for information presented in prescription drug labeling in the Physician Labeling Rule (PLR) format to assist health care providers in assessing benefit versus risk and in subsequent counseling of pregnant women and nursing mothers who need to take medication, thus allowing them to make informed and educated decisions for themselves and their children. The PLLR removes pregnancy letter categories – A, B, C, D and X. The PLLR also requires the label to be updated when information becomes outdated."
- Links: Final Rule
Pregnancy Exposure Registry
The USA has is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to drugs (by trade name) during pregnancy. The information below is extracted from, and not a complete summary of, PLLR requirements.
Pregnancy Risk Summary
Drugs with systemic absorption
- When use of a drug is contraindicated during pregnancy, that information must be stated first in the Risk Summary
- Risk statement based on human data
- Risk statement based on animal data
- Risk statement based on pharmacology
- Background risk information in general population
- Background risk information in disease population
Risk Based on Animal Data
Systemic drug absorption
There are no adequate and well-controlled studies of [TRADENAME] in pregnant women. The limited available information on [TRADENAME] use during pregnancy is not sufficient to inform a drug-associated risk of major birth defects or miscarriage. In animal reproduction studies, oral administration of [drug name] to pregnant rats and rabbits during the period of organogenesis at doses up to 40 and 20 times the maximum recommended human dose (MRHD), respectively, resulted in decreased fetal body weight gain and delayed skeletal ossification but no teratogenic effects were observed. Decreased fetal body weight and delayed skeletal ossification were not observed at doses up to 10 and 5 times the MRHD in rats and rabbits, respectively [see Data].
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15- 20%, respectively.
Pregnancy Clinical Considerations
Clinical Considerations (five optional subheadings)
- Disease-Associated Maternal and/or Embryo/Fetal Risk
- Dose Adjustments During Pregnancy and the Post- Partum Period
- Maternal Adverse Reactions
- Fetal/Neonatal Adverse Reactions
- Labor or Delivery
Lactation Risk Summary
Systemic drug absorption
- Presence of drug in milk (if unknown, must state so)
- Concentration in milk
- Actual or estimated infant daily dose
- Effects of drug on the breastfed infant (if unknown, must state so)
- Effects of the drug on milk production (if unknown, must state so)
- Risk/Benefit Statement
Females and Males of Reproductive Potential
Include when there are requirements or recommendations for pregnancy testing and/or contraception and/or when human and/or animal data suggest drug effects on fertility.
- Pregnancy Testing
Example of Labelling
Based on its mechanism of action, TRADENAME can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Female patients of reproductive potential should have a negative pregnancy test ...
Advise female patients of reproductive potential to use effective contraception during treatment and for at least 2 weeks after the last dose of TRADENAME. Advise patients that TRADENAME can reduce the effectiveness of oral contraceptives and to use alternative effective contraception during treatment with TRADENAME [see Warnings and Precautions (5.x), Drug Interactions (7.x), Clinical Pharmacology (12.x)].
Decreased fertility and ovarian toxicity were observed in female rats treated with DRUGNAME. Advise female patients of reproductive potential ...
Effects on spermatogenesis have been observed in animals treated with DRUGNAME. Advise male patients of the potential risk...
FDA September 2014 - Discussion - anesthetic drugs to infants and young children
- Pernia S & DeMaagd G. (2016). The New Pregnancy and Lactation Labeling Rule. P T , 41, 713-715. PMID: 27904304
- Mitchell AA, Gilboa SM, Werler MM, Kelley KE, Louik C & Hernández-Díaz S. (2011). Medication use during pregnancy, with particular focus on prescription drugs: 1976-2008. Am. J. Obstet. Gynecol. , 205, 51.e1-8. PMID: 21514558 DOI.
- Leda L Ramoz, Nima M Patel-Shori Recent changes in pregnancy and lactation labeling: retirement of risk categories. Pharmacotherapy: 2014, 34(4);389-95 PubMed 24390829
- Michael Levine, Ayrn D O'Connor Obstetric toxicology: teratogens. Emerg. Med. Clin. North Am.: 2012, 30(4);977-90 PubMed 23137407
- Brucker MC & King TL. (2017). The 2015 US Food and Drug Administration Pregnancy and Lactation Labeling Rule. J Midwifery Womens Health , 62, 308-316. PMID: 28556499 DOI.
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- FDA Pregnancy and Lactation Labeling Rule
- U.S. Food and Drug Administration FDA
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Cite this page: Hill, M.A. (2018, November 15) Embryology USA Drug Categories. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/USA_Drug_Categories
- © Dr Mark Hill 2018, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G