Pregnant and nursing patients benefit from ‘ambitious’ changes to drug labeling for safety
FDA’s new system improves on the limited utility of the ‘A-B-C-D-X’ scheme
Data need to be understandable to health care providers across disciplines and to patients with varying levels of education for the label to have a meaningful impact on clinical care.
As noted, there is no mandate for funding the meticulous pharmacovigilance required to provide definitive data for labeling. It is unclear if the potential benefits of the new labeling can be reaped without adequate financing of the pharmacovigilance mechanisms required to inform patients adequately.
Role of pregnancy registries
Over the past 2 decades, pregnancy registries have emerged as a rapid, systematic means of collecting important reproductive safety data on the risk for major malformations after prenatal exposure to a medication or a class of medications.5,6 Such registries enhance the rigor of available cohort studies and other analyses of reproductive safety data that have been derived from large administrative databases.
NPRAA and NPRAD. Recently, the National Pregnancy Registry for Atypical Antipsychotics (NPRAA) and the National Pregnancy Registry for Antidepressants (NPRAD) were established in an effort to obtain reproductive safety data about fetal exposure to second-generation antipsychotics (SGAs) and to newer antidepressants.7 Based at Massachusetts General Hospital in Boston, NPRAA and NPRAD systematically and prospectively evaluate the risk of malformations among infants who have been exposed in utero to an SGA or an antidepressant.
The structure of both registries are the same, modeled after the North American Antiepileptic Drug Registry.5,8 Data are collected prospectively from pregnant women, age 18 to 45, by means of 3 telephone interviews conducted proximate to enrollment, at 7 months’ gestation, and at 2 or 3 months’ postpartum.
Participants include (1) pregnant women who have a history of fetal exposure to an SGA or an antidepressant, or both, and (2) a comparison group of non-exposed pregnant women who have a history of a psychiatric illness. Authorization for release of medical records is obtained for obstetric care, labor and delivery, and neonatal care (≤6 months of age).
Information on the presence of major malformations is abstracted from the medical record, along with other data on neonatal and maternal health outcomes. Identified cases of a congenital malformation are sent to a dysmorphologist, who has been blinded to drug exposure, for final adjudication. Release of findings is dictated by a governing Scientific Advisory Board.
Results so far. Results are available from the NPRAA.9 As of December 2014, 487 women were enrolled: 353 who used an SGA and 134 comparison women. Medical records were obtained for 82.2% of participants. A total of 303 women completed the study and were eligible for inclusion in the analysis. Findings include:
- Of 214 live births with first-trimester exposure to an SGA, 3 major malformations were confirmed. In the control group (n = 89), 1 major malformation was confirmed
- The absolute risk of a major malformation was 1.4% for an exposed infant and 1.1% for an unexposed infant
- The odds ratio for a major malformation, comparing exposed infants with unexposed infants, was 1.25 (95% CI, 0.13–12.19).
It is reasonable, therefore, to conclude that, as a class, SGAs are not major teratogens. Although the confidence intervals around the odds ratio estimate remain wide, with the probability for change over the course of the study, it is unlikely that risk will rise to the level of known major teratogens, such as valproate and thalidomide.10,11
Help with decision-making
Given recent FDA guidance about the importance of pregnancy registries (www.fda.gov/pregnancyregistries), such carefully collected data might help clinicians and patients make informed choices about treatment. Future efforts of NPRAA and NPRAD will focus on sustaining growth in enrollment of participants so that the reproductive safety of SGAs and newer antidepressants can be delineated more clearly.
Last, you can refer potential participants to NPRAA and NPRAD by calling 1-866-961-2388. More information is available at www.womensmentalhealth.org.
