Almost half of all women report using four or more medications (other than prenatal vitamins) during their pregnancy.1 In one study of eight US health maintenance organizations, 64% of the 152,531 pregnancies analyzed showed documentation of at least one prescription medication during pregnancy, with an average of two prescriptions.2 Once women are hospitalized for delivery, medications including analgesics/anesthetics, oxytocics, antibiotics, and antihypertensives form the basis of many of our interventions. Most of the time, these medications are used off-label, without supporting studies in pregnancy. Because of ethical, medicolegal, and fetal safety concerns regarding pregnant women, few pharmacokinetic, pharmacodynamic or clinical trials were conducted during pregnancy until the past decade. Toxicologists focused on fetal exposure, but, in the absence of evidence, few pharmacologists or obstetricians recognized that pregnancy itself was a “special population.” Pregnant women have a unique drug response to the classical formulation of ADME (which stands for “absorption, distribution, metabolism and excretion”), which differs significantly from the average adult male or nonpregnant female.
Extrapolation of pharmacokinetic data from drug studies largely conducted in nonpregnant subjects to pregnant women fails to account for the impact of physiologic and metabolic changes that occur during pregnancy. To optimally use medications in pregnancy, we need the information that comes from studying drugs in pregnant women.
Concerns about the lack of studies in pregnant women were addressed by both the US Food and Drug Administration (FDA) and the National Institutes of Health (NIH) in a series of conferences in the 1990s and early 2000s that led to a number of significant changes. A guidance for industry on the design and conduct of pharmacokinetic studies in pregnant women was published by the FDA in November 2004.3 In 2002, the FDA started requiring the pharmaceutical industry to establish postmarketing registries for drugs that can provide data to be used in the new labeling. After many years of review, the FDA introduced new pregnancy labeling in June 2015, which eliminates the old A, B, C, D, and X pregnancy categories.4 Instead, the new labeling provides descriptive summaries from animal and human data and a large section on clinical considerations to help guide the prescribing provider. In 2004, the NIH began funding an obstetrical pharmacology research network that has produced multiple pharmacokinetic studies with drugs we frequently use.
The 21st Century Cures Act, passed by Congress in December 2016, included a Task Force on Research Specific to Pregnant and Lactating Women to advise the Secretary of Health and Human Services regarding gaps in knowledge and research on safe and effective therapies for pregnant women and lactating women. A report will be submitted to the secretary in September 2018.
In this chapter, guidelines for commonly used medications in our hospitalist practice will be presented based on recommendations from the American College of Obstetricians and Gynecologists (ACOG), other societies, and the research literature. When pharmacokinetic ...