Joanna M. Pangilinan, PharmD
How is drug safety during pregnancy determined in the absence of definitive evidence, and what are the best resources for clinicians and women?
Response from Joanna M. Pangilinan, PharmD
Pharmacist, Department of Pharmacy, University of Michigan, Ann Arbor
You may be surprised how common it is for women to take medications during pregnancy. Mitchell and colleagues found that over 70% of women take at least 1 over-the-counter (OTC) or prescription medication during the first trimester of pregnancy, and about 50% take at least 1 prescription medication during pregnancy. Over the past 3 decades, medication administration during the first trimester has increased dramatically: Use of 4 or more medications has tripled, and use of prescription medications has increased over 60%.[1,2]
Determination of fetal risk associated with medication use can be complex. Even with available data from human and animal studies, case reports, postmarketing surveillance, and voluntary reporting systems, clinical information often is lacking. Adam and colleagues found that the fetal risk of over 95% of medications approved in the past 10 years, if taken during pregnancy, was "undetermined."
Some of the factors that influence the amount of fetal exposure to medications include maternal drug pharmacokinetics, drug pharmacology, active transport of drug with respect to placental circulation, and fetal clearance. Consequences of drug exposure and fetal risk may depend on embryonic state; drug use during the first trimester, the period of organogenesis, is potentially the most teratogenic.
Although prescription and OTC medications are tested for general safety before approval, most drug trials, with the exception of those for conditions specific to pregnancy, actively exclude pregnant women and remove women from investigation if pregnancy occurs. Testing on pregnant animals may be done for some medications, but these results may not always be relatable to human processes and development. Thus, information regarding the safety of prescription and OTC medication use on the growing fetus is sparse, particularly for drugs that are newly available on the market. In addition, animal testing may not be performed on OTC medications or dietary supplements, rendering safety determinations even more challenging for such agents. Women should be counseled that safety information and general guidance regarding OTC medication use during pregnancy can be found on the Drug Facts label.
Clinicians should consult many sources when evaluating the safety of medication use during preconception and pregnancy. Most clinicians are probably familiar with the fetal risk categories (A, B, C, D, and X) developed by the US Food and Drug Administration (FDA).