Am Fam Physician. 2003 Jun 15;67(12):2476-2478.
In this issue of American Family Physician, Black and Hill1 review the safety profiles of many over-the-counter (OTC) medications in pregnancy. This is important considering the approximately 6 million pregnancies that occur in the United States annually,2 and it is not unusual for women to take medications during pregnancy or to become pregnant while on therapy. In one survey,3 more than 80 percent of pregnant women used a medication (excluding vitamins and minerals), with approximately 30 percent using more than four drugs. During the past 25 years, the average number of drugs taken during pregnancy has increased from 1.7 to 2.9 products. Six of the top 10 drugs used were OTC products.3
Prescribing medications for pregnant patients can be extremely challenging for any physician. Compared with other areas of medicine, in which data are abundant, studies and data involving pregnant women and medication use are negligible. Several important factors lay the foundation for making prescribing decisions for pregnant patients.4 It is critical to assess each patient's understanding of her disease, including the risks of lack of treatment and the possibility of an adverse pregnancy outcome related to the disease. It is equally important to assess each patient's need for certainty about the risks of medications to the fetus. Physicians also must understand each patient's tolerance of possible adverse pregnancy outcomes, including her knowledge of the overall background rate of developmental abnormalities. Finally, physicians must understand their own risk tolerance and need for certainty.
Since the thalidomide tragedy in the 1960s, women of childbearing age and their physicians have tended to greatly overestimate the likelihood that drugs cause birth defects.5 Unfortunately, because of this concern, pregnant women frequently are treated inappropriately or, worse, not treated at all for serious medical conditions. Another tragic consequence is that women decide to terminate their pregnancy because of the misguided belief that a medication they took will cause birth defects in their infants. Physicians and pharmaceutical companies also may encourage pregnancy termination because of their unrealistic perception of risk or because of fear of litigation.6
Black and Hill1 recommend that patients consult health care professionals before taking any medications during pregnancy. Most prescription drug labeling advises use of a product during pregnancy “only if the potential benefit justifies the potential risk to the fetus,” while in most cases OTC product packaging is required to include the statement,“If pregnant or breastfeeding, ask a health professional before use.” Where can family physicians look for information to make a rational clinical assessment of benefit or risk to their pregnant patients?
The official drug labeling (or package inserts), also published in the Physicians' Desk Reference, is one source of information, but rarely provides up-to-date information regarding teratogenic risks in human pregnancies. Health care professionals may not be aware of the multiple other resources available that can assist in assessing reproductive toxicities from drug exposures. For example, the online REPRORISK system, which is available from Micromedex, contains four teratogen information databases: REPROTEXT, REPROTOX (www.reprotox.org), Shepard's Catalog of Teratogenic Agents,7 and Teratogen Information System (TERIS).8 These periodically updated, scientifically reviewed resources critically evaluate the literature regarding drug exposures in human and animal pregnancies.
Other sources of information include the more than 20 comprehensive multidisciplinary Teratogen Information Services located in the United States and Canada, which provide patient counseling and risk assessments regarding potential teratogenic exposures (www.otispregnancy.org). Many Teratogen Information Services, such as Motherisk (www.motherisk.org), employ genetic counselors who are excellent resources for pre- and postconception counseling. The National Society of Genetic Counselors (www.nsgc.org) also can locate genetic counselors in most geographic regions.
The availability of up-to-date, factual information is imperative to providing good health care for pregnant women and their developing infants. The U.S. Food and Drug Administration (FDA) approves both prescription and OTC medications and regulates the information contained in product labeling. Current FDA regulations, promulgated in 1979, require labeling a prescription medication to contain a pregnancy subsection, which includes a pregnancy letter category (A, B, C, D, or X) that addresses fetal risk of developmental abnormalities or, for categories D and X, addresses risk weighed against potential benefit. The FDA recognizes that these categories can be misleading and the pregnancy subsection is inadequate for prescribing drugs to pregnant women or for counseling about fetal risks.
The FDA Pregnancy Labeling Task Force is working to improve the quantity and quality of data available on the use of medications during pregnancy. The task force also is in the process of revising the pregnancy labeling regulations to delete the pregnancy categories scheme and promote more useful clinical information in a narrative format.9
Kathleen Uhl, M.D., is medical team leader at the U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Pregnancy Labeling Task Force, Rockville, Md.
Dianne L. Kennedy, M.P.H., R.Ph., is program manager at the U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Pregnancy Labeling Task Force.
Sandra L. Kweder, M.D., is deputy director at the U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs.
Address correspondence to Kathleen Uhl, M.D., U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Pregnancy Labeling Task Force, 1351 Rockville Pike (HFD-020), Rockville, MD 20852 [e-mail: email@example.com]. Reprints are not available from the authors.
1. Black RA, Hill DA. Over-the-counter medications in pregnancy. Am Fam Physician. 2003;67:2517–24.
2. Martin JA, Hamilton BE, Ventura SJ, Menacker F, Park MM. Births: final data for 2000. Natl Vital Stat Rep. 2002;50:1–101.
3. Mitchell AA, Hernández-Díaz S, Louik C, Werler MM. Medication use in pregnancy: 1976–2000. Pharmacoepidemiol Drug Safety. 2001;10:S146.
4. Kweder SL, Lee RV. Prescribing for the pregnant patient. In: Lee RV, Rosene-Montella K, Barbour LA, Gerner PR, Keely E, eds. Medical care of the pregnant patient. Philadelphia: American College of Physicians, 2000:69–86.
5. Pole M, Einarson A, Pairaudeau N, Einarson T, Koren G. Drug labeling and risk perceptions of teratogenicity: a survey of pregnant Canadian women and their health professionals. J Clin Pharmacol. 2000;40:573–7.
6. Hegenbarth K, Maurer U, Kroisel PM, Fickert P, Trauner M, Stauber RE. No evidence for mutagenic effects of ribavirin: report of two normal pregnancies. Am J Gastroenterol. 2001;96:2286–7.
7. Shepard TH. Catalog of teratogenic agents. 10th ed. Baltimore: Johns Hopkins University Press, 2001.
8. Friedman JM, Polifka JE. Teratogenic effects of drugs: a resource for clinicians (TERIS). 2d ed. Baltimore: Johns Hopkins University Press, 2000.
9. Kweder SL, Kennedy DL, Rodriguez E. Turning the wheels of change: FDA and pregnancy labeling. The International Society for Pharmacoepidemiology. Scribe Newsletter 2000;3:2–4,10.
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