Medications to be avoided during pregnancy
The Federal Drug Administration has published guidelines for labeling medications for potential teratogenic effects. These guidelines establish 5 risk categories.
Category A: Adequate and well controlled studies in pregnant women have not shown an increase in risk of fetal abnormalities.
Category B: Animal reproductive studies have failed to show risk and no adequate or well-controlled studies in pregnant women.
Category C: Animal reproductive studies have shown a risk the fetus and no adequate or well-controlled studies in pregnant women. The labeling does include that potential benefit of the drug may outweigh the potential risk.
Category D: Positive evidence of human fetal risk based on use or studies in humans. Includes a risk/benefit statement for use in serious or life threatening disease.
Category X: Positive evidence of animal or human fetal abnormalities. Risk the use of the drug clearly outweighs benefit.
21CFR201.57 [Revised as of April 1, 2007]
Despite established warning guidelines for the use of drugs in pregnancy, medication use in pregnancy is higher than might be expected. Two recent studies have addressed the prevalence of medication prescribed during pregnancy1-2. Both were retrospective studies, one was a cohort study and one was cross sectional study. The studies showed that 50-64% of the pregnant women were prescribed at least on medication. More alarmingly, from 2.9% - 9.4% of the women were prescribed a category D or X medication. Added to these figures is the fact that the FDA categories may viewed as not based on enough evidence3. This is especially true for new medications, in which there has been little experience in humans, so most of the data is based on animal studies3.
This would seem to be a situation in which alerts could be used in clinical decision support systems. The most sensitive method would be to require alerts in all women of child bearing age. This could require a patient history question to evaluate the risk of pregnancy and an appropriately timed pregnancy test.
A recent study randomized all women into a study and control groups, with the control group receiving usual care without alerts4. Alerts were based on clinical and administrative data and were sent to the pharmacist when a prescription was filled. The pharmacist confirmed the pregnancy status with the patient and, if needed, consulted with the prescribing physician. While there was a statistically significant reduction in targeted medications prescribed in pregnancy, it only reduced the rate by about one half. The study stopped before completion due to two types of false-positive alerts.
Although this is an important area in which clinical decision support can aid in decreasing the prescription of potentially teratogenic drugs to pregnant women, there are substantial barriers. The current labeling system relies on risk-benefit decision making, the identification and confirmation of pregnancy is problematic and it may require patient, physician and pharmacy verification systems.
1.Andrade SE, Gurwitz JH, Davis RL, Chan KA, et al. Prescription drug use in pregnancy. Am J. Obstet Gynecol. 2004;191:398-407
2. Lee E, Maneno MK, Smith L, Weiss SR, et al. National patterns of medication use during pregnancy. Pharmocoepi Drug Safety. 2006;15:537-545.
3. Doering PL, Boothby LA, Cheok M. Review of pregnancy labeling of prescription drugs: is the current system adequate to inform of risks? Am J. Obstet Gynecol. 2002;187(2), 333-339.
4. Raebel MA, Carroll NM, Kelleher JA, Chester EA, et al. Randomized trail to improve prescribing safety during pregnancy. J Am Med Inform Assoc. 2007;14:440-450.