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Medication News & Update

FDA Public Health Advisory
Angiotensin-Converting Enzyme Inhibitor (ACE inhibitor) Drugs and Pregnancy

[ACE inhibitor drugs include Benazepril (Lotensin), Captopril (Capoten), Enalapril/Enalaprilat (Vasotec oral and injectable), Fosinopril (Monopril), Lisinopril (Zestril and Prinivil), Moexipril (Univasc), Perindopril (Aceon),
Quinapril (Accupril), Ramipril (Altace), and Trandolapril (Mavik)]
 

A new study in the New England Journal of Medicine suggests that angiotensin-converting enzyme inhibitor drugs (ACE inhibitors or ACEIs) may be associated with increased risk of birth defects when used in the first three months of pregnancy. While the results of this single study do not establish a causal relationship between exposure to the drugs early in pregnancy and birth defects, they are concerning. ACE inhibitors are already known to have risks to the developing infant when used in the last six months of pregnancy. The prescribing information for all ACE inhibitor drugs has long emphasized that women who become pregnant should be taken off ACE inhibitors as soon as possible to avoid exposure of the fetus in the second and third trimesters, which is known to cause fetal abnormalities, especially related to the kidneys and related structures. The findings from this new study, which was supported by funding from the Agency for Healthcare Policy & Research and FDA, confirm the importance of this recommendation.

ACE inhibitor drugs are used to treat high blood pressure by slowing the body’s production of a hormone that constricts blood vessels. The labels for all the ACE inhibitors begin with a boxed warning that the drugs may harm unborn babies in the second and third trimester of pregnancy. FDA recommends the following:

• Healthcare providers who care for women of reproductive age should counsel those who are treated with an ACE inhibitor about the potential risks of these drugs throughout pregnancy, especially during the second and third trimesters.
• Pregnant women should only be prescribed ACE inhibitors if the expected benefit clearly exceeds the potential risk.
• Women who become pregnant should have their ACE inhibitor changed to a different medication as soon as possible.
• Women who are taking ACE inhibitors to treat high blood pressure should tell their healthcare professionals if they are planning a pregnancy or think they might be pregnant.

The observational study published on June 8, 2006 (one that reports on patients who are being treated with usual medical care, not in a clinical trial) reports that babies whose mothers had taken an ACE inhibitor during the first three months of pregnancy had an increased risk of birth defects, compared with babies whose mothers had not taken any drugs for high blood pressure.

ACE inhibitors are labeled with a pregnancy category D for the last six months (the second and third trimesters) and C for the first three months. Pregnancy category D means that there have been studies in pregnant women showing that the drug was associated with some risk for the unborn baby (fetus), but the benefit of the drug may still outweigh that risk for some patients. Pregnancy category C means that the risk in pregnancy is possible but unknown, because no good studies of pregnant women have been done, and animal studies either have shown risk in pregnancy or have not been done. For more information about the pregnancy categories and also about the risk of leaving diseases untreated in pregnant women, see the story posted at http://www.fda.gov/fdac/features/2001/301_preg.html#danger

At this time, based on this one observational study, the FDA does not plan to change the pregnancy categories for ACE inhibitors. FDA will work with the Agency for Healthcare Quality and Research to identify other potential sources of data that will help determine the degree of risk associated with first trimester exposures to these drugs.

For the recent study, see William O. Cooper, Sonia Hernandez-Diaz, Patrick G. Arbogast, Judith A. Dudley, Shannon Dyer, Patricia S. Gideon, Kathi Hall, and Wayne A. Ray. "Major congenital malformations after first-trimester exposure to ACE inhibitors." New England Journal of Medicine, volume 354 number 23, pages 2443-2451. June 8, 2006.