FDA Advisory - ACE inhibitor use during pregnancy may be associated with birth defects

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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 O. , -,

G. Arbogast, Judith A. Dudley, Dyer, 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.

http://www.fda.gov/cder/drug/advisory/ACEI.htm

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Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

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