FDA Alert 12/2005
Increase in the Risk of Congenital Malformations

Preliminary results of two recent studies indicate that paroxetine increases the risk of congenital malformations, particularly cardiovascular malformations. Based on the new data, paroxetine’s pregnancy category is being changed from C to D. Patients taking paroxetine who become pregnant or who are currently in their first trimester of pregnancy should be alerted to the potential risk to the fetus. Discontinuing paroxetine therapy or switching to another antidepressant should be considered for these patients. For individual patients, however, the benefits of continuing paroxetine may outweigh the potential risk to the fetus. Paroxetine should generally not be initiated in women who are in their first
trimester of pregnancy or in women who plan to become pregnant.

The FDA is currently awaiting the final results of the recent studies and accruing additional data pertaining to the use of paroxetine in pregnancy in order to better characterize the risk of paroxetine. The FDA will update this sheet as new information becomes available.

This information reflects FDA’s preliminary analysis of data concerning this drug. FDA is considering, but has not reached a final conclusion about this information. FDA intends to update this sheet when additional information or analyses become available.

Recommendations
See above

Data Summary
Preliminary analyses from two recent unpublished epidemiological studies have shown that paroxetine use in the first trimester of pregnancy is associated with an increased risk of specific types of congenital malformations. In a study based on Swedish national registry data, infants exposed to paroxetine in early pregnancy had an approximately two-fold increased risk for cardiac defects compared to the entire national registry population, about 2% in paroxetineexposed infants vs. 1% in the total population. The majority of cardiac defects in paroxetineexposed infants were atrial and ventricular septal defects.

In a separate study using a United States (U.S.) insurance claims database, infants of women who received paroxetine in the first trimester had a 1.5-fold increased risk of cardiovascular malformations compared to infants of women who received other antidepressants in the first trimester, 1.5% in the paroxetine-exposed infants vs. 1% in infants exposed to other antidepressants. The majority of the cardiovascular defects observed in this study were ventricular septal defects. Exposure to paroxetine in the first trimester was also associated with an approximately two-fold higher risk for overall congenital malformations (including cardiovascular malformations) compared to exposure to other antidepressants in the first trimester, about 4% vs. 2% prevalence of all congenital malformations. Separate analyses were not done for any specific malformations other than cardiovascular malformations.

The FDA is in the process of accruing additional data to better characterize the risk of paroxetine.

Report serious adverse events to FDA's MedWatch at 1-800-FDA-1088;
or www.fda.gov/medwatch/report/hcp.htm

Questions?
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