Birth Defect Risk Leads To Paxil Label Change


New data linking paroxetine use during the first trimester of pregnancy with increased risk of major congenital malformations has prompted changes to the drug's label.

Preliminary results of a retrospective epidemiologic study sponsored by GlaxoSmithKline Inc., the drug's maker, show paroxetine (marketed as Paxil), was associated with more congenital malformations (adjusted odds ratio 2.20) and more cardiovascular malformations (adjusted odds ratio 2.08) than other antidepressants in almost 3,600 pregnant women.

The prevalence of congenital malformations in the study was 4%, compared with about 3% in the general population.

The prevalence of cardiovascular malformations was 2%, compared with about 1% in the general population, according to a “Dear Healthcare Professional” letter issued by the company and the Food and Drug Administration.

Ventricular septal defects were the most common cardiovascular malformation in the study.

The GSK findings, along with those from two other recently published abstracts, warrant the voluntary label change, according to the company.

In one of the abstracts, Pia Wogelius, Ph.D., of the epidemiology department at Aarhus University Hospital, Denmark, and colleagues reported a link between SSRIs and major congenital malformations, including cardiac malformations. The risk of malformation was increased among women who had prescriptions for SSRIs filled in the 30 days before conception through the end of the first trimester, compared with those who had no SSRI prescriptions filled during the same period. These data did not specifically look at Paxil use.

The other abstract described a preliminary analysis of data obtained from the National Birth Defects Prevention Study suggesting an association between SSRI use between 1 month before and 3 months after conception and a significantly increased risk of omphalocele. The risk was greatest among paroxetine users, Sura Alwan, a Ph.D. student at the University of British Columbia, Vancouver, reported at the annual meeting of the Teratology Society.

SSRI use in that study also was linked with an increased risk of tetralogy of Fallot, she told FAMILY PRACTICE NEWS.

The Paxil labeling changes will be in the pregnancy subsection of the “precautions” section of the labels for Paxil and Paxil CR. The new language cites the GSK data but also notes that these data conflict with those from previous studies, including those from the Swedish Medical Birth Registry, which showed no increased risk of major malformations in infants born to 708 women exposed to SSRIs—including paroxetine—during pregnancy.

The conflicting data make it difficult to establish a causal relationship between SSRI use and major congenital malformations. Due to the lack of adequate and well-controlled studies, Paxil maintains its Pregnancy Category C status, according to GSK.

“As with all Pregnancy Category C drugs, health care providers are advised to carefully weigh the potential risks and benefits of using paroxetine therapy in women during pregnancy,” the company said in the letter.

Results of the GSK study are posted at the company's Clinical Trial Register at

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