The announcement appeared in the April 18 Federal Register. The government's National Toxicology Program's Center for the Evaluation of Risks to Human Reproduction (CERHR) will conduct the investigation.
Although the company that makes the drug, Eli Lilly and Co. of Indianapolis, has never conducted a clinical trial in pregnant women, it points to several other studies that did not find any increase in malformation, neurodevelopment problems, postnatal complications or impaired central nervous system development in infants of mothers taking the drug.
"One study did show an increased admission rate to the special care nursery, although no specific reason for this increase was identified," says Blair Austin, a company spokesman.
"Toxicology studies for fluoxetine conducted at Lilly support that there are no compound-related adverse effects on fertility," Austin adds.
Prozac, an antidepressant, debuted in 1987 and quickly became a blockbuster. To date, more than 48 million people worldwide have taken Prozac, according to Eli Lilly figures, and more than 12,000 individuals have participated in clinical trials. "Thousands of scientific papers have referenced Prozac, making it among the most studied medications in history," the company states.
This month's decision to re-evaluate was prompted largely by the fact that the drug was recently approved to treat a wider range of people under a different brand name, Sarafem. Eli Lilly sold the rights to Sarafem to Galen Holdings of Northern Ireland in December 2002. Galen could not be reached for comment.
"A couple of reasons explain why interest has recently increased," says Mike Shelby, CERHR's director. "Number one is the recent FDA approval for its use in 7- to 17-year-olds, which means that children in their formative development years are being exposed or potentially exposed to it in higher numbers, as well as the fact that it is being prescribed for premenstrual dysphoric disorder [PMDD], exposing women of childbearing age."
According to the CERHR, an anonymous individual nominated Prozac to the center with no specific reason cited. "We consider every agent that's nominated to us," Shelby explains. The decision to evaluate is based on four criteria: production volume, the level of public concern (as indicated in the mass media), evidence of human exposure, and the volume of scientific literature available. Clearly, Prozac met all of these criteria. "The committee gave it the nod of approval, and so we are moving ahead with evaluation," Shelby says.
According to a preliminary literature review done by CERHR, there is little evidence of reproductive hazards. Some studies showed effects such as premature delivery, decreased weight gain, breathing difficulties, increased admissions to special care nurseries or increased irritability, with late gestation or perinatal exposure to the drug.
Animal studies have shown a possible reduction in duration of pregnancy and fetal weight.
There has been no association found between prenatal exposure and malformation, neonatal complications or neurodevelopmental toxicity.
CERHR is now soliciting input from the public and experts and is also looking for experts to serve on the panel. The expert panel evaluation is expected to take place in late 2003 or early 2004.
Lilly says it is not pursuing any label changes for Prozac regarding use in pregnancy or lactation. "As with any medication, the use of antidepressants during pregnancy or the post-partum period should be based on an assessment of the risk of the mother's continued depression to both the mother and the baby, and the projected benefit and risks of treating that depression with medication," Austin says.