pills, a stetoscpe and a gavel
27 May 2015

The FDA Has Announced Health Risks Associated With Zofran Before. But What Are They?

A number of recent scientific studies have linked the potent anti-nausea drug Zofran to an increased risk of major birth defects. These are troubling results, not least because Zofran, first approved in 1991 to treat the severe nausea and vomiting commonly caused by chemotherapy, has also come into use as a morning sickness treatment. pills, a stetoscpe and a gavel

Although the drug has never been approved for use in pregnancy, physicians have been prescribing Zofran to women suffering from nausea and vomiting during the first trimester for over two decades. It’s understandable that Zofran’s recent association to major birth defects, including cleft palate and congenital heart defects, has received significant attention from the media.

But we’ve noticed several websites that have made erroneous claims about the US Food & Drug Administration’s response to these studies. Various sources are reporting that the FDA has publicly warned physicians against prescribing Zofran to pregnant women.

That is false.

Neither the FDA nor GlaxoSmithKline, Zofran’s manufacturer, have addressed the drug’s link to increased risks of birth defects. And with at least seven lawsuits now filed, all claiming that Zofran caused severe birth defects, their silence has become conspicuous.

The FDA Has Warned The Public About Zofran Health Risks. But Not About Its Association To Birth Defects.

But the past four years have seen the FDA make several major safety announcements in regard to Zofran. Medical experts have noted that these new warnings may have implications for pregnant women who are prescribed the drug.

FDA Places Zofran On Adverse Event Reporting System

Early in 2013, the FDA announced that Zofran was being placed on its Adverse Event Reporting System (FAERS). FAERS is a database administered by the FDA, designed for drugs that the agency believes may be associated with significant health risks. Physicians and consumers can directly submit reports of adverse events that they suspect are linked to pharmaceutical products, and the FDA uses the data to evaluate public health concerns and determine whether or not regulatory action is necessary.

While two studies published in 2013 found an increased risk of major birth defects among babies exposed to Zofran prenatally, Zofran wasn’t added to FAERS in response to those results. Instead, the FDA cited concerns over a condition called serotonin syndrome to explain its choice.

What Is Serotonin Syndrome?

Serotonin is an important neurotransmitter, a chemical that cells release to send messages to one another, produced primarily in the gastrointestinal tract.

Researchers believe that rising serotonin levels are the primary trigger of nausea and vomiting, and Zofran prevents nausea by blocking serotonin from reaching brain cells. But many other drugs, including common antidepressants, also block serotonin. When serotonin isn’t allowed to reach corresponding receptors in the brain, the neurotransmitter quickly accumulates. This buildup can lead to serotonin syndrome, which is technically a type of poisoning.

Untreated, serotonin syndrome can be fatal, and symptoms include disorientation, hallucinations and even coma.

Are Pregnant Women At Risk Of Developing Serotonin Syndrome?

According to the Mayo Clinic, serotonin syndrome does not occur naturally. Rather, it’s the result of taking two or more drugs that affect the body’s natural serotonin levels simultaneously. Serotonin syndrome can also develop if the dosage of one such drug is increased.

But as the New York Times recently reported, up to 14% of women take antidepressants during pregnancy, and the US Centers for Disease Control has found that these women are predominantly treated with Selective Serotonin Reuptake Inhibitors, or SSRIs. Like Zofran, SSRIs increase the body’s serotonin levels.

Between 75% and 90% of pregnant women being treated with antidepressants will also experience morning sickness. Medical experts have noted that the combination of Zofran and an SSRI may increase the risk of a woman developing serotonin syndrome.

FDA Revises Zofran’s Warning Label

In 2011, the FDA announced that it had received reports linking Zofran to abnormal activity in the heart’s electrical system. As a result, the agency instructed GlaxoSmithKline to perform a study that would investigate Zofran’s effects on cardiac function.

But before the study was completed, the FDA said that it would be making alterations to Zofran’s labeling. The changes warned physicians to avoid prescribing Zofran to patients who already have certain heart conditions, including a rare abnormality known as Torsade de Pointes that can be fatal.

After receiving the results of GlaxoSmithKline’s research, the FDA made another announcement, saying that the study’s results suggested that “a 32 mg single intravenous dose” of Zofran’s active ingredient “may affect the electrical activity of the heart,” potentially pre-disposing patients to develop Torsade de Pointes.

GlaxoSmithKline eventually pulled the 32 milligram intravenous dosage of Zofran off the market completely, and now Zofran’s labeling includes a warning to “avoid ZOFRAN in patients with congenital long QT syndrome,” an abnormality that can increase the risk of developing Torsade de Pointes.

Are Pregnant Women At Risk For Torsades de Pointes?

The labeling revision also says that “monitoring is recommended in patients with electrolyte imbalances,” a key contributor to the development of abnormal heart function.

Unable to ingest vital minerals like calcium and magnesium, many women suffering from severe nausea and vomiting, or hyperemesis gravidarum, develop electrolyte imbalances. In conjunction with Zofran, these women may be at a greater risk of developing long QT syndrome, and even Torsade de Pointes.