Pregnancy Category

Description

A

No risk in controlled human studies: Adequate and well-controlled human studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).

B

No risk in other studies: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

C

Risk not ruled out: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

D

Positive evidence of risk:  There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

X

Contraindicated in Pregnancy: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

N

FDA has not yet classified the drug into a specified pregnancy category.

Zofran was first approved for use in the U.S. in 1991. In 2005, Zofran was the 20th highest-selling brand-name drug in the United States, with sales totaling $839,256,543. Once it became available as a generic drug the following year, it was even more popular because it was more affordable.  Zofran, however, is a pregnancy Class B drug (see Table below). Drugs in this particular class do not have well-controlled studies backing them up to adequately demonstrate that they are safe for use in pregnancy. This is especially disturbing, considering that it has become the first choice for treating severe nausea in the past several years.

What is Off Label?

The term, “off label” means that a drug is being prescribed for a condition for which FDA approval has not been given.  While there is no law preventing a doctor from prescribing off-label drugs, it must be remembered that such practices come with the potential that harm can result from their use. In other words, there is no demonstrated evidence that the drug will be safe or even effective.  This is what resulted when Zofran was being prescribed to pregnant women: mothers were being given this drug for morning sickness in early pregnancy, and more and more evidence is showing that the drug can cause birth defects. Babies are being born with heart defects, kidney problems, and other physical defects including cleft lip and cleft palate.

Now the lawsuits are beginning to come in, despite the fact that for years now researchers have been warning us about this particular drug and its potential dangers to unborn children. In February 2015 at least two lawsuits have been filed accusing GlaxoSmithKline of promoting Zofran’s off label use as treatment for nausea and vomiting in pregnancy while failing to warn patients that it could harm the developing fetus. Because the majority of women experience at least some nausea and vomiting during the first trimester, taking any drug (over the counter meds included) during the first trimester when the fetus is most vulnerable is risky at best.

Some Studies on Zofran

In 2006, a Hong Kong based research study showed that Zofran definitely crossed the human placenta in the first trimester of pregnancy. “The developmental significance of this drug exposure requires further investigation” (Siu, Chan, & Lau, 2006).

In 2011 first warned about such risks. And while labels already warned about irregular heart rhythm risks, there was no warning about how the drug could cause a fatal condition called Torsades de Pointes, a condition that interferes with electrical activity in the heart.

In 2012 there were more studies, including one suggesting an increased risk of cleft palate associated with the use of Zolfran. One of the researcher’s concerns was that safety data were based on fewer than 200 births. “Based on the data available today, ondansetron use cannot be assumed to be safe during pregnancy” (Koren, 2012).

A study by Andurka et al. (2012) found that ondansetron was associated with an increased risk for birth defects and “warranted further investigation.”

Another 2012 study investigating the teratogenic effect of Zofran (teratogens are agents that can disrupt the development of the unborn child, leading to birth defects) found that the risks for cardiovascular defect significantly increased with use of the drug. Data were based on 1,349 infants whose mothers took the drug in early pregnancy between 1998 and 2012 (Danielsson, Wikner, & Källén, 2012).

In March 2013, the FDA identified a potential safety issue, linking 5-HT3 receptor agonists, including Zofran, with serotonin syndrome. According to Koren (2013) “Serotonin syndrome occurs with the co-administration of two or more drugs that affect serotonin, usually selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase (MAO) inhibitors. Cases of possible or probable serotonin syndrome have been reported with the use of ondansetron… and the potential for serotonin syndrome with an SSRI and ondansetron should be considered. Symptoms include cognitive or behavioral changes, including confusion or agitation, autonomic instability, and neuromuscular changes.”

In August 2013, a group of Danish researchers using data from the national registries published data from almost 900,000 pregnancies between 1997 and 2010). They found “a twofold increase detected a twofold in congenital heart defects associated with ondansetron during the first trimester of pregnancy. Of the 1,248 women who filled a prescription for ondansetron during the first trimester, 4.7% (58) had a baby with a congenital malformation, compared with 3.5% (31,357) of those who were not exposed to ondansetron; this represented a 30% increased risk (adjusted odds ratio, 1.3). The increased risk was mostly due to the increased prevalence of heart defects” (as cited by Koren, 2013).

In December of 2013, researchers in Australia found that there was an increased risk of major birth defects, preterm births, and that babies were smaller when born to mothers using Zofran (Colvin et al., 2013).

Current Lawsuits

On February 12, 2014, a lawsuit was filed in U.S. District Court of Pennsylvania by a woman alleging that her use of Zofran during pregnancies in 2004 and 2006 resulted in both children being born with serious heart abnormalities. On February 16, 2015, a second complaint was filed in the U.S. District Court of Massachusetts on behalf of a child who was born with several congenital heart defects due to the mother’s use of Zofran during the first trimester of pregnancy.

Both lawsuits noted that in 2012, GlaxoSmithKline agreed to pay $3 billion to resolve charges with the U.S. Department of Justice regarding the improper marketing of several medications, including Zofran. Finally, both lawsuits pointed to various studies indicating a causative relationship between birth defects and Zofran.

The Bottom Line

The fact is that all drugs cross the placenta or have the potential of causing harm to an unborn child, and taking any drug while pregnant or breastfeeding, over the counter or otherwise, should not be taken lightly. Be sure to discuss safety issues regarding all medications, herbal remedies, and supplements with your health care provider before using them. Since women who are pregnant are not typically included in studies to determine safety of new medications before they come on the market, less than 10% of medications approved by the U.S. Food and Drug Administration (FDA) since 1980 have enough information to determine their risk for birth defects. It is beyond dispute, however, that taking certain medications during pregnancy can cause serious birth defects. Use extreme caution then if you are pregnant, may become pregnant, or are nursing and are using any medication. (http://www.cdc.gov/pregnancy/meds/)