Before a drug can be marketed in the United States, it must be approved by the US Food & Drug Administration. This is an extremely lengthy process, and its most important stage is that of clinical trials. These large studies, funded and managed entirely by a drug’s manufacturer, use human subjects to test the safety and efficacy of a medication.
In the case of “efficacy,” the FDA is looking for evidence that a drug has beneficial results in treating the condition or conditions for which it will be marketed. “Safety” is a matter of rooting out any adverse side effects.
But due to ethical concerns, it is rare that a clinical trial will include pregnant women as test subjects. Thus it is rare that a drug will be approved specifically to treat conditions, like morning sickness, that commonly occur during pregnancy.
This is true for GlaxoSmithKline’s Zofran. The effects of Zofran were never investigated in clinical trials that included pregnant women, and thus there are no clinical trials targeting pregnant women that would provide us with a way of knowing what side effects it may cause in them or harm it may do to developing babies.
What Are The Side Effects Of Zofran on Babies in Pregnancy
|Main Reported Side Effects||Our Firm Accepting Cases?|
|Atrial Septal Defect (ASD)||Yes|
|Ventricular Septal Defect (VSD)||Yes|
|Atrioventricular Septal Defect||Yes|
How Do We Know Which Drugs Are Safe During Pregnancy?
The short answer to that question is that we learn when pregnant women start taking them. This means that with a drug being given to pregnant women, manufacturers and doctors need to be extremely vigilant, following up to see what happens and gathering data on adverse events. Again, only in extremely uncommon instances do drug manufacturers conduct clinical trials to determine the effects a medication has specifically on pregnant women and their children.
We’ll use Zofran as an example to illustrate this process. But note that Zofran may actually be a more complex case than usual, because it is being used to treat symptoms of pregnancy, not pre-existing conditions that a mother may happen to have.
1. Approve Drugs For Use In The General Population
Medications are approved for specific conditions experienced in the general public. But some of these conditions will be very similar to symptoms that arise during pregnancy.
After comprehensively reviewing the results of clinical trials, the US Food & Drug Administration approved Zofran for two conditions:
- the “prevention of nausea and vomiting associated with initial and repeat courses of emetogenic* cancer therapy”
- the “prevention of postoperative nausea and / or vomiting”
*having the potential to cause vomiting
Those two indications are current as of September 2014, the last time the FDA altered Zofran’s warning label.
Obviously, one of pregnancy’s most common symptoms is nausea and vomiting: morning sickness. Women who suffer from hyperemesis gravidarum, morning sickness’ most extreme form, often lose too much weight or develop nutritional imbalances. Under the most severe circumstances, these side effects of pregnancy can in turn harm unborn babies. An ordinary amount of nausea is generally not cause for concern, but rather a sign of a healthy pregnancy. Only in the most extreme cases is a child or mother in danger.
In this way, a new (albeit unapproved) indication for selling Zofran presented itself: treating morning sickness in pregnant women.
2. Prescribe The Drug To Pregnant Women
After reaching the market, doctors can prescribe these drugs to pregnant women, even though they have not been explicitly approved for use during pregnancy and their effects on a developing baby have not been demonstrated.
Of course, most doctors do not take this lightly. It’s well understood that prescription drug use is generally discouraged during pregnancy. But many medical conditions present a danger to pregnant women and unborn babies in their own right. It’s a matter of weighing the potential risks of leaving these conditions untreated against those a medication may pose during pregnancy. This is why adequate warnings from the manufacturer are so important – so that doctors can weigh risks against benefits.
In the case of Zofran, we know that physicians have prescribed the drug for (at least) cases of hyperemesis gravidarum since before 2002.
3. Keep A Registry
Over time, the health community will begin to gain an understanding of a drug’s effects during pregnancy.
Many medications have their own “Pregnancy Registries,” where mothers and their physicians can report adverse reactions or, after their child is born, potential effects on a developing fetus. As more and more data is collected, researchers can begin analyzing it to develop theories about a drug’s likely effects during pregnancy.
According to the FDA’s current list of Pregnancy Registries, there is not yet one for Zofran or its active ingredient ondansetron.
“Epidemiological” studies compare groups of women who have taken a certain drug to groups who have not. By comparing one group to the other, researchers can determine whether a certain condition or birth defect is more common in a group prescribed a drug than it is in a group never exposed to the drug. This increase in occurrence, or “incidence,” doesn’t necessarily mean that the drug causes an adverse condition, but it indicates that more research should be conducted.
If other studies also find the same danger associated with a drug, the FDA can elect to alter the drug’s warning label and inform physicians of the increased risks.
Are There Any Studies On Zofran’s Effects During Pregnancy?
Zofran has been FDA approved since 1991, and pregnant women have been taking it for more than a decade, so the health community has sufficient data to initiate epidemiological studies on its own.
To date, at least five studies have been conducted using birth records to examine Zofran’s effects on developing babies. Four have found an increased association between ondansetron and birth defects, including cleft palate and congenital heart defects.
The FDA has yet to announce an opinion on these results, and has not made any suggestions that Zofran’s warning label will be altered to reflect their conclusions. In relation to pregnancy, the label currently reads:
“Reproduction studies have been performed in pregnant rats and rabbits […] and have revealed no evidence of impaired fertility or harm to the fetus due to ondansetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.”
Notably, several recently-filed lawsuits have alleged that the results of these animal studies did present evidence of harm, both to the pregnant animals and their developing fetuses. For more information on the ongoing litigation against GlaxoSmithKline, click here.
Zofran’s Potential Side Effects
As with most (if not all) medications, Zofran’s active ingredient ondansetron may cause secondary, undesirable complications in addition to its presumed benefit: the prevention of nausea and vomiting.
Below, we’ve provided a description of these side effects as explained on Zofran’s current prescription information label. But remember that these effects were discovered in clinical trials conducted to receive FDA approval for only two indications: nausea and vomiting as a result of chemotherapy and surgical anesthesia. As a result, all of the human subjects in the studies were undergoing one of those treatments. In other words, we only know which side effects were experienced by patients in chemotherapy, or those who had just had surgery.
Perhaps most common, and occurring in around 7% of all patients studied in clinical trials, are diarrhea, headache and fever. Constipation is also common, and is frequently mentioned as a side effect by pregnant women taking Zofran.
In patients being treated for postoperative nausea and vomiting, the most common side effect is headache, experienced by around 10% of all patients.
Results From Postmarketing Experience
Zofran’s label also includes a section called “Postmarketing experience.”
After a drug is approved and released on the market, physicians and patients are able to report adverse reactions to the FDA. Sometimes, the agency decides to include these reports on a warning label if they are serious, reportedly frequently or the FDA believes that they may be directly caused by a drug.
In Zofran’s case, the FDA has seen fit to mention:
- Cardiovascular complications, including arrhythmia, an abnormal heartbeat.
- Flushing, a reddening of the skin.
- Rare hypersensitivity reactions. These are like allergic reactions, and may indicate that the immune system is particularly sensitive to the presence of ondansetron.
- Abnormalities in the liver’s enzymes
- “Oculogyric crisis,” a condition in which the eyes rotate upwards for prolonged periods.
- Certain skin rashes, like hives.
- Transient blindness, usually when the drug is administered intravenously.