In recent months, our law firm have been investigating the link between Zofran taken for morning sickness during the first trimester of pregnancy and serious fetal injuries involving this product.
Call us anytime, or email me directly - mark(at)markzamora.com (You can also read more at www.zofran-injuries.com)
What is it? Ondansetron (INN), originally marketed under the brand name Zofran, is a serotonin 5-HT3 receptor antagonist used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery. For some women, it was used to treat nausea.
We believe there is now evidence that Zofran may allegedly be the cause of defects in children. The FDA never approved this drug for morning sickness and GlaxoSmithKline (GSK), the maker of this drug, paid a $2 billion settlement in a civil lawsuit that involved allegations that GSK illegally promoted its Zofran drug to be prescribed to expectant mothers. This settlement did not include payments for injuries suffered due to the use of Zofran.
Here is a timeline of this product:
January 5, 1993:
The New York Times reported that the FDA approved a pill form of Zofran.
January 4, 1991:
The FDA approved Zofran (ondansetron) for chemotherapy-related nausea and
vomiting
June 22, 1995: GlaxoWellcome submited a New Drug Application to the FDA for a 4mg/5mL dose of Zofran (ondansetron hydrochloride)
June 24, 1997: The FDA approved GlaxoWellcome's New Drug Application (see June 22, 1995, entry).
March 9, 1999:
The FDA issued a warning letter to GlaxoWellcome
regarding its marketing of anti-nausea drug Zofran. According
to that letter, Glaxo failed to warn consumers about Zofran's adverse side
effects while touting its effectiveness with statements such as:
·
"Zofran can,"
·
"24-hour control," and
·
"Prevention of emesis I to 2 days after chemotherapy."
June 22, 1995: GlaxoWellcome submited a New Drug Application to the FDA
for a 4mg/5mL dose of Zofran (ondansetron hydrochloride)
June 24, 1997: The FDA approved GlaxoWellcome's New Drug Application
December 27, 2006: The FDA approved generic versions of Zofran .
August 2011: To test Zofran's cardiac risks, GlaxoSmithKline began a study titled "A Randomized, Double-blind, Four-period Crossover Study to Investigate the Effect of Intravenous Ondansetron, a 5-HT3 Antagonist, on Cardiac Conduction as Compared to Placebo and Moxifloxacin in Healthy Adult Subjects"
September 2011: GlaxoSmithKline revised Zofran labels to include the following, per the FDA:
- "Information regarding post-marketing case reports of Torsade de Pointes;
- Recommendation to avoid use in patients with known congenital long QT syndrome;
- ECG monitoring recommendation in patients with electrolyte abnormalities, congestive heart failure, bradyarrhythmias or patients taking other medicinal products that lead to QT prolongation."
September 15, 2011: The FDA issued a Drug Safety Communication regarding Zofran That alert stated that:
- Zofran may change the heart's electrical activity and that change could cause an abnormal heart rhythm such as Torsade de Pointes; and
- Zofran's labels would therefore be revised. Per the FDA:
The labels are being revised to include a warning to avoid use in patients with congenital long QT syndrome because these patients are at particular risk for Torsade. Additionally, recommendations for ECG monitoring in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias, or in patients taking other medications that can lead to QT prolongation.
The FDA also ordered Zofran maker GlaxoSmithKline to conduct QT prolongation studies.
January 2012:The CDC’s Nation Center on Birth Defects and Developmental Disabilities publishes a report finding that Zofran (ondansetron) taken during the first trimester of pregnancy doubles the risk of a cleft palate birth defect.
There were over 9,000 pregnant women in the study overall, both cases and controls; 67% reported NVP and 15% used some kind of agent to treat NVP. The study used data from the National Birth Defects Prevention Study, looking at the association between NVP and treatments for NVP and cleft palate, and other noncardiac birth defects. Link here.
June 2012: GlaxoSmithKline (GSK), the maker of Zofran, pleads guilty to federal criminal health care fraud charges for violations of the Food, Drug, and Cosmetic Act relating to three of its branded drugs. At the same time, GSK also agrees to pay $1 billion in criminal penalties as well as $2 billion in civil penalties to resolve a federal whistleblower lawsuit that included claims that GSK wrongfully promoted Zofran for off-label promotion for use in expectant mothers, and paying kickbacks to doctors to prescribe Zofran for such off-label use.
This $3 billion dollar penalty is the largest combined federal and state health care fraud recovery in a single global resolution in the history of the United States.
August 2013: Two papers relating to Zofran and birth defects are presented at the International Society of Parmacoepidemiology. The first paper concludes that Zofran (ondansetron) taken during pregnancy was not associated with a significantly increased risk of adverse fetal outcomes. Importantly, the second paper includes the data from the first paper but covered more years and more pregnant woman that the first study and came to an opposite conclusion: There is a doubling of the risk of cardiac malformations. Specifically, there was a significant increase in the prevalence of major congenital heart defects in children whose mothers redeemed a presdription of Zofran (ondansetron) during in the first trimester of pregnancy.
August 2013: Two papers relating to Zofran and birth defects are presented at the International Society of Parmacoepidemiology. The first paper concludes that Zofran (ondansetron) taken during pregnancy was not associated with a significantly increased risk of adverse fetal outcomes. Importantly, the second paper includes the data from the first paper but covered more years and more pregnant woman that the first study and came to an opposite conclusion: There is a doubling of the risk of cardiac malformations. Specifically, there was a significant increase in the prevalence of major congenital heart defects in children whose mothers redeemed a presdription of Zofran (ondansetron) during in the first trimester of pregnancy.
July 2014: American researchers confirm earlier reports that Zofran (ondansetron) crosses the placental barrier during pregnancy in relatively high concentrations (approximately 40% of the maternal plasma levels) after just three oral doses. The authors conclude that the high lipid solubility of Zofran (ondansetron) increases its ability to be taken up into fetal tissue in larger amounts.
August 2014: A Swedish study investigating the risk of birth defects from Zofran (ondansetron) reports that this drug poses a significantly increased risk for cardiac septum defects in the offspring of women who took Zofran during the first trimester of pregnancy.
From the FDA in 2013:
Potential Signals of Serious Risks/New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS) between January– March 2013
The table below lists the names of products and potential signals of serious risks/new safety information that were identified for these products during the period January - March 2013 in the FAERS database. The appearance of a drug on this list does not mean that FDA has concluded that the drug has the listed risk. It means that FDA has identified a potential safety issue, but does not mean that FDA has identified a causal relationship between the drug and the listed risk. If after further evaluation the FDA determines that the drug is associated with the risk, it may take a variety of actions including requiring changes to the labeling of the drug, requiring development of a Risk Evaluation and Mitigation Strategy (REMS), or gathering additional data to better characterize the risk.
FDA wants to emphasize that the listing of a drug and a potential safety issue on this Web site does not mean that FDA is suggesting prescribers should not prescribe the drug or that patients taking the drug should stop taking the medication. Patients who have questions about their use of the identified drug should contact their health care provider. FDA will complete its evaluation of each potential signal/new safety information and issue additional public communications as appropriate.
Potential Signals of Serious Risks/New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS) January - March 2013
| Product Name: Active Ingredient (Trade) or Product Class | Potential Signal of a Serious Risk / New Safety Information | Additional Information
(as of March 1, 2014)
|
|---|
Metoprolol succinate extended release products
|
Lack of therapeutic effect, possibly related to product quality issues
|
FDA decided that no action is necessary at this time based on available information.
|
Serotonin-3 (5-HT3) receptor antagonist products (Aloxi, Kytril, Zofran, Zuplenz)
|
Serotonin syndrome
|
FDA is continuing to evaluate this issue to determine the need for any regulatory action.
|
