What is Zofran: A Timeline of the Drug
The drug Zofran, also known as ondansetron, was introduced into the market to help ease nausea and stop vomiting in cancer patients that are going through chemotherapy as well as post-operative patients whose pain medication gave them the same nausea symptoms. However, it also was eventually used as morning sickness relief in pregnant woman. Unfortunately, Zofran was never approved for this and it has caused severe birth defects in infants whose mothers were taking the drug during their pregnancy. The drug maker, GlaxoSmithKline, who wrongfully promoted this off-label use of the drug has pleaded guilty to health care fraud and is paying three billion dollars in charges.
The Following is a timeline of the drug Zofran’s History:
January 4, 1991: Zofran was approved by the FDA for chemotherapy related nausea.
January 5, 1993: The FDA approved a pill form of Zofran.
June 22, 1995: The drug company Glaxo Wellcome submits a New Drug Application to the FDA for a 4mg/5mL dose of Zofran.
June 24, 1997: The FDA approves Glaxo Wellcome’s New Drug Application. (See Above)
March 9, 1999: Glaxo Wellcome is issued a warning letter from the FDA regarding the company’s marketing of Zofran. According to the letter, Glaxo Wellcome failed to warn consumers about the adverse side effects of Zofran.
December 27, 2006: Generic versions of Zofran are approved by the FDA
August 2011: GlaxoSmithKilne (The now merged company of Glaxo Wellcome and SmithKline Beecham) begin a new study to test the cardiac risks of Zofran.
September 15, 2011: The FDA issued a Drug Safety Communication regarding Zofran. The alert stated the following:
“Zofran may change the hearts electrical activity and that change could cause an abnormal heart rhythm such as Torsades De Pointes; and therefore Zofran’s labels will 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 Torsades. Additionally, recommendations for ECG monitoring in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesaemia), congestive heart failure, bradyarrhythmias or in patients taking other medications that can lead to QT prolongation. “
The FDA also ordered GlazxoSmithKline to conduct QT prolongation studies.
The company followed through and revised their labels to include the above warnings.
January 2012: The Center for Disease Control’s National Center on Birth Defects publishes a report finding that Zofran (ondansetron) taken during the first trimester of pregnancy doubles the risk of a cleft palate birth defect.
June 29, 2012: The FDA issued a Drug Safety Communication in which it stated that the 32mg dose of Zofran “may affect the electrical activity of the heart (QT interval Prolongation.)” This could cause some patients to develop Torsades De Pointes, a potentially fatal heart rhythm. The alert also stated that Glaxo was removing this dosage from Zofran labels and that “no single intravenous dose should exceed 16mg.”
July 2012: GlaxoSmithKline 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. The company 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 Glaxo wrongfully promoted Zofran for off-label use in expectant mothers, and paying kickbacks to doctors to prescribe Zofran for such off-label use.
This three 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.
July 5, 2012: The FDA released a podcast stating preliminary results of Glaxo’s study (see September 5th, 2011) showed that the 32mg dose of Zofran could cause QT interval prolongation which could in turn cause a fatal heart rhythm known as Torsades De Pointes.
December 4, 2012: The FDA issued a Drug Safety Communication in which it stated that brand name and generic versions of Zofran were being recalled in the 32mg dose.
The alert also reiterated the June 2012 warning that a single IV dose should not exceed 16mg.
August 2013: Two papers relating to Zofran and birth defects are presented at the International Society of Pharmacoepidemiology. The first paper concludes that Zofran 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 then the first study and came to an opposite conclusion: There is a doubling risk of cardiac malformations. Specifically, there was a significant increase in the prevalence of major congenital heart defects in children whose mothers redeemed a prescription of Zofran during the first trimester of pregnancy.
July 2014: American researchers confirm earlier reports that Zofran 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 the drug 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 reports that this drug poses a significantly increased risk from cardiac septum defects in the offspring of women who took Zofran the first trimester of their pregnancy.
This is certainly not going to be the end of the Zofran (Ondansetron) timeline. The drug and the drug makers have a long road ahead of them. If you had taken Zofran while you were pregnant and your child was born with birth defects such as: cleft lip, cleft palate, or heart abnormalities (including a hole in their heart), don’t hesitate to call an attorney and discuss your legal options.
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