ZOFRAN

Plaintiffs around the country have filed claims for injuries sustained after taking the anti-nausea medication, Zofran, originally manufactured by GlaxoSmithKline, LLC (“GSK”).[1] Plaintiffs in the Zofran litigation claim that prenatal exposure to the drug caused their children to be born with severe birth defects and that the defendant drug manufacturers (1) “unlawfully promoted Zofran for ‘off-label’ use during pregnancy; (2) hid evidence that Zofran can increase the risk for congenital defects; and (3) failed to warn the public of Zofran’s alleged risks.”[2]

The FDA approved Zofran, known generically as ondansetron, in 1991 to be used as a treatment for nausea and vomiting in cancer patients and post-surgical patients.[3] Zofran belongs to a class of drugs known as antiemetics and selective 5-HT3-receptor antagonists.[4]

Soon after gaining FDA approval, GSK began to promote the off-label use of Zofran as treatment for nausea and vomiting during pregnancy (“NVP”).[5] NVP is a very common affliction for pregnant women in the United States, with 50% to 80% of women experiencing it during the first trimester.[6] In serious cases, if NVP is left untreated, it can develop into hyperemis gravidarum.[7] Hyperemis gravidarum is described by the Hyperemesis Education and Research Foundation as “unrelenting, excessive pregnancy-related nausea and/ or vomiting that prevents adequate intake of food and fluids,” if the condition is left untreated it can lead to malnutrition and dehydration.[8]

Zofran quickly became a popular treatment for NVP, and it is estimated that over one million women in the United States were prescribed Zofran for this purpose, despite the lack of FDA approval.[9] In 2006, Zofran lost its patent protection, and Novartis and its subsidiary, Sandoz, began to manufacture the generic, ondansetron.[10]  In July 2010, the FDA approved Zuplenz, an oral soluble version of Zofran, based on its bioequivalence to Zofran.[11] In 2014, Galena Biopharma acquired the rights to market Zuplenz, and in 2015, Novartis acquired the rights to market Zofran.[12]

The FDA has classified Zofran, Zuplenz, and ondansetron as Pregnancy Risk Category B drugs, which means “animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.”[13][14] As early as the 1980’s, studies began to reveal a link between Zofran and risks to pregnant women. While FDA approval of Zofran was pending, GSK conducted clinical research that revealed “clinical signs of toxicity, premature births, intrauterine fetal death and impairment of ossification (incomplete bone growth)”[15] were associated with Zofran.[16]

In 2011, the Center for Disease Control and the Slone Epidemiology Center in Boston conducted a study, examining the risk of Zofran on pregnancy.[17] The results of the study revealed a twofold increase in the risk of cleft palate defects in babies whose mothers’ took Zofran during the first trimester of pregnancy.[18] Also in 2011, the FDA published a Safety Communication informing the public that it was continuing to review the link between Zofran and abnormal changes in the electrical activity of the heart.[19] An additional Safety Communication to alert the public that the 32-mg intravenous doses of Zofran, the largest dosage available, was being taken off the market was issued by the FDA in December 2012.[20]

In February 2013, the New England Journal of Medicine published a study looking at data from 608,385 pregnant women in Denmark, including those who were exposed to ondansetron during pregnancy and those who were not.[21]The study found “[o]ndansetron taken during pregnancy was not associated with a significantly increased risk of adverse fetal outcomes.”[22]

Conversely, Copenhagen University Hospital Bispebjerg and the Copenhagen Mental Health Center conducted another study that examined 903,207 births from women who both took and did not take a prescription of ondansetron during their pregnancy. The Danish study found “an increase in the prevalence of major congenital heart defects in children whose mothers redeemed a prescription of ondansetron in the first trimester of pregnancy.”[23]  

In March 2013, FDA Adverse Events Report reported linked Zofran use in pregnant women who also took a selective serotonin reuptake inhibitor (“SSRI”) to serotonin syndrome, a life threatening condition for both mother and child.[24]

Finally, in December 2014, Reproductive Toxicology published a Swedish study, which included 1349 infants born between 1998-2012, whose mothers took ondansetron early on in their pregnancy.[25] The study found that ondansetron increased the risk of cardiovascular defects in children, most notably, septal heart defects.[26]