Zofran (ondansetron) has been linked to a number of birth defects, including heart defects, cleft lip and cleft palate and musculoskeletal abnormalities. The U.S. Food and Drug Administration (FDA) only approved Zofran to reduce nausea and vomiting in patients who have undergone chemotherapy, surgery or radiation treatment, but it is often used off-label to treat pregnant women with morning sickness. Introduced in 1991, Zofran prevents nausea and vomiting by blocking serotonin in the brain. It belongs to a class of drugs known as 5HT3 receptor antagonists. Allegations of off-label marketing and evidence of birth defects has prompted some users to file lawsuits against the manufacturer, GlaxoSmithKline (GSK).
Zofran Birth Defects
Zofran (ondansetron) has been linked to a number of birth defects, including heart defects, cleft lip and cleft palate and musculoskeletal abnormalities.
Zofran Birth Defects
Research Links Zofran to Increased Risk of Birth Defects
Zofran may affect a developing fetus by crossing the placental barrier. According to court documents, fetal tissue samples show that Zofran concentrations can be as high as 41 percent. The drug is also present in the breast milk. Birth defects linked to Zofran include:
- mental disabilities
- physical deformities
- vision and hearing problems
- heart defects
- cleft lip and cleft palate
- stomach issues
- club foot
- webbed toes
- skull deformities
- abnormal blood pressure
In 2014, the American Journal of Obstetrics and Gynecology published a review questioning the safety of Zofran in pregnant women. The author is Dr. Gideon Koren, MD of The Motherisk Program, the Hospital for Sick Children and University of Toronto. According to the review, 80 percent of pregnant women experience nausea and vomiting in pregnancy. Koren notes that the use of Zofran increased between 2008 and 2013, from 50,000 to 110,000 monthly prescriptions “despite unresolved issues regarding fetal safety and Food and Drug Administration warnings about serious dysrhythmias.”
Motherrisk is a non-profit Canadian organization dedicated to helping and informing expectant mothers about health concerns. It received 190 calls about Zofran in 2012 alone. “Here is a drug not meant for pregnancy, given in pregnancy, with no data. So how do you know it’s safe for a baby? It’s an extrapolation that doctors do,” said Dr. Koren, who is the director. “They think it’s the last chance for your patient. They think that there’s an edge for that drug compared to other drugs,”
Dr. Koren pointed to a 2013 study involving 900,000 Danish women indicating a “2-fold increased risk of cardiac malformations with ondansetron (Zofran), leading to an overall 30 percent increased risk of major congenital malformations.” The review stated that the FDA has approved drugs for morning sickness, such as doxylamine and pyridoxine and therefore “there is no reason for women to be exposed to a drug of unproven maternal and fetal safety.”
A large 2011 study conducted by the Slone Epidemiology Center in Boston, Massachusetts and the Center for Disease Control and Prevention showed that Zofran was linked to a two-fold increased risk of cleft palate defects among children born by women who took the medication during their first trimester
There is also evidence of Zofran’s birth defects in GSK’s own clinical studies, court documents suggest. Data from animal studies showed “clinical signs of toxicity, premature births, intrauterine fetal deaths, and impairment of ossification (incomplete bone growth)” in data submitted for FDA approval in the 1980s. Some animals also showed signs of congenital heart defects and developmental retardation.
GSK Settles Government Allegations of Off-label Marketing for Pregnant Women
One of the main issues surrounding Zofran is off-label marketing. The FDA does not allow drug companies to market their drugs for uses not approved by the agency, although doctors can do so as they see fit. GSK has faced lawsuits alleging that it marketed Zofran off-label for pregnant women experiencing morning sickness. Both consumers and the government have filed such claims.
GlaxoSmithKline agreed to pay $3 billion to resolve fraud allegations and failure to report safety issues in July 2012. According to the United States Department of Justice, it was the largest health care fraud settlement in US history and the largest payment ever made by a drug maker at the time. The settlement resolved allegations involving several drugs, including Zofran. In particular, the government alleged that GSK marketed some forms of Zofran to treat morning sickness in pregnant women even though the FDA had not approved it for this purpose. The settlement also resolves allegations that the company paid illegal kickbacks to health care professionals to promote the use of Zofran and other medications.
“Patients rely on their physicians to prescribe the drugs they need,” said U.S. Attorney for Colorado John Walsh, according to the DOJ release. “The pharmaceutical industries’ drive for profits can distort the information provided to physicians concerning drugs. This case will help to ensure that your physician will make prescribing decisions based on good science and not on misinformation, money or favors provided by the pharmaceutical industry.”
According to the release, Stuart F. Delery, Acting Assistant Attorney General for the Justice Department’s Civil Division said: “This landmark settlement demonstrates the Department’s commitment to protecting the American public against illegal conduct and fraud by pharmaceutical companies,…Doctors need truthful, fair, balanced information when deciding whether the benefits of a drug outweigh its safety risks. By the same token, the FDA needs all necessary safety-related information to identify safety trends and to determine whether a drug is safe and effective. Unlawful promotion of drugs for unapproved uses and failing to report adverse drug experiences to the FDA can tip the balance of those important decisions, and the Justice Department will not tolerate attempts by those who seek to corrupt our health care system in this way.”