Zofran (ondansetron) is an anti-nausea and anti-vomiting medication manufactured by GlaxoSmithKline. The U.S. Food and Drug Administration (FDA) has only approved it for patients undergoing chemotherapy, radiation treatment or surgery.
Zofran first hit the market in 1991. The drug prevents nausea and vomiting by blocking serotonin in the brain and belongs to a class of drugs known as 5HT3 receptor antagonists.
There have been some safety concerns involving Zofran, including its off-label use. Doctors can prescribe drugs off-label as they see fit, but pharmaceutical companies are not allowed to promote their products for unapproved uses. GlaxoSmithKline allegedly marketed Zofran off-label for pregnant women experiencing morning sickness. In July 2012, the company agreed to pay $3 billion to settle allegations of fraud and failure to report safety data for several drugs, including Zofran. The federal government had alleged that GSK touted Zofran for unapproved uses and paid illegal kickbacks to health care professionals to promote its use.
The off-label use of Zofran to treat morning sickness is especially worrisome given that the drug has been linked to an increased risk of congenital birth defects. Zofran birth defects may include mental disabilities, physical deformities, vision and hearing problems, heart defects, cleft lip and cleft palate, stomach issues, club foot, webbed toes, skull deformities and abnormal blood pressure. A number of Zofran morning sickness lawsuits have been filed over this issue.
Studies and Side Effects
Zofran may lead to birth defects by crossing the placental barrier; it is also present in breast milk. Concentrations of the drug can be as high as 41 percent in fetal tissue samples, court documents indicate.
The Slone Epidemiology Center in Boston, Massachusetts and the Center for Disease Control and Prevention showed that Zofran is associated with a two-fold increased risk of cleft palate defects in a large 2011 study. This risk was present when pregnant women took the medication in their first trimester.
The American Journal of Obstetrics and Gynecology published a review of Zofran in December 2014. The review, which was authored by Dr. Gideon Koren, cited a “2-fold increased risk of cardiac malformations with ondansetron (Zofran), leading to an overall 30 percent increased risk of major congenital malformations” in a 2013 study involving 900,000 Danish women. Nausea and vomiting occurs in about 80 percent of pregnant women. Roughly 1 million expectant mothers are exposed to the drug each year, but the authors of the study emphasize that there are other FDA-approved treatments for this purpose. “There is no reason for women to be exposed to a drug of unproven maternal and fetal safety,” Dr. Koren wrote.
The link between Zofran and birth defects also appears to be apparent in GSK’s own clinical studies. Court documents indicate that there were “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. There were also some signs of congenital heart defects and developmental retardation.
Other serious side effects associated with the use of Zofran include Serotonin Syndrome and long QT Syndrome. In patients with Serotonin Syndrome, there are abnormally high levels of serotonin in the body. While it is a necessary neurotransmitter, excessively high concentrations could be life-threatening. Patients may experience symptoms such as high fever, irregular heartbeat, seizures and unconsciousness. The FDA warns that “The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue). Some of the reported cases were fatal. Serotonin syndrome occurring with overdose of another 5-HT3 receptor antagonist alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT3 receptor antagonist use occurred in a post-anesthesia care unit or an infusion center.”
In patients with long QT syndrome, the heart beat becomes fast and chaotic. Long QT syndrome may lead to sudden fainting, seizures and, in some cases, death.
According to the National Institute of Health U.S. National Library of Medicine, patients taking Zofran should seek emergency medical help if they experience the following side effects:
- blurred vision or vision loss
- swelling of the eyes, face, lips, tongue, throat, hands, feet, ankles, or lower legs
- difficulty breathing or swallowing
- chest pain
- shortness of breath
- dizziness, light-headedness, or fainting
- fast, slow or irregular heartbeat
- hallucinations (seeing things or hearing voices that do not exist)
- excessive sweating
- nausea, vomiting, or diarrhea
- loss of coordination
- stiff or twitching muscles
- coma (loss of consciousness)
In June 2012, the FDA announced the recall of the 32 mg single intravenous dose of Zofran due to potential heart problems. The agency said that preliminary results of a clinical study indicated that the drug may interfere with the electrical activity of the heart, causing QT interval prolongation. This condition could trigger Torsades de Pointes, a potentially fatal heart rhythm, the FDA warned.
The agency stated that these risks are higher in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias and patients taking medications that prolong the QT interval.
The risk of Zofran side effects may increase when certain other drugs are used, including:
- SSRIs (antidepressants such as Paxil or Zoloft)
- SNRIs (antidepressants such as Cymbalta and Pristiq)
- Phenytoin, Rifampin, Carbemazepine