Zofran was originally developed in the 1980s by GlaxoSmithKline, an English pharmaceutical company, and later approved in the United States by the FDA. Upon the drug’s U.S. patent expiration in 2006, it was the 20th highest-selling brand name drug in the country. In 2015, GlaxoSmithKline’s oncology division was sold to Novartis, who acquired the trademark rights to Zofran as part of the transaction.
The World Health Organization has included ondansetron – the active ingredient in Zofran – on it’s list of essential medicines needed for a country’s basic health-care system. Since the patent on ondansetron expired more than a decade ago, it is available in many generic forms throughout the world. In the U.S., the two most common brand names for ondansetron are Zofran and Zuplenz.
Due to some of the problems related to Zofran and birth defects, GlaxoSmithKline – the original manufacturer and marketer of the drug – is the subject of hundreds of lawsuits. In 2015, Novartis purchased the oncology division of GlaxoSmithKline, and as a result Novartis is now also named as a defendant in lawsuits claiming Zofran-related damages after March 23, 2015.
In October 2015, lawsuits related to Zofran were transferred to the District of Massachusetts under MDL No. 2657. This transfer was agreed to by both the plaintiffs and the defendants as a way to improve the efficiency of the proceedings. Cases remain as individual complaints; however, because many of the cases have similar claims and evidence, they can be handled much faster than going through the court system separately.
According to the long-form complaint common to all the participants of MDL 2657, plaintiffs allege that serotonin signalling is an important regulator of embryonic development. In marketing Zofran as a safe morning sickness drug, GlaxoSmithKline (and later Novartis) failed to warn patients, medical providers, and the general public of the potential dangers to prenatal exposure to the drug. Furthermore, since the FDA has never approved Zofran to treat morning sickness, the companies violated federal laws and regulations related to drug marketing.
Zofran Safety Concerns
There are a number of safety concerns related to ondansetron. The most common adverse effects, according to the FDA, are headache, fatigue, constipation, and diarrhea. However, much more severe conditions can result from taking Zofran, including serotonin syndrome and arrhythmia, each of which can result in death.
Zofran helps prevent nausea and vomiting by blocking serotonin, a chemical produced naturally in the gastrointestinal tract (among other places within the body). Due to the physiological effects of blocking serotonin in this way, taking Zofran could lead to a variety of severe effects, including:
These symptoms are most frequently reported in patients who are taking other types of drugs that affect serotonin levels, including selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue.
Zofran and Abnormal Heart Rhythms
There is evidence that Zofran can affect what is known as that QT interval – that is, the heart’s electrical cycle – which can in turn affect the rhythm of the heart. Specifically, Zofran can increase the QT interval, leading to an abnormal heart condition known as torsades de pointes, or “twisting of the points.” This is a serious cardiac condition that can lead to sudden death by heart attack.
While this condition can occur with any form and dosage of ondansetron, it has been most closely linked with the intravenous (IV) 32 mg dosage. In December 2012, the FDA issued a safety warning about the dangers of IV ondansetron, and as a result several manufacturers took their versions of the drug off the market, including Baxter Healthcare, Hospira, Teva, Bedford Labs, and Claris.
Uses of Zofran
|Brand Names||Zofran, Zofran ODT, Zuplenz|
|Generic Name||ondansetron, ondansetron hydrochloride|
|Manufacturer||Novartis/GlaxoSmithKline (Zofran), MidaTech Pharma (Zuplenz), others (generic)|
|Common Dosages||4 mg (children), 8 mg, 16 mg, 24 mg|
|FDA Approval||First approved in 1991; label updated in September 2016|
Zofran is an antiemetic – that is, an antinausea drug – used most often to treat the side effects of cancer treatment, including chemotherapy and radiation therapy. It may also be used to prevent nausea and vomiting during or after surgery, typically a side effect of anesthesia medications.
As a prophylactic treatment, Zofran is typically given to the patient approximately 30 minutes before their cancer treatment or 1 hour before being given anesthesia in preparation for surgery. It will usually be administered for up to 8 hours after the cancer treatment or surgery.
Although it has not been approved by the FDA for use by pregnant women in combating pregnancy-related nausea, Zofran has been prescribed by many doctors as an off-label treatment for morning sickness. Worldwide attention was brought to this off-label use of Zofran in 2012 and 2014 when Kate Middleton, the wife of Prince William of England, was prescribed the drug for each of her two pregnancies.
The risks related to pregnant women and fetuses are disputed and still largely unknown. The FDA has stated that studies have reported “inconsistent outcomes,” and that many of the studies have problems with their methodologies that prevent the agency from making a determination about Zofran’s safety. A retrospective review published in July 2016 concluded that there is no evidence of harm to embryos or fetuses; however, more studies are likely necessary to determine whether there are any risks involved with pregnant women taking the drug. Other studies have shown an increase in heart-related problems of babies born to mothers who were taking Zofran while pregnant.
According to a 2013 study published in the Journal of Clinical Outcomes Management, ondansetron is prescribed frequently in hospitals for reasons other than to prevent nausea and vomiting related to treatment of cancer or surgery. In fact, the study indicated that elderly patients were more likely to receive ondansetron than standard antiemetic treatment in hospital settings, despite there being no clear evidence in suggesting that ondansetron is more effective at treating nausea and vomiting for non-indicated uses than standard drugs. The authors of the study called for changes in hospital policy and practices to rein in these off-label uses.
Separately, a 2006 study looked at the effects of Zofran on children who visited a pediatric emergency department with gastroenteritis (a viral infection that can cause diarrhea and vomiting) and dehydration. According to the results of the study, children who took Zofran were less likely to vomit, and those who vomited did so fewer times than those who took a placebo.