One of the less-known dangers associated with the off-label use of Zofran during pregnancy is the risks of cardiovascular accidents. Several cases of arrhythmias (abnormal heart rhythm) have been widely investigated in the past few years. Although cardiovascular issues represent a potentially fatal adverse reaction, they seem to be an often underrated side effect of this drug 1. Ondansetron is, in fact, contraindicated and should be considered unsafe in several populations of patients because of the risk of QT prolongation and irregular heart rhythm. An accurate review of the current scientific literature highlighted how some specific conditions may trigger the dangerous cardiovascular events associated with this medication 5, 6. These conditions include congestive heart failure, congenital long QT syndrome, bradyarrhythmias, electrolyte abnormalities, as well as patients taking other drugs which may prolong the QT interval.
Serious cardiovascular risk – the FDA issues a recall
In December 2012, the U.S. Food and Drug Administration (FDA) issued a recall for the 32 mg intravenous (IV) dose, as the risk for life-threatening cardiovascular accidents including sudden death was deemed too high 3. This particular Zofran dosage was thus removed from the market in early 2013 because of the potential for serious cardiac risks. A few months earlier FDA issued a warning about appropriate dosing, explicitly stating that “no single intravenous dose should exceed 16 mg.” According to their update warning in fact:
“32 mg single intravenous dose of ondansetron (Zofran, ondansetron hydrochloride, and generics) may affect the electrical activity of the heart (QT interval prolongation), which could pre-dispose patients to develop an abnormal and potentially fatal heart rhythm known as Torsades de Pointes. 4”
Even though ondansetron’s safety was reviewed, and important additional information for patients and healthcare professionals were added, the magnitude of these risks in gestating women was never properly measured. A large portion of the media’s attention focused, in fact, on the risk of fetal malformations and serotonin syndrome, especially since the manufacturer GlaxoSmithKline became the target of the largest pharmaceutical fraud settlement in the U.S. history. In 2012 in fact, the U.S. Department of Justice (DOJ) accused GSK of fraudulent promotion of this medication as an off-label drug to treat morning sickness and nausea and vomiting in pregnancy (NVP). Although the FDA only provided approval to this antiemetic to suppress these symptoms during chemotherapy and radiotherapy cancer treatments and surgical interventions, GSK sold it to pregnant women marketing it as a safe medication. The pharmaceutical company was eventually forced to plead guilty of criminal behavior and agreed to pay $3 billion to settle its criminal and civil liability 2.
Zofran during pregnancy – the unaddressed danger
Pregnant women suffering from the most severe form of NVP called hyperemesis gravidarum are often affected by significant electrolyte imbalance, and ondansetron should be thus considered contraindicated. Unless electrolyte abnormalities such as hypomagnesemia or hypokalemia are corrected prior to the infusion of the antiemetic drug, Zofran can outright kill or seriously harm a woman by causing her an irregular heart rhythm. However, FDA never approved this medication for use during pregnancy, so this specific danger has never been adequately addressed by the regulator 7.
But what hyperemesis gravidarum is? This condition is the most severe and intractable form of NVP and is characterized by incoercible vomiting. This may, in turn, cause malnourishment, weight loss and dehydration as the patient loses her fluids through vomit, and cannot rehydrate or nourish herself anymore because of excessive nausea. Symptoms and consequences of this condition include fatigue, nutritional disorders, physical stress, ketosis, and electrolyte imbalances 8. All these symptoms can also be detrimental to the health of the cardiovascular apparatus, and for this reason, ondansetron should be considered an high-risk medication instead of a potential treatment.
Torsades de pointes (TdP) and QT prolongation are two specific types of abnormal heart rhythm that can increase the risk of developing potentially fatal arrhythmias and ventricular fibrillations, which can lead to sudden cardiac death. Prolonged QT intervals and TdP should be treated immediately in the Emergency Room as they can quickly degenerate into ventricular fibrillation, a condition known for its high mortality rates 9. Patients showing symptoms such as shortness of breath, irregular heartbeat, dizziness, or fainting while taking Zofran should seek immediate care.
Article written by: Dr. Claudio Butticè, Pharm.D.
Last Updated: 2016/08/10