Zofran is an anti-nausea drug that has been linked to severe cardiovascular side effects. When it is used during the first three months of pregnancy, it may also increase the risk of having a baby with a birth defect.
What is Zofran?
Zofran (ondansetron) is a drug used to treat nausea and vomiting caused by chemotherapy. It is also used in lower doses after surgery. Zofran belongs to a class of drugs called 5-HT3 serotonin receptor antagonists. It was first marketed by the drug company GlaxoSmithKline (GSK) and was approved by the FDA in 1991. It is now available as a generic medication (ondansetron).
Zofran Pregnancy Side Effects
The side effects of using Zofran to treat morning sickness during the first trimester of pregnancy are unknown. Although it is commonly used “off-label,” Zofran is not approved by the FDA for pregnancy and no placebo-controlled studies have investigated the risk of birth defects.
Some studies are reassuring. In February 2013, the New England Journal of Medicine published a study involving 600,000 births in Denmark and found no association between Zofran and birth defects. However, this study was limited because half of the women started taking Zofran after the 10th week of pregnancy when their baby was no longer at risk of heart defects, cleft lip, and other side effects.
In August 2013, Zofran was linked to a 30% increased risk of birth defects and a doubled risk of heart defects. The study, “Ondansetron use in early pregnancy and the risk of congenital malformations,” examined data on 900,000 pregnancies in Denmark from 1997-2010. Birth defects occurred in about 4.7% of babies exposed to Zofran in the first trimester, compared to 3.5% of non-exposed babies.
In June 2014, the Toronto Star published an investigative report linking Zofran and nearly two dozen cases of birth defects in Canada. These side effects included heart defects, kidney malformations, musculoskeletal abnormalities, and more.
We are evaluating the following pregnancy risks:
- Birth defects
- Heart defects
- Heart murmur
- Atrial septal defect (“hole in the heart”)
- Cleft lip
- Cleft palate
Case reports also suggest Zofran may increase the risk of the following side effects:
- Fetal growth restriction (poor growth in the womb)
- Kidney defects
- Life-threatening complications for mother (serotonin syndrome, irregular heart rhythm, Torsade de Pointes, etc.)
- Fetal or maternal death
Zofran Cardiovascular Side Effects
The most serious side effects of Zofran occur when it interferes with electrical activity in the heart. This can lead to a fatal irregular heart rhythm. Specific cardiac side effects include:
- Chest pain or discomfort
- Fatal, pounding, slow, or irregular heart rhythm
- QT interval prolongation
- Torsades de Pointes
- Ventricular arrhythmia
Other Serious Side Effects
- Blurred vision
- Allergic reaction, which may be life-threatening
- Swelling of the lips, face, tongue
- Weakness, fatigue
- Diarrhea or constipation
- And more
QT Interval and Torsade de Pointes
Studies of Zofran have linked it to a cardiac disorder called QT interval prolongation, which can lead to a fatal irregular heart rhythm disorder called Torsades de Pointes.
QT interval prolongation is an electrical disorder that occurs when the heart has an abnormally long “recovery” period between beats. An interval above 440 milliseconds is considered prolonged. In studies of Zofran, a 32-mg IV dose was associated with an average difference of 20 milliseconds. An IV dose of 8-mg was associated with a difference of 6 milliseconds.
Torsades de Pointes, or “twisting of the spikes,” is a life-threatening heart rhythm disorder that occurs when the QT interval is 600 milliseconds or greater. It can potentially degenerate into a quivering, ineffective heartbeat called ventricular fibrillation that is associated with loss of blood pressure, fainting, and sudden death.
Zofran and FDA Warnings
In September 2011, the FDA warned that Zofran may increase the risk of “developing prolongation of the QT interval of the electrocardiogram, which can lead to an abnormal and potentially fatal heart rhythm, including Torsades de Pointes.” The label was updated to warn against prescribing Zofran to people with certain risk factors.
After cardiac risks were identified, the FDA required the manufacturer to conduct a study to determine what doses of Zofran may cause QT interval prolongation. In June 2012, the study found that QT interval prolongation could occur after a single 32-mg dose of Zofran.
FDA Investigates Serotonin Syndrome and Zofran
The FDA is evaluating evidence linking Zofran and serotonin syndrome, a potentially life-threatening side effect that occurs when levels of serotonin get too high.
Zofran treats nausea by influencing serotonin levels. Many other medications, such as SSRI antidepressants, also influence serotonin. It is possible that combining these medications could increase the risk of serotonin syndrome.
Side effects of serotonin syndrome include:
- Agitation or restlessness
- Rapid heartbeat and high blood pressure
- Loss of muscle coordination, twitching or rigid muscles
- Heavy sweating
- High fever
- Irregular heartbeat
- Loss of consciousness
On December 4, 2012, the U.S. Food and Drug Administration (FDA) recalled 32-mg Zofran due to concerns about cardiac problems. The 32-mg formulation is pre-mixed and given as a single intravenous dose. In a statement, the FDA said they do not expect the recall to contribute to a drug shortage because the “32-mg dose makes up a very small percentage of the current market.”