Zofran Side Effects

Zofran may cause headaches, drowsiness, constipation and other mild side effects. In rare cases, the anti-nausea medication can cause erratic heartbeats and high serotonin levels, which may be life-threatening. The drug has also been said to cause birth defects, though research findings are mixed.

Zofran Pills
Zofran Side Effects
  1. Common Side Effects Headache and drowsiness are the drug’s most frequent side effects.
  2. Abnormal Heart Rhythms Zofran can cause QT interval prolongation and a potentially fatal heart rhythm called torsades de pointes.
  3. Serotonin Syndrome Larger doses of Zofran or using the medication in combination with other drugs can cause a dangerous rise in serotonin levels.
  4. Birth Defects Some research has shown an increased risk of septal defects of the heart in infants whose mothers took Zofran while pregnant.

Zofran (ondansetron) is used to relieve the nausea and vomiting commonly associated with cancer treatments like chemotherapy and radiation. It can also be used to prevent and treat post-surgical nausea and vomiting.

Common side effects associated with Zofran include headache, drowsiness, constipation and the chills. In clinical trials, nearly a quarter of patients taking 8 mg of the drug twice daily experienced a headache. Malaise occurred in 13 percent of patients, constipation in 9 percent and diarrhea was reported in 6 percent.

In rare cases, the drug can cause serious and potentially harmful side effects. These adverse reactions include long QT syndrome, a potentially deadly heart problem, and serotonin syndrome, a life-threatening combination of symptoms resulting from the overactive production of serotonin.

Zofran can mask the signs and symptoms of a bowel obstruction in patients who’ve just had abdominal surgery or who are taking chemotherapy. Such patients should be closely monitored for decreased bowel activity or signs of an ileus, a paralysis of the bowel that prevents contents from moving through the intestines.

Did You Know?
Oral Zofran tablets that dissolve under the tongue contain phenylalanine, a chemical in aspartame. Patients with Phenylketonuria (PKU), a genetic condition that causes a buildup of phenylalanine in the body, should avoid the medication
Source: FDA Prescribing label for Zofran

Though uncommon, the medication can cause severe allergic reactions, such as anaphylaxis and bronchospasm, according to the drug’s label. If a hypersensitivity reaction occurs, a patient should seek immediate medical attention and stop using the drug.

The anti-nausea medicine is often prescribed to treat nausea associated with pregnancy and morning sickness, but this is an off-label, or unapproved, use of the drug. Some studies have linked the drug to birth defects and hundreds of Zofran lawsuits have been filed in federal court.

Abnormal Heart Rhythms

Irregular heartbeats may develop in patients taking Zofran. According to the drug’s label, reported arrhythmias have included heartbeats that are too fast (tachycardia) or too slow (bradycardia) or that are too fast and originate from the wrong part of the heart (ventricular and supraventricular tachycardia).

Some patients have reported developing atrial fibrillation, a rapid and quivering heartbeat. Serious electrocardiogram (ECG) changes — including second-degree heart block and QT interval prolongation — have also been reported.

A QT interval is the measure of time between the start of the “Q wave” and the end of the “T wave” in the heart’s electrical cycle. This cycle is normally between 350 and 440 milliseconds, but Zofran can sometimes lengthen the interval.

Signs and symptoms of arrhythmias linked to lengthened QT interval include:
  • Unexplained fainting
  • Seizures
  • Drowning or near drowning
  • Sudden cardiac arrest (death)

A prolonged QT interval is a serious abnormality and can lead to a potentially fatal arrhythmia known as torsades de pointes.

Torsades de pointes is a form of ventricular tachycardia (VT), a rapid heartbeat starting in the lower chambers of the heart (ventricles). This abnormal heartbeat can degenerate into ventricular fibrillation, which can lead to sudden cardiac death.

Safety Warning
In 2012, Zofran manufacturer GlaxoSmithKline announced it was removing the 32 mg single intravenous dose of the drug because it could predispose patients to an abnormal and potentially fatal heart rhythm called torsades de pointes.
Source: U.S. Food and Drug Association
A 2017 article in the Texas Heart Institute Journal described two patients who developed torsades de pointes after being administered ondansetron in the hospital:
  • One patient, a 51-year-old woman who was being treated for severe nausea and vomiting, developed torsades de pointes approximately one day after receiving six doses of IV ondansetron. She became “unresponsive and pulseless” and had to be revived with CPR.
  • The other patient, a 51-year-old man, developed QT prolongation and bouts of ventricular tachycardia but did not lose consciousness. He had been suffering from chronic diarrhea and had low potassium levels, which can adversely affect heart function.

Some episodes of torsades de pointes are limited and do not cause symptoms. However, patients may experience palpitations — sensations of hard, fast and/or irregular heartbeats — and lightheadedness. Patients with torsades de pointes have an increased risk of fainting and suffering from sudden cardiac death.

Zofran’s label advises doctors to perform heart monitoring of people who are taking the drug along with other medications that can also lead to QT prolongation or in patients with:
  • Certain electrolyte abnormalities (such as low potassium or low magnesium)
  • Congestive heart failure
  • Abnormally slow heartbeats (bradyarrythmias)

The drug’s label also warns health providers to avoid using the medication in patients who have had long QT syndrome since birth.

Serotonin Syndrome Risk

Serotonin syndrome — a dangerous condition caused by an excess of serotonin in the body — has also been reported in patients using Zofran. In most cases, the patients were using the drug along with antidepressants or other medications that increase serotonin levels.

Some of the reported cases were fatal, according to the drug’s label. The majority of the cases occurred in a post-anesthesia care unit or infusion center, but a Zofran overdose can also lead to serotonin syndrome.

Serotonin syndrome has been reported in patients taking Zofran and these serotonergic drugs:
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin and norepinephrine reuptake inhibitors (SNRIs)
  • Monoamine oxidase inhibitors (MAOIs)

The condition is triggered by increased nerve-cell activity, resulting from a buildup of too much serotonin in the body or the brain.

Normally, the chemical helps to regulate several critical body functions including digestion, blood flow, body temperature and breathing. It also assists in the proper functioning of nerve and brain cells, which impacts mood. But excessive amounts of serotonin cause an overstimulation of the central nervous system.

Signs and symptoms of serotonin syndrome can include:
  • Irritability, restlessness or anxiety
  • Dilated pupils
  • Nausea, vomiting and diarrhea
  • Fast heartbeat and high blood pressure
  • Hallucinations
  • Increased body temperature
  • Loss of coordination
  • Overactive reflexes
  • Muscle spasms or rigidity
  • Tremors or shivering
  • Rapid changes in blood pressure
  • Confusion or disorientation

In more severe cases, symptoms may include unresponsiveness, coma, seizures, irregular heartbeat and death.

Birth Defects

Zofran is frequently prescribed to pregnant women suffering from morning sickness and hyperemesis gravidarum, a condition that causes severe nausea, vomiting and weight loss. But the drug has not been approved for treating these conditions, and the risks associated with taking the drug during pregnancy are unclear.

Hundreds of women have filed suit against manufacturer GlaxoSmithKline claiming that use of the drug during pregnancy caused their babies to be born with birth defects, such as cleft palates and heart defects. Research findings are mixed.

A 2014 study by Swedish researchers in the journal of Reproductive Toxicology found a “statistically significant” increased risk of cardiovascular defects — including septal defects (holes between the chambers) of the heart — among infants whose mother’s took ondansetron early in their pregnancy. The study looked at 1,349 infants born between 1989 and 2012.

Other studies, however, have found no association between the use of ondansetron and birth defects.

A 2016 study in the journal Reproductive Toxicology examined the outcomes of more than 1,000 pregnancies during which the mother took ondansetron and found no evidence of increased risk of birth defects. In fact, pregnant women with hyperemesis gravidarum who took ondansetron had fewer miscarriages and higher live birth rates than those who didn’t, according to the study.

The drug’s label, meanwhile, notes that the offspring of rabbits and rats have shown “evidence of harm to the fetus” when the drug was administered at six to 24 times the maximum daily dose for humans. But the manufacturer concludes that current evidence “does not reliably inform the association” between Zofran and birth defects.

Please seek the advice of a medical professional before making health care decisions.

Related Pages
Nurse Amy Keller
Written By Amy Keller, RN Registered Nurse

Amy Keller is a registered nurse and award-winning journalist with 22 years of experience writing about politics, business, health and other topics. At Drugwatch, she draws on her clinical experience and investigative reporting skills to write about consumers’ health concerns such as the safety of online pharmacies. She also provides informed analysis on complex health issues. Some of her qualifications include:

  • Recipient of USF’s Nurse Alumni Nightingale award for excellence in nursing
  • Guest Faculty Speaker, “Moving Forward with Patient- and Family-Centered Care Intensive Training Seminar”
  • Member of Sigma Theta Tau International Honor Society of Nursing
Edited By

15 Cited Research Articles

  1. ACP Internist. (2011, September 20). Ondansetron contraindicated in patients with QT prolongation. Retrieved from https://acpinternist.org/weekly/archives/2011/09/20/6.htm
  2. American Academy of Pediatrics. (2011, September 16). Zofran, generic label update: avoid use in patients with long QT syndrome. Retrieved from http://www.aappublications.org/content/early/2011/09/16/aapnews.20110916-1
  3. Anderka, M. et al. (2011, November 19). Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects. Retrieved from https://onlinelibrary.wiley.com/doi/abs/10.1002/bdra.22865
  4. Cocchio, C. (2016, February 2). QT Prolongation Observed with Ondansetron: A Clinical Concern? Retrieved from https://www.pharmacytimes.com/contributor/craig-cocchio-pharmd/2016/02/qt-prolongation-observed-with-ondansetron-a-clinical-concern
  5. Danielsson, B., Wikner, B.N. & Källén B. (2014, December). Use of ondansetron during pregnancy and congenital malformations in the infant. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25450422
  6. Fejzo, M.S., MacGibbon, K.W., Mullin, P.M. (2016, July). Ondansetron in Pregnancy and Risk of Adverse Fetal Outcomes in the United States. Retrieved from https://www.sciencedirect.com/science/article/pii/S0890623816300910?via%3Dihub
  7. Lee, D.Y., Trinh, T. & Roy, S.K. (2017, October). Torsades de Pointes after Ondansetron Infusion in 2 Patients. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731596/
  8. Li, K., Vo, K., Lee, B.K., Addo, N., & Coralic, Z. (2018, March 1). Effect of a Single Dose of I.V. Ondansetron on QTc Interval in Emergency Department Patients. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29317399
  9. Mitchell, L.B. (2017, September). Long QT Syndrome and Torsades de Pointes Ventricular Tachycardia. Retrieved from https://www.merckmanuals.com/professional/cardiovascular-disorders/arrhythmias-and-conduction-disorders/long-qt-syndrome-and-torsades-de-pointes-ventricular-tachycardia
  10. National Center for Advancing Translational Sciences. (2013, October 4). Long QT syndrome. Retrieved from https://rarediseases.info.nih.gov/diseases/6922/long-qt-syndrome
  11. National Heart, Lung, and Blood Institute. (n.d.). Long QT Syndrome. Retrieved from https://www.nhlbi.nih.gov/health-topics/long-qt-syndrome#Treatment
  12. U.S. National Library of Medicine. (2016, October 27). Label: Zofran – ondansetron hydrochloride injection. Retrieved from  https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7d61d98-fe86-4340-9b86-47eb92acaa0e
  13. U.S. National Library of Medicine. (2015, December 15). Ondansetron. Retrieved from https://medlineplus.gov/druginfo/meds/a601209.html
  14. U.S. National Library of Medicine. (2018, October 1). Serotonin syndrome. Retrieved from  https://medlineplus.gov/ency/article/007272.htm
  15. U.S. National Library of Medicine (2018, October 1). Ventricular tachycardia. Retrieved from  https://medlineplus.gov/ency/article/000187.htm
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