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Zofran Side Effects

Among the side effects from taking Zofran (ondansetron) are headaches, drowsiness, lightheadedness and constipation. In rare cases, the anti-nausea medication causes erratic heartbeats and potentially life-threatening high serotonin levels.

Last Modified: September 5, 2023
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Common Zofran Side Effects

Zofran (ondansetron) is used to relieve nausea and vomiting regularly associated with cancer treatments such as chemotherapy and radiation. Doctors can also use it to prevent and treat post-surgical nausea and vomiting.

Providers often prescribe Zofran for nausea associated with pregnancy and morning sickness, but this is an off-label, or unapproved, use of the drug.

Common Zofran side effects include:
  • Headache
  • Constipation
  • Chills
  • Drowsiness
  • Tiredness
  • Weakness

These side effects are not serious unless they linger more than a few days. Zofran can also mask signs of a bowel obstruction in people who have just had abdominal surgery or those going through chemotherapy or radiation therapy.

Even common side effects from the drug are rare, but you may feel sick to your stomach after taking Zofran. The medication blocks serotonin from entering certain cells of the nervous system in charge of the nausea reflex.

Severe Allergic Reactions to Ondansetron

Other serious reactions include long QT syndrome, a potentially deadly heart problem, and serotonin syndrome, a life-threatening combination of symptoms resulting from the overactive production or accumulation of serotonin. Although uncommon, ondansetron can cause severe allergic reactions, such as anaphylaxis and bronchospasm.

One study from 2021 reported that an 82-year-old woman visited an emergency room with symptoms of vertigo, vomiting and general weakness. Attending physicians gave her IV ondansetron, and she developed acute respiratory distress and then cardiac arrest. She died soon thereafter. Probable cause listed for her death was the medication.

Abnormal Heart Rhythms

People who take Zofran can develop irregular heart rhythms. According to the medication’s label, reported arrhythmias include heartbeats that are too fast (tachycardia), too slow (bradycardia), or that are too fast and originate from the wrong part of the heart (ventricular and supraventricular tachycardia).

Some people reported atrial fibrillation, a rapid, quivering heartbeat. Providers also documented significant electrocardiogram changes, including second-degree heart block and QT interval prolongation, a serious abnormality and can lead to a potentially fatal arrhythmia known as torsades de pointes.

Arrhythmias can show an array of symptoms, including:
  • Skips in heartbeats
  • Fluttering sensations in the neck or chest
  • Fainting or near fainting
  • Pounding heartbeats
  • Dizziness or lightheadedness
  • Shortness of breath
  • Seizures
  • Sudden cardiac arrest (and sudden death)

Zofran’s label warns providers not to prescribe the drug to people who have had long QT syndrome since birth. It also advises doctors to monitor the hearts of people who are taking Zofran along with certain other medications that can also lead to QT prolongation, and those who have congestive heart failure, abnormally slow heartbeats and certain electrolyte abnormalities such as low potassium or low magnesium.

Serotonin Syndrome from Zofran

One of the risks of taking Zofran is the possibility of serotonin syndrome, a dangerous condition caused by an excess of serotonin in the body. It has been reported in people who take Zofran, particularly if they also take antidepressants or other medications that increase serotonin levels.

A 2021 study reported serotonin syndrome was seen in people taking Zofran and any of three classes of antidepressant drugs that are high in serotonin. They are selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and monoamine oxidase inhibitors (MAOIs).

Signs and symptoms of serotonin syndrome include:
  • Ocular clonus (involuntary eye movement)
  • Hyperreflexia (twitching, spastic movements)
  • Agitation
  • Anxiety
  • Restlessness
  • Disorientation
  • Diaphoresis (excess sweating)
  • Hyperthermia
  • Tachycardia
  • Nausea
  • Vomiting
  • Tremors
  • Muscle rigidity
  • Dilated pupils
  • Dry mucus membranes
  • Flushed skin
  • Increased bowel sounds

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

Excessive amounts of serotonin cause an overstimulation of the central nervous system. Issues often arise in a post-anesthesia care unit or infusion center.

Taking Zofran During Pregnancy

Zofran is often prescribed to pregnant women who endure morning sickness and hyperemesis gravidarum, a condition that causes severe nausea, vomiting and weight loss. The medication is not approved by the U.S. Food and Drug Administration for such use, and for years the risks were unclear.

Six cohort studies and two case-control studies show Zofran crosses the placental barrier, and early pregnancy use increased the risk of heart and orofacial defects.

Hundreds of women filed Zofran lawsuits against GlaxoSmithKline, alleging the medication caused birth defects to their babies.

A large 2021 study of more than 450,000 pregnancies in three countries showed no association between ondansetron and an increased risk to newborns compared to other anti-nausea drugs. That includes stillbirths, congenital malformations and spontaneous abortions.

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