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Zofran side effects and how to avoid them

Learn about the common and serious side effects of Zofran, a popular prescription medication used to prevent nausea and vomiting in patients undergoing radiation therapy, chemotherapy, or surgery.

Zofran side effects | Serious side effects | Irregular heartbeat | Serotonin syndrome | How long do side effects last? | Warnings | Interactions | How to avoid side effects

Zofran is a brand-name prescription drug used to prevent nausea and vomiting in people undergoing cancer chemotherapy, radiation therapy, or surgery. Ondansetron hydrochloride, the active ingredient in Zofran, belongs to a class of antiemetics (anti-nausea drugs) called 5-HT3 receptor antagonists. These drugs block serotonin, a chemical in the brain that passes signals between nerves. By blocking serotonin, ondansetron shuts down the “chemoreceptor trigger zone,” the area of the brain responsible for the nausea reflex. Zofran is a widely-used drug, but it may not be right for everyone. Side effects can be a problem, particularly for people with certain medical or physical conditions. 

Common side effects of Zofran

The most common side effects of Zofran include:

  • Headache
  • Drowsiness
  • Diarrhea
  • Fatigue
  • Feeling bad (malaise)
  • Constipation
  • Fever
  • Dizziness
  • Agitation or anxiety
  • Urinary retention
  • Itching

Serious side effects of Zofran

Ondansetron can cause serious side effects including:

  • Abnormal heart rhythms (arrhythmias)
  • Serotonin syndrome
  • Temporary blindness
  • Drug-induced movement problems (extrapyramidal effects including twitching, slurred speech, and involuntary rolling of the eyes upward)
  • Severe allergic reactions such as anaphylaxis

Zofran and irregular heartbeats

Zofran can affect the heart’s rhythm. In particular, Zofran affects the QT interval, the time it takes for the bottom chambers of the heart to contract and then fully relax. Zofran can increase that time, a phenomenon called QT prolongation or long QT syndrome. If QT prolongation is too great, the bottom chambers lose their rhythm and start to beat wildly, causing conditions such as torsades de pointes, a potentially life-threatening heart condition. When taking Zofran, get immediate medical attention at any sign of QT prolongation such as:

  • Palpitations
  • Shortness of breath
  • Chest pain
  • Lightheadedness
  • Fainting

Healthcare providers do not know the exact incidence of QT prolongation in people taking Zofran, but as a side effect, it is more likely in people who already have heart rhythm abnormalities, a family history of QT prolongation, slow heart rate, congestive heart failure, heart attack, or an electrolyte imbalance such as low magnesium, low calcium, or low potassium. It is also more likely when Zofran is combined with other drugs that lengthen the QT interval such as selective serotonin reuptake inhibitors (SSRIs), antipsychotics, antifungal drugs, and some types of antibiotics.

Zofran and serotonin syndrome

Serotonin syndrome is a drug-induced condition that occurs when serotonin levels in the brain get too high, causing the brain to become overstimulated. Symptoms are usually mild and last for only a few days, but the most severe cases can be life-threatening. In most cases, serotonin syndrome is brought on by taking more than one drug that affects serotonin levels. However, ondansetron and similar drugs—5-HT3 receptor antagonists including granisetron and dolasetron—can cause serotonin syndrome when taken alone. The exact incidence is not known, but get medical help at any sign of serotonin syndrome such as:

  • Agitation
  • Hallucinations
  • Rapid heartbeat
  • High or low blood pressure
  • Dizziness
  • Sweating
  • Flushing
  • Fever
  • Tremor
  • Muscle rigidity
  • Overactive reflexes
  • Loss of coordination
  • Nausea

How long do side effects last?

Most common Zofran side effects such as headache, drowsiness, constipation, and diarrhea go away when the drug is discontinued. Zofran has a half-life of three to four hours in healthy adults, but this may be increased to six to eight hours in older adults. This means it takes the body three to four hours to eliminate half a dose of Zofran from the body, so the entire dose should be eliminated in 15 to 20 hours. That’s when most side effects should fade.

Some more serious side effects may take longer to resolve. Some, like serotonin syndrome, severe allergic reactions, or heart rhythm abnormalities, may require emergency medical treatment to get better. Severe heart rhythm problems, however, may produce lifelong complications.

Zofran contraindications & warnings

Physical and medical conditions may affect the safety or effectiveness of Zofran, so some people may not be able to take Zofran and others may require dosing changes or closer monitoring for adverse reactions.

Abuse and dependence

The U.S. Food and Drug Administration (FDA) does not classify ondansetron as a controlled substance, meaning it has no potential for abuse or physical dependence. Ondansetron is given either as a single dose or for no longer than a few days during cancer treatment, radiation treatment, or surgery. Withdrawal symptoms are not experienced when ondansetron treatment is discontinued.


An overdose of Zofran can be a serious medical emergency or even fatal, so get emergency medical attention if too much Zofran has been taken. A Zofran overdose will cause symptoms such as temporary vision loss, severe constipation, light-headedness, and fainting. In addition, serotonin syndrome has been reported in children who have overdosed on Zofran.


When a drug is never given to people with certain medical conditions, those medical conditions are called contraindications. Zofran is contraindicated in people who have a known hypersensitivity to ondansetron because of the risk of severe allergic reactions. Zofran is also contraindicated in people who have congenital long QT syndrome because of the risk of serious heart rhythm abnormalities.

Healthcare professionals will avoid Zofran or use it cautiously in people with certain medical conditions such as:

  • People with a family history of long QT syndrome because of the risk of serious heart rhythm abnormalities
  • People with a history of heart rhythm abnormalities, heart attack, or heart failure
  • Irregular heartbeats are also a risk if ondansetron is given to people with electrolyte imbalances, particularly low magnesium, low potassium, or low calcium. 
  • Zofran is used cautiously and with extra monitoring in people at risk of gastrointestinal obstruction, including people who have undergone recent abdominal surgery.
  • People with phenylketonuria, a hereditary condition that can produce a toxic buildup in the body of the amino acid phenylalanine. 

Pregnancy and nursing

There is not enough research about the use of ondansetron during pregnancy or breastfeeding to be certain if it is safe for an unborn baby or infant. There is currently no evidence that ondansetron has caused birth defects, miscarriages, or harm to a breastfeeding infant. Pregnant or nursing women should consult a healthcare professional before taking Zofran.


The U.S. Food and Drug Administration (FDA) has approved ondansetron in children as young as 6 months to prevent nausea due to cancer chemotherapy and as young as 1 month to prevent postoperative nausea and vomiting (PONV). However, for children younger than 4 years of age, a generic ondansetron intravenous injection will be given instead of Zofran tablets.


People older than 65 are given ondansetron in the same doses as younger adults. However, some older adults may need to be monitored or tested regularly for side effects. Seniors eliminate the drug from their bodies more slowly than younger adults. They are also more likely to experience heart rhythm problems. 

Zofran interactions

As with any other prescription drug, certain drug interactions can cause problems when people are taking ondansetron. Some drugs are never given with ondansetron, while others may require dosing changes or more careful monitoring for side effects such as:

  • Zofran is never given along with the Parkinson’s medication Apokyn (apomorphine). The combination can cause serious side effects such as loss of consciousness, heart arrhythmias (QT prolongation), and dangerously low blood pressure (hypotension). 
  • Because of the risk of potentially fatal heart arrhythmias, Zofran is never given with the antipsychotic drugs pimozide and thioridazine, the antiarrhythmic drugs dofetilide or Multaq (dronedarone), or a drug similar to Zofran called cisapride.
  • Antipsychotic medications, antiarrhythmics (drugs that correct the heart’s rhythm), azole antifungal drugs, macrolide antibiotics, and fluoroquinolone antibiotics.
  • Serotonergic drugs should either be avoided or used with careful monitoring when someone is also taking ondansetron. These drugs include
  • The strongest CYP3A4 inhibitors are usually avoided with Zofran, but the Zofran dose may be reduced when combined with less strong inhibitors. Alternatively, some drugs “switch on” CYP3A4 and speed up the breakdown of ondansetron, reducing its effectiveness. The strongest of these drugs—such as phenytoin, carbamazepine, or rifampin—may require the Zofran dose to be increased.

How to avoid Zofran side effects

For the most part, Zofran’s side effects are minor—usually a headache, drowsiness, and constipation. A few tips, however, can reduce both the incidence and severity of side effects.

1. Take Zofran as directed

Take Zofran tablets exactly as instructed. The typical dose is 8–16 mg in one to eight doses taken over a few days. Do not skip a dose or stop taking the medicine early. The doctor may give special instructions if you vomit after taking Zofran tablets, so follow these instructions carefully.

2. Tell the healthcare provider about all medical conditions

The first step in avoiding serious side effects is to make sure the prescribing healthcare professional knows about your medical conditions and medical history. For ondansetron, side effects are more likely in people with the following medical conditions:

  • Heart disease
  • Heart rhythm abnormalities
  • Slow heartbeats
  • Electrolyte imbalance
  • Any history or family history of QT prolongation
  • Any intestinal blockage
  • Liver disease
  • Any history of allergies to ondansetron, granisetron, palonosetron, or dolasetron

While there is no certainty about the risks, make sure to tell the healthcare provider about pregnancy, breastfeeding, or any plans to get pregnant or breastfeed.

3. Tell the healthcare provider about all medications

Drug interactions between ondansetron and other medications can also cause problems. The healthcare provider particularly needs to know if you are taking any of the following medications:

Do not take other prescriptions or over-the-counter medicines until checking in with a doctor or other healthcare provider.

4. Be careful about driving and other risky activities

Zofran can cause drowsiness, dizziness, and other impairments. For most people, these effects will be minor. Still, it’s a good idea to be careful about driving, operating machinery, or participating in potentially hazardous activities when taking Zofran.

5. Contact a healthcare provider if vomiting continues

If vomiting continues, contact a healthcare provider. An additional dose may be prescribed or the healthcare provider may switch to another medication.

6. Watch for signs of heart rhythm problems

Contact a doctor if there are any signs of heartbeat problems such as palpitations, lightheadedness, or chest pain.

7. Watch for signs of intestinal problems

Consult with a healthcare provider if abdominal pain or swelling is experienced. It may be a sign of a serious blockage.