Ondansetron Side Effects: What's Normal and What's Not

Ondansetron is one of the most widely prescribed anti-nausea medications in the world, and for most people, it works well with few problems. But like any medication, it can cause side effects.

This guide covers the common side effects you might experience, the serious ones to watch for, and when you should contact your doctor. If you're new to this medication, you may also want to read our overview of what Ondansetron is and how it's used.

What Is Ondansetron?

Ondansetron (brand name Zofran) is a 5-HT3 receptor antagonist — a type of medication that blocks serotonin signals that trigger nausea and vomiting. It's FDA-approved for preventing nausea from chemotherapy, radiation therapy, and surgery. Doctors also prescribe it off-label for morning sickness, stomach flu, and other causes of nausea. To learn more about how Ondansetron works, see our detailed explainer.

Common Side Effects

Most people who take Ondansetron experience mild side effects, if any. According to FDA labeling, the most common side effects include:

• Headache — The most frequently reported side effect, occurring in up to 27% of patients in clinical trials
• Constipation — Common, especially with repeated dosing. Staying hydrated and eating fiber can help.
• Fatigue or drowsiness — Some people feel tired after taking Ondansetron, though it's generally less sedating than older anti-nausea medications like Promethazine
• Diarrhea — Less common than constipation but still reported in clinical trials
• Dizziness — Usually mild and temporary

These side effects are typically mild and go away on their own within a few hours or after you stop taking the medication. Most people find that the benefit of controlling nausea far outweighs these minor effects.

Serious Side Effects

Serious side effects from Ondansetron are uncommon, but they do occur. Seek medical attention right away if you experience any of the following:

QT Prolongation and Heart Rhythm Changes

Ondansetron can cause a heart rhythm change called QT prolongation, which in rare cases can lead to a dangerous arrhythmia called Torsades de Pointes. The FDA issued a safety communication about this risk in 2012 and withdrew the 32 mg single IV dose.

Symptoms to watch for:

• Fast or irregular heartbeat
• Fainting or feeling like you might faint
• Severe dizziness

This risk is higher if you have a heart condition called congenital long QT syndrome, take other medications that affect heart rhythm, or have electrolyte imbalances (low potassium or magnesium).

Serotonin Syndrome

When Ondansetron is taken with other medications that increase serotonin levels (such as SSRIs, SNRIs, Tramadol, or Fentanyl), there is a risk of serotonin syndrome — a potentially life-threatening condition. See our guide on Ondansetron drug interactions for the full list.

Symptoms include:

• Agitation or restlessness
• Rapid heartbeat
• Muscle twitching or stiffness
• High fever
• Loss of coordination
• Nausea, vomiting, or diarrhea

Severe Allergic Reactions

Anaphylaxis is rare but has been reported. Seek emergency help if you experience:

• Difficulty breathing or swallowing
• Swelling of the face, lips, tongue, or throat
• Hives or severe skin rash

Other Serious Effects

• Masking of bowel obstruction — Ondansetron can mask symptoms of a progressive bowel obstruction (ileus) or stomach distension. If you have abdominal surgery, your doctor will monitor for this.
• Liver damage (rare) — Hepatotoxicity has been reported in rare cases. Tell your doctor if you develop yellowing of the skin or eyes, dark urine, or unusual fatigue.

Side Effects in Specific Populations

Pregnancy

Ondansetron is classified as Pregnancy Category B, meaning animal studies have not shown harm but there are limited human studies. It is widely prescribed for morning sickness and hyperemesis gravidarum. Talk to your OB/GYN about the benefits and risks for your situation.

Liver Impairment

Patients with severe liver problems should not take more than 8 mg per day, as the medication is processed by the liver and levels may build up.

Children

Ondansetron is approved for children aged 6 months and older for specific indications. Dosing is weight-based in pediatric patients. Side effects are similar to those in adults.

Elderly Patients

Older adults may be more susceptible to QT prolongation, especially if they take other heart medications or have low electrolyte levels.

How to Manage Common Side Effects

If you experience mild side effects, here are some practical tips:

• Headache — Over-the-counter pain relievers like Acetaminophen (Tylenol) usually help. Drink plenty of water.
• Constipation — Increase fiber intake, drink more fluids, and stay active. A mild stool softener may help if needed.
• Drowsiness — Avoid driving or operating heavy machinery until you know how Ondansetron affects you.
• Dizziness — Stand up slowly and avoid sudden movements. This usually passes quickly.

If side effects are bothersome or don't go away, talk to your doctor. They may adjust your dose or suggest an alternative medication.

Final Thoughts

Ondansetron is generally well-tolerated and remains one of the safest and most effective anti-nausea medications available. Most side effects are mild — headache and constipation being the most common. Serious side effects like QT prolongation and serotonin syndrome are rare but important to know about, especially if you take other medications.

Always tell your doctor about your full medication list before starting Ondansetron. If you need help finding this medication at a pharmacy near you, Medfinder can help you check stock in real time.