Ondansetron, sold under the brand names Zofran, Zofran ODT, and Zuplenz, is typically used to treat nausea and vomiting after surgery, cancer chemotherapy, or radiation. The following article provides more detailed information on the use, side effects, and drawbacks of this drug.

Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific and clinical literature. Please discuss your medications with your doctor.

What Is Ondansetron?

Ondansetron is an antiemetic drug, which means that it can prevent nausea and vomiting.

Ondansetron reduced nausea and vomiting in a study of 15 patients undergoing chemotherapy (open-label) over 30 years ago. It was then patented by the Glaxo Group Ltd. in Great Britain and approved by the U.S. Food and Drug Administration (FDA) in 1991 [R].

Ondansetron is approved for preventing nausea and vomiting after surgery, chemotherapy, or radiation. However, it is now being tested for a variety of other uses, including vomiting in acute gastroenteritis, which is a type of stomach inflammation commonly seen in children [R].

Mechanism of Action

Chemotherapy causes nerves in the digestive tract to release serotonin, which can trigger nausea and vomiting. Ondansetron blocks these serotonin receptors (5-HT3), which are located on the vagus nerve endings along the digestive tract, and in the brain [R, R, R].

Since ondansetron acts on serotonin in the brain, it may improve symptoms in schizophrenia [R].

Uses of Ondansetron

1) Nausea and Vomiting

Caused by Chemotherapy

In a large study (meta-analysis of 26 randomized controlled trials), ondansetron reduced nausea and vomiting caused by chemotherapy [R].

After Radiation

Ondansetron prevented nausea and vomiting caused by radiation [R].

Twenty patients (double-blind randomized controlled trial) undergoing total body radiation therapy who received this drug had less nausea and vomiting compared to placebo [R].

After Surgery

Ondansetron prevented postoperative nausea and vomiting (PONV) after general anesthesia in a study of 112 patients (double-blind randomized controlled trial) [R].

Studies have (double-blind randomized controlled trials) confirmed that it is effective in preventing PONV [R, R].

Ondansetron has recently been compared to many other similar drugs, (like ramosetron and palonosetron) in clinical trials for the treatment of PONV. These similar drugs worked as well as ondansetron [R, R].

Caused by Stomach Infections

Ondansetron prevented vomiting caused by acute gastroenteritis in studies of 1,215 participants (systematic review of 10 RCTs) [R].

Acute gastroenteritis is vomiting and/or diarrhea that occurs for more than 7 days in a row, most often caused by viral infection [R].

The usual treatment is intravenous fluid for rehydration and prescription drugs like ondansetron for the prevention of vomiting. Ondansetron prevented vomiting in multiple studies in children with acute gastroenteritis (compared to the placebo) [R, R, R].

In Pregnancy

Ondansetron reduced nausea and vomiting in a study of 160 pregnant women (double-blind randomized controlled trial). Half received ondansetron and the rest another antiemetic (metoclopramide) for 24 hours. Ondansetron had fewer side effects but was more expensive.

2) Irritable Bowel Syndrome w/ Diarrhea (IBS-D)

Ondansetron helps improve symptoms of irritable bowel syndrome with diarrhea (IBS-D) [R].

It controlled symptoms of IBS-D in a preliminary study (pilot double-blind randomized controlled trial) of 14 patients. Ondansetron can cause constipation (otherwise considered a side effect), which reduces the urgency of diarrhea in patients with IBS [R].

In a study (randomized controlled trial) of 120 patients with IBS, ondansetron improved stool consistency and reduced frequency and urgency of diarrhea [R].

3) May Decrease Chronic Fatigue

In a study (pilot) of 19 patients with chronic fatigue syndrome, ondansetron decreased fatigue and improved physical capacity [R].

4) May Help Tourette’s Syndrome

Ondansetron reduced tics in a study (pilot) of 6 men with Tourette’s syndrome who didn’t improve with antipsychotics (haloperidol) [R].

5) May Reduce Fibromyalgia

In a study of 21 patients with fibromyalgia, ondansetron reduced pain [R].

6) May Improve OCD

In a study (double-blind randomized controlled trial) of 46 OCD patients, ondansetron combined with an antidepressant (fluvoxamine) reduced symptoms more than the antidepressant alone [R].

7) May Reduce Hallucinations in Parkinson’s

In a study (open trial) of 7 Parkinson’s patients, ondansetron reduced hallucinations associated with treatment (levodopa) [R].

8) Improves Symptoms in Schizophrenia

In 202 patients (3 double-blind randomized controlled trialS, 2 case reports) with schizophrenia, ondansetron reduced symptoms, improved cognitive function, and caused fewer side effects than antipsychotics [R].

Ondansetron was added on to standard treatment (antipsychotics) for schizophrenia in several studies. It may improve symptoms of low mood and social isolation (negative symptoms) [R, R].

9) Helps Narcotic Withdrawal

Ondansetron prevented morphine withdrawal symptoms in mice and humans (8 men) [R].

Pregnant mothers with drug addictions can give birth to babies with neonatal withdrawal syndrome (NAS). Symptoms include tremors, dehydration, fever, diarrhea, and vomiting in the newborns. Ondansetron may help prevent NAS. A study of 39 babies, 40 pregnant and 20 non-pregnant women determined ondansetron dosing for NAS [R].

10) Helps Shivering After Anesthesia

Shivering is a common symptom after anesthesia. In a meta-analysis of 6 trials including 533 patients, ondansetron reduced shivering after anesthesia [R].

11) May Reduce Seizures and Memory Loss

In mice, ondansetron reduced seizures and improved memory. This is probably due to its activation of the memory-forming part of the brain, the hippocampus [R].

Side Effects

The most common side effects of ondansetron are headache, dizziness, constipation, and diarrhea [R].

Ondansetron may increase liver enzymes, which is a sign of liver damage. However, it is difficult to determine if this is the effect of ondansetron or cancer treatment [R].

Rare side effects include restlessness and uncontrollable eye and facial movements [R].

Zofran disintegrating tablets contain phenylalanine, and should not be taken by people with phenylketonuria [R].

Ondansetron may cause persistent and painful erections (priapism) [R, R].

The FDA issued a warning that high doses of ondansetron may cause abnormal heart rhythms, potentially leading to arrhythmias. This calls for healthcare providers to monitor high-risk patients using an electrocardiogram (ECG) while taking ondansetron. Risk factors include a history of heart failure, arrhythmias, and other medication (such as opioids, antidepressants, antipsychotics, antiarrhythmics, antihistamines, and SSRIs). In some cases, it can be fatal [R, R, R, R, R].


Hypersensitivity to ondansetron or any of its components [R].

Use with apomorphine as the two together may cause excess low blood pressure (hypotension) [R].

Pregnancy and Breast Feeding Considerations

Ondansetron was a pregnancy risk category B. In general, there are no definitive studies that have shown ondansetron to be a risk to the fetus. However, caution is always advised if you are going to take the medication while pregnant, and the benefits of taking the medication should be weighed versus any potential risk to the fetus. Please speak to your doctor or a qualified healthcare professional.

Drug Interactions

Droperidol and dexamethasone can increase the anti-nausea effects of ondansetron [R, R].

Ondansetron reduces the effectiveness of tramadol, which is usually taken after surgery to relieve pain [R].

Ondansetron can cause serotonin syndrome when combined with other drugs (fentanyl, paroxetine, duloxetine, and bupropion) [R].

Other drugs metabolized by CYP enzymes can interact with ondansetron [R].

Forms and Dosage

Ondansetron can be taken orally as tablets or solutions, or as injections (intravenously or intramuscularly) [R].

Single dosage for oral tablets and solutions is 8 mg, intravenously 8 mg, and intramuscularly 4 mg. After oral use, it takes 30 minutes for ondansetron to achieve an effect [R].


ABCB1 – Variants in this gene increase or decrease how well ondansetron gets into the brain [R, R].

HTR3B – Variants in this gene may lead to failure of ondansetron to treat nausea and vomiting [R].

CYP2D6 & CYP3A – These genes encode the cytochrome P-450 enzyme, used to break down ondansetron. Having multiple copies of these genes increases the removal of ondansetron, which decreases the effect of the drug on nausea and vomiting [R, R].

Limitations and Caveats

It is not recommended to treat nausea and vomiting in pregnancy with ondansetron, due to lack of safety data [R, R].

Aside from reducing nausea and vomiting, other uses of ondansetron need additional research to confirm the findings. These are currently limited.

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