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 [1].

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 [2].

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 [3, 4, 5].

Since ondansetron acts on serotonin in the brain, it may improve symptoms in schizophrenia [6].

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 [7].

After Radiation

Ondansetron prevented nausea and vomiting caused by radiation [8].

Twenty patients (double-blind randomized controlled trial) undergoing total body radiation therapy who received this drug had less nausea and vomiting compared to placebo [9].

After Surgery

Ondansetron prevented postoperative nausea and vomiting (PONV) after general anesthesia in a study of 112 patients (double-blind randomized controlled trial) [10].

Studies have (double-blind randomized controlled trials) confirmed that it is effective in preventing PONV [11, 12].

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 [13, 14].

Caused by Stomach Infections

Ondansetron prevented vomiting caused by acute gastroenteritis in studies of 1,215 participants (systematic review of 10 RCTs) [15].

Acute gastroenteritis is vomiting and/or diarrhea that occurs for more than 7 days in a row, most often caused by viral infection [16].

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) [15, 17, 18].

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) [19].

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 [20].

In a study (randomized controlled trial) of 120 patients with IBS, ondansetron improved stool consistency and reduced frequency and urgency of diarrhea [19].

3) May Decrease Chronic Fatigue

In a study (pilot) of 19 patients with chronic fatigue syndrome, ondansetron decreased fatigue and improved physical capacity [21].

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) [22].

5) May Reduce Fibromyalgia

In a study of 21 patients with fibromyalgia, ondansetron reduced pain [23].

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 [24].

7) May Reduce Hallucinations in Parkinson’s

In a study (open trial) of 7 Parkinson’s patients, ondansetron reduced hallucinations associated with treatment (levodopa) [25].

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 [6].

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) [26, 27].

9) Helps Narcotic Withdrawal

Ondansetron prevented morphine withdrawal symptoms in mice and humans (8 men) [28].

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 [29].

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 [30].

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 [31].

Side Effects

The most common side effects of ondansetron are headache, dizziness, constipation, and diarrhea [13].

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 [32].

Rare side effects include restlessness and uncontrollable eye and facial movements [33].

Zofran disintegrating tablets contain phenylalanine, and should not be taken by people with phenylketonuria [34].

Ondansetron may cause persistent and painful erections (priapism) [35, 36].

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 [37, 37, 38, 39, 40].


Hypersensitivity to ondansetron or any of its components [41].

Use with apomorphine as the two together may cause excess low blood pressure (hypotension) [41].

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 [42, 43].

Ondansetron reduces the effectiveness of tramadol, which is usually taken after surgery to relieve pain [44].

Ondansetron can cause serotonin syndrome when combined with other drugs (fentanyl, paroxetine, duloxetine, and bupropion) [45].

Other drugs metabolized by CYP enzymes can interact with ondansetron [46].

Forms and Dosage

Ondansetron can be taken orally as tablets or solutions, or as injections (intravenously or intramuscularly) [47].

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 [48].


ABCB1 – Variants in this gene increase or decrease how well ondansetron gets into the brain [49, 50].

HTR3B – Variants in this gene may lead to failure of ondansetron to treat nausea and vomiting [51].

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 [52, 46].

Limitations and Caveats

It is not recommended to treat nausea and vomiting in pregnancy with ondansetron, due to lack of safety data [53, 54].

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

Natural Alternatives

Dealing with nausea and vomiting can be a distressing experience, especially when standard medications aren’t working. It’s common for patients to seek natural alternatives to avoid taking more drugs [55].

Research has identified several natural substances that work similarly to ondansetron. These substances have potential as an alternative option or as an add-on to conventional treatment.

You should always consult your doctor before changing or stopping your medications. It’s also important to let your doctor know of all the supplements you are currently taking, in case of potential interactions.

1) Ginger

Ginger can potentially be used for a wide variety of conditions, nausea and vomiting included.

According to cell studies, ginger inhibits serotonin (5-HT3) receptors. Gingerol, shogaol, and zingerone (compounds found inside ginger) were all able to block the receptor [56, 57, 58].

Ginger’s effect on substance P, acetylcholine receptors, and gut movement may also play a role [59].

A review of 12 clinical trials including 1278 women examined ginger’s effect on nausea and vomiting caused by pregnancy. They found that ginger reduces nausea, but it does not significantly reduce vomiting. No side effects or safety concerns were reported [60].

Ginger also reduces nausea and vomiting related to seasickness and surgery, based on another review [61].

The evidence is a little less clear for chemotherapy-induced nausea and vomiting. One review identified 5 clinical trials that support the use of ginger. However, 2 studies found no effect [62].

Ginger may also be helpful as an add-on to ondansetron for post-surgery nausea and vomiting. A study of 100 people found that ginger and ondansetron are more effective than ondansetron alone [63].

Here’s a tip: cooking or heating ginger can change the compounds inside, potentially reducing its serotonin blocking ability. Fresh, raw ginger may be more effective at preventing nausea and vomiting [64, 65].

2) Menthol

Menthol is a natural compound found in different plant oils, like peppermint. Most people know it as the ingredient that creates a cooling sensation in various food and skin products [66].

Besides its cooling effect, menthol may have several other health benefits, such as preventing nausea and vomiting [65].

Research in cells shows that menthol blocks serotonin (5-HT3) receptors, similar to ondansetron [67, 65, 68].

A study of 200 people found that peppermint oil capsules reduce the severity and frequency of nausea and vomiting. A similar effect was seen with spearmint oil. There were no side effects reported with either supplement [69].

Many studies have also looked at peppermint oil’s potential as aromatherapy.

For example, one study of 123 patients found that inhaling peppermint oil reduced nausea in post-surgery patients. Other studies have found similar benefits to nausea and vomiting [70, 71, 72].

Some other health benefits of menthol include pain relief, itching relief, and antibacterial properties [67, 73].

3) Cannabis

Cannabis plants contain compounds called cannabinoids, most notably THC and CBD. These cannabinoids act on cannabinoid receptors in the body, causing many of the effects associated with marijuana [74].

Both CBD and THC are able to block serotonin (5-HT3) at its receptor, based on cell studies [75, 76].

Cannabinoid receptors are also linked to anti-nausea and anti-vomiting effects [77, 78].

The FDA has already approved two synthetic THC medications (dronabinol and nabilone) for the treatment of chemotherapy-induced nausea and vomiting [79].

A large systematic review looking at cannabinoids for nausea and vomiting related to chemotherapy was recently completed. Researchers found that cannabinoids are more effective than placebo and as effective as some medications, like prochlorperazine [80].

However, cannabinoids are also associated with more side effects, like drowsiness and cognitive impairment [80].

In the end, the researchers conclude that there is not enough evidence yet to say if cannabinoids should be used or not [80].

4) Diet & Lifestyle Changes to Prevent Nausea

Certain foods and drinks are known to trigger nausea and vomiting in some people.

Some common food triggers include [81]:

  • Fatty, greasy, or fried foods
  • Very sweet foods
  • Spicy foods
  • Grilled foods
  • Foods with a strong odor
  • Caffeine
  • Alcohol
  • Preserved foods
  • Poultry, eggs
  • Monosodium glutamate (MSG)

Of course, any foods that cause an allergic reaction should also be avoided. Food intolerances are usually milder than an allergy, but can also cause nausea and vomiting [82]. In short, avoiding food triggers and eating a quality diet can effectively prevent nausea and vomiting [81, 83].

Certain habits may also be contributing to your nausea and vomiting. Changing these habits can be an easy and effective way to reduce or prevent symptoms [81].

Some general lifestyle recommendations are [81, 84, 85]:

  • Eat and drink slowly
  • Eat smaller portions
  • Eat more frequently, something small every 1 – 2 hours
  • Drink liquids separately from solid food, preferably 30 min apart
  • Do not lie down after eating for at least 1 hour
  • Rest after eating
  • Wear loose-fitting clothes

If You Have Food Sensitivities

I recommend following my lectin avoidance diet, named as such because I think that lectins are the single major trigger of autoimmune disease. However, they are not the only trigger. And this diet is not a one-size-fits-all regimen. It may not suit EVERYONE’s needs, but it’s a good template from which to build a personalized diet.

If you suffer from food sensitivities, the Lectin Avoidance Diet helps you figure out which foods are inflammatory, and which are less inflammatory for you.

About the Author

Mathew Eng, PharmD


Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.

Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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