

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.
Note: 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 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].
Contraindications
Hypersensitivity to ondansetron or any of its components [R].
Use with apomorphine as the two together may cause excess low blood pressure (hypotension) [R]. .
Safety During Pregnancy and Breast Feeding
Ondansetron is pregnancy risk category B. The FDA defines category B as: “animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women”. If a woman does experience nausea and/or vomiting while pregnant, alternative medications should be considered first before ondansetron [R, R].
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].
Genetics
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.
I would suggest that you mention in greater detail some of the risks of this medication. I recently took this medication for the first time via 2 sublingual tablets while receiving care at an immediate care facility. A few hours later, I began to have suicidal thoughts. It would be more accurate to say that the only thoughts coming into my head were concerning specific ways that I could kill myself. Fortunately, I was able to identify these thoughts and did not harm myself, but I could not have trusted myself to be alone during that period of time as the desire to harm myself was incredibly overwhelming (I should also add that I do not have any history of suicidal thoughts or tendencies and do not suffer from depression or other mental illnesses.)
Evidently suicidal thoughts are likely to occur the first few times a person takes this medication, however I was not informed of this when the medication was administered. I only found this out when I did a little digging on the possible side effects of this medication. When I brought this up with my physician later on they told me that this is not a known side effect, however that is inaccurate when you look at the drug information. I mentioned my frightening experience with Zofran to a family member who took the drug while undergoing chemotherapy. She recalled at least one specific incident in which she asked her husband to hide his handgun where she could not find it because she felt she might harm herself. She was never warned about this side effect by her doctor or pharmacist when it was prescribed for her, which is unacceptable. The administration of this drug in cancer patients seems particularly problematic to me since cancer patients are likely to experience major depression and may not be able to resist the suicidal thoughts that this medication can bring about. It is frightening that doctors and pharmacists not only fail to warn patients about this side effect, but as I experienced, tell their patients that suicidal thoughts are not documented, thereby making it seem as if you as the patient have experienced something that is remarkably rare.
Hi Julie,
Thank you for the comment and information. I couldn’t find an article to link so I didn’t add this information to the post but I’ll leave your comment for people to see.
Thanks!
Caroline
Thank you for informations