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5 Uses of Ondansetron (Zofran) + Side Effects

Written by Mathew Eng, PharmD | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Mathew Eng, PharmD | Last updated:

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Ondansetron, sold under the brand name Zofran, 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.

What Is Ondansetron?

Ondansetron (brand name Zofran) is a prescription medication that is used to prevent nausea and vomiting.

Ondansetron is FDA-approved for the prevention of nausea and vomiting that is caused by chemotherapy, radiation, and surgery. This medication is often the drug of choice for preventing nausea and vomiting in these conditions [1].

Ondansetron is sometimes used off-label to treat several other conditions, including nausea and vomiting associated with pregnancy and gastroenteritis (also known as the stomach flu) [2, 3].

Mechanism of Action

Ondansetron primarily works by blocking serotonin (5-HT3) receptors.

Serotonin is a neurotransmitter that plays a variety of roles in the body, including memory, cognition, and mood. Serotonin also triggers nausea and vomiting when it binds to certain receptors in the brain stem [4].

Toxins and upsetting foods can trigger a sharp increase in serotonin, leading to nausea and vomiting. Chemotherapy and radiation therapy can trigger this effect as well [4].

Ondansetron blocks serotonin from binding to these receptors, which ultimately can reduce the feeling of nausea and vomiting [4].

Uses of Ondansetron

FDA-Approved Uses

1) Chemotherapy-Induced Nausea and Vomiting

Ondansetron is one of the first-line medications used to prevent nausea and vomiting associated with chemotherapy [5].

A systematic review of 26 clinical trials found that ondansetron reduces nausea and vomiting caused by chemotherapy. The review also suggests that ondansetron has similar effectiveness to other drugs in the same class [6].

However, the review also found that ondansetron was not as effective as palonosetron (a drug in the same class as ondansetron) for preventing delayed nausea and vomiting, which is a type of nausea and vomiting that occurs days after treatment with chemotherapy [6].

2) Radiation Therapy-Related Nausea and Vomiting

Nausea and vomiting can affect 50-80% of people undergoing radiation therapy. Ondansetron is commonly used to prevent this [7].

One review compared the guidelines put out by several cancer institutions, such as the European Society of Clinical Oncology and the American Society of Clinical Oncology. The review found that all institutions agreed that ondansetron should be used to prevent radiation-induced nausea and prevent in all high-risk patients [7].

However, it’s not as clear if ondansetron should be used in patients who are at low risk for nausea and vomiting [7].

3) Surgery-Related Nausea and Vomiting

The anesthesia medications used during surgery can cause significant nausea and vomiting following the procedure. Ondansetron is sometimes administered immediately after surgery to prevent this [8].

A randomized placebo-controlled trial of 84 patients undergoing surgery found that ondansetron may significantly reduce the incidence of nausea and vomiting. A similar study in 50 surgical patients found similar results [9, 10].

Another randomized trial of 112 patients undergoing general anesthesia suggests that ondansetron is more effective at preventing nausea and vomiting than haloperidol, another drug sometimes used for this purpose [11].

Off-Label Uses

Ondansetron is used for several off-label conditions, which we’ll discuss in the following sections. If you are prescribed this medication, always take the medication as directed by your doctor.

4) Pregnancy-Related Nausea and Vomiting

Ondansetron is sometimes used to prevent nausea and vomiting associated with pregnancy, including morning sickness.

In a randomized trial of 36 women, ondansetron reduced nausea and vomiting better than pyridoxine and doxylamine, which are also used to prevent nausea and vomiting during pregnancy [12].

Similarly, a randomized trial of 160 pregnant women suggests that ondansetron may also be more effective than metoclopramide for preventing nausea and vomiting [13].

5) Stomach Flu (Gastroenteritis) Related Nausea and Vomiting

The stomach flu, also called gastroenteritis, is caused by an infection in the intestines, which can cause fever, diarrhea, nausea, and vomiting.

A systematic review of 10 clinical trials including 1,215 children found that ondansetron may help reduce vomiting associated with the stomach flu in kids. This may also help improve rehydration therapy, which is important in severe cases of stomach flu [3].

Clinical Research on Ondansetron

Clinical research is exploring the use of ondansetron for several other conditions, which are described below. However, this research is preliminary and investigational only. The safety and effectiveness of ondansetron for these conditions is unclear until more studies are performed.

Schizophrenia Symptoms

A systematic review of 5 clinical trials including 304 patients suggests that ondansetron may help reduce the negative symptoms of schizophrenia when used as an add-on to conventional treatment. Negative symptoms in schizophrenia include apathy, lack of social interest, and loss of motivation [14].

Shivering Associated with Anesthesia

Shivering is a common symptom after receiving anesthesia. In a meta-analysis of 6 trials including 533 patients, ondansetron reduced shivering after anesthesia [15].

Irritable Bowel Syndrome w/ Diarrhea (IBS-D)

A randomized placebo-controlled trial of 120 patients with irritable bowel syndrome found that ondansetron may improve diarrhea symptoms, including loose stools, frequency, and urgency [16].

Chronic Fatigue Syndrome

A pilot study of 19 patients with chronic fatigue syndrome suggests that ondansetron may decrease fatigue and improve physical capacity [17].

Tourette’s Syndrome

Ondansetron reduced tics in a pilot study of 6 men with Tourette’s syndrome who did not respond to conventional treatment [18].

Fibromyalgia

In a preliminary study of 21 patients with fibromyalgia, ondansetron reduced pain in about half of the participants [19].

OCD Symptoms

A randomized placebo-controlled trial of 46 OCD patients found that ondansetron combined with an antidepressant (fluvoxamine) may reduce OCD symptoms more than the antidepressant alone [20].

Hallucinations in Parkinson’s Disease

An open trial with 7 Parkinson’s patients suggests that ondansetron may reduce hallucinations associated with levodopa, a medication used for Parkinson’s [21].

Safety of Ondansetron

Side Effects

Ondansetron can cause several side effects. If any side effects persist or worsen, let your doctor know. This is also not a complete list of possible side effects. Tell your doctor if you experience any serious side effects or notice any effects not listed here.

Some common side effects include [22]:

  • Headache
  • Fatigue
  • Constipation
  • Diarrhea

Some serious side effects include [22]:

  • Chest pain
  • Irregular heartbeat
  • Stomach pain
  • Muscle stiffness
  • Vision changes
  • Severe dizziness

Precautions

Use in Heart Rhythm Disorders

Ondansetron has been shown to disrupt heart rhythm, specifically, a measurement called the QT interval. This medication should be avoided in those with long QT syndrome. For those taking ondansetron, heart rhythm should be monitored in those at risk for abnormal heart rhythm or in people taking other drugs that may affect the QT interval [22].

Serotonin Syndrome

Serotonin syndrome is a life-threatening disorder that can occur when taking one or more medications that increase serotonin levels, such as ondansetron. Always let your doctor know of all the medications and supplements you are taking to avoid harmful interactions.

Some common symptoms of serotonin syndrome include high body temperature, agitation, tremors, sweating, and dilated pupils, which can lead to seizures and death. Seek immediate medical attention if you suspect you are experiencing this disorder.

Contraindications

Those who are allergic or sensitive to ondansetron or any of its components should not take this medication [22].

Those who take the medication apomorphine should not take ondansetron, as the two together may cause excessive low blood pressure (hypotension) [23].

Pregnancy and Breastfeeding Considerations

According to the FDA, ondansetron is generally considered safe for use during pregnancy [22].

However, there is some evidence that there may be some risks. A systematic review of 8 clinical trials suggests that ondansetron is associated with a very small increase in the incidence of heart defects in newborns. Researchers suggest considering other treatment options before using ondansetron [24].

It’s unclear if ondansetron is present in breast milk. A doctor will weigh the benefits and risks when determining if the use of ondansetron is appropriate during breastfeeding.

Drug Interactions

The following drugs have been reported to interact with ondansetron. However, this is not a complete list, let your doctor know of all the medications you are currently taking to avoid any unexpected interactions.

  • Apomorphine
  • Medications that increase QT prolongation, such as amiodarone and sotalol
  • Medications that increase serotonin, which includes many types of antidepressants
  • Tramadol
  • Phenytoin
  • Certain antibiotics, including clarithromycin and erythromycin

Forms and Dosage

The dosing of ondansetron can vary. Always take this medication as directed by a doctor.

Ondansetron can be taken orally as tablets, orally disintegrating tablets, or solutions. Ondansetron can also be injected (intravenously or intramuscularly) [25].

Ondansetron tablets are available in 4 mg and 8 mg. Dosing can vary depending on age, other health conditions, and the condition being treated. In general, ondansetron is administered shortly before a procedure (chemotherapy/radiation/surgery) and then given regularly for several days after [22].

Genetics

ABCB1 – Variants in this gene may increase or decrease how well ondansetron gets into the brain [26, 27].

HTR3B – Variants in this gene may lead to the failure of ondansetron to treat nausea and vomiting [28].

CYP2D6 & CYP3A – These genes encode the cytochrome P-450 enzyme, used to break down ondansetron. Having multiple copies of these genes may increase the removal of ondansetron, which may decrease the effectiveness of the drug on nausea and vomiting [29, 30].

Complementary Treatments

The following section details some complementary treatments that may help with nausea or vomiting. 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. These alternatives should not be used to replace medical treatment.

1) Diet & Lifestyle Changes

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

Some common food triggers include [31]:

  • 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)

Certain habits may also be contributing to nausea and vomiting. Changing these habits may help to reduce or prevent symptoms [31].

Some general lifestyle recommendations are [31, 32, 33]:

  • 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

2) Ginger

According to research, ginger may help reduce nausea and vomiting.

A review of 12 clinical trials including 1,278 women examined ginger’s effect on nausea and vomiting caused by pregnancy. Researchers found that ginger may reduce nausea, but it does not significantly reduce vomiting. No side effects or safety concerns were reported [34].

Ginger may also reduce nausea and vomiting related to seasickness and surgery, according to another review of 6 studies [35].

The evidence is less clear for chemotherapy-induced nausea and vomiting. One systematic review identified 3 clinical trials that support the use of ginger and 2 trials that found no effect [36].

Ginger may also be helpful as an add-on to ondansetron for post-surgery nausea and vomiting. A randomized study of 100 people undergoing surgery found that ginger and ondansetron may be more effective than ondansetron alone [37].

Menthol

Menthol is a natural compound found in different plant oils, like peppermint. It is commonly used for its ability to create a cooling sensation in various food and skin products [38].

A randomized trial of 200 people found that peppermint oil capsules may reduce the severity and frequency of nausea and vomiting related to chemotherapy. A similar effect was seen with spearmint oil. There were no side effects reported with either supplement [39].

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

For example, one study of 123 patients found that inhaling peppermint oil may reduce nausea in post-surgery patients. Several studies have found similar benefits to nausea and vomiting [40, 41, 42].

About the Author

Mathew Eng

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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