7 Zofran Side Effects You Should Know About

Zofran (ondansetron) is one of the most commonly used anti-nausea medications. It’s FDA approved to prevent nausea and vomiting caused by chemotherapy, radiation treatment, or surgery. Zofran works by blocking a chemical called serotonin from triggering nausea in the brain and gut. It’s available as a generic and comes in several different forms, such as tablets (regular and dissolvable), liquid, and injection.

Most people take Zofran without any issues. But it does have some side effects to know about while you’re taking it.

Zofran side effects at a glance

Most Zofran side effects are mild in nature. But there are a few more serious side effects you should be aware of. We’ve listed mild and serious Zofran side effects reported in clinical studies below. Keep in mind that other side effects are possible. Talk to your healthcare team about any issues that arise while taking Zofran, even if they aren’t listed here.

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Mild Zofran side effects:

• Headache

• Fatigue

• Constipation

• Diarrhea

• Hiccups

• Dizziness

• Anxiety

Rare, but serious Zofran side effects:

• Serotonin syndrome

• Heart problems

• Masking the signs of a bowel issue

• Allergic reactions

Below, we’ll dive into seven possible Zofran side effects in more detail, including ways you can manage them.

1. Headache

Headaches are one of the most common Zofran side effects. This includes mild headaches as well as more bothersome migraine headaches in some people. It’s unknown exactly why this happens.

There are a couple of ways to deal with headaches caused by Zofran. You can talk with your healthcare team about over-the-counter (OTC) options. This may include medications such as ibuprofen (Advil, Motrin) or acetaminophen (Tylenol). Rest, hydration, and placing an ice pack on your head may also help.

EXPERT PICKS: WHAT TO READ NEXT

• Does Zofran work for nausea? Hear people’s firsthand accounts about taking Zofran (ondansetron) for different types of nausea.

• Nausea medications: Learn about the different over-the-counter and prescription options for treating nausea.

• Zofran dosages: Read about the recommended Zofran dosages for different types of nausea.

Usually, the headache will go away once you stop taking Zofran. But if it’s bothersome, let your prescriber know. A severe or persistent headache could be a sign of a serious medical problem, so it’s important to have it checked.

2. Fatigue

Fatigue (feeling tired and weak) is another possible side effect of Zofran. Remember that fatigue can also be a side effect of the condition that’s causing your nausea (such as surgery or cancer treatment). So Zofran may not be the only factor.

A few tips to help manage fatigue include:

• Get a good night’s rest.

• Eat a well-balanced diet.

• Stay active.

• Take rest breaks throughout the day.

Use caution when driving until you know how Zofran affects you. If you have persistent fatigue, let your prescriber know. They can help determine the cause and how best to manage it.

3. Constipation

Constipation can occur while taking Zofran, but it isn’t common.

Ways to manage constipation include:

• Drinking plenty of water throughout the day

• Increasing your fiber intake

• Trying OTC medications such as docusate sodium (Colace) or polyethylene glycol (Miralax), but check with your healthcare team first to make sure they’re safe for you

Constipation that doesn’t go away could be a sign of a more serious problem, such as a bowel blockage (obstruction). People who are receiving chemotherapy or having stomach surgery are at a higher risk for bowel issues.

Zofran can mask nausea and vomiting, which are other common symptoms of a blocked or paralyzed bowel. So it’s important to let your prescriber know right away if you have constipation that doesn’t go away or other signs of a bowel problem, such as stomach pain and bloating.

4. Diarrhea

Diarrhea is another Zofran side effect that’s not common for most people. If it does happen, be sure to drink plenty of liquids to avoid dehydration. A bland diet, such as bananas, rice, and applesauce, can also help.

If needed, ask your pharmacist or prescriber about OTC diarrhea medications. Not all of them may be safe to take with ondansetron or your other medications.

Let your healthcare team know if your diarrhea lasts longer than 2 days or if you develop a fever. This could be a sign of a more serious problem.

5. Hiccups

Hiccups can occur in some people taking Zofran. Certain chemotherapy treatments and anesthesia used during surgery can also cause hiccups. And Zofran treats nausea caused by both of these. So it’s hard to know the true cause of hiccups in some cases.

Hiccups typically resolve on their own within a couple of days. The following tips may also help:

• Hold your breath.

• Breathe into a paper bag.

• Drink a cold beverage.

• Swallow sugar.

• Smell vinegar or smelling salts.

If you have hiccups that last for more than 2 days, let your healthcare team know. They can help find the cause and the right treatment for you.

6. Serotonin syndrome

Serotonin syndrome is a rare, but serious Zofran side effect. It happens when there’s too much serotonin in the body. Serotonin syndrome is more likely if you take Zofran with other medications that raise serotonin levels, such as antidepressants.

Signs of serotonin syndrome include:

• Agitation

• Hallucinations (seeing or hearing things that are not real)

• Fast heart rate

• Dizziness

• Tremors (shakiness)

• Seizures

If you notice any signs of serotonin syndrome, get immediate medical help.

It’s important to review your full medication list with your prescriber before taking Zofran. This can help reduce the risk of serotonin syndrome and ensure Zofran is a safe option for you.

7. Heart rhythm problems

People taking Zofran may experience heart rhythm problems. This includes an irregular heart rate known as long QT syndrome. Bradycardia (slow heart rate) can also happen. Changes to your heart rhythm are more common with injectable Zofran.

If you’re living with heart failure, have electrolyte imbalances (e.g., low potassium or magnesium levels), or are taking other medications that cause heart rhythm problems, your prescriber may need to keep a close eye on your heart function.

Let your healthcare team know right away if you notice lightheadedness, changes in heart rate, or fainting spells while taking Zofran.

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Written by:

ThienLy Neal, PharmD

ThienLy Neal, PharmD, has over 10 years experience in the pharmacy field, including in such settings as retail, hospital, compounding, and managed care. She has led various clinical programs while focusing on medication adherence programs, specialty drug initiatives, and polypharmacy safety initiatives.

Edited by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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