Does Ondansetron Cause Diarrhea?

October 13, 2025 •

3 min read

Clinical trial data indicate that ondansetron can cause diarrhea as a side effect, although some reports suggest a higher percentage of patients may experience constipation. This medication, commonly known as Zofran, works by blocking serotonin receptors to prevent nausea and vomiting, but this action can also influence bowel motility.

Quick Summary

Ondansetron can cause both diarrhea and constipation by altering gut motility via its serotonin receptor-blocking effects. The incidence of diarrhea is well-documented in clinical studies, and specific management strategies can help mitigate this side effect.

Key Points

Diarrhea is a Known Side Effect: Clinical trials confirm that ondansetron can cause diarrhea, although it is not universal and tends to be less common than constipation in some patient populations.
Serotonin Blockade Affects Bowels: Ondansetron works by blocking serotonin receptors (5-HT$_3$) throughout the body, including the gastrointestinal tract, which can disrupt normal gut motility and lead to bowel changes.
Hydration is Crucial for Management: If diarrhea occurs, the primary management strategy is to increase fluid intake to prevent dehydration, which is especially important for patients recovering from illness or surgery.
Dietary Adjustments Can Help: Consuming a bland, low-fiber diet can help firm up stools and reduce the frequency and severity of diarrhea caused by ondansetron.
Consult a Doctor for Persistent Diarrhea: If diarrhea lasts more than 48 hours or becomes severe, it's essential to consult a healthcare provider to rule out other issues and discuss safe anti-diarrheal medication options.
Risk of Constipation Also Exists: Due to its effect on gut motility, ondansetron can also cause constipation, which may be more prevalent depending on the patient and dosage.

Understanding Ondansetron's Role in Digestion

Ondansetron, a 5-HT$_3$ receptor antagonist, primarily serves as a powerful antiemetic to prevent nausea and vomiting, particularly for patients undergoing chemotherapy, radiation therapy, or surgery. The medication works by blocking serotonin, a neurotransmitter that plays a crucial role in regulating gastrointestinal (GI) motility. While its therapeutic effect is centered on the stomach and brain, the blockage of 5-HT$_3$ receptors throughout the digestive tract can have unintended consequences for bowel function.

The Dual GI Side Effects: Diarrhea and Constipation

Interestingly, ondansetron can lead to either constipation or diarrhea, and the occurrence often depends on the patient and the underlying condition. Clinical trials have reported varying rates for both, suggesting that an individual's unique response to the drug is a major factor.

Mechanism of Action and GI Effects

Serotonin's Role: Serotonin is a key player in the GI tract, where it helps stimulate bowel movements. By blocking 5-HT$_3$ receptors, ondansetron can disrupt these signals.
Effect on Motility: The overall impact of this blockade on intestinal motility is complex. While studies suggest it can slow colonic transit time, potentially leading to constipation, it can also manifest as diarrhea in some individuals.
Condition-Specific Variation: A patient's prior gut health, dehydration status, and even the type of treatment (e.g., chemotherapy vs. gastroenteritis) can influence which side effect they experience. For instance, one study found a notable link between oral ondansetron for pediatric gastroenteritis and an increased risk of diarrhea.

Prevalence of Diarrhea and Constipation

In many clinical contexts, constipation is the more commonly reported side effect for ondansetron. However, the occurrence of diarrhea is not insignificant and varies based on the specific studies and patient populations.


Comparison of Diarrhea vs. Constipation as Side Effects	Aspect	Diarrhea	Constipation
Incidence	Reported in 2–16% of patients in clinical trials, depending on the study.	Reported in 6–11% of patients in clinical trials, often cited as more common.
Mechanism	The exact cause is not fully understood but is likely linked to the complex way ondansetron alters gut motility.	Caused by the overall slowing of colonic transit due to 5-HT$_3$ receptor blockade.
Associated Factors	Sometimes observed in pediatric patients with gastroenteritis.	Can be exacerbated by co-administration with opioids and underlying dehydration.
General Perception	Less frequently reported than constipation, but still a common concern.	Often cited as one of the most frequent GI side effects.

How to Manage Ondansetron-Induced Diarrhea

If you experience diarrhea while taking ondansetron, several strategies can help manage the symptoms. It is crucial to consult your healthcare provider before taking any new medications or changing your diet to ensure it is appropriate for your specific situation.

Stay Hydrated: Diarrhea can cause dehydration. Drink plenty of clear fluids like water, electrolyte-fortified sports drinks, and broth.
Eat Bland Foods: Follow a bland diet, such as the BRAT diet (bananas, rice, applesauce, toast), to help bind the stool.
Limit High-Fiber and Irritating Foods: Avoid foods that can worsen diarrhea, including spicy, fried, or greasy foods, as well as high-fiber fruits, vegetables, and whole grains.
Talk to Your Doctor: Your healthcare provider may recommend over-the-counter anti-diarrheal medication, like loperamide (Imodium), but it is essential to get their guidance first.
Monitor Symptoms: If diarrhea persists for more than 48 hours, or is accompanied by fever or severe abdominal pain, contact your doctor immediately.

When to Seek Medical Attention

While ondansetron's side effects are generally mild, some require immediate medical attention. If you experience severe or persistent diarrhea, it is vital to contact your healthcare provider, as it could be a sign of a more serious issue, such as a bowel blockage. Symptoms of serotonin syndrome, a rare but serious side effect, can also include severe diarrhea. Other red-flag symptoms include agitation, confusion, fever, or a fast heartbeat.

Conclusion

In summary, ondansetron (Zofran) can indeed cause diarrhea, although it is more commonly associated with constipation. This is a consequence of the drug's mechanism, which involves blocking serotonin receptors that influence gastrointestinal motility. The likelihood of experiencing diarrhea or constipation can depend on the individual and the underlying medical condition. For those who experience diarrhea, staying hydrated and following a bland diet can help manage the symptoms, but persistent or severe cases warrant immediate medical consultation. Being aware of the potential for both opposing side effects is key to effectively managing treatment with ondansetron. For more detailed information on ondansetron's side effects, reliable medical sources can be consulted.

Frequently Asked Questions

Diarrhea is a reported side effect of ondansetron, though it is not universally experienced. Some clinical studies show that constipation may occur more frequently, while others indicate diarrhea can affect a significant percentage of patients.

Ondansetron blocks serotonin (5-HT$_3$) receptors, which play a role in regulating the natural movement of the gut. While this blockade primarily prevents nausea, its effect on gut motility can sometimes lead to diarrhea, especially in certain individuals.

To manage ondansetron-induced diarrhea, focus on staying well-hydrated by drinking plenty of fluids. Eating bland, low-fiber foods like bananas, rice, applesauce, and toast can also help bind the stool.

Yes, ondansetron can cause both diarrhea and constipation. Its effect on the gastrointestinal tract is complex, and individual patient factors can determine which of these opposing side effects may occur.

You should contact your healthcare provider if your diarrhea is severe, persists for more than two days, or is accompanied by other serious symptoms like fever, severe abdominal pain, or signs of serotonin syndrome.

Yes, patient experience with ondansetron can vary. For example, some studies have noted a higher risk of diarrhea in children receiving the medication for gastroenteritis.

It is important to consult your doctor or pharmacist before taking any anti-diarrheal medications, as they can interfere with ondansetron or be contraindicated with other medications you may be taking.