Does Ondansetron Cause Constipation? Understanding the Risk and Management

October 10, 2025 •

3 min read

Clinical trials indicate that 6% to 11% of patients taking ondansetron (Zofran) for chemotherapy-induced nausea and vomiting have reported experiencing constipation. Understanding if and why does ondansetron cause constipation is crucial for managing this common potential side effect effectively.

Quick Summary

Ondansetron, an antiemetic, can cause constipation by blocking serotonin receptors in the gut, which slows intestinal movement. Risk is influenced by dosage and individual factors. This guide explains the mechanism and provides management strategies.

Key Points

Cause: Ondansetron causes constipation by blocking serotonin (5-HT3) receptors in the gut, which are responsible for stimulating intestinal movement.
Frequency: The risk of ondansetron-induced constipation is common but varies. Clinical studies for chemotherapy-induced nausea report rates between 6% and 11%.
Management: Increase fluid intake, eat a high-fiber diet, and engage in regular physical activity to help prevent and manage constipation.
Medication: If lifestyle changes are insufficient, over-the-counter stool softeners or laxatives may be used with a healthcare provider's approval.
Risk Factors: Higher doses, dehydration, and concurrent use of other constipating medications (like opioids) can increase the risk of constipation.
When to See a Doctor: Consult a healthcare provider if constipation persists for several days, causes severe discomfort, or is accompanied by other concerning symptoms.

What is Ondansetron (Zofran)?

Ondansetron, also known as Zofran, is a medication used to prevent nausea and vomiting. It is a 5-HT3 receptor antagonist, effective for managing nausea caused by chemotherapy, radiation therapy, and surgery. The drug works by blocking serotonin's action in areas of the brain and GI tract involved in vomiting. While effective against nausea, it can cause side effects, including headache, fatigue, and constipation.

The Mechanism: Why Ondansetron Causes Constipation

Serotonin's Role in Gut Motility

Serotonin (5-HT) is crucial for regulating intestinal motility in the GI tract. It stimulates 5-HT3 receptors on nerve endings, promoting the muscle contractions that move waste through the colon.

Blocking Serotonin's Signal

Ondansetron blocks serotonin from binding to 5-HT3 receptors. While this prevents nausea in the brain, the same effect in the GI tract slows down intestinal movement. This delay in colonic transit allows more water to be absorbed from stool, leading to constipation.

How Common is Constipation from Ondansetron?

The frequency of ondansetron-induced constipation varies.

For Chemotherapy-induced nausea and vomiting (CINV): Studies show constipation rates between 6% and 11%.
Dose-dependent risk: Higher doses may increase the risk of constipation. One study found that dose adjustment limited severe constipation. Overdose can lead to severe constipation.
Individual variation: Genetic factors may influence susceptibility to this side effect.

Factors Influencing the Risk of Constipation

Factors that can increase the risk of constipation with ondansetron include:

Dehydration
Low fiber diet
Lack of physical activity
Taking other constipating medications, like opioids
Pre-existing GI motility issues

Practical Strategies for Managing and Preventing Ondansetron-Induced Constipation

Lifestyle Modifications

To manage or prevent constipation:

Increase fluid intake to 8-10 glasses daily.
Eat high-fiber foods such as fruits, vegetables, and whole grains. Prunes and bran cereal are particularly helpful.
Stay active with regular exercise.
Try to have a bowel movement at a consistent time each day.

When to Consider Medications

If lifestyle changes are not enough, over-the-counter options may help. Always consult your healthcare provider before starting new medications.

Stool softeners: Docusate sodium (Colace) softens stool.
Bulk-forming laxatives: Fiber supplements (Metamucil, Citrucel) add bulk to stool.
Osmotic laxatives: Polyethylene glycol (MiraLAX) draws water into the colon.

Ondansetron vs. Other Antiemetics

The table below compares ondansetron to other antiemetics regarding their mechanisms and common GI side effects.


Antiemetic Class	Example Medication	Mechanism of Action	Common GI Side Effects	Constipation Risk	Considerations
5-HT3 Antagonists	Ondansetron (Zofran)	Blocks serotonin (5-HT3) receptors.	Constipation, headache, fatigue.	High to moderate.	Effective for CINV; constipation is a known risk.
Dopamine Antagonists	Metoclopramide (Reglan)	Blocks dopamine receptors and increases gut motility.	Diarrhea, drowsiness, restlessness.	Low; can treat constipation.	Good option if constipation is a concern. Risk of extrapyramidal side effects.
NK1 Antagonists	Aprepitant (Emend)	Blocks substance P receptors.	Fatigue, constipation.	Moderate; often used in combination.	Used for CINV; sometimes with ondansetron.
Antihistamines	Dimenhydrinate (Dramamine)	Blocks histamine receptors.	Drowsiness, dry mouth, blurred vision.	Moderate; can slow the gut.	Less effective for severe nausea like CINV.

When to Contact a Healthcare Provider

Seek medical advice if:

Constipation lasts more than 2-3 days despite management.
You experience severe abdominal pain, bloating, or swelling.
There are signs of impaction, like watery diarrhea after no bowel movement.
You find blood in your stool.
Side effects impact your quality of life.

Conclusion

Ondansetron can cause constipation by blocking serotonin receptors in the gut, which slows intestinal movement. This is a documented side effect, with risk influenced by dose and individual factors. Managing ondansetron-induced constipation often involves lifestyle changes like increased fluid and fiber intake and physical activity. Over-the-counter medications like stool softeners or laxatives may also be used under medical supervision. Healthcare providers can consider alternative antiemetics for those at higher risk or with severe constipation. Discussing side effects with your medical team is essential for effective nausea control with minimal discomfort. More information on constipation can be found on the Cleveland Clinic website: Constipation: Symptoms & Causes.

Frequently Asked Questions

Constipation from ondansetron is typically temporary and may resolve shortly after you stop taking the medication. However, the duration can vary by individual. Maintaining a high-fiber diet and staying hydrated can help resolve it faster.

Ondansetron causes constipation by blocking serotonin (5-HT3) receptors in the gastrointestinal tract. This action slows down the natural muscular contractions (motility) of the intestines that are necessary for moving waste through the colon.

Immediately increase your fluid intake by drinking more water, especially non-caffeinated drinks. Try to add high-fiber fruits and vegetables to your diet and get some light exercise, like walking.

Yes, many healthcare providers recommend taking a stool softener, such as docusate sodium, to prevent or manage constipation while on ondansetron. Always check with your doctor or pharmacist first to ensure it is safe for your specific situation.

Yes, studies suggest that the risk of constipation from ondansetron is dose-dependent, meaning higher doses are associated with a greater risk. In some fixed-dose trials, severe constipation occurred more frequently.

Yes, some antiemetics have different side effect profiles. For example, metoclopramide is a prokinetic agent that actually increases gut motility, making diarrhea a more common side effect than constipation.

You should contact a healthcare provider if constipation lasts for more than a couple of days despite management efforts, if you experience severe abdominal pain, or if you notice blood in your stool.