What drugs are contraindicated with ondansetron? A comprehensive guide to drug interactions

October 13, 2025 •

2 min read

Ondansetron is a commonly prescribed antiemetic medication used to prevent nausea and vomiting from surgery, chemotherapy, or radiation. While effective, the U.S. Food and Drug Administration (FDA) and other health authorities have identified several critical contraindications and interactions that can lead to serious adverse events. Understanding what drugs are contraindicated with ondansetron is essential for ensuring patient safety and avoiding life-threatening complications.

Quick Summary

The anti-nausea drug ondansetron has several drug interactions, most notably a severe contraindication with apomorphine. Other risks include serotonin syndrome with serotonergic drugs and potentially dangerous heart rhythm changes when combined with QT-prolonging agents.

Key Points

Absolute Contraindication with Apomorphine: Never combine ondansetron with apomorphine, a Parkinson's drug, due to the high risk of severe hypotension and loss of consciousness.
High Risk of QT Prolongation: Ondansetron can prolong the heart's QT interval, a risk amplified by concurrent use of antiarrhythmics, certain antibiotics, and antipsychotics.
Serotonin Syndrome Potential: Combining ondansetron with other serotonergic agents like SSRIs, SNRIs, and MAOIs increases the risk of developing serotonin syndrome.
Reduced Efficacy with CYP3A4 Inducers: Antiepileptic drugs such as carbamazepine and phenytoin can reduce ondansetron's effectiveness by speeding up its metabolism.
Crucial for Medication Reconciliation: Always inform your healthcare provider of all medications, including supplements like St. John's wort, to avoid dangerous drug interactions.

Apomorphine: The Absolute Contraindication

The most critical drug interaction for ondansetron is its absolute contraindication with apomorphine. Apomorphine, used for Parkinson's disease, can cause severe hypotension (profoundly low blood pressure) and loss of consciousness when combined with ondansetron. This combination is explicitly forbidden in prescribing information.

Drugs That Increase the Risk of QT Prolongation

Ondansetron can prolong the heart's QT interval, increasing the risk of a fatal arrhythmia. Combining it with other QT-prolonging medications, such as certain antiarrhythmics, antipsychotics, antibiotics (like macrolides and fluoroquinolones), and antifungals, elevates this risk. Patients with existing heart conditions or electrolyte imbalances are more susceptible.

Serotonergic Agents and the Risk of Serotonin Syndrome

Combining ondansetron with drugs that raise serotonin levels can lead to serotonin syndrome. This can cause symptoms from mild (sweating, tremors) to life-threatening (agitation, confusion, high fever). Interacting medications include SSRIs, SNRIs, MAOIs, some opioids, migraine triptans, linezolid, methylene blue, and St. John's wort.

Pharmacokinetic Interactions: Affecting Ondansetron’s Efficacy

Certain medications can alter how the body processes ondansetron, potentially reducing its effectiveness. Drugs that induce the CYP3A4 enzyme, like carbamazepine, phenytoin, and rifampin, can increase ondansetron's metabolism. This can result in lower blood levels of ondansetron and a diminished antiemetic effect.

Comparison of Major Ondansetron Interactions


Drug Class / Example	Interaction Mechanism	Clinical Effect	Management Strategy
Apomorphine	Unknown, likely profound pharmacodynamic effect	Severe hypotension, loss of consciousness	Absolute contraindication. Avoid concomitant use.
SSRI / SNRI Antidepressants	Additive serotonergic effects	Serotonin syndrome	Monitor for symptoms; consider alternative antiemetics if risk is high.
QT-Prolonging Drugs	Additive effect on cardiac repolarization	Prolonged QT interval, risk of Torsade de Pointes	Avoid use in patients with cardiac risk factors; monitor ECG if unavoidable.
CYP3A4 Inducers (Carbamazepine, Phenytoin)	Increased metabolism of ondansetron	Reduced efficacy of ondansetron	Consider alternative antiemetics or dose adjustments; monitor for treatment failure.
MAOIs (Selegiline, Phenelzine)	Additive serotonergic effects	High risk of serotonin syndrome	Avoid concomitant use. Requires a washout period.

Navigating Medication Safety

It is vital to inform your doctor about all medications, supplements, and herbal products you are taking before starting ondansetron. This allows healthcare providers to identify potential drug interactions and assess risks. They can then recommend the safest approach, which might involve choosing a different antiemetic or close monitoring.

Conclusion: Prioritizing Medication Safety

Ondansetron is effective for nausea and vomiting, but carries risks of interaction. The most serious is with apomorphine. Other significant interactions involve medications affecting heart rhythm and serotonin levels. Understanding what drugs are contraindicated with ondansetron is crucial for both patients and healthcare providers to ensure safe use and minimize serious adverse events. Always consult the latest FDA prescribing information for current details.

Frequently Asked Questions

Combining ondansetron with certain antidepressants, such as SSRIs and SNRIs, can increase the risk of serotonin syndrome. While not an absolute contraindication, your doctor should be aware and may need to monitor you closely for symptoms.

Apomorphine, used for Parkinson's disease, is strictly contraindicated with ondansetron because the combination can cause a sudden and severe drop in blood pressure (hypotension) and even loss of consciousness.

Ondansetron can prolong the QT interval of the heart's electrical rhythm. When taken with other QT-prolonging drugs like certain antibiotics or antiarrhythmics, it increases the risk of a dangerous irregular heartbeat called Torsade de Pointes.

Yes, some antibiotics, particularly macrolides (e.g., azithromycin) and fluoroquinolones (e.g., moxifloxacin), can interact with ondansetron by also prolonging the QT interval. This risk needs careful medical consideration.

Yes, herbal supplements like St. John's wort can interact with ondansetron. St. John's wort can speed up the breakdown of ondansetron, making it less effective, and also has serotonergic effects that could increase the risk of serotonin syndrome.

Symptoms of serotonin syndrome can include agitation, hallucinations, rapid heart rate, fever, muscle rigidity or spasms, and loss of coordination. Seek immediate medical attention if these symptoms occur.

Caution is advised if you have a history of heart problems such as congestive heart failure, bradyarrhythmias (slow heart rate), or long QT syndrome. Ondansetron should be used under careful medical supervision and possibly with ECG monitoring in these cases.