What drugs should not be taken with ondansetron?

October 10, 2025 •

3 min read

Over 16,000 screening electrocardiograms (ECG) would be needed to identify a single asymptomatic case of Long QT syndrome, which can be exacerbated by ondansetron. This makes understanding what drugs should not be taken with ondansetron a crucial step for ensuring patient safety and avoiding potentially serious medication interactions.

Quick Summary

Ondansetron, an antiemetic, has severe drug interactions, most notably with apomorphine due to hypotension risk. It also interacts with serotonergic and QT-prolonging medications, increasing the risk for serotonin syndrome and cardiac arrhythmias.

Key Points

Apomorphine Interaction: Never combine ondansetron with apomorphine, a medication for Parkinson's disease, as it can cause profound low blood pressure and unconsciousness.
Serotonin Syndrome Risk: Avoid combining ondansetron with other serotonergic agents, including SSRI/SNRI antidepressants, opioids like tramadol, and St. John's wort, to prevent serotonin syndrome.
QT Prolongation Warning: Be cautious when taking ondansetron with other drugs that prolong the QT interval, such as certain antibiotics, antiarrhythmics, and antipsychotics, due to increased risk of cardiac arrhythmias.
Reduced Effectiveness: Some antiepileptic drugs, like carbamazepine and phenytoin, can reduce the effectiveness of ondansetron by speeding up its metabolism.
High-Risk Patients: Patients with pre-existing heart conditions, congenital long QT syndrome, or electrolyte imbalances require close monitoring when using ondansetron.
IV vs. Oral Dosing: The risk of QT prolongation is more pronounced with intravenous administration, and high-dose IV ondansetron was withdrawn from the market for this reason.

Ondansetron, commonly known by the brand name Zofran, is an antiemetic used to prevent and treat severe nausea and vomiting. While effective, it carries risks of severe or life-threatening side effects when combined with certain medications. Key interactions involve a direct contraindication with apomorphine, risks of serotonin syndrome with serotonergic agents, and the potential for QT prolongation and dangerous heart arrhythmias with cardiac and other drugs.

Apomorphine: The Absolute Contraindication

Combining ondansetron with apomorphine, a medication for advanced Parkinson's disease, is strictly contraindicated. This combination can cause severe hypotension and loss of consciousness. Healthcare providers must find alternative antiemetics for patients requiring both medications.

Serotonin Syndrome with Serotonergic Medications

Ondansetron blocks serotonin 5-HT3 receptors. Taking it with other drugs that increase serotonin can cause serotonin syndrome, a life-threatening condition. Medications with this risk include SSRIs (e.g., sertraline, fluoxetine, escitalopram), SNRIs (e.g., venlafaxine, duloxetine), MAOIs (e.g., phenelzine, selegiline), tramadol, linezolid, and St. John's wort. Symptoms include confusion, agitation, sweating, muscle twitching, rapid heartbeat, and high fever. Close monitoring by a healthcare provider is necessary.

QT Prolongation and Cardiac Arrhythmias

Ondansetron can prolong the heart's QT interval, increasing the risk of a dangerous heart rhythm called Torsades de Pointes. This risk increases when combined with other QT-prolonging drugs. These include antiarrhythmics (amiodarone, quinidine, dronedarone), certain antibiotics (macrolides, fluoroquinolones), specific antifungals (ketoconazole, fluconazole, posaconazole), antipsychotics (thioridazine, ziprasidone, quetiapine), and some opioids (buprenorphine, methadone). The FDA has limited the maximum single IV dose of ondansetron due to this risk. Patients with heart conditions, electrolyte abnormalities, or those taking multiple QT-prolonging medications are at higher risk.

Metabolism-Altering Drug Interactions

Certain drugs can reduce ondansetron's effectiveness by speeding up its metabolism. Antiepileptic drugs like carbamazepine and phenytoin, which induce the CYP3A4 liver enzyme, can lower ondansetron blood levels. St. John's wort has a similar effect.

Comparison of Major Ondansetron Interaction Risks


Interaction Type	Risk Level	Example Drugs	Resulting Condition
Apomorphine	Contraindicated	Apomorphine (Apokyn)	Severe hypotension, loss of consciousness
Serotonergic Agents	High Risk	SSRIs (Zoloft, Prozac), SNRIs (Cymbalta, Effexor), Tramadol, Linezolid	Serotonin Syndrome
QT-Prolonging Drugs	High Risk	Antiarrhythmics (Amiodarone), Antibiotics (Azithromycin), Antifungals (Ketoconazole), Antipsychotics (Ziprasidone)	Cardiac Arrhythmias (e.g., Torsades de Pointes)
Enzyme Inducers	Moderate Risk	Carbamazepine, Phenytoin, St. John's wort	Reduced ondansetron effectiveness

Practical Steps for Medication Safety

Patients taking ondansetron, especially those with heart conditions or on multiple medications, require careful management. Always provide your healthcare provider with a complete list of all medications and supplements. An ECG may be recommended for high-risk patients. Seek immediate medical attention if you experience symptoms of severe interactions, such as dizziness, irregular heartbeat, confusion, or agitation.

Conclusion

Ondansetron is effective for nausea and vomiting but has significant drug interaction risks. It is absolutely contraindicated with apomorphine, and combining it with serotonergic or QT-prolonging drugs can lead to serotonin syndrome or cardiac arrhythmias. Open communication with healthcare professionals and awareness of potential interactions are crucial for safe use. Always consult your doctor or pharmacist to review your medication list before using ondansetron. Learn more about drug safety information from the FDA.

Frequently Asked Questions

Combining ondansetron with antidepressants, particularly SSRIs and SNRIs, can increase the risk of a rare but serious condition called serotonin syndrome. You should inform your doctor about your antidepressant use, and they will determine if the combination is safe or requires close monitoring.

Ondansetron is contraindicated with apomorphine due to the risk of severe hypotension (dangerously low blood pressure) and potential loss of consciousness when the two medications are combined.

You should use caution with antiarrhythmic drugs like amiodarone and quinidine, as they can increase the risk of QT prolongation and life-threatening heart arrhythmias when combined with ondansetron.

Yes, some antibiotics, such as azithromycin, erythromycin, and fluoroquinolones like ciprofloxacin, can increase the risk of QT prolongation when taken with ondansetron. Discuss all medications with your doctor.

Symptoms of serotonin syndrome include confusion, agitation, sweating, muscle twitching, rapid heartbeat, and high fever. If you experience these symptoms, seek immediate medical attention.

Yes, the herbal supplement St. John's wort can potentially reduce the effectiveness of ondansetron by speeding up its metabolism. Discuss the use of all supplements with your doctor.

Routine ECGs are not typically needed for all patients on oral ondansetron. However, your doctor may recommend monitoring if you are at higher risk, such as those with heart failure, electrolyte abnormalities, or those taking other QT-prolonging drugs.