What Meds Are Contraindicated with Zofran?

October 15, 2025 •

2 min read

Zofran (ondansetron) is a widely used antiemetic, but its interactions with other drugs can lead to serious health risks. Understanding what meds are contraindicated with Zofran is crucial for patient safety, particularly concerning heart rhythm and serotonin levels.

Quick Summary

A guide to medications that should not be taken with Zofran (ondansetron). Key contraindications include apomorphine and drugs that increase the risk of QT prolongation and serotonin syndrome, such as certain antidepressants and antipsychotics.

Key Points

Absolute Contraindication: Never take Zofran (ondansetron) with apomorphine due to the risk of severe low blood pressure and loss of consciousness.
QT Prolongation Risk: Zofran can cause a potentially fatal heart rhythm problem, a risk that increases when taken with certain antiarrhythmics, antipsychotics, and antibiotics.
Serotonin Syndrome Risk: Combining Zofran with antidepressants (like SSRIs and SNRIs), triptans, or some pain medications can lead to a life-threatening condition called serotonin syndrome.
Antidepressant Interactions: Many common antidepressants, including Zoloft (sertraline) and Cymbalta (duloxetine), interact with Zofran, raising the risk of serotonin syndrome.
Reduced Efficacy: Some seizure medications and antibiotics (like rifampin) can make Zofran less effective by causing your body to break it down faster.
Consult a Professional: Always provide your healthcare provider with a full list of your medications to avoid dangerous interactions.
Monitor for Symptoms: Be aware of symptoms like fainting, dizziness, fast heartbeat, confusion, or high fever, and seek medical help if they occur.

Understanding Zofran and Its Mechanism

Zofran, generic name ondansetron, is an antiemetic used to prevent nausea and vomiting from surgery, chemotherapy, and radiation. It is a 5-HT3 receptor antagonist, blocking serotonin's action. Due to its effects on serotonin and cardiac electrical activity, it can interact dangerously with other medications.

Absolute Contraindication: Apomorphine

Apomorphine (Apokyn), used for Parkinson's disease, is absolutely contraindicated with Zofran. This combination can cause severe hypotension and loss of consciousness.

The Two Major Risks: QT Prolongation and Serotonin Syndrome

Major risks with Zofran involve QT prolongation and serotonin syndrome.

QT Prolongation: An Electrical Heart Problem

Zofran can prolong the QT interval, which can lead to the dangerous heart rhythm Torsades de Pointes. This risk is heightened when combined with other QT-prolonging drugs.

Risky drug classes include:

Certain Antiarrhythmics: Amiodarone, quinidine, sotalol.
Antipsychotics: Thioridazine, ziprasidone, haloperidol, risperidone.
Antibiotics: Macrolides (azithromycin) and fluoroquinolones (ciprofloxacin, levofloxacin).
Antifungals: Ketoconazole, fluconazole.
Other 5-HT3 Antagonists: Dolasetron, granisetron.

Serotonin Syndrome: A Potentially Fatal Condition

Combining Zofran with drugs that increase serotonin can cause serotonin syndrome. Symptoms range from mild to severe, including high fever, confusion, and seizures.

Drugs that increase this risk:

SSRIs: Sertraline, escitalopram, fluoxetine.
SNRIs: Duloxetine, venlafaxine.
MAOIs: Phenelzine.
Opioid Pain Medications: Tramadol, fentanyl.
Migraine Medications (Triptans): Sumatriptan.
Herbal Supplements: St. John's Wort.

Comparison Table of Interacting Drug Classes


Drug Class/Medication	Primary Risk with Zofran	Example Drugs
Dopamine Agonists	Profound Hypotension	Apomorphine (Absolute Contraindication)
QT-Prolonging Agents	Irregular Heart Rhythm	Amiodarone, Sotalol (Antiarrhythmics), Thioridazine, Ziprasidone (Antipsychotics), Azithromycin, Ciprofloxacin (Antibiotics)
Serotonergic Agents	Serotonin Syndrome	Sertraline (Zoloft), Duloxetine (Cymbalta), Tramadol, Sumatriptan (Imitrex)
CYP3A4 Inducers	Reduced Zofran Efficacy	Phenytoin, Carbamazepine, Rifampin

Other Notable Interactions

CYP3A4 inducers like phenytoin, carbamazepine, and rifampin can reduce Zofran's effectiveness.

Conclusion

Communicating thoroughly with healthcare providers about all medications is vital due to Zofran's extensive interaction list. The absolute contraindication with apomorphine and risks of QT prolongation and serotonin syndrome with many common drugs necessitate careful management. Always provide a full list of all medications and supplements to ensure safe Zofran use.

For more detailed information on ondansetron interactions, you can visit the U.S. Food and Drug Administration (FDA) page.

Frequently Asked Questions

The most serious interaction is with apomorphine (used for Parkinson's disease). This combination is contraindicated and can cause a severe drop in blood pressure and loss of consciousness.

Taking SSRI antidepressants like Zoloft (sertraline) with Zofran can increase the risk of a rare but serious condition called serotonin syndrome. You should only take this combination under close medical supervision.

Some antibiotics, particularly macrolides (e.g., azithromycin) and fluoroquinolones (e.g., ciprofloxacin), can increase the risk of a serious heart rhythm problem called QT prolongation when taken with Zofran. Consult your doctor before combining them.

QT prolongation is a change in the heart's electrical system that can lead to a life-threatening irregular heartbeat. Zofran is known to cause this, and the risk is higher when combined with other drugs that have the same effect.

Symptoms can include agitation, confusion, fast heart rate, high fever, muscle stiffness, sweating, and tremors. In severe cases, it can lead to seizures and be fatal. Seek medical attention if you experience these symptoms.

While many OTC pain relievers are safe, some, like tramadol, can increase the risk of serotonin syndrome when taken with Zofran. Always check with a pharmacist or doctor.

Yes, Zofran can interact with many heart medications, especially antiarrhythmics like amiodarone and sotalol, increasing the risk of serious cardiac events. It's crucial to inform your cardiologist you are taking Zofran.