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Ondansetron interactions to avoid

Ondansetron is commonly used to treat nausea, but combining it with certain medications can trigger serious heart problems or serotonin syndrome. Find out what to avoid when taking this powerful antiemetic.
Marissa Walsh headshot
By | Updated on Jul. 28, 2025 Medically reviewed by Kristi C. Torres, Pharm.D.
Three Rx pill bottles: Ondansetron interactions

Key takeaways

  • The most dangerous ondansetron interactions include consumption with other medications known to have serotonergic effects independently or have QT-prolonging potential.

  • Other less serious drug interactions can occur between ondansetron and other prescription, over-the-counter (OTC), and supplements, which can result in side effects that may be managed or avoided altogether by avoiding the combination.

  • In the event of a drug interaction with ondansetron, it is always best to seek immediate attention from a healthcare professional.

In this article:

Ondansetron, known under the brand name Zofran, is a selective 5-HT3 receptor antagonist that functions as an antiemetic to aid in the prevention of nausea and vomiting from chemotherapy or radiation therapy, treatment of severe and acute nausea and vomiting, and the prevention and treatment of postoperative nausea and vomiting. Ondansetron is available as an injection, an oral solution, an oral tablet, and an orally-disintegrating tablet. Ondansetron can interact with certain cardiac medications, some antibiotics, and medications used for depression and mood disorders. Ondansetron can also affect the metabolism of other medicines, exacerbating side effects associated with individual drugs. It’s important to be aware of ondansetron interactions as some of them can cause life-threatening effects after a single dose that warrant immediate medical attention. You should never take ondansetron if you have a history of an allergic reaction to ondansetron or a drug in the same class.

Ondansetron drug interactions

Ondansetron can interact with several categories of medications. It is important to disclose all medications you are taking when discussing the need for an ondansetron prescription with your prescriber and pharmacist. Many possible interactions can affect the absorption of ondansetron. More critically, many ondansetron interactions can increase the chance of a cardiac arrhythmia, or irregular heartbeat, which could potentially be fatal. The table below outlines some of the most significant interactions with ondansetron.

Drug class or group name Drug name Interactions/side effects
Antifungals Increased risk of a cardiac arrhythmia known as torsade de pointes (TdP) as well as QT interval prolongation. Diflucan (fluconazole), Nizoral (ketoconazole), and Noxafil (posaconazole) are contraindicated with ondansetron.
Cardiac antiarrhythmic drugs Increased risk of a cardiac arrhythmia known as torsade de pointes (TdP) as well as QT interval prolongation. Multaq (dronedarone) inhibits the metabolism of ondansetron and is contraindicated.
Fluoroquinolone antibiotics
  • Cipro (ciprofloxacin)
  • Factive (gemifloxacin)
  • Levaquin (levofloxacin)
  • Avalox (moxifloxacin)
 Increased risk of a cardiac arrhythmia known as torsade de pointes (TdP) as well as QT interval prolongation.
Other antibiotics Increased risk of a cardiac arrhythmia known as torsade de pointes (TdP) as well as QT interval prolongation.
Antimalarial drugs Increased risk of a cardiac arrhythmia known as torsade de pointes (TdP) as well as QT interval prolongation.
Chemotherapy agents (cancer drug treatment)
  • Propulsid (cisapride)
  • Nolvadex (tamoxifen)
  • Krazati (adagrasib)
  • Retevmo (selpercatinib)
 Increased risk of a cardiac arrhythmia known as torsade de pointes (TdP) as well as QT interval prolongation.
Antipsychotics Increased risk of a cardiac arrhythmia known as torsade de pointes (TdP) as well as QT interval prolongation.
Antidepressants Increased risk of a cardiac arrhythmia known as torsade de pointes (TdP) as well as QT interval prolongation. Increased risk of serotonin syndrome.
Analgesics (pain medications) Increased risk of a cardiac arrhythmia known as torsade de pointes (TdP) as well as QT interval prolongation. Increased risk of serotonin syndrome.
Other nausea agents
  • Kytril (granisetron)
  • Emend (aprepitant)
  • Phenergan (promethazine)
  • Anzemet (dolasetron)
 Increased risk of a cardiac arrhythmia known as torsade de pointes (TdP) as well as QT interval prolongation.

Disclaimer: This chart is not intended to be comprehensive. Check with your healthcare professional or pharmacist about a given drug you are taking when you are prescribed ondansetron.

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Ondansetron drug interactions

The most serious medications that ondansetron interferes with include serotonergic medications, other drugs that prolong the QT interval, and some antibiotics. Always check the package insert to see interactions and warnings for ondansetron and the class of medications you are taking. Your health care provider can provide more comprehensive information on the interactions with ondansetron.

Serotonergic Agents

As a selective 5HT3 receptor antagonist, Ondansetron blocks serotonin peripherally and centrally. Therefore, combining with other medications in the 5HT3 receptor antagonist class will increase the potential risk of cardiac events such as torsade de pointes and QT prolongation. Increased free serotonin can also increase the risk of serotonin syndrome. 

Monoamine oxidase inhibitors, or MAOIs, were the first class of antidepressants developed. These medications work by blocking an enzyme, monoamine oxidase, which removes serotonin from the brain. By inhibiting this enzyme, increased serotonin levels remain available to regulate, allowing feelings of focus, emotional stability, and overall happiness. When a medication that inhibits monoamine oxidase is combined with serotonergic drugs like ondansetron, the serotonergic effect of MAOIs can be enhanced, which could result in a serious medical condition known as serotonin syndrome.

MAOIs include:

Additional medications which inhibit monoamine oxidase, but are not antidepressants, include:

Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs) intentionally raise serotonin levels to help with depression symptoms and mood disorders. While ondansetron is not intended for long-term use in most cases, it is important to note that individuals may develop serotonin syndrome and serotonin toxicity if both are used for some time. The prescribing information for ondansetron notes that serotonin syndrome and serotonin toxicity have been reported with the use of 5HT3 antagonists alone or in combination with other serotonergic agents. Therefore, patients combining these prescription drugs should be closely monitored for the emergence of these conditions. Keep the use of ondansetron to the lowest effective dose and shortest duration possible if use can not be avoided.

Selective serotonin reuptake inhibitors, in addition to sertraline, include: 

Serotonin and norepinephrine reuptake inhibitors (SNRIs) include: 

Tricyclic antidepressants (TCAs) include:

Other medications with secondary serotonergic effects:

QT-prolonging Agents

The QT interval is the part of an electrocardiogram (EKG) report that represents the time it takes the heart to contract and recover. Long QT syndromes can be inherited and are the result of an issue with the heart’s electrical conduction such that it takes longer than normal to recharge between heartbeats, which is due to an issue with ion channels and the flow of ions (sodium, calcium, potassium, and chloride) in and out of heart muscle cells to produce electrical activity. Medications can also cause acquired long QT syndrome. When the QT interval is prolonged, the risk for irregular heartbeats like ventricular tachycardias is increased, which can result in cardiac arrest and sudden death due to the heart’s inability to pump blood throughout the body effectively. 

Many medications can independently prolong the QT interval, including: 

Antiarrhythmic medications

Antimicrobials

Antipsychotic medications

Ondansetron demonstrated a mean increase in the QT interval from baseline by 20 milliseconds when given as 4 mg intravenously in the emergency department. Combining the use of other drugs known to prolong the QTc may further increase the risk for serious side effects, with at least one study identifying the use of an additional QT-prolonging drug as the most common risk factor among patients with an identified QT prolongation. Patients prescribed ondansetron, especially those at higher risk for cardiac abnormalities, such as those with heart failure or electrolyte abnormalities (including blood potassium and magnesium levels), should be monitored with an EKG before receiving the first dose. A history of an abnormal heart rhythm or other cardiac health conditions may make you more prone to this adverse event.

Apomorphine

Apomorphine is a dopamine agonist used in the management of Parkinson’s disease, often as adjunctive therapy with other anti-Parkinsonian agents. The combination of ondansetron and other 5HT3 antagonists, including granisetron, dolasetron, and palonosetron, are contraindicated with apomorphine, given the risk of enhanced hypotensive effects. The mechanism of the interaction remains unknown, but apomorphine prescribing information reports cases of profound hypotension and resultant loss of consciousness due to concomitant use of it with ondansetron. This combination should not be administered.

Metformin

Metformin is a very popular medication prescribed for the management of Type 2 diabetes mellitus. The combination of metformin with ondansetron may increase the blood levels of metformin, such that individuals on concomitant therapy must be monitored for metformin effects or toxicities. A pharmacokinetic study of individuals receiving ondansetron daily demonstrated increased metformin exposure and maximum serum concentrations in 21% of individuals and decreased metformin renal elimination in 36% of participants. This has implications for individuals, including lower blood glucose levels, which can result in serious effects. The mechanism of this interaction is believed to be inhibition of specific transporters in the body by ondansetron, responsible for active renal elimination of metformin.

It’s important to note that these lists are not all-inclusive. Always check with a healthcare professional for questions about any drug-drug interactions, especially when you start a new drug.

Ondansetron food interactions

Ondansetron may be absorbed slightly better when taken with food but can be taken without considering meals. Its adverse effects may cause constipation or diarrhea, which, coupled with its indication for nausea and vomiting, may preclude the ability to take it with meals. Those with severe nausea may be unable to eat food.

Other ondansetron interactions

In addition to prescription drugs, there are also side effects to be aware of with products we may consume without awareness of potential interactions. Knowing how anything you put into your body can interact with another product is important. 

Ondansetron and alcohol 

If you need to take ondansetron, it’s unlikely you’re in the mood to drink alcohol. While there is no immediate interaction, side effects of both may be exacerbated when combined with drowsiness, headache, and agitation. Some dosage forms of ondansetron contain sodium benzoate, a metabolite of benzyl alcohol. Large doses of benzyl alcohol have been associated with potentially fatal toxicity in pediatrics, specifically neonates. Therefore, these formulations of ondansetron should be used with great caution in this population. 

Ondansetron and supplements

Products readily available over the counter may interact with prescription medications like ondansetron. St. John’s wort is a supplement with serotonergic effects that could enhance the ondansetron‘s serotonergic effects. The combination should be taken together with great caution. Tell your pharmacist about any vitamins, herbal products, and supplements you may be taking.

Ondansetron and Phenylketonuria

Phenylketonuria, a medical condition also known as PKU, is an uncommon inherited disorder that results in the accumulation of a specific amino acid called phenylalanine due to a change in the gene that creates the enzyme needed to break down phenylalanine. The buildup of this amino acid can result in long-term intellectual disabilities, so afflicted individuals must follow a diet that limits phenylalanine. Ondansetron orally disintegrating (Zofran ODT) tablets contain phenylalanine, so their use must be avoided in those affected individuals living with phenylketonuria. 

How to minimize ondansetron interactions

Always carry a complete list of medications, including those that are non-prescription. Provide this list any time you receive medical advice with new therapy recommendations to help minimize the risk of drug interactions. When starting a new medication, it is advisable to read the included drug information and discuss any new signs or symptoms with your healthcare professional, no matter how mild. 

When to talk to a healthcare provider about ondansetron interactions

This article is only a partial list of ondansetron interactions. Be mindful of the risk of additive side effects and direct drug interactions, which may occur when ondansetron is used in combination with prescription and over-the-counter medications or supplements. Communicate directly with a healthcare professional anytime you require ondansetron so that a comprehensive review of interactions of both medications, diet, and conditions can occur to ensure a proper monitoring plan is put in place. 

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