Ondansetron, often prescribed under the brand name Zofran, is a widely used antiemetic that prevents nausea and vomiting associated with chemotherapy, radiation, and surgery. While generally safe, its use alongside certain other medications can lead to dangerous and sometimes life-threatening interactions. For this reason, it is critical for patients and healthcare providers to be fully aware of the specific substances that should not be mixed with ondansetron.
The Absolute Contraindication: Apomorphine
The combination of ondansetron and apomorphine is an absolute contraindication. Apomorphine is used for Parkinson's disease, and when combined with ondansetron, it can cause severe hypotension (dangerously low blood pressure) and loss of consciousness. Healthcare providers avoid prescribing these together due to the severity of this reaction.
High Risk of Serotonin Syndrome
Serotonin syndrome is a serious condition caused by excessive serotonin. While ondansetron is a 5-HT3 receptor antagonist, combining it with other drugs that increase serotonin can raise the risk of this syndrome. Medications to be cautious with include:
- SSRIs and SNRIs: Like sertraline, citalopram, escitalopram, fluoxetine, venlafaxine, and duloxetine.
- MAOIs: Older antidepressants such as phenelzine and isocarboxazid.
- Triptans: Anti-migraine medications like sumatriptan and rizatriptan.
- Certain Opioids: Notably tramadol.
Symptoms can include agitation, confusion, fever, rapid heart rate, and muscle twitching. Seek immediate medical attention if these occur.
Risk of QT Interval Prolongation
Ondansetron can prolong the QT interval, increasing the risk of a rare, fatal heart rhythm. This risk is heightened when combined with other QT-prolonging drugs. Examples include:
- Antiarrhythmics: Such as amiodarone and quinidine.
- Antibiotics: Including macrolides and fluoroquinolones.
- Antifungals: Like fluconazole and ketoconazole.
- Antipsychotics: For example, risperidone and ziprasidone.
Individuals with heart conditions, electrolyte imbalances, or a family history of Long QT syndrome face higher risk.
Interactions Affecting Ondansetron's Efficacy
Some drugs and supplements can make ondansetron less effective by speeding up its metabolism. Antiepileptic drugs like carbamazepine and phenytoin, and the herbal supplement St. John's Wort, can have this effect.
Other Notable Interactions
- Tramadol: Concurrent use may reduce the effectiveness of both ondansetron and tramadol. There's also risk of serotonin syndrome and seizures.
- Metformin: Ondansetron can increase blood levels of metformin, potentially increasing side effects.
- Alcohol: While no direct interaction is known, alcohol can worsen nausea and other side effects, making it hard to assess ondansetron's effect.
Comparison of Key Ondansetron Interactions
| Type of Interaction | Drugs Involved (Examples) | Risk Factor | What Can Happen |
|---|---|---|---|
| Absolute Contraindication | Apomorphine (Apokyn) | Severe hypotension | Dangerous drop in blood pressure and loss of consciousness. |
| Serotonin Syndrome Risk | SSRIs, SNRIs, MAOIs, Triptans, Tramadol | Elevated serotonin levels | Agitation, confusion, hallucinations, rapid heartbeat, and muscle twitching. |
| QT Prolongation Risk | Certain antiarrhythmics, antibiotics, antifungals, antipsychotics | Combined heart rhythm effects | Increased risk of fatal heart arrhythmia (torsades de pointes). |
| Reduced Effectiveness | Carbamazepine, Phenytoin, St. John's Wort | Increased ondansetron metabolism | The antiemetic effect of ondansetron may be diminished or lost. |
| Altered Drug Levels | Metformin | Inhibition of drug transporters | Higher-than-intended blood levels of metformin, increasing side effects. |
| Masked Symptoms | Alcohol | Exacerbated nausea | Nausea or other side effects worsened by alcohol could mask ondansetron's effect. |
Conclusion
Safe use of ondansetron requires awareness of potential interactions. The absolute contraindication is with apomorphine. Combining ondansetron with other serotonergic drugs risks serotonin syndrome, while mixing with QT-prolonging drugs increases heart rhythm risks. Always inform your doctor or pharmacist about all medications and supplements you take to ensure safety. This information is a guide; consult a healthcare professional for individual medical advice.
