Understanding What You Should Not Mix with Sumatriptan

October 10, 2025 •

4 min read

According to health authorities, certain drug combinations can lead to serious adverse effects when taking sumatriptan. Understanding what you should not mix with sumatriptan is crucial for safe and effective migraine treatment and to prevent potentially life-threatening complications.

Quick Summary

This article details the medications to strictly avoid when taking sumatriptan, such as MAOIs, ergot derivatives, and other triptans. It explains the dangerous side effects associated with mixing these drug classes and provides guidelines for safe usage.

Key Points

Avoid MAOIs: Do not mix sumatriptan with Monoamine Oxidase Inhibitors (MAOIs), including certain antidepressants and medications for Parkinson's, and wait at least 14 days after stopping an MAOI.
Strictly Separate Triptans and Ergots: Never take sumatriptan within 24 hours of another triptan or an ergot-containing medication to avoid dangerously constricted blood vessels.
Watch for Serotonin Syndrome with Antidepressants: While the risk is low, combining sumatriptan with SSRIs, SNRIs, or other serotonergic drugs warrants caution due to the risk of Serotonin Syndrome.
Be Aware of Other Serotonergic Drugs: Other medications and supplements, including Tramadol and St. John's Wort, can increase serotonin levels and should be discussed with a doctor.
Inform Your Doctor Completely: Always provide your full medication history to your healthcare provider to help identify potential drug interactions and ensure safe use.
Recognize Emergency Symptoms: If you experience a rapid heart rate, confusion, or agitation after taking sumatriptan, seek immediate medical attention.

Primary Drug Interactions to Avoid

Monoamine Oxidase Inhibitors (MAOIs)

Monoamine oxidase (MAO) is an enzyme that helps break down various chemicals in the brain, including sumatriptan. Monoamine Oxidase Inhibitors (MAOIs) are a class of medications, often used for depression or Parkinson's disease, that block this enzyme. When MAOIs are taken with sumatriptan, the MAO enzyme is inhibited, preventing the body from properly metabolizing sumatriptan. This causes sumatriptan levels to build up in the body, which can lead to serious side effects and increase the risk of a dangerous condition known as Serotonin Syndrome.

Examples of MAOIs to avoid include:

Isocarboxazid (Marplan)
Phenelzine (Nardil)
Tranylcypromine (Parnate)
Methylene blue injection
Linezolid (Zyvox)

Due to this interaction, sumatriptan should not be taken within 14 days of discontinuing an MAOI.

Ergot Derivatives

Both sumatriptan and ergot derivatives work to constrict blood vessels, a key mechanism in treating migraines. Taking these two types of medications together, or too close together, can cause an additive effect of vasoconstriction. This can lead to dangerously high blood pressure and restrict blood flow to vital organs, potentially causing a heart attack, stroke, or gangrene.

Examples of ergot-containing drugs include:

Ergotamine (Ergomar)
Dihydroergotamine (Migranal, Trudhesa)
Methylergonovine
Ergotamine/Caffeine (Migergot)

It is essential to avoid using sumatriptan within 24 hours of taking any ergot derivative.

Other Triptans

As sumatriptan is itself a triptan, combining it with another triptan medication is highly dangerous for the same reason as combining with ergots: excessive vasoconstriction. Taking multiple triptans within a short period can compound the effects and increase the risk of serious cardiovascular events, including heart attack and stroke.

Examples of other triptans to avoid include:

Almotriptan (Axert)
Eletriptan (Relpax)
Frovatriptan (Frova)
Naratriptan (Amerge)
Rizatriptan (Maxalt)
Zolmitriptan (Zomig)

A 24-hour waiting period is required when switching from sumatriptan to another triptan, and vice versa.

The Complex Risk of Serotonin Syndrome

Serotonin Syndrome is a potentially life-threatening condition caused by an overabundance of serotonin in the brain. While sumatriptan itself increases serotonin levels, the risk of developing Serotonin Syndrome is significantly elevated when combined with other serotonergic medications. This includes many commonly prescribed antidepressants.

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

There have been isolated reports of Serotonin Syndrome in patients using both a triptan and an SSRI or SNRI. However, robust clinical studies indicate that the actual risk is extraordinarily low and may be no higher than using an SSRI or SNRI alone. Despite this, the FDA issued a public health advisory, and caution is still warranted. Patients should be aware of the symptoms and consult their doctor.

Examples of SSRIs and SNRIs include:

SSRIs: Citalopram (Celexa), Escitalopram (Lexapro), Fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft)
SNRIs: Desvenlafaxine (Pristiq), Duloxetine (Cymbalta), Venlafaxine (Effexor XR)

Other Serotonergic Agents

Other medications and supplements can also increase serotonin levels and pose a risk when combined with sumatriptan. These include:

Tramadol (Ultram)
Certain tricyclic antidepressants (TCAs) like Amitriptyline
The herbal supplement St. John's Wort

Comparison of Major Sumatriptan Drug Interactions


Drug Class	Example Drugs	Primary Risk	Timeframe to Avoid
MAO Inhibitors	Isocarboxazid, Phenelzine, Tranylcypromine, Linezolid	Serotonin Syndrome	Wait at least 14 days after stopping an MAOI
Ergot Derivatives	Ergotamine, Dihydroergotamine	Excessive Vasoconstriction, high blood pressure, heart attack, stroke	Do not use within 24 hours of sumatriptan
Other Triptans	Rizatriptan, Zolmitriptan, Eletriptan	Excessive Vasoconstriction, high blood pressure, heart attack, stroke	Do not use within 24 hours of sumatriptan
SSRIs/SNRIs	Sertraline, Fluoxetine, Venlafaxine	Serotonin Syndrome (Extremely Low Risk, but possible)	Consult a doctor; use with caution

What to Do in Case of a Reaction

If you experience symptoms of Serotonin Syndrome or extreme vasoconstriction after taking sumatriptan and another medication, seek emergency medical help immediately. Symptoms may include:

Rapid heartbeat
Agitation or restlessness
Hallucinations
Confusion
Stiff or twitching muscles
Sweating and shivering
Severe headache
Nausea, vomiting, and diarrhea

Safe Practices for Sumatriptan Use

To ensure safe and effective treatment with sumatriptan, always follow these guidelines:

Inform your doctor and pharmacist: Provide a complete list of all prescription medications, over-the-counter drugs, and herbal supplements you are taking.
Follow timing rules: Adhere strictly to the 14-day rule for MAOIs and the 24-hour rule for ergot derivatives and other triptans.
Do not overuse: Using sumatriptan too frequently (more than 10 days per month) can lead to medication overuse headaches, which may become more frequent or worse.
Be aware of other conditions: Inform your doctor if you have a history of heart disease, stroke, uncontrolled high blood pressure, liver or kidney disease, or certain heart rhythm disorders, as sumatriptan may be contraindicated.
Avoid certain substances: While not a direct interaction, alcohol and caffeine can act as migraine triggers for some individuals. If you suspect this applies to you, discuss it with your healthcare provider.

Conclusion

Taking sumatriptan for migraine relief can be highly effective, but it is critical to be vigilant about potential drug interactions. Mixing sumatriptan with MAOIs, ergot derivatives, or other triptans can lead to serious and life-threatening complications due to excessive serotonin and/or vasoconstriction. Although the risk is lower with antidepressants like SSRIs and SNRIs, caution is still necessary. Always disclose your full medication history to your healthcare provider to ensure your treatment plan is safe and tailored to your specific needs.

For more information on the proper use of sumatriptan, you can visit the MedlinePlus drug information page.

Frequently Asked Questions

Yes, it is generally considered safe to take nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or pain relievers like acetaminophen with sumatriptan. They work differently to relieve pain and are often used together, but you should still consult your doctor first.

You should wait at least 24 hours between using sumatriptan and taking an ergot-containing medication like dihydroergotamine. This waiting period prevents excessive blood vessel constriction.

Symptoms of Serotonin Syndrome can include agitation, confusion, rapid heart rate, high blood pressure, muscle stiffness or twitching, sweating, fever, and digestive issues like diarrhea or nausea.

If you have accidentally taken sumatriptan too close to an MAOI, seek emergency medical help immediately. This combination can cause a severe buildup of sumatriptan in the body and potentially lead to Serotonin Syndrome.

While alcohol does not have a direct interaction with sumatriptan, it is a known trigger for migraines in many people and can potentially worsen headaches. It's often best to limit or avoid alcohol, especially during a migraine episode.

Yes, overusing sumatriptan or other acute migraine medications (more than 10 days per month) can cause headaches to come back and become worse. This is known as medication overuse headache.

Using multiple triptans too closely can cause your blood vessels to narrow excessively. This increases the risk of serious cardiovascular problems, including dangerously high blood pressure, heart attack, or stroke.

If you have uncontrolled high blood pressure, you should not take sumatriptan. If your blood pressure is controlled, your doctor will likely use caution and monitor you, as sumatriptan can increase blood pressure.