What meds should I avoid with triptans? A Guide to Drug Interactions

October 10, 2025 •

4 min read

An estimated 3.4 strokes occur annually per 100,000 migraine sufferers, highlighting the importance of cautious medication use. When managing migraines with triptans, knowing what meds should I avoid with triptans is crucial to prevent serious adverse effects, including potentially life-threatening interactions.

Quick Summary

Taking triptans with certain medications can cause dangerous drug interactions, such as excessive vasoconstriction or serotonin syndrome. Key drug classes to avoid include MAOIs, ergots, other triptans within 24 hours, and specific serotonergic antidepressants like SSRIs and SNRIs. Patient safety depends on careful medication management.

Key Points

Avoid MAOIs: Do not take triptans within 14 days of using a monoamine oxidase inhibitor (MAOI) due to a severe risk of serotonin syndrome and toxicity.
Separate Ergots: Never use a triptan within 24 hours of taking an ergotamine-containing medication to prevent excessive blood vessel constriction.
Be Cautious with Serotonergic Drugs: Although the risk is low, monitor for symptoms of serotonin syndrome when combining triptans with antidepressants like SSRIs or SNRIs.
Inform Your Doctor of All Medications: Always provide a complete list of prescription, over-the-counter, and herbal supplements to your healthcare provider to identify all potential interactions.
Do Not Mix Triptans: Avoid taking a different type of triptan within 24 hours to prevent compounded vasoconstriction effects.
Adjust for Specific Interactions: Certain drugs, like propranolol with rizatriptan or CYP3A4 inhibitors with eletriptan, require dose adjustments or alternative treatment choices.

Understanding Triptans and the Importance of Avoiding Drug Interactions

Triptans are a class of drugs, including sumatriptan (Imitrex) and rizatriptan (Maxalt), used to treat acute migraine attacks by narrowing blood vessels in the brain and blocking pain pathways. While effective, triptans have a significant potential for drug interactions that can lead to severe complications. Understanding these risks and knowing what medications to avoid is paramount for patient safety. These interactions typically arise from additive effects on blood vessels, changes in how the body processes the medication, or compounding the effects of neurotransmitters like serotonin.

The Absolute Contraindications: MAOIs and Ergots

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs are a class of antidepressants that block the enzyme monoamine oxidase, which is responsible for breaking down neurotransmitters like serotonin and norepinephrine. Several triptans, such as sumatriptan, rizatriptan, and zolmitriptan, are also metabolized by this enzyme. Taking a triptan with an MAOI can significantly increase triptan levels in the body, leading to toxicity and a higher risk of serotonin syndrome. For this reason, the use of triptans is contraindicated within 14 days of taking an MAOI.

Examples of MAOIs to avoid: isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Emsam), and tranylcypromine (Parnate).

Ergotamine-Containing Medications

Both triptans and ergot-containing medications, such as ergotamine and dihydroergotamine (DHE), cause blood vessel constriction. Combining these drugs can lead to a dangerous, additive effect, resulting in excessive vasoconstriction and a higher risk of cardiovascular events like heart attack and stroke. It is crucial to wait at least 24 hours between taking an ergot medication and a triptan.

Interactions with Other Serotonin-Affecting Medications

SSRIs and SNRIs

Antidepressants that increase serotonin levels, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are frequently prescribed alongside triptans for patients with comorbid anxiety or depression. The concern with combining these medications is the potential, albeit rare, for serotonin syndrome. Symptoms can range from mild (agitation, restlessness) to severe (seizures, high fever) and require immediate medical attention.

SSRIs: citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft).
SNRIs: duloxetine (Cymbalta), venlafaxine (Effexor XR).

Other Serotonergic Agents

Other drugs can also increase serotonin levels and interact with triptans, including certain opioids like tramadol, dextromethorphan (found in many cough medicines), and herbal supplements like St. John's wort. Always inform your doctor about all medications and supplements you are taking.

Other Notable Triptan Drug Interactions

Other Triptans: Do not take a different triptan within 24 hours of taking your current one. This can compound the vasoconstrictive effects, increasing the risk of serious side effects.
Propranolol: This beta-blocker can increase the blood levels of rizatriptan (Maxalt). Your doctor may need to adjust your rizatriptan dose if you take propranolol.
CYP3A4 Inhibitors: Some triptans, like eletriptan (Relpax), are metabolized by the CYP3A4 liver enzyme. Combining eletriptan with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) can significantly increase its concentration and should be avoided.
Cimetidine: This heartburn medication can increase the concentration of zolmitriptan in the blood and should be used with caution.

Comparison of Triptan Interactions


Medication Class	Mechanism of Interaction	Risk	Management Strategy
Monoamine Oxidase Inhibitors (MAOIs)	Blocks triptan metabolism, increasing concentration and serotonin levels.	High risk of serotonin syndrome and triptan toxicity.	Absolute contraindication. Do not use triptans within 14 days of taking an MAOI.
Ergotamines (e.g., DHE)	Additive vasoconstrictive effects.	High risk of excessive blood vessel constriction, increasing risk of stroke/heart attack.	Absolute contraindication. Wait at least 24 hours between doses.
Other Triptans	Additive vasoconstrictive effects.	Risk of excessive blood vessel constriction.	Absolute contraindication. Wait at least 24 hours between doses.
SSRIs/SNRIs	Additive effect on serotonin levels.	Low but present risk of serotonin syndrome.	Monitor closely for symptoms; discuss all medications with your doctor.
Propranolol	Increases rizatriptan levels in blood.	Increased risk of side effects from rizatriptan.	Rizatriptan dose may need to be lowered.
CYP3A4 Inhibitors	Increases levels of eletriptan in blood.	Increased risk of side effects from eletriptan.	Avoid combining or use an alternative triptan.

The Critical Role of Your Healthcare Provider

Given the complexity of drug interactions, it is essential to have an open and honest conversation with your healthcare provider and pharmacist about all the medications you take, including over-the-counter drugs, herbal supplements, and vitamins. They have the expertise to identify potential risks and help you create a safe treatment plan. In some cases, a different triptan or an alternative migraine medication may be necessary to avoid dangerous combinations. New options, like CGRP inhibitors, have emerged for patients who have contraindications to triptans. For more detailed information on specific migraine treatments and their interactions, consult authoritative sources such as the American Migraine Foundation (AMF) or medical databases.

Conclusion

Triptans are powerful and effective tools for managing acute migraine attacks, but their use requires careful consideration of potential drug interactions. Absolute contraindications exist for combining triptans with MAOIs and ergot-containing medications, primarily due to the risk of serotonin syndrome and severe vasoconstriction. While the risk of serotonin syndrome with SSRIs and SNRIs is low, it remains a possibility that requires monitoring. Always disclose your full medication history to your healthcare provider to ensure your migraine treatment plan is both effective and safe. Never self-adjust your medications based on online information alone.

Frequently Asked Questions

Yes, triptans can generally be taken with over-the-counter pain relievers such as acetaminophen (Tylenol) or NSAIDs like ibuprofen, though excessive use can cause rebound headaches. Always follow dosing instructions and consult your doctor if you have concerns.

Serotonin syndrome is a potentially life-threatening condition caused by an excess of serotonin in the body. Symptoms can include agitation, confusion, rapid heart rate, muscle rigidity, and shivering. Seek immediate medical attention if you experience these symptoms.

You must wait at least 24 hours between taking an ergot medication, such as dihydroergotamine, and a triptan. This waiting period helps prevent dangerous, additive blood vessel constriction.

No, triptans are generally not recommended for individuals with a history of heart disease, uncontrolled high blood pressure, or other cardiovascular issues due to their vasoconstrictive effects. Alternative migraine treatments may be necessary.

Triptans that are metabolized by MAO, including sumatriptan, rizatriptan, and zolmitriptan, must be avoided with MAO inhibitors. Eletriptan, frovatriptan, and naratriptan are not broken down by MAO and might be better alternatives, but a doctor should always be consulted.

Oral contraceptives can have minor pharmacokinetic effects on some triptans, such as increasing the exposure to frovatriptan, but this is not typically clinically significant. Always inform your doctor about all hormonal birth control.

Newer alternatives to triptans include gepants (ubrogepant, rimegepant) and ditans (lasmiditan). These medications work differently and are options for patients with cardiovascular contraindications to triptans.