Treximet interacts with SSRIs, blood thinners, other triptans, and more. Learn which drugs to avoid and what to tell your doctor before taking Treximet.
Treximet combines two active ingredients — Sumatriptan and Naproxen Sodium — which means it carries drug interactions from both a triptan and an NSAID. Some of these interactions are serious enough to be contraindicated (meaning the drugs should never be taken together), while others require careful monitoring.
This guide covers the most important Treximet drug interactions, including prescription medications, over-the-counter drugs, supplements, and food. Always tell your doctor about everything you take before starting Treximet.
A drug interaction happens when one medication changes how another medication works in your body. This can happen in several ways:
Because Treximet contains two different drugs, it has a wider range of potential interactions than a single-ingredient medication.
These interactions are serious and, in some cases, contraindicated — meaning you should not take these medications with Treximet.
Status: Contraindicated
Do not take Treximet if you have used an MAO inhibitor within the past 14 days. MAO inhibitors include:
MAO inhibitors block the breakdown of Sumatriptan in your body, which can lead to dangerously high levels and increased risk of serotonin syndrome.
Status: Contraindicated within 24 hours
Do not take another triptan within 24 hours of Treximet. Other triptans include:
Combining triptans increases the risk of serotonin syndrome and dangerous blood vessel constriction.
Status: Contraindicated within 24 hours
Ergotamine-containing medications (like Cafergot and Migranal/Dihydroergotamine) should not be used within 24 hours of Treximet. Both drug classes cause blood vessel constriction, and combining them can lead to prolonged vasospasm.
Status: Use with caution — risk of serotonin syndrome
Many migraine patients also take antidepressants. If you take an SSRI or SNRI, talk to your doctor before using Treximet. Medications in this category include:
The combination can cause serotonin syndrome — a potentially life-threatening condition with symptoms including agitation, hallucinations, rapid heartbeat, fever, muscle stiffness, and loss of coordination. While many patients do take triptans and SSRIs together under medical supervision, you should be aware of the warning signs.
Status: Increased bleeding risk
The Naproxen Sodium in Treximet increases bleeding risk, especially when combined with blood thinners such as:
If you take a blood thinner, your doctor needs to weigh the bleeding risk carefully.
Status: Increased lithium toxicity
NSAIDs like Naproxen can increase lithium levels in the blood, potentially leading to lithium toxicity. If you take Lithium (Lithobid, Eskalith) for bipolar disorder, your doctor may need to monitor your lithium levels more closely when you use Treximet.
Status: Increased methotrexate toxicity
NSAIDs can reduce the kidney's ability to clear Methotrexate from the body, leading to toxic levels. If you take Methotrexate for rheumatoid arthritis, psoriasis, or cancer treatment, tell your doctor before using Treximet.
Naproxen can reduce the effectiveness of blood pressure medications including:
The combination can also increase the risk of kidney problems. If you take blood pressure medication, your doctor should monitor your kidney function and blood pressure.
NSAIDs can reduce the effectiveness of diuretics like Furosemide (Lasix) and Hydrochlorothiazide (HCTZ). This can lead to fluid retention and higher blood pressure.
Do not take additional NSAIDs while using Treximet — it already contains 500 mg of Naproxen Sodium. Avoid:
Combining NSAIDs significantly increases the risk of GI bleeding and stomach ulcers.
TCAs like Amitriptyline (Elavil) and Nortriptyline (Pamelor) — sometimes used for migraine prevention — may increase the risk of serotonin syndrome when combined with Treximet's Sumatriptan component.
Using Naproxen with Cyclosporine (Neoral, Sandimmune) can increase the risk of kidney damage.
NSAIDs can increase blood levels of Digoxin (Lanoxin), which is used for heart failure and certain heart rhythm problems.
Alcohol significantly increases the risk of GI bleeding when combined with the Naproxen Sodium in Treximet. Even moderate drinking raises this risk. Avoid alcohol on days you take Treximet, and limit alcohol use in general if you use Treximet regularly.
There are no specific food restrictions with Treximet. Taking it with a small amount of food may help reduce stomach upset, but it's not required.
Before starting Treximet, give your doctor a complete list of:
Also mention if you:
Treximet is an effective migraine treatment, but its two active ingredients mean it has a broader range of drug interactions than many people expect. The most critical interactions involve MAO inhibitors (contraindicated), other triptans (avoid within 24 hours), SSRIs/SNRIs (serotonin syndrome risk), and blood thinners (bleeding risk).
The safest approach is to always tell your doctor and pharmacist about every medication and supplement you take. For more on Treximet safety, read about side effects to watch for. And when you're ready to fill your prescription, use Medfinder to find Treximet in stock near you.
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