Migraine Drug Interactions FAQ | American Migraine Foundation (2023)

Learn how drugs commonly used to treat migraine can interact with each other and medications for other conditions

People can take many medications together as part of a complete migraine treatment plan. But it’s important to tell your doctor any migraine drug you’re taking so you’re both aware of possible interactions.

It’s helpful for your doctor to know all the treatments you’re using. That includes over-the-counter drugs, herbals, vitamins and supplements. In doing this, they can avoid prescribing medications that could interact or cause compounding side effects. Non-medical treatments, like acupuncture, are also good to talk to your doctor about. This is so they have a full picture of your migraine treatment plan.

We rounded up a few frequently asked questions about migraine drug interactions but recommend always talking to your doctor or pharmacist before starting a new medication for the most up-to-date information about drug interactions.

What medicines interact with triptans?

Triptans are a family of drugs that were specifically developed for the acute treatment of migraine. They are available in oral (pill) form, injections and nasal sprays.

Triptans and Ergot Alkaloids

Triptans may narrow normal heart arteries by up to 20%, and ergots may constrict arteries even more. For that reason, you should not combine 2 different triptans or take a triptan with ergots on the same day. Although the exact process is unclear, the concern is that combining those drugs could result in excessive blood vessel narrowing.

You should avoid combining:

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  1. Ergots with one of the eight triptan formulations: almotriptan (Axert®), eletriptan (Relpax®), frovatriptan (Frova®), naratriptan (Amerge®), rizatriptan (Maxalt®), sumatriptan (Imitrex®, Treximet®) and zolmitriptan (Zomig®).
  2. Two different triptans in the same day. This does not include switching forms of the same drug, such as switching from a tablet of sumatriptan (Imitrex® or Treximet®) to an injection of sumatriptan.

Triptans and SSRIs/SNRIs

Many migraine patients have depression, anxiety and migraine, all of which may require treatment. It is common for migraine patients to be on triptans and a serotonin reuptake inhibitor antidepressant (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI). Both triptans and common antidepressants affect serotonin, a naturally occurring “messenger” protein found primarily in the gastrointestinal system, certain blood cells (platelets) and the central nervous system (brain and brainstem).

There is a rare condition called serotonin syndrome, which can cause confusion; changes in blood pressure, increased pulse and increased sweating; and muscle changes like twitching, jerking and clumsy gait. The risk of serotonin syndrome is rare. But knowing the side effects and safety risks can alert you to potential interactions so you can change treatment quickly.

SSRIs include citalopram (Celexa®), escitalopram (Lexapro®), fluoxetine (Prozac®), fluvoxamine (Luvox®), paroxetine (Paxil®), and sertraline (Zoloft®). SNRIs include venlafaxine (Effexor®), desvenlaxine (Pristiq®), duloxetine (Cymbalta®). Although very few studies look at the risk of serotonin syndrome in migraine patients taking triptans with SSRIs and SNRIs, most doctors agree that the risk is rare.

Triptans and MAOIs

An enzyme called monoamine oxidase (MAO) breaks down some or all of four triptans: almotriptan (Axert), rizatriptan (Maxalt), sumatriptan (Imitrex), and zolmitriptan (Zomig). At the same time, some antidepressants used as anti-migraine drugs work by inhibiting MAO (MAOIs). If you take one of those triptans and one of those MAOIs at the same time, the MAOI will inhibit the very enzyme your body needs to break down that triptan.

The MAOI antidepressants that inhibit MAO include isocarboxazid (Marplan®), phenelzine (Nardil®), and tranyscypromine (Parnate®). It’s recommended not to use rizatriptan (Maxalt®), sumatriptan (Imitrex®), and zolmitriptan (Zomig®) if you are taking an MAOI.

However, there are several triptans that are not broken down by MAO—eletriptan (Relpax®), frovatriptan (Frova®), and naratriptan (Amerge®)—that would be better options. Another option is almotriptan (Axert®), which breaks down in several ways. It’s important to talk to your doctor about using a specific triptan if you’re on a MAO inhibitor.

Triptans and Other Drugs Broken Down by the Liver

Certain liver enzymes are responsible for breaking down drugs. It’s important to not take two drugs broken down by the same enzyme because that could raise the level of one or both of those drugs.

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Zolmitriptan (Zomig®) breaks down through the same enzyme as cimetidine (Tagamet®), the anti-ulcer medication sold over the counter; the SSRI fluvoxamine (Luvox®), and certain antibiotics. The antibiotics include quinolones such as ciprofloxacin (Cipro®), gatifloxacin (Tequin®), levofloxacin (Levaquin®), and norfloxacin (Noroxin®). When these drugs are taken with zolmitriptan, they raise the amount of zolmitriptan in the blood.

Eletriptan (Relpax®) break down through the same enzyme as clarithromycin (Biaxin®), itraconozole, ketoconozole, nefazodone (Serzone®), ritonovir, and troleandomycin. You should not take these drugs within 72 hours of each other. Ubrogepant (Ubrelvy®) and Rimegepant (Nurtec® ODT) are two new medications for acute migraine relief that are also metabolized by this liver enzyme. (See more about gepants below.)

Rizatriptan and Propranolol

Propranolol (Inderal®) increases blood levels of rizatriptan (Maxalt®) by 70 percent, so your doctor will likely recommend a lower dose of rizatriptan when taking both.

What medicines interact with ergot alkaloids?

Ergots are a class of drug that specifically relieves headache pain, including dihydroergotamine and ergotamine. These drugs are not used commonly, and are typically reserved for patients who don’t respond to analgesics or triptans.

Ergot Alkaloids and Triptans

Ergots may constrict arteries, and triptans may narrow normal heart arteries by up to 20%. For that reason, ergots should not be taken with triptans on the same day. The concern is that doing so could result in excessive blood vessel narrowing. However, no large studies have been done to evaluate this effect, so the exact narrowing process is unclear.

You should avoid combining:

  1. Ergots such as caffeine/ergotamine (Cafergot®, Ergomar®) and dihydroergotamine (DHE-45®/Migranal®).
  2. Ergots with one of the eight triptans: almotriptan (Axert®), eletriptan (Relpax®), frovatriptan (Frova®), naratriptan (Amerge®), rizatriptan (Maxalt®), sumatriptan (Imitrex®, Treximet®) and zolmitriptan (Zomig®).

Ergot Alkaloids and Other Drugs Broken Down by the Liver

DHE (Migranal®) breaks down through the same liver enzyme as almotriptan (Axert®), eletriptan (Relpax®), Ubrogepant (Ubrelvy®) and Rimegepant (Nurtec® ODT). Taking more than one migraine drug metabolized by the same liver enzyme creates interactions of one or both medications, raising their levels.

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What medicines interact with anti-epileptics and anti-seizure medications?

Certain anti-seizure medications can prevent migraine. Topiramate (Topamax®) is an anti-seizure medication that also has uses for migraine prevention.

Some anti-epilepsy drugs make birth control pills or oral contraceptives (OCPs) less effective. Taking topiramate at the FDA recommended dose of 100mg per day has no reported effect on birth control effectiveness. However, taking topiramate at over 200mg per day decreased the estrogen part of OCPs by 18%. Anticonvulsants gabapentin (Neurontin®) and valproate (Depakote®) don’t interact with OCPs.

Taking valproate (Depakote®) with butalbital (Fiorinal®) and benzodiazepines such as alprazolam (Xanax®), lorazepam (Ativan®), and zolpidem (Ambien®) and others can potentially cause liver problems.

What medications interact with lasmiditan (Reyvow®)?

Lasmiditan (Reyvow®) is a new medication for acute migraine relief similar to triptans. One possible side effect is sleepiness, which may be more significant if you combine the treatment with other central nervous system (CNS) depressants (such as benzodiazepines like Valium® and Xanax®). Another possible side effect is lower heart rate, especially if you combine lasmiditan with other heart rate lowering medications (such as propranolol).

What medicines interact with onabotulinumtoxinA (Botox®)?

OnabotulinumtoxinA (Botox®) is an approved treatment for chronic migraine (more than 15 headache days per month). Doctors inject this treatment into head and neck muscles every three months. OnabotulinumtoxinA does not have interactions with other migraine drug classes and may be a good option for patients on multiple other medications.

However, onabotulinumtoxinA can interact with certain antibacterial medications, muscle relaxants and anticholinergic drugs (used to treat many conditions, including urinary incontinence). It’s important to talk to your doctor about all the medications you’re taking prior to starting onabotulinumtoxinA treatments.

What medications interact with CGRP antagonists?

Anti-CGRP migraine treatments were specifically created to prevent migraine and are designed to target CGRP (calcitonin gene-related peptide), the protein known for causing migraine. They are a newer class of treatment and include fremanezumab (AJOVY®), erenumab (Aimovig®) Galcanezumab (Emgality®) and eptinezumab (Vyepti). Anti-CGRP medications do not have any known interactions with other migraine drug classes. They may be a good option for patients on multiple other medications.

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What medications interact with gepants?

Gepants are a newer class of migraine drug that also works to block CGRP (calcitonin gene-related peptide), the protein known for causing migraine. Gepants work to block CGRP from attaching to its receptor and initiating those pain signals.

Ubrogepant (Ubrelvy®) and Rimegepant (Nurtec® ODT) are metabolized by the same liver enzyme as DHE (Migranal®), almotriptan (Axert®) and eletriptan (Relpax®). Using more than one drug broken down by that enzyme could raise the levels of one or both of the drugs. Many drugs break down through this same liver enzyme, so it’s important to talk to your doctor or pharmacist about all of the medications you’re taking to check for potential interactions.

Other drugs that affect the same liver enzyme include ketoconazole, itraconazole, clarithromycin, cyclosporine, ciprofloxacin, fluconazole, fluvoxamine, rifampin, phenytoin and barbiturates. We don’t recommend using gepants when combining with any of those medications, or else you may need to modify your dosage.

Gepants can also interact with certain fruits, including grapefruit, pomegranate and starfruit. Common supplements, including turmeric, licorice, feverfew, evening primrose, dong quai, echinacea, goldenseal, curcumin and St. John’s Wart also interact with Gepants.

There are many acute and preventive medications that can help you manage your migraine. Working with your doctor can help ensure that you get the most from your medications, unlock their benefits and protect your health.

The American Migraine Foundation is committed to improving the lives of those living with this debilitating disease. For more of the latest news and information on migraine, visit the AMF Resource Library. For help finding a healthcare provider, check out our Find a Doctor tool. Together, we are as relentless as migraine.


What is the best drug combination for migraine? ›

A fixed combination of aspirin, acetaminophen, and caffeine was found to provide significantly more relief than each medication by itself. Excedrin Migraine and Excedrin Extra Strength are two OTC medications that contain aspirin, acetaminophen, and caffeine.

What happens if migraine cocktail doesn't work? ›

If the migraine cocktail does not appear to be working, doctors may try other medications, such as valproic acid, an epilepsy drug that also works for severe migraine pain in around 10–15 minutes.

What is the fastest working migraine medicine? ›

In clinical studies, some people had pain freedom within 2 hours. UBRELVY is the #1 prescribed branded treatment for migraine attacks in adults—it's not for prevention of migraine.

What is a migraine cocktail over the counter? ›

An OTC “migraine cocktail” refers to a combination of medications that work safely together to address migraine pain. Excedrin is an OTC pain reliever that combines 250 mg of aspirin, 250 mg of acetaminophen, and 65 mg of caffeine.

What is in migraine cocktail? ›

Typically these cocktails contain three ingredients: Acetaminophen (Paracetamol), aspirin, and caffeine. Excedrin Migraine is a migraine cocktail, so you may already be taking one without realizing it. Speak to your doctor if you need this kind of medication frequently.

What is the new as needed migraine medication? ›

“The FDA approval of ZAVZPRET marks a significant breakthrough for people with migraine who need freedom from pain and prefer alternative options to oral medications,” said Angela Hwang, Chief Commercial Officer, President, Global Biopharmaceuticals Business, Pfizer.

What is the first choice drug for migraine? ›

Acetaminophen and nonsteroidal anti-inflammatory drugs are first-line treatments for mild to moderate migraines, whereas triptans are first-line treatments for moderate to severe migraines.

What is the vitamin cocktail for migraines? ›

What is Myers Cocktail and What is in It? The Myers' Cocktail is a mix of vitamins and nutrients such as Calcium, Magnesium, Vitamin C, Vitamins B and B Complex including Vitamin B5, B6, and B12, and more. It was designed to reduce and treat symptoms of many different chronic conditions such as migraines.

What are the top 3 migraine medicine? ›

Naproxen and ibuprofen are non-steroidal anti-inflammatory drugs that are sometimes taken to treat acute migraines. Tylenol (acetaminophen) and aspirin are choices to relieve pain in migraines in addition to NSAIDs.

What is the drug of choice for migraines and cluster headaches? ›

Best documented drugs for preventive treatment of cluster headache are verapamil and lithium, and possibly effective drugs are gabapentin, topiramate, divalproex sodium, and melatonin.

What are second line drugs for migraine? ›

Agents that could be used as second-line therapy for migraine prophylaxis in adults (listed by evidence of effectiveness) include gabapentin (Neurontin), naproxen (Naprosyn) or naproxen sodium (Anaprox), timed-release dihydroergotamine mesylate (DHE-45), candesartan (Atacand), lisinopril (Zestril), atenolol (Tenormin), ...


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3. Migraine and Menopause | AMF Webinar
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4. Integrative Treatment Options for Migraine
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5. Migraine and COVID-19 Update | AMF Webinar
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6. Staying Active with Migraine
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