Consider the Route of Administration

Different migraines require different treatment approaches. Migraine is a debilitating disease that can be further complicated when certain symptoms are present.

In the Migraine in America Symptoms and Treatment (MAST) Study, published in Headache, October 2018, almost 96% (3796/3930) of all respondents had at least one unmet acute migraine need.1 The top 6 unmet needs were rapid onset of attack (65%), disability (56%), sleep-related onset (50%), inadequate 2-hour pain freedom (48%), recurrence within 24 hours (38%), and attack-related nausea.1 As the number of unmet needs increased, so did comorbid conditions and symptom severity.1

The American Headache Society recommends a non-oral triptan formulation for the following patient types:2-4

Migraine-Related Gastroparesis

Gastroparesis, or delayed gastric emptying, as well as nausea and vomiting are frequently part of the migraine symptom profile.5

The autonomic nervous system (ANS) is believed to play a critical role in the connection between migraine and gastrointestinal (GI) dysfunction due to overlapping symptomatology, including nausea, vomiting, dyspepsia, and gastroparesis.6,7 Research suggests that migraine-associated GI symptoms may result from disruptions in the gut-brain axis, involving both central and enteric autonomic pathways.5 These disruptions can lead to altered gastric motility, as seen in delayed gastric emptying during and between migraine attacks.5-7

Delayed gastric emptying can impair medication absorption of drugs with high intestinal permeability, complicating migraine management.5,8

Published papers on the connection between GP and migraine.

A link between gastrointestinal disorders and migraine: Insights into the gut-brain connection.

Aurora SK, Shrewsbury SB, Ray S, Hindiyeh N, Nguyen L. Headache. 2021 Apr;61(4):576-589.

Why triptan treatment can fail: focus on gastrointestinal manifestations of migraine.

Newman LC. Headache. 2013;53 Suppl 1:11-6.

Migraine and gastroparesis from a gastroenterologist’s perspective.

Parkman HP. Headache. 2013;53 (Suppl 1):4-10.

Stratified Care

Treatment guidelines for migraine vary, with step care escalating treatment after failures, and stratified care tailoring initial treatment based on severity.

The Disability in Strategies of Care (DISC) study, published in JAMA, 2000, conducted by Lipton et al., compared stratified care, step care across attacks, and step care within attacks for the treatment of migraine.9 This randomized, controlled trial involved 835 adult migraine patients with MIDAS grades II–IV.9 The study concluded that stratified care provides significantly better clinical outcomes than step care strategies, as measured by headache response and disability time.9 Key findings of the study include:9

Optimizing Acute Care

The American Migraine Prevalence and Prevention (AMPP) studies, published in Neurology, 2015, highlight the significant burden of migraine and the need for individualized and optimized acute care strategies. One key takeaway from these studies is that many patients rely on ineffective or delayed treatment, contributing to increased disability and progression to chronic migraine.10-11 Physicians should prioritize early and effective acute treatment, selecting medications based on attack severity, comorbidities, and patient response history.

American Migraine Prevalence and Prevention Study12
Suboptimal acute migraine management is linked to a higher risk of progression to chronic migraine within a 12-month period 12

Rates and odds ratios of transition from EM to CM by treatment efficacy category in the fully adjusted model

References
1)  Lipton RB, et al. Unmet Acute Treatment Needs From the 2017 Migraine in America Symptoms and Treatment Study. Headache. 2019 Sep;59(8):1310-1323.
2)  AHS 2018 Consensus Statement.
3)  AHS 2021 Consensus Statement: Update on integrating new migraine treatments into clinical practice.
4)  Rothrock JF, Friedman DI. Information for health care professionals: triptan therapy for acute migraine. American Headache Society. https://americanheadachesociety.org. Accessed 2025.
5)  Aurora SK, et al. A link between gastrointestinal disorders and migraine: Insights into the gut-brain connection. Headache. 2021 Apr;61(4):576-589.
6)  Petrarca, K. (2023, September 21). What is the Relationship Between Migraine and Gastroparesis? Association of Migraine Disorders. https://www.migrainedisorders.org/what-is-the-relationship-between-migraine-and-gastroparesis/. Accessed 2025
7)  Cámara-Lemarroy CR, et al. Gastrointestinal disorders associated with migraine: A comprehensive review. World J Gastroenterol. 2016 Sep 28;22(36):8149-60.
8)  Silberstein SD. Migraine symptoms: results of a survey of self-reported migraineurs. Headache. 1995 Jul-Aug;35(7):387-96
9)  Lipton RB, et al. Stratified care vs step care strategies for migraine: the Disability in Strategies of Care (DISC) Study: A randomized trial. JAMA. 2000 Nov 22-29;284(20):2599-605.
10)  Diamond S, et al. Patterns of diagnosis and acute and preventive treatment for migraine in the United States: results from the American Migraine Prevalence and Prevention study. Headache. 2007 Mar;47(3):355-63.
11)  Serrano D, et al. Acute treatment optimization in episodic and chronic migraine: results of the American Migraine Prevalence and Prevention (AMPP) Study. Headache. 2015 Apr;55(4):502-18.
12)  Lipton RB, et al. Ineffective acute treatment of episodic migraine is associated with new-onset chronic migraine. Neurology 2015;84:688–695
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Do not take Zembrace® SymTouch® if you have hemiplegic migraines or basilar migraines or to treat cluster headache.

IMPORTANT SAFETY INFORMATION
Zembrace SymTouch (Zembrace) can cause serious side effects, including heart attack and other heart problems, which may lead to death. Stop use and get emergency medical help if you have any signs of heart attack:

  • discomfort in the center of your chest that lasts for more than a few minutes or goes away and comes back
  • severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw
  • pain or discomfort in your arms, back, neck, jaw or stomach
  • shortness of breath with or without chest discomfort
  • breaking out in a cold sweat
  • nausea or vomiting
  • feeling lightheaded

Zembrace is not for people with risk factors for heart disease (high blood pressure or cholesterol, smoking, overweight, diabetes, family history of heart disease) unless a heart exam shows no problem.

Do not use Zembrace if you have:

  • history of heart problems
  • narrowing of blood vessels to your legs, arms, stomach, or kidney (peripheral vascular disease)
  • uncontrolled high blood pressure
  • hemiplegic or basilar migraines. If you are not sure if you have these, ask your provider.
  • had a stroke, transient ischemic attacks (TIAs), or problems with blood circulation
  • severe liver problems
  • taken any of the following medicines in the last 24 hours: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, ergotamines, or dihydroergotamine. Ask your provider for a list of these medicines if you are not sure.
  • are taking certain antidepressants, known as monoamine oxidase (MAO)-A inhibitors or it has been 2 weeks or less since you stopped taking a MAO-A inhibitor. Ask your provider for a list of these medicines if you are not sure.
  • an allergy to sumatriptan or any of the components of Zembrace or Tosymra

Tell your provider about all of your medical conditions and medicines you take, including vitamins and supplements.

Zembrace can cause dizziness, weakness, or drowsiness. If so, do not drive a car, use machinery, or do anything where you need to be alert.

Zembrace may cause serious side effects including:

  • changes in color or sensation in your fingers and toes
  • sudden or severe stomach pain, stomach pain after meals, weight loss, nausea or vomiting, constipation or diarrhea, bloody diarrhea, fever
  • cramping and pain in your legs or hips; feeling of heaviness or tightness in your leg muscles; burning or aching pain in your feet or toes while resting; numbness, tingling, or weakness in your legs; cold feeling or color changes in one or both legs or feet
  • increased blood pressure including a sudden severe increase even if you have no history of high blood pressure
  • medication overuse headaches from using migraine medicine for 10 or more days each month. If your headaches get worse, call your provider.
  • serotonin syndrome, a rare but serious problem that can happen in people using Zembrace or Tosymra, especially when used with anti-depressant medicines called SSRIs or SNRIs. Call your provider right away if you have: mental changes such as seeing things that are not there (hallucinations), agitation, or coma; fast heartbeat; changes in blood pressure; high body temperature; tight muscles; or trouble walking.
  • hives (itchy bumps); swelling of your tongue, mouth, or throat
  • seizures even in people who have never had seizures before

The most common side effects of Zembrace include: pain and redness at injection site; tingling or numbness in your fingers or toes; dizziness; warm, hot, burning feeling to your face (flushing); discomfort or stiffness in your neck; feeling weak, drowsy, or tired.

Tell your provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of Zembrace. For more information, ask your provider.

This is the most important information to know about Zembrace but is not comprehensive. For more information, talk to your provider and read the Patient Information and Instructions for Use. You can also visit https://www.tonixpharma.com or call 1-888-869-7633.

You are encouraged to report adverse effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

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