About Tosymra®

Uniquely formulated to
enhance absorption,
delivering bioequivalence
to a 4 mg sumatriptan
subcutaneous injection1

Image for Tosymra® (sumatriptan nasal spray) 10 mg

Not actual size.

Formulation

The first and only triptan nasal spray to use Intravail® technology2,3

Intravail® enhances systemic absorption of sumatriptan across the nasal mucosa, thereby avoiding the GI tract and first-pass hepatic metabolism2,4

Reached peak plasma levels 8x faster than Imitrex® (sumatriptan) nasal spray1*

Graph: Tosymra® 10 mg vs Imitrex nasal spray 20 mg (N=18 each). PK not indicative of efficacy; clinical significance unknown.

Data limitations: PK data are not indicative of efficacy and the clinical significance is not known.

*Study Design: Randomized, single-dose, three-way crossover trial in healthy, fasted adult males (N=18) comparing TOSYMRA delivered via monodose and multidose intranasal devices with commercially available intranasal sumatriptan 20 mg. Blood samples were collected at frequent intervals through 24 hours post-dose for pharmacokinetic evaluation of sumatriptan and TOSYMRA; safety and tolerability were monitored throughout.1

  • Thought to facilitate paracellular absorption by transiently relaxing tight junctions, allowing drug passage5
  • Non‑toxic, odorless, and non‑irritating even when tested at >100X the concentration used in TOSYMRA5
  • Relative bioavailability of TOSYMRA was approximately 87% (90% Cl, 82, 94) of that obtained following 4 mg subcutaneous injection of sumatriptan4

TOSYMRA Delivered rapid absorption similar to subcutaneous sumatriptan1†

Graph: Tosymra® 10 mg Tmax 10 min vs sumatriptan 4 mg SC Tmax 15 min. PK not indicative of efficacy or clinical significance.

TOSYMRA: median Tmax (min, max)=10 min (5, 23)

Sumatriptan 4 mg SC: median Tmax (min, max)=15 min (5, 30)‡

Data limitations: PK data are not indicative of efficacy and the clinical significance is not known.

†Study Design: Open-label, randomized, single-dose, three-way crossover bioavailability trial in healthy, fasted adults (N=78; Males=57) comparing TOSYMRA with subcutaneous sumatriptan 4 mg and 6 mg SC. Blood samples were collected through 24 hours post-dose for pharmacokinetic evaluation of sumatriptan and TOSYMRA; safety and tolerability were monitored throughout.1

‡Sumatriptan 6 mg SC was studied as well, however the efficacy and safety of TOSYMRA nasal spray was demonstrated based on the bioavailability to sumatriptan 4 mg SC injection.1

CI, confidence interval; PK, pharmacokinetic; SC, subcutaneous.

Dosing and Administration

Tip (Nose)

plunger
(thumb)

Spray
(Nozzle)

Labeled diagram of Tosymra® 10 mg nasal spray device: tip (nose), spray nozzle, plunger (thumb). Not actual size.

Not actual size.

Designed for intranasal delivery4

Sample prescription for Tosymra® (sumatriptan nasal spray) 10 mg

Administration Considerations: The recommended dose of TOSYMRA is 10 mg given as a single spray in one nostril. The maximum cumulative dose that may be given in 24 hours is 30 mg, with doses separated by at least 1 hour.4

Refer to the Instructions for Use.

Clinical Data

Migraine relief when it matters most4

The efficacy of TOSYMRA was demonstrated based on bioavailability to sumatriptan 4 mg subcutaneous injection, which has shown4:

2-hour timepoint indicator

Migraine relief was achieved at 2 hours*† (reported in 57% of patients vs 21% for placebo)4

10-minute timepoint indicator

Migraine relief began in as little as 10 minutes*† (reported in 13% of patients vs 5% for placebo)4

*Study Design: Randomized, double-blind, single-attack, placebo‑controlled trial, where six different doses of sumatriptan injection, including 4 mg, were compared (n=30 in each group) with placebo (n=62). Migraine relief was evaluated at 10 and 30 minutes; and 1 and 2 hours after dose.4

†Relief is defined as the reduction of moderate or severe pain to no or mild pain after dosing without use of rescue medication.4

Safety

TOSYMRA (sumatriptan nasal spray) demonstrated an established safety profile with a low dose (10 mg)4,6

The most common adverse reactions with TOSYMRA included local irritative symptoms, which were application site reactions, dysgeusia, and throat irritation reported in approximately 46% of treated patients. Approximately 0.5% were reported as severe.4,7

6-month, open-label, repeat-dose study in 167 adult subjects (19-64 years of age). 134 subjects completed the study with 3,292 doses evaluated over 2,211 migraine attacks and 19.7 mean doses utilized by patients. After 1 hour, patients were allowed to take either a second dose or a rescue medication if the pain relief was insufficient. If a second dose of TOSYMRA was taken and pain relief was still inadequate after 2 hours, patients were allowed to use their rescue medication.7

Most common Treatment-Emergent Adverse Events (≥5% of subjects)7,8

Most common Treatment-Emergent Adverse Events (≥5% of subjects)7,8
Incidence per
individual dose		Patients*
n		Total events
n
Application site pain†17.3%51 (30.5%)568
Dysgeusia7.0%35 (21.0%)232
Upper respiratory tract infection0.7%18 (10.8%)24
Nasopharyn-gitis0.4%12 (7.2%)13
Sinusitis‡0.4%11 (6.6%)12
Application site reaction1.0%9 (5.4%)32

2.9% of doseswere associated with triptan‑related adverse events.

Most were mild and none were severe7

5 patients (3%)discontinued due to adverse events7

~82% of attacksdid not require a rescue medication7

Data limitations: The true incidence of AEs related to TOSYMRA could not be determined due to lack of placebo control.4

*Percent of patients experiencing the event at least once during the course of the study.7

†Included nasal or nostril burning or stinging.7

‡Only one event of sinusitis was considered “possibly related” to TOSYMRA.7

References: 1. Munjal S, Gautam A, Offman E, Brand‐Schieber E, Allenby K, Fisher DM. A Randomized Trial Comparing the Pharmacokinetics, Safety, and Tolerability of DFN‐02, an Intranasal Sumatriptan Spray Containing a Permeation Enhancer, With Intranasal and Subcutaneous Sumatriptan in Healthy Adults. Headache J Head Face Pain. 2016;56(9):1455-1465. doi:10.1111/head.12905 2. Maggio ET. Intravail™: highly effective intranasal delivery of peptide and protein drugs. Expert Opin Drug Deliv. 2006;3(4):529-539. doi:10.1517/17425247.3.4.529 3. Martin V, Hoekman J, Aurora SK, Shrewsbury SB. Nasal Delivery of Acute Medications for Migraine: The Upper Versus Lower Nasal Space. J Clin Med. 2021;10(11):2468. doi:10.3390/jcm10112468 4. Tosymra® (sumatriptan) [prescribing information]. Berkeley Heights, NJ: Tonix Medicines, Inc.; 2023. 5. Maggio ET, Pillion DJ. High efficiency intranasal drug delivery using Intravail® alkylsaccharide absorption enhancers. Drug Deliv Transl Res. 2013;3(1):16-25. doi:10.1007/s13346-012-0069-z 6. Brar Y. Sumatriptan. StatPearls. Published online November 2023. https://www.ncbi.nlm.nih.gov/books/NBK470206/ 7. Munjal S, Brand-Schieber E, Allenby K, Spierings ELH, Cady RK, Rapoport AM. A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10 mg plus permeation enhancer DDM, for the acute treatment of episodic migraine. J Headache Pain. 2017;18(1):31. doi:10.1186/s10194-017-0740-3 8. National Library of Medicine. Other (not including serious) adverse events. ClinicalTrials.gov. Published August 28, 2017. Accessed March 27, 2026. https://clinicaltrials.gov/study/NCT02279082?id=NCT02279082&viewType=Card&rank=1&tab=results

Learn about Zembrace® SymTouch®,
a subcutaneous sumatriptan injection

Discover

Navigate
Access and Support

Explore

INDICATION/LIMITATIONS OF USE

ZEMBRACE® SymTouch® (sumatriptan succinate) injection and TOSYMRA® (sumatriptan) nasal spray are indicated for the acute treatment of migraine with or without aura in adults. ZEMBRACE SymTouch or TOSYMRA should only be used where a clear diagnosis of migraine has been established. ZEMBRACE SymTouch and TOSYMRA are not indicated for the prevention of migraine attacks or for the treatment of cluster headache.

IMPORTANT SAFETY INFORMATION

ZEMBRACE SymTouch and TOSYMRA are contraindicated in patients with:

  • Ischemic coronary artery disease (CAD) or coronary artery vasospasm, including Prinzmetal's angina
  • Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders
  • History of stroke, transient ischemic attack (TIA), or hemiplegic or basilar migraine
  • Peripheral vascular disease
  • Ischemic bowel disease
  • Uncontrolled hypertension
  • Recent (ie, within 24 hours) use of ergotamine-containing or ergot-type medication, or another 5-hydroxytryptamine1 (5-HT1) agonist
  • Concurrent or recent (within 2 weeks) use of a monoamine oxidase-A (MAO-A) inhibitor
  • Hypersensitivity to sumatriptan (angioedema and anaphylaxis seen)
  • Severe hepatic impairment

WARNINGS AND PRECAUTIONS

  • Myocardial ischemia/infarction, Prinzmetal's angina: These events may occur even in patients without known cardiovascular disease. Perform cardiac evaluation in triptan-naive patients with multiple risk factors and, if satisfactory, administer the first dose of ZEMBRACE SymTouch or TOSYMRA in a medically supervised setting
  • Arrhythmias: Life-threatening disturbances of cardiac rhythm, including ventricular tachycardia and ventricular fibrillation leading to death, have been reported within a few hours following the administration of 5-HT1 agonists. Discontinue ZEMBRACE SymTouch or TOSYMRA if these disturbances occur
  • Sensations of chest/throat/neck/jaw pain, tightness, pressure, or heaviness: Commonly occur after treatment with 5-HT1 agonists and are usually noncardiac in origin. Perform a cardiac evaluation in patients with cardiac risk
  • Cerebrovascular events: Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities. Discontinue ZEMBRACE SymTouch or TOSYMRA if a cerebrovascular event occurs. Before treating headaches in patients not previously diagnosed with migraine or in patients who present with atypical symptoms, exclude other potentially serious neurological conditions
  • Other vasospasm reactions: 5-HT1 agonists, including ZEMBRACE SymTouch and TOSYMRA, may cause noncoronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction, splenic infarction, and Raynaud's syndrome. In patients who experience symptoms or signs suggestive of a vasospastic reaction following the use of any 5-HT1 agonist, rule out a vasospastic reaction before using ZEMBRACE SymTouch or TOSYMRA
  • Medication overuse headache: Overuse of acute migraine drugs may lead to exacerbation headache (medication overuse headache). Detoxification of patients, including withdrawal of the overused drugs and treatment of withdrawal symptoms, may be necessary
  • Serotonin syndrome: May occur with triptans, including ZEMBRACE SymTouch and TOSYMRA, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors. The onset of symptoms usually occurs within minutes to hours of receiving a new or greater dose of a serotonergic medication. Discontinue ZEMBRACE SymTouch or TOSYMRA if serotonin syndrome is suspected
  • Increase in blood pressure: Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported in patients treated with 5-HT1 agonists. Monitor blood pressure in patients treated with ZEMBRACE SymTouch or TOSYMRA
  • Hypersensitivity reactions: Hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients receiving sumatriptan. Such reactions can be life threatening or fatal. ZEMBRACE SymTouch and TOSYMRA are contraindicated in patients with a history of hypersensitivity reaction to sumatriptan
  • Seizures: Seizures have been reported following administration of sumatriptan, with or without predisposing factors. ZEMBRACE SymTouch or TOSYMRA should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold
  • Local irritation: For TOSYMRA nasal spray only, local irritative symptoms were reported in approximately 46% of patients with TOSYMRA in an open-label trial that allowed repeated use of TOSYMRA over the course of 6 months. The most common local irritative symptoms were application site reaction (eg, burning sensations in the nose), dysgeusia, and throat irritation. Approximately 0.5% of the cases were reported as severe

ADVERSE REACTIONS

The most common adverse reactions (≥5% and >placebo) were injection site reactions (for ZEMBRACE SymTouch only), tingling, dizziness/vertigo, warm/hot sensation, burning sensation, feeling of heaviness, pressure sensation, flushing, feeling of tightness, and numbness/paresthesia.

For TOSYMRA nasal spray only, in an open-label study allowing repeated use of TOSYMRA over 6 months, 46% of patients reported local irritative symptoms, the most common of which were application site reaction, dysgeusia, and throat irritation.

DRUG INTERACTIONS

  • Ergot-containing drugs: Reported to cause prolonged vasoplastic reactions
  • MAO-A inhibitors: Increase systemic exposure by 2-fold
  • Other 5-HT1 agonists: Vasoplastic effects may be additive
  • SSRIs, SNRIs, TCAs, and MAO inhibitors: Serotonin syndrome has been reported

USE IN SPECIFIC POPULATIONS

Pregnancy: Disease-Associated Maternal and/or Embryo/Fetal Risk: Several studies have suggested that women with migraine may be at increased risk of preeclampsia during pregnancy.

Lactation: Sumatriptan is excreted in human milk following subcutaneous administration. There are no data on the effects of sumatriptan on a breastfed infant or the effects on milk production. Infant exposure can be minimized by avoiding breastfeeding for 12 hours after treatment with ZEMBRACE SymTouch or TOSYMRA.

Pediatric use: The safety and effectiveness in pediatric patients have not been established. ZEMBRACE SymTouch or TOSYMRA is not recommended for use in patients younger than 18 years of age.

Geriatric patients: Clinical trials of sumatriptan did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger patients. Dose selection for an elderly patient should usually start at the low end of the dosing range. A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (eg, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving ZEMBRACE SymTouch or TOSYMRA.

Please see additional safety information in the full Prescribing Information for ZEMBRACE SymTouch and TOSYMRA.

To report suspected adverse reactions, contact Tonix Medicines, Inc. at 1‑888‑869‑7633, or the FDA at 1‑800‑FDA‑1088 or www.fda.gov/medwatch.

MLT‑HCP‑260015 05/26

MLT‑HCP‑260013 05/26