FDA label 1b32d254-9be1-4601-9a8c-a039d4cd5a01

5 WARNINGS AND PRECAUTIONS Myocardial ischemia/infarction and Prinzmetal's angina : Perform cardiac evaluation in patients with multiple cardiovascular risk factors ( 5.1 ) Arrhythmias : Discontinue ONZETRA Xsail if occurs ( 5.2 ) Chest/throat/neck/jaw pain, tightness, pressure, or heaviness : Generally not myocardial ischemia; evaluate high risk patients for CAD ( 5.3 ) Cerebral hemorrhage, subarachnoid hemorrhage, and stroke : Discontinue ONZETRA Xsail if occurs ( 5.4 ) Gastrointestinal ischemia and infarction events, peripheral vasospastic reactions : Discontinue ONZETRA Xsail if occurs ( 5.5 ) Medication overuse headache : Detoxification may be necessary ( 5.6 ) Serotonin syndrome : Discontinue ONZETRA Xsail if occurs ( 5.7 ) Seizures : Use with caution in patients with epilepsy or a lowered seizure threshold ( 5.10 ) 5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina The use of ONZETRA Xsail is contraindicated in patients with ischemic or vasospastic CAD. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of sumatriptan. Some of these reactions occurred in patients without known CAD. 5-HT 1 agonists, including ONZETRA Xsail, may cause coronary artery vasospasm (Prinzmetal's angina), even in patients without a history of CAD. Perform a cardiovascular evaluation in triptan-naïve patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving ONZETRA Xsail. If there is evidence of CAD or coronary artery vasospasm, ONZETRA Xsail is contraindicated . For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of ONZETRA Xsail in a medically supervised setting and performing an electrocardiogram (ECG) immediately following administration of ONZETRA Xsail. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of ONZETRA Xsail. 5.2 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-HT 1 agonists. Discontinue ONZETRA Xsail if these disturbances occur. ONZETRA Xsail is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders . 5.3 Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure Sensations of tightness, pain, pressure, and heaviness in the chest, throat, neck, and jaw commonly occur after treatment with 5-HT 1 agonists including other products containing sumatriptan and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of ONZETRA Xsail is contraindicated in patients with known CAD and those with Prinzmetal's variant angina. 5.4 Cerebrovascular Events Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have occurred in patients treated with 5-HT 1 agonists including other products containing sumatriptan, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT 1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). ONZETRA Xsail is contraindicated in patients with a history of stroke or TIA. Discontinue ONZETRA Xsail if a cerebrovascular event occurs. Before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, exclude other potentially serious neurological conditions. 5.5 Other Vasospasm Reactions 5-HT 1 agonists, including ONZETRA Xsail, may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud's syndrome. In patients who experience symptoms or signs suggestive of a non-coronary vasospastic reaction following the use of any 5-HT 1 agonist, rule out a vasospastic reaction before using ONZETRA Xsail . Transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT 1 agonists including sumatriptan. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT 1 agonists have not been clearly established. 5.6 Medication Overuse Headache Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, nonsteroidal anti-inflammatory drugs or combinations of these drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary. 5.7 Serotonin Syndrome Serotonin syndrome may occur with triptans, including ONZETRA Xsail, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions (7.4) ] . Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Discontinue ONZETRA Xsail if serotonin syndrome is suspected. 5.8 Increase in Blood Pressure Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported on rare occasions in patients treated with 5-HT 1 agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with ONZETRA Xsail. ONZETRA Xsail is contraindicated in patients with uncontrolled hypertension. 5.9 Hypersensitivity Reactions Hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients receiving sumatriptan. Such reactions can be life-threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens. ONZETRA Xsail is contraindicated in patients with a history of hypersensitivity reaction to sumatriptan. 5.10 Seizures Seizures have been reported following administration of sumatriptan. Some have occurred in patients with either a history of seizures or concurrent conditions predisposing to seizures. There are also reports in patients where no such predisposing factors are apparent. ONZETRA Xsail should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in more detail in other sections of the prescribing information: Myocardial ischemia, myocardial infarction, and Prinzmetal's angina [see Warnings and Precautions (5.1) ] Arrhythmias [see Warnings and Precautions (5.2) ] Chest, throat, neck and/or jaw pain/tightness/pressure [see Warnings and Precautions (5.3) ] Cerebrovascular events [see Warnings and Precautions (5.4) ] Other vasospasm reactions [see Warnings and Precautions (5.5) ] Medication overuse headache [see Warnings and Precautions (5.6) ] Serotonin syndrome [see Warnings and Precautions (5.7) ] Increase in blood pressure [see Warnings and Precautions (5.8) ] Hypersensitivity reactions [see Contraindications (4) and Warnings and Precautions (5.9) ] Seizures [see Warnings and Precautions (5.10) ] In controlled studies with ONZETRA Xsail, the most common adverse reactions (incidence of ≥ 2% and greater than placebo) were abnormal taste, nasal discomfort, rhinorrhea, and rhinitis ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Currax Pharmaceuticals LLC at 1-800-793-2145 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug, and may not reflect the rates observed in practice. Table 1 lists adverse reactions that occurred in 2 placebo-controlled clinical trials in 301 patients with migraine who took at least 1 dose of ONZETRA Xsail or placebo. Only adverse reactions that occurred at a frequency of 2% or more with ONZETRA Xsail and that occurred at a frequency greater than the placebo group are included in Table 1. Table 1: Adverse Reactions Reported by at Least 2% of Patients in 2 Controlled Migraine Trials Percent of Patients Reporting Adverse Reaction ONZETRA N=151 Placebo N=150 Abnormal Taste 20 3 Nasal Discomfort 11 Limited examinations of the nose and throat did not reveal any clinically noticeable injury in these patients. 1 Rhinorrhea 5 2 Rhinitis 2 0 There is insufficient data with ONZETRA Xsail to assess the impact of age, gender, and race on adverse effects. 6.2 Postmarketing Experience The following adverse reaction has been identified during post approval use of ONZETRA Xsail. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate its frequency or establish a causal relationship to drug exposure. Epistaxis has been identified during post approval use of ONZETRA Xsail as an adverse reaction.

<table width="90%"><caption>Table 1: Adverse Reactions Reported by at Least 2% of Patients in 2 Controlled Migraine Trials </caption><col width="34%" align="left" valign="top"/><col width="33%" align="center" valign="top"/><col width="33%" align="center" valign="top"/><thead><tr styleCode="Botrule"><th styleCode="Lrule Rrule"/><th styleCode="Rrule" colspan="2">Percent of Patients Reporting</th></tr><tr><th styleCode="Lrule Rrule" valign="middle">Adverse Reaction</th><th styleCode="Rrule">ONZETRA N=151</th><th styleCode="Rrule">Placebo N=150</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Abnormal Taste</td><td styleCode="Rrule">20</td><td styleCode="Rrule">3</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Nasal Discomfort</td><td styleCode="Rrule">11<footnote>Limited examinations of the nose and throat did not reveal any clinically noticeable injury in these patients.</footnote></td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Rhinorrhea</td><td styleCode="Rrule">5</td><td styleCode="Rrule">2</td></tr><tr><td styleCode="Lrule Rrule">Rhinitis</td><td styleCode="Rrule">2</td><td styleCode="Rrule">0</td></tr></tbody></table>