Sumatriptan injection is indicated in adults for (1) the acute treatment of migraine, with or without aura, and (2) the acute treatment of cluster headache.

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Limitations of Use:

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The maximum single recommended adult dose of sumatriptan injection for the acute treatment of migraine or cluster headache is 6 mg injected subcutaneously. For the treatment of migraine, if side effects are dose limiting, lower doses (1 mg to 5 mg) may be used [see Clinical Studies (14.1)]. For the treatment of cluster headache, the efficacy of lower doses has not been established.

The maximum cumulative dose that may be given in 24 hours is 12 mg, two 6-mg injections separated by at least 1 hour. A second 6-mg dose should only be considered if some response to a first injection was observed.

In patients receiving doses other than 4 mg or 6 mg, use the 6-mg single-dose vial. Visually inspect the vial for particulate matter and discoloration before administration. Do not use if particulates and discolorations are noted.

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Sumatriptan injection is contraindicated in patients with:

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The use of sumatriptan injection 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 injection. Some of these reactions occurred in patients without known CAD. Sumatriptan injection may cause coronary artery vasospasm (Prinzmetal’s angina), even in patients without a history of CAD.

Perform a cardiovascular evaluation in triptan-naive patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving sumatriptan injection. If there is evidence of CAD or coronary artery vasospasm, sumatriptan injection is contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of sumatriptan injection in a medically supervised setting and performing an electrocardiogram (ECG) immediately following administration of sumatriptan injection. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of sumatriptan injection.

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 sumatriptan injection if these disturbances occur. Sumatriptan injection is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

Sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw commonly occur after treatment with sumatriptan injection and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of sumatriptan injection is contraindicated in patients with CAD and those with Prinzmetal’s variant angina.

Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). Discontinue sumatriptan injection if a cerebrovascular event occurs.

Before treating headaches in patients not previously diagnosed with migraine or cluster headache or in patients who present with atypical symptoms, exclude other potentially serious neurological conditions. Sumatriptan injection is contraindicated in patients with a history of stroke or TIA.

Sumatriptan injection 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 non-coronary vasospasm reaction following the use of any 5-HT1 agonist, rule out a vasospastic reaction before receiving additional injections of sumatriptan.

Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1 agonists has not been clearly established.

Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or combination 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.

Serotonin syndrome may occur with sumatriptan injection, 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 aberrations (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 sumatriptan injection if serotonin syndrome is suspected.

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-HT1 agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with sumatriptan injection. Sumatriptan injection is contraindicated in patients with uncontrolled hypertension.

Hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients receiving sumatriptan injection. 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. Sumatriptan injection is contraindicated in patients with a history of hypersensitivity reaction to sumatriptan.

Seizures have been reported following administration of sumatriptan injection. 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. Sumatriptan injection should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Migraine Headache

Table 1 lists adverse reactions that occurred in 2 U.S. placebo-controlled clinical trials in patients with migraines (Studies 2 and 3) following either a single 6-mg dose of sumatriptan injection or placebo. Only reactions that occurred at a frequency of 2% or more in groups treated with sumatriptan injection 6 mg and that occurred at a frequency greater than the placebo group are included in Table 1.

Table 1. Adverse Reactions in Pooled Placebo-Controlled Trials in Patients with Migraine (Studies 2 and 3)

<div class="scrollingtable"><table width="100%"> <col width="47%"/> <col width="38%"/> <col width="15%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="3" valign="top"><span class="Sup">a</span>Includes injection site pain, stinging/burning, swelling, erythema, bruising, bleeding.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Adverse Reaction</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Sumatriptan Injection</span> <br/> <span class="Bold">6 mg Subcutaneous</span> <br/> <span class="Bold">(n = 547)</span> <br/> <span class="Bold">%</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> <br/> <span class="Bold">(n = 370)</span> <br/> <span class="Bold">%</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Atypical sensations<br/> Tingling<br/> Warm/hot sensation<br/> Burning sensation<br/> Feeling of heaviness<br/> Pressure sensation<br/> Feeling of tightness<br/> Numbness<br/> Feeling strange<br/> Tight feeling in head</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">42<br/>14<br/>11<br/>7<br/>7<br/>7<br/>5<br/>5<br/>2<br/>2</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">9<br/>3<br/>4<br/>&lt;1<br/>1<br/>2<br/>&lt;1<br/>2<br/>&lt;1<br/>&lt;1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Cardiovascular<br/> Flushing<br/> Chest discomfort<br/> Tightness in chest<br/> Pressure in chest</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <br/>7<br/>5<br/>3<br/>2</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <br/>2<br/>1<br/>&lt;1<br/>&lt;1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Ear, nose, and throat<br/> Throat discomfort<br/> Discomfort: nasal cavity/sinuses</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <br/>3<br/>2</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <br/>&lt;1<br/>&lt;1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Injection site reaction<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">59</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">24</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Miscellaneous<br/> Jaw discomfort</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <br/>2</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <br/>0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Musculoskeletal<br/> Weakness<br/> Neck pain/stiffness<br/> Myalgia</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <br/>5<br/>5<br/>2</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <br/>&lt;1<br/>&lt;1<br/>&lt;1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Neurological<br/> Dizziness/vertigo<br/> Drowsiness/sedation<br/> Headache</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <br/>12<br/>3<br/>2</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <br/>4<br/>2<br/>&lt;1</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Skin<br/> Sweating</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <br/>2</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <br/>1</p> </td> </tr> </tbody> </table></div>

The incidence of adverse reactions in controlled clinical trials was not affected by gender or age of the patients. There were insufficient data to assess the impact of race on the incidence of adverse reactions.

Cluster Headache

In the controlled clinical trials assessing the efficacy of sumatriptan injection as a treatment for cluster headache (Studies 4 and 5), no new significant adverse reactions were detected that had not already been identified in trials of sumatriptan injection in patients with migraine.

Overall, the frequency of adverse reactions reported in the trials of cluster headache was generally lower than in the migraine trials. Exceptions include reports of paresthesia (5% sumatriptan injection, 0% placebo), nausea and vomiting (4% sumatriptan injection, 0% placebo), and bronchospasm (1% sumatriptan injection, 0% placebo).

The following adverse reactions have been identified during postapproval use of sumatriptan tablets, sumatriptan nasal spray, and sumatriptan injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular

Hypotension, palpitations.

Neurological

Dystonia, tremor.

Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and sumatriptan injection within 24 hours of each other is contraindicated.

MAO-A inhibitors increase systemic exposure by 2-fold. Therefore, the use of sumatriptan injection in patients receiving MAO-A inhibitors is contraindicated [see Clinical Pharmacology (12.3)].

Because their vasospastic effects may be additive, co-administration of sumatriptan injection and other 5-HT1 agonists (e.g., triptans) within 24 hours of each other is contraindicated.

Cases of serotonin syndrome have been reported during co-administration of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7)].

Risk Summary

Data from a prospective pregnancy exposure registry and epidemiological studies of pregnant women have not detected an increased frequency of birth defects or a consistent pattern of birth defects among women exposed to sumatriptan compared with the general population (see Data). In developmental toxicity studies in rats and rabbits, oral administration of sumatriptan to pregnant animals was associated with embryolethality, fetal abnormalities, and pup mortality. When administered by the intravenous route to pregnant rabbits, sumatriptan was embryolethal (see Data).

In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of major birth defects among deliveries to women with migraine ranged from 2.2% to 2.9% and the reported rate of miscarriage was 17%, which were similar to rates reported in women without migraine.

Clinical Considerations

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.

Data

Human Data

The Sumatriptan/Naratriptan/Treximet (sumatriptan and naproxen sodium) Pregnancy Registry, a population-based international prospective study, collected data for sumatriptan from January 1996 to September 2012. The Registry documented outcomes of 626 infants and fetuses exposed to sumatriptan during pregnancy (528 with earliest exposure during the first trimester, 78 during the second trimester, 16 during the third trimester, and 4 unknown). The occurrence of major birth defects (excluding fetal deaths and induced abortions without reported defects and all spontaneous pregnancy losses) during first-trimester exposure to sumatriptan was 4.2% (20/478 [95% CI: 2.6% to 6.5%]) and during any trimester of exposure was 4.2% (24/576 [95% CI: 2.7% to 6.2%]). The sample size in this study had 80% power to detect at least a 1.73-to 1.91-fold increase in the rate of major malformations. The number of exposed pregnancy outcomes accumulated during the registry was insufficient to support definitive conclusions about overall malformation risk or for making comparisons of the frequencies of specific birth defects. Of the 20 infants with reported birth defects after exposure to sumatriptan in the first trimester, 4 infants had ventricular septal defects, including one infant who was exposed to both sumatriptan and naratriptan, and 3 infants had pyloric stenosis. No other birth defect was reported for more than 2 infants in this group.

In a study using data from the Swedish Medical Birth Register, live births to women who reported using triptans or ergots during pregnancy were compared with those of women who did not. Of the 2,257 births with first-trimester exposure to sumatriptan, 107 infants were born with malformations (relative risk 0.99 [95% CI: 0.91 to 1.21]). A study using linked data from the Medical Birth Registry of Norway to the Norwegian Prescription Database compared pregnancy outcomes in women who redeemed prescriptions for triptans during pregnancy, as well as a migraine disease comparison group who redeemed prescriptions for sumatriptan before pregnancy only, compared with a population control group. Of the 415 women who redeemed prescriptions for sumatriptan during the first trimester, 15 had infants with major congenital malformations (OR 1.16 [95% CI: 0.69 to 1.94]) while for the 364 women who redeemed prescriptions for sumatriptan before, but not during, pregnancy, 20 had infants with major congenital malformations (OR 1.83 [95% CI: 1.17 to 2.88]), each compared with the population comparison group. Additional smaller observational studies evaluating use of sumatriptan during pregnancy have not suggested an increased risk of teratogenicity.

Animal Data

Oral administration of sumatriptan to pregnant rats during the period of organogenesis resulted in an increased incidence of fetal blood vessel (cervicothoracic and umbilical) abnormalities. The highest no-effect dose for embryofetal developmental toxicity in rats was 60 mg/kg/day. Oral administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in increased incidences of embryolethality and fetal cervicothoracic vascular and skeletal abnormalities. Intravenous administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in an increased incidence of embryolethality. The highest oral and intravenous no-effect doses for developmental toxicity in rabbits were 15 and 0.75 mg/kg/day, respectively.

Oral administration of sumatriptan to rats prior to and throughout gestation resulted in embryofetal toxicity (decreased body weight, decreased ossification, increased incidence of skeletal abnormalities). The highest no-effect dose was 50 mg/kg/day. In offspring of pregnant rats treated orally with sumatriptan during organogenesis, there was a decrease in pup survival. The highest no-effect dose for this effect was 60 mg/kg/day. Oral treatment of pregnant rats with sumatriptan during the latter part of gestation and throughout lactation resulted in a decrease in pup survival. The highest no-effect dose for this finding was 100 mg/kg/day.

Risk Summary

Sumatriptan is excreted in human milk following subcutaneous administration (see Data). There are no data on the effects of sumatriptan on the breastfed infant or the effects of sumatriptan on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for sumatriptan injection and any potential adverse effects on the breastfed infant from sumatriptan or from the underlying maternal condition.

Clinical Considerations

Infant exposure to sumatriptan can be minimized by avoiding breastfeeding for 12 hours after treatment with sumatriptan injection.

Data

Following subcutaneous administration of a 6-mg dose of sumatriptan injection in 5 lactating volunteers, sumatriptan was present in milk.

Safety and effectiveness in pediatric patients have not been established. Sumatriptan injection is not recommended for use in patients younger than 18 years of age.

Two controlled clinical trials evaluated sumatriptan nasal spray (5 mg to 20 mg) in 1,248 pediatric migraineurs aged 12 to 17 years who treated a single attack. The trials did not establish the efficacy of sumatriptan nasal spray compared with placebo in the treatment of migraine in pediatric patients. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults.

Five controlled clinical trials (2 single-attack trials, 3 multiple-attack trials) evaluating oral sumatriptan (25 mg to 100 mg) in pediatric patients aged 12 to 17 years enrolled a total of 701 pediatric migraineurs. These trials did not establish the efficacy of oral sumatriptan compared with placebo in the treatment of migraine in pediatric patients. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults. The frequency of all adverse reactions in these patients appeared to be both dose- and age-dependent, with younger patients reporting reactions more commonly than older pediatric patients.

Postmarketing experience documents that serious adverse reactions have occurred in the pediatric population after use of subcutaneous, oral, and/or intranasal sumatriptan. These reports include reactions similar in nature to those reported rarely in adults, including stroke, visual loss, and death. A myocardial infarction has been reported in a 14-year-old male following the use of oral sumatriptan; clinical signs occurred within 1 day of drug administration. Clinical data to determine the frequency of serious adverse reactions in pediatric patients who might receive subcutaneous, oral, or intranasal sumatriptan are not presently available.

Clinical trials of sumatriptan injection did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving sumatriptan injection [see Warnings and Precautions (5.1)].

Coronary vasospasm was observed after intravenous administration of sumatriptan injection [see Contraindications (4)]. Overdoses would be expected from animal data (dogs at 0.1 g/kg, rats at 2 g/kg) to possibly cause convulsions, tremor, inactivity, erythema of the extremities, reduced respiratory rate, cyanosis, ataxia, mydriasis, injection site reactions (desquamation, hair loss, and scab formation), and paralysis.

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The elimination half-life of sumatriptan is about 2 hours [see Clinical Pharmacology (12.3)]; therefore, monitoring of patients after overdose with sumatriptan injection should continue for at least 10 hours or while symptoms or signs persist.

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It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan.

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Sumatriptan Injection, USP contains sumatriptan succinate, a selective 5-HT1B/1D receptor agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1), and it has the following structure:

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The empirical formula is C14H21N3O2S•C4H6O4, representing a molecular weight of 413.5. Sumatriptan succinate is a white to off-white powder that is readily soluble in water and in saline.

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Sumatriptan Injection, USP is a clear, colorless to pale yellow, sterile, nonpyrogenic solution for subcutaneous injection. Each 0.5 mL of sumatriptan injection, USP 12 mg/mL solution contains 8.4 mg of sumatriptan succinate equivalent to 6 mg of sumatriptan and 3.5 mg of sodium chloride, USP in Water for Injection, USP. The pH range of the solution is approximately 4.2 to 5.3. The osmolality of the injection is 291 mOsmol.

{ "type": "p", "children": [], "text": "Sumatriptan Injection, USP is a clear, colorless to pale yellow, sterile, nonpyrogenic solution for subcutaneous injection. Each 0.5 mL of sumatriptan injection, USP 12 mg/mL solution contains 8.4 mg of sumatriptan succinate equivalent to 6 mg of sumatriptan and 3.5 mg of sodium chloride, USP in Water for Injection, USP. The pH range of the solution is approximately 4.2 to 5.3. The osmolality of the injection is 291 mOsmol." }

Sumatriptan binds with high affinity to human cloned 5-HT1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine and cluster headaches through agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

Blood Pressure

Significant elevation in blood pressure, including hypertensive crisis, has been reported in patients with and without a history of hypertension [see Warnings and Precautions (5.8)].

Peripheral (Small) Arteries

In healthy volunteers (N = 18), a trial evaluating the effects of sumatriptan on peripheral (small vessel) arterial reactivity failed to detect a clinically significant increase in peripheral resistance.

Heart Rate

Transient increases in blood pressure observed in some patients in clinical trials carried out during sumatriptan’s development as a treatment for migraine were not accompanied by any clinically significant changes in heart rate.

Absorption

The bioavailability of sumatriptan via subcutaneous site injection to 18 healthy male subjects was 97% ± 16% of that obtained following intravenous injection.

After a single 6-mg subcutaneous manual injection into the deltoid area of the arm in 18 healthy males (age: 24 ± 6 years, weight: 70 kg), the maximum serum concentration (Cmax) of sumatriptan was (mean ± standard deviation) 74 ± 15 ng/mL and the time to peak concentration (Tmax) was 12 minutes after injection (range: 5 to 20 minutes). In this trial, the same dose injected subcutaneously in the thigh gave a Cmax of 61 ± 15 ng/mL by manual injection versus 52 ± 15 ng/mL by autoinjector techniques. The Tmax or amount absorbed was not significantly altered by either the site or technique of injection.

Distribution

Protein binding, determined by equilibrium dialysis over the concentration range of 10 to 1,000 ng/mL is low, approximately 14% to 21%. The effect of sumatriptan on the protein binding of other drugs has not been evaluated.

Following a 6-mg subcutaneous injection into the deltoid area of the arm in 9 males (mean age: 33 years, mean weight: 77 kg) the volume of distribution central compartment of sumatriptan was 50 ± 8 liters and the distribution half‑life was 15 ± 2 minutes.

Metabolism

In vitro studies with human microsomes suggest that sumatriptan is metabolized by MAO, predominantly the A isoenzyme. Most of a radiolabeled dose of sumatriptan excreted in the urine is the major metabolite indole acetic acid (IAA) or the IAA glucuronide, both of which are inactive.

Elimination

After a single 6-mg subcutaneous dose, 22% ± 4% was excreted in the urine as unchanged sumatriptan and 38% ± 7% as the IAA metabolite.

Following a 6-mg subcutaneous injection into the deltoid area of the arm, the systemic clearance of sumatriptan was 1,194 ± 149 mL/min and the terminal half-life was 115 ± 19 minutes.

Specific Populations

Age

The pharmacokinetics of sumatriptan in the elderly (mean age: 72 years, 2 males and 4 females) and in subjects with migraine (mean age: 38 years, 25 males and 155 females) were similar to that in healthy male subjects (mean age: 30 years).

Patients with Hepatic Impairment

The effect of mild to moderate hepatic disease on the pharmacokinetics of subcutaneously administered sumatriptan has been evaluated. There were no significant differences in the pharmacokinetics of subcutaneously administered sumatriptan in moderately hepatically impaired subjects compared with healthy controls. The pharmacokinetics of subcutaneously administered sumatriptan in patients with severe hepatic impairment has not been studied. The use of sumatriptan injection in this population is contraindicated [see Contraindications (4)].

Racial Groups

The systemic clearance and Cmax of subcutaneous sumatriptan were similar in black (n = 34) and Caucasian (n = 38) healthy male subjects.

Drug Interaction Studies

Monoamine Oxidase-A Inhibitors

In a trial of 14 healthy females, pretreatment with an MAO-A inhibitor decreased the clearance of subcutaneous sumatriptan, resulting in a 2-fold increase in the area under the sumatriptan plasma concentration-time curve (AUC), corresponding to a 40% increase in elimination half-life.

Carcinogenesis

In carcinogenicity studies in mouse and rat, sumatriptan was administered orally for 78 weeks and 104 weeks, respectively, at doses up to 160 mg/kg/day (the high dose in rat was reduced from 360 mg/kg/day during Week 21). The highest dose to mice and rats was approximately 130 and 260 times the single MRHD of 6 mg administered subcutaneously on a mg/m2 basis. There was no evidence in either 2 species of an increase in tumors related to sumatriptan administration.

Mutagenesis

Sumatriptan was negative in in vitro (bacterial reverse mutation [Ames], gene cell mutation in Chinese hamster V79/HGPRT, chromosomal aberration in human lymphocytes) and in vivo (rat micronucleus) assays.

Impairment of Fertility

When sumatriptan (5, 50, 500 mg/kg/day) was administered orally to male and female rats prior to and throughout the mating period, there was a treatment-related decrease in fertility secondary to a decrease in mating in animals treated with doses greater than 5 mg/kg/day. It is not clear whether this finding was due to an effect on males or females or both.

When sumatriptan was administered by subcutaneous injection to male and female rats prior to and throughout the mating period, there was no evidence of impaired fertility at doses up to 60 mg/kg/day.

Corneal Opacities

Dogs receiving oral sumatriptan developed corneal opacities and defects in the corneal epithelium. Corneal opacities were seen at the lowest dose tested, 2 mg/kg/day, and were present after 1 month of treatment. Defects in the corneal epithelium were noted in a 60-week study. Earlier examinations for these toxicities were not conducted and no-effect doses were not established; however, the relative plasma exposure at the lowest dose tested was approximately 3 times the human exposure after a 6-mg subcutaneous dose.

In controlled clinical trials enrolling more than 1,000 patients during migraine attacks who were experiencing moderate or severe pain and 1 or more of the symptoms enumerated in Table 3, onset of relief began as early as 10 minutes following a 6-mg sumatriptan injection. Lower doses of sumatriptan injection may also prove effective, although the proportion of patients obtaining adequate relief was decreased and the latency to that relief is greater with lower doses.

In Study 1, 6 different doses of sumatriptan injection (n = 30 each group) were compared with placebo (n = 62) in a single-attack, parallel-group design; the dose-response relationship was found to be as shown in Table 2.

<div class="scrollingtable"><table width="100%"> <col width="19%"/> <col width="19%"/> <col width="19%"/> <col width="12%"/> <col width="12%"/> <col width="19%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="6" valign="top"><span class="Sup">a</span> Relief is defined as the reduction of moderate or severe pain to no or mild pain after dosing without use of rescue medication.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Toprule" colspan="6" valign="middle"> <p class="First"> <span class="Bold">Table 2. Proportion of Patients with Migraine Relief and Incidence of Adverse Reactions by Time and by Dose of Sumatriptan Injection in Study 1</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" rowspan="2" valign="middle"> <p class="First"> <span class="Bold">Dose of Sumatriptan Injection</span> </p> </td><td align="center" class="Botrule Lrule Rrule" colspan="4" valign="middle"> <p class="First"> <span class="Bold">Percent Patients with Relief<span class="Sup">a</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" rowspan="2" valign="middle"> <p class="First"> <span class="Bold">Adverse Reactions Incidence</span> <br/> <span class="Bold">(%)</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">at 10 Minutes</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">at 30 Minutes</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">at 1 Hour</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">at 2 Hours</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">Placebo</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">15</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">24</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">21</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">55</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1 mg</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">10</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">40</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">43</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">40</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">63</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2 mg</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">23</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">57</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">43</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">63</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">3 mg</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">17</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">47</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">57</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">60</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">77</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">4 mg</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">13</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">37</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">50</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">57</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">80</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">6 mg</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">10</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">63</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">73</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">70</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">83</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">8 mg</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">23</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">57</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">80</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">83</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">93</p> </td> </tr> </tbody> </table></div>

In 2 randomized, placebo-controlled clinical trials of sumatriptan injection 6 mg in 1,104 patients with moderate or severe migraine pain (Studies 2 and 3), the onset of relief was less than 10 minutes. Headache relief, as defined by a reduction in pain from severe or moderately severe to mild or no headache, was achieved in 70% of the patients within 1 hour of a single 6-mg subcutaneous dose of sumatriptan injection. Approximately 82% and 65% of patients treated with sumatriptan injection 6 mg had headache relief and were pain free within 2 hours, respectively.

Table 3 shows the 1- and 2-hour efficacy results for sumatriptan injection 6 mg in Studies 2 and 3.

<div class="scrollingtable"><table width="100%"> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tbody class="Headless"> <tr class="First"> <td class="Toprule" colspan="5" valign="top"> <p class="First"> <span class="Bold">Table 3. Proportion of Patients with Pain Relief and Relief of Migraine Symptoms after 1 and 2 Hours of Treatment in Studies 2 and 3</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" rowspan="2" valign="middle"> <p class="First"> <span class="Bold">1-Hour Data</span> </p> </td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">Study 2</span> </p> </td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">Study 3</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Placebo</span> <br/> <span class="Bold">(n=190)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Sumatriptan Injection</span> <br/> <span class="Bold">6 mg</span> <br/> <span class="Bold">(n = 384)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Placebo</span> <br/> <span class="Bold">(n=180)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Sumatriptan Injection 6 mg</span> </p> <p> <span class="Bold">(n = 350)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patients with pain relief (Grade 0/1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">18%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">70%<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">26%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">70%<span class="Sup">a</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patients with no pain</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">5%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">48%<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">13%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">49%<span class="Sup">a</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patients without nausea</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">48%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">73%<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">50%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">73%<span class="Sup">a</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patients without photophobia</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">23%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">56%<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">25%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">58%<span class="Sup">a</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patients with little or no clinical disability<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">34%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">76%<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">34%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">76%<span class="Sup">a</span> </p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tfoot> <tr class="First"> <td align="left" colspan="5" valign="top"><span class="Sup">a</span><span class="Italics">P</span> &lt;0.05 versus placebo.</td> </tr> <tr> <td align="left" colspan="5" valign="top"><span class="Sup">b</span> A successful outcome in terms of clinical disability was defined prospectively as ability to work mildly impaired or ability to work and function normally.</td> </tr> <tr> <td align="left" colspan="5" valign="top"><span class="Sup">c</span> Includes patients that may have received an additional placebo injection 1 hour after the initial injection.</td> </tr> <tr class="Last"> <td align="left" colspan="5" valign="top"><span class="Sup">d</span> Includes patients that may have received an additional of 6 mg sumatriptan injection 1 hour after the initial injection.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="middle"> <p class="First"> <span class="Bold">2-Hour Data</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">Study 2</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">Study 3</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Placebo<span class="Sup">c</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Sumatriptan Injection </span> <br/> <span class="Bold">6 mg<span class="Sup">d</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Placebo<span class="Sup">c</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Sumatriptan Injection 6 mg</span><span class="Sup">d</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patients with pain relief (Grade 0/1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">31%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">81%<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">39%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">82%<span class="Sup">a</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patients with no pain</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">11%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">63%<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">19%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">65%<span class="Sup">a</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patients without nausea</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">56%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">82%<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">63%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">81%<span class="Sup">a</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patients without photophobia</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">31%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">72%<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">35%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">71%<span class="Sup">a</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patients with little or no clinical disability<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">42%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">85%<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">49%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">84%<span class="Sup">a</span> </p> </td> </tr> </tbody> </table></div>

Sumatriptan injection also relieved photophobia, phonophobia (sound sensitivity), nausea, and vomiting associated with migraine attacks.

The efficacy of sumatriptan injection was unaffected by whether or not the migraine was associated with aura, duration of attack, gender or age of the patient, or concomitant use of common migraine prophylactic drugs (e.g., beta-blockers).

The efficacy of sumatriptan injection in the acute treatment of cluster headache was demonstrated in 2 randomized, double-blind, placebo-controlled, 2-period crossover trials (Studies 4 and 5). Patients aged 21 to 65 years were enrolled and were instructed to treat a moderate to very severe headache within 10 minutes of onset. Headache relief was defined as a reduction in headache severity to mild or no pain. In both trials, the proportion of individuals gaining relief at 10 or 15 minutes was significantly greater among patients receiving 6 mg of sumatriptan injection compared with those who received placebo (see Table 4).

<div class="scrollingtable"><table width="100%"> <col width="33%"/> <col width="16%"/> <col width="20%"/> <col width="16%"/> <col width="16%"/> <tfoot> <tr class="First"> <td align="left" colspan="5" valign="top"><span class="Sup">a</span><span class="Italics">P</span> &lt;0.05.</td> </tr> <tr class="Last"> <td align="left" colspan="5" valign="top">n = Number of headaches treated.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Toprule" colspan="5" valign="top"> <p class="First"> <span class="Bold">Table 4. Proportion of Patients with Cluster Headache Relief by Time in Studies 4 and 5</span> </p> </td> </tr> <tr> <td valign="top"></td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">Study 4</span> </p> </td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">Study 5</span> </p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Placebo</span> <br/> <span class="Bold">(n=39)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Sumatriptan Injection</span> <br/> <span class="Bold">6 mg</span> <br/> <span class="Bold">(n=39)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Placebo</span> <br/> <span class="Bold">(n=88)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Sumatriptan Injection</span> <br/> <span class="Bold">6 mg</span> <br/> <span class="Bold">(n=92)</span> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Patients with pain relief (no/mild)</p> </td><td valign="middle"></td><td valign="middle"></td><td valign="middle"></td><td class="Lrule Rrule" valign="middle"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>5 Minutes post-injection</dd> </dl> </td><td align="center" valign="middle"> <p class="First">8%</p> </td><td align="center" valign="middle"> <p class="First">21%</p> </td><td align="center" valign="middle"> <p class="First">7%</p> </td><td align="center" class="Lrule Rrule" valign="middle"> <p class="First">23%<span class="Sup">a</span> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>10 Minutes post-injection</dd> </dl> </td><td align="center" valign="middle"> <p class="First">10%</p> </td><td align="center" valign="middle"> <p class="First">49%<span class="Sup">a</span> </p> </td><td align="center" valign="middle"> <p class="First">25%</p> </td><td align="center" class="Lrule Rrule" valign="middle"> <p class="First">49%<span class="Sup">a</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>15 Minutes post-injection</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">26%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">74%<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">35%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">75%<span class="Sup">a</span> </p> </td> </tr> </tbody> </table></div>

An estimate of the cumulative probability of a patient with a cluster headache obtaining relief after being treated with either sumatriptan injection or placebo is presented in Figure 1.

Figure 1. Time to Relief of Cluster Headache from Time of Injectiona

a The figure uses Kaplan-Meier (product limit) Survivorship Plot. Patients taking rescue medication were censored at 15 minutes.

The plot was constructed with data from patients who either experienced relief or did not require (request) rescue medication within a period of 2 hours following treatment. As a consequence, the data in the plot are derived from only a subset of the 258 headaches treated (rescue medication was required in 52 of the 127 placebo-treated headaches and 18 of the 131 headaches treated with sumatriptan injection).

Other data suggest that treatment with sumatriptan injection is not associated with an increase in early recurrence of headache and has little effect on the incidence of later-occurring headaches (i.e., those occurring after 2, but before 18 or 24 hours).

Sumatriptan Injection, USP contains sumatriptan (base) as the succinate salt and is supplied as a clear, colorless to pale yellow, sterile, nonpyrogenic solution as follows:

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Single-Dose Vial:

{ "type": "p", "children": [], "text": "\nSingle-Dose Vial:\n" }

Sumatriptan Injection, USP single-dose vial (6 mg/0.5 mL):

{ "type": "p", "children": [], "text": "Sumatriptan Injection, USP single-dose vial (6 mg/0.5 mL):" }

{ "type": "", "children": [], "text": "" }

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from light.

{ "type": "p", "children": [], "text": "Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from light." }

Advise the patient to read the FDA-approved patient labeling (Patient Information).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Patient Information)." }

Risk of Myocardial Ischemia and/or Infarction, Prinzmetal’s Angina, Other Vasospasm-Related Events, Arrhythmias, and Cerebrovascular Events

{ "type": "p", "children": [], "text": "\nRisk of Myocardial Ischemia and/or Infarction, Prinzmetal’s Angina, Other Vasospasm-Related Events, Arrhythmias, and Cerebrovascular Events\n" }

Inform patients that sumatriptan injection may cause serious cardiovascular side effects such as myocardial infarction or stroke. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, irregular heartbeat, significant rise in blood pressure, weakness, and slurring of speech, and should ask for medical advice if any indicative sign or symptoms are observed. Apprise patients of the importance of this follow-up [see Warnings and Precautions (5.1, 5.2, 5.4, 5.5, 5.8)].

{ "type": "p", "children": [], "text": "Inform patients that sumatriptan injection may cause serious cardiovascular side effects such as myocardial infarction or stroke. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, irregular heartbeat, significant rise in blood pressure, weakness, and slurring of speech, and should ask for medical advice if any indicative sign or symptoms are observed. Apprise patients of the importance of this follow-up [see Warnings and Precautions (5.1, 5.2, 5.4, 5.5, 5.8)]." }

Hypersensitivity Reactions

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Inform patients that anaphylactic reactions have occurred in patients receiving sumatriptan injection. 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 [see Contraindications (4), Warnings and Precautions (5.9)].

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Concomitant Use with Other Triptans or Ergot Medications

{ "type": "p", "children": [], "text": "\nConcomitant Use with Other Triptans or Ergot Medications \n" }

Inform patients that use of sumatriptan injection within 24 hours of another triptan or an ergot- type medication (including dihydroergotamine or methysergide) is contraindicated [see Contraindications (4), Drug Interactions (7.1, 7.3)].

{ "type": "p", "children": [], "text": "Inform patients that use of sumatriptan injection within 24 hours of another triptan or an ergot- type medication (including dihydroergotamine or methysergide) is contraindicated [see Contraindications (4), Drug Interactions (7.1, 7.3)]." }

Serotonin Syndrome

{ "type": "p", "children": [], "text": "\nSerotonin Syndrome\n" }

Caution patients about the risk of serotonin syndrome with the use of sumatriptan injection or other triptans, particularly during combined use with SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7), Drug Interactions (7.4)].

{ "type": "p", "children": [], "text": "Caution patients about the risk of serotonin syndrome with the use of sumatriptan injection or other triptans, particularly during combined use with SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7), Drug Interactions (7.4)].\n" }

Medication Overuse Headache

{ "type": "p", "children": [], "text": "\nMedication Overuse Headache\n" }

Inform patients that use of acute migraine drugs for 10 or more days per month may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6)].

{ "type": "p", "children": [], "text": "Inform patients that use of acute migraine drugs for 10 or more days per month may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6)]." }

Pregnancy

{ "type": "p", "children": [], "text": "\nPregnancy\n" }

Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant [see Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant [see Use in Specific Populations (8.1)]." }

Lactation

{ "type": "p", "children": [], "text": "\nLactation \n" }

Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.2)]." }

Ability to Perform Complex Tasks

{ "type": "p", "children": [], "text": "\nAbility to Perform Complex Tasks\n" }

Treatment with sumatriptan injection may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks after administration of sumatriptan injection.

{ "type": "p", "children": [], "text": "Treatment with sumatriptan injection may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks after administration of sumatriptan injection." }

How to Use Sumatriptan Injection

{ "type": "p", "children": [], "text": "\nHow to Use Sumatriptan Injection\n" }

Provide patients instruction on the proper use of sumatriptan injection if they are able to self-administer sumatriptan injection in medically unsupervised situations.

{ "type": "p", "children": [], "text": "Provide patients instruction on the proper use of sumatriptan injection if they are able to self-administer sumatriptan injection in medically unsupervised situations." }

Inform patients that the injection is intended to be given subcutaneously and intramuscular or intravascular delivery should be avoided. Instruct patients to use injection sites with an adequate skin and subcutaneous thickness to accommodate the length of the needle.

{ "type": "p", "children": [], "text": "Inform patients that the injection is intended to be given subcutaneously and intramuscular or intravascular delivery should be avoided. Instruct patients to use injection sites with an adequate skin and subcutaneous thickness to accommodate the length of the needle." }

Manufactured for:

{ "type": "p", "children": [], "text": "Manufactured for:" }

Baxter Healthcare Corporation

{ "type": "p", "children": [], "text": "\nBaxter Healthcare Corporation\n" }

Deerfield, IL 60015 USA

{ "type": "p", "children": [], "text": "Deerfield, IL 60015 USA" }

Manufactured by:

{ "type": "p", "children": [], "text": "Manufactured by: " }

Baxter Pharmaceuticals India Private Ltd

{ "type": "p", "children": [], "text": "\nBaxter Pharmaceuticals India Private Ltd\n" }

Ahmedabad 382213, India

{ "type": "p", "children": [], "text": "Ahmedabad 382213, India" }

2021-10-06

{ "type": "p", "children": [], "text": "2021-10-06" }

<div class="scrollingtable"><table width="100%"> <col width="100%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Patient Information</span> </p> <p> <span class="Bold">Sumatriptan Injection, USP (</span>soo-ma-TRIP-tan<span class="Bold">)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">What is the most important information I should know about sumatriptan injection?</span> </p> <p> <span class="Bold">Sumatriptan injection can cause serious side effects, including:</span> </p> <p> <span class="Bold">Heart attack and other heart problems. Heart problems may lead to death.</span> </p> <p> <span class="Bold">Stop taking sumatriptan injection and get emergency medical help right away if you have any of the following symptoms of a heart attack:</span> </p> <dl> <dt>•</dt> <dd>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</dd> <dt>•</dt> <dd>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</dd> <dt>•</dt> <dd>pain or discomfort in your arms, back, neck, jaw, or stomach</dd> <dt>•</dt> <dd>shortness of breath with or without chest discomfort</dd> <dt>•</dt> <dd>breaking out in a cold sweat</dd> <dt>•</dt> <dd>nausea or vomiting</dd> <dt>•</dt> <dd>feeling lightheaded</dd> </dl> <p>Sumatriptan injection is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. You have a higher risk for heart disease if you:</p> <dl> <dt>•</dt> <dd>have high blood pressure</dd> <dt>•</dt> <dd>have high cholesterol levels</dd> <dt>•</dt> <dd>smoke</dd> <dt>•</dt> <dd>are overweight</dd> <dt>•</dt> <dd>have diabetes</dd> <dt>•</dt> <dd>have a family history of heart disease</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">What is sumatriptan injection?</span> </p> <p>Sumatriptan injection is a prescription medicine used to treat acute migraine headaches with or without aura and acute cluster headaches in adults who have been diagnosed with migraine or cluster headaches.</p> <p>Sumatriptan injection is not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines.</p> <p>Sumatriptan injection is not used to prevent or decrease the number of migraine or cluster headaches you have.</p> <p>It is not known if sumatriptan injection is safe and effective in children under 18 years of age.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Do not take sumatriptan injection if you have:</span> </p> <dl> <dt>•</dt> <dd>heart problems or a history of heart problems.</dd> <dt>•</dt> <dd>narrowing of blood vessels to your legs, arms, stomach, or kidneys (peripheral vascular disease).</dd> <dt>•</dt> <dd>uncontrolled high blood pressure.</dd> <dt>•</dt> <dd>severe liver problems.</dd> <dt>•</dt> <dd>hemiplegic migraines or basilar migraines. If you are not sure if you have these types of migraines, ask your healthcare provider.</dd> <dt>•</dt> <dd>had a stroke, transient ischemic attacks (TIAs), or problems with your blood circulation.</dd> <dt>•</dt> <dd>taken any of the following medicines in the last 24 hours:</dd> <dt> </dt> <dd>o almotriptan (AXERT) o eletriptan (RELPAX)</dd> <dt> </dt> <dd>o frovatriptan (FROVA) o naratriptan (AMERGE)</dd> <dt> </dt> <dd>o rizatriptan (MAXALT, MAXALT-MLT) o sumatriptan and naproxen (TREXIMET)</dd> <dt> </dt> <dd>o ergotamines (CAFERGOT, ERGOMAR, MIGERGOT) o dihydroergotamine (D.H.E. 45, MIGRANAL)</dd> <dt> </dt> <dd>Ask your healthcare provider if you are not sure if your medicine is listed above.</dd> <dt>•</dt> <dd>an allergy to sumatriptan or any of the ingredients in sumatriptan injection. See the end of this leaflet for a complete list of ingredients in sumatriptan injection.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Before taking sumatriptan injectiontell your healthcare provider about all of your medical conditions, including if you:</span> </p> <dl> <dt>•</dt> <dd>have high blood pressure</dd> <dt>•</dt> <dd>have high cholesterol</dd> <dt>•</dt> <dd>have diabetes</dd> <dt>•</dt> <dd>smoke</dd> <dt>•</dt> <dd>are overweight</dd> <dt>•</dt> <dd>have heart problems or family history of heart problems or stroke</dd> <dt>•</dt> <dd>have kidney problems</dd> <dt>•</dt> <dd>have liver problems</dd> <dt>•</dt> <dd>are allergic to latex</dd> <dt>•</dt> <dd>have had epilepsy or seizures</dd> <dt>•</dt> <dd>are not using effective birth control</dd> <dt>•</dt> <dd>are pregnant or plan to become pregnant. It is not known if sumatriptan injection can harm your unborn baby.</dd> <dt>•</dt> <dd>are breastfeeding or plan to breastfeed. Sumatriptan passes into your breast milk. It is not known if this can harm your baby. Talk with your healthcare provider about the best way to feed your baby if you take sumatriptan injection.</dd> </dl> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p> <p>Sumatriptan injection and certain other medicines can affect each other, causing serious side effects.</p> <p> <span class="Bold">Especially tell your healthcare provider if</span> you take antidepressant medicines called:</p> <dl> <dt>•</dt> <dd>selective serotonin reuptake inhibitors (SSRIs)</dd> <dt>•</dt> <dd>serotonin norepinephrine reuptake inhibitors (SNRIs)</dd> <dt>•</dt> <dd>tricyclic antidepressants (TCAs)</dd> <dt>•</dt> <dd>monoamine oxidase inhibitors (MAOIs)</dd> </dl> <p>Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure.</p> <p>Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">How should I take sumatriptan injection?</span> </p> <dl> <dt>•</dt> <dd>Certain people should take their first dose of sumatriptan injection in their healthcare provider’s office or in another medical setting. Ask your healthcare provider if you should take your first dose in a medical setting.</dd> <dt>•</dt> <dd>Use sumatriptan injection exactly as your healthcare provider tells you to use it.</dd> <dt>•</dt> <dd>Your healthcare provider may change your dose. Do not change your dose without first talking with your healthcare provider.</dd> <dt>•</dt> <dd>For adults, the usual dose is a single injection given just below the skin.</dd> <dt>•</dt> <dd>You should give an injection as soon as the symptoms of your headache start, but it may be given at any time during a migraine or cluster headache attack.</dd> <dt>•</dt> <dd>If you did not get any relief after the first injection, do not give a second injection without first talking with your healthcare provider. </dd> <dt>•</dt> <dd>If your headache comes back or you only get some relief after your first injection, you can take a second injection 1 hour after the first injection, but not sooner.</dd> <dt>•</dt> <dd>Do not take more than 12 mg in a 24-hour period.</dd> <dt>•</dt> <dd>If you use too much sumatriptan injection, call your healthcare provider or go to the nearest hospital emergency room right away.</dd> <dt>•</dt> <dd>You should write down when you have headaches and when you take sumatriptan injection so you can talk with your healthcare provider about how sumatriptan injection is working for you.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">What should I avoid while taking sumatriptan injection?</span> </p> <p>Sumatriptan injection can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery, or do anything where you need to be alert.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of sumatriptan injection?</span> </p> <p> <span class="Bold">Sumatriptan injection may cause serious side effects.</span> See “What is the most important information I should know about sumatriptan injection?”</p> <p>These serious side effects include:</p> <dl> <dt>•</dt> <dd>changes in color or sensation in your fingers and toes (Raynaud’s syndrome)</dd> <dt>•</dt> <dd>stomach and intestinal problems (gastrointestinal and colonic ischemic events). Symptoms of gastrointestinal and colonic ischemic events include:</dd> <dt> </dt> <dd>o sudden or severe stomach pain o nausea or vomiting</dd> <dt> </dt> <dd>o stomach pain after meals o constipation or diarrhea</dd> <dt> </dt> <dd>o weight loss o bloody diarrhea</dd> <dt> </dt> <dd>o fever</dd> <dt>•</dt> <dd>problems with blood circulation to your legs and feet (peripheral vascular ischemia). Symptoms of peripheral vascular ischemia include:</dd> <dt>o</dt> <dd>cramping and pain in your legs or hips</dd> <dt>o</dt> <dd>feeling of heaviness or tightness in your leg muscles</dd> <dt>o</dt> <dd>burning or aching pain in your feet or toes while resting</dd> <dt>o</dt> <dd>numbness, tingling, or weakness in your legs</dd> <dt>o</dt> <dd>cold feeling or color changes in 1 or both legs or feet</dd> <dt>•</dt> <dd>medication overuse headaches. Some people who use too many sumatriptan injection may have worse headaches (medication overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with sumatriptan injection.</dd> <dt>•</dt> <dd>serotonin syndrome. Serotonin syndrome is a rare but serious problem that can happen in people using sumatriptan injection, especially if sumatriptan injection is used with anti‑depressant medicines called SSRIs or SNRIs.</dd> <dt>•</dt> <dd>Call your healthcare provider right away if you have any of the following symptoms of serotonin syndrome:</dd> <dt>o</dt> <dd>mental changes such as seeing things that are not there (hallucinations), agitation, or coma</dd> <dt>o</dt> <dd>fast heartbeat</dd> <dt>o</dt> <dd>changes in blood pressure</dd> <dt>o</dt> <dd>high body temperature</dd> <dt>o</dt> <dd>tight muscles</dd> <dt>o</dt> <dd>trouble walking</dd> <dt>•</dt> <dd>hives (itchy bumps); swelling of your tongue, mouth or throat.</dd> <dt>•</dt> <dd>seizures. Seizures have happened in people taking sumatriptan injection who have never had seizures before. Talk with your healthcare provider about your chance of having seizures while you take sumatriptan injection.</dd> </dl> <p>The most common side effects of sumatriptan injection include:</p> <dl> <dt>•</dt> <dd>pain or redness at your injection site</dd> <dt>•</dt> <dd>tingling or numbness in your fingers or toes</dd> <dt>•</dt> <dd>dizziness</dd> <dt>•</dt> <dd>warm, hot, burning feeling to your face (flushing)</dd> <dt>•</dt> <dd>discomfort or stiffness in your neck</dd> <dt>•</dt> <dd>feeling weak, drowsy, or tired</dd> </dl> <p>Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</p> <p>These are not all the possible side effects of sumatriptan injection. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">How should I store sumatriptan injection?</span> </p> <dl> <dt>•</dt> <dd>Store sumatriptan injection at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F).</dd> <dt>•</dt> <dd>Store your medicine away from light.</dd> <dt>•</dt> <dd>Keep your medicine in the packaging or carrying case provided with it.</dd> </dl> <p> <span class="Bold">Keep sumatriptan injection and all medicines out of the reach of children.</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">General information about the safe and effective use of sumatriptan injection</span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use sumatriptan injection for a condition for which it was not prescribed. Do not give sumatriptan injection to other people, even if they have the same symptoms you have. It may harm them.</p> <p>This Patient Information leaflet summarizes the most important information about sumatriptan injection. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about sumatriptan injection that is written for healthcare professionals.</p> <p>For more information, contact Baxter at 1-877-725-2747</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">What are the ingredientsinsumatriptan injection?</span> </p> <p>Active ingredient: sumatriptan succinate</p> <p>Inactive ingredients: sodium chloride, USP and water for injection, USP</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Manufactured for:</p> <p> <span class="Bold">Baxter Healthcare Corporation</span> </p> <p>Deerfield, IL 60015 USA</p> <p>Manufactured by: </p> <p> <span class="Bold">Baxter Pharmaceuticals India Private Ltd</span> </p> <p>Ahmedabad 382213, India</p> <p>2021-10-06</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Patient Information</span>\n</p>\n<p>\n<span class=\"Bold\">Sumatriptan Injection, USP (</span>soo-ma-TRIP-tan<span class=\"Bold\">)</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about sumatriptan injection?</span>\n</p>\n<p>\n<span class=\"Bold\">Sumatriptan injection can cause serious side effects, including:</span>\n</p>\n<p>\n<span class=\"Bold\">Heart attack and other heart problems. Heart problems may lead to death.</span>\n</p>\n<p>\n<span class=\"Bold\">Stop taking sumatriptan injection and get emergency medical help right away if you have any of the following symptoms of a heart attack:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</dd>\n<dt>•</dt>\n<dd>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</dd>\n<dt>•</dt>\n<dd>pain or discomfort in your arms, back, neck, jaw, or stomach</dd>\n<dt>•</dt>\n<dd>shortness of breath with or without chest discomfort</dd>\n<dt>•</dt>\n<dd>breaking out in a cold sweat</dd>\n<dt>•</dt>\n<dd>nausea or vomiting</dd>\n<dt>•</dt>\n<dd>feeling lightheaded</dd>\n</dl>\n<p>Sumatriptan injection is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. You have a higher risk for heart disease if you:</p>\n<dl>\n<dt>•</dt>\n<dd>have high blood pressure</dd>\n<dt>•</dt>\n<dd>have high cholesterol levels</dd>\n<dt>•</dt>\n<dd>smoke</dd>\n<dt>•</dt>\n<dd>are overweight</dd>\n<dt>•</dt>\n<dd>have diabetes</dd>\n<dt>•</dt>\n<dd>have a family history of heart disease</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is sumatriptan injection?</span>\n</p>\n<p>Sumatriptan injection is a prescription medicine used to treat acute migraine headaches with or without aura and acute cluster headaches in adults who have been diagnosed with migraine or cluster headaches.</p>\n<p>Sumatriptan injection is not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines.</p>\n<p>Sumatriptan injection is not used to prevent or decrease the number of migraine or cluster headaches you have.</p>\n<p>It is not known if sumatriptan injection is safe and effective in children under 18 years of age.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Do not take sumatriptan injection if you have:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>heart problems or a history of heart problems.</dd>\n<dt>•</dt>\n<dd>narrowing of blood vessels to your legs, arms, stomach, or kidneys (peripheral vascular disease).</dd>\n<dt>•</dt>\n<dd>uncontrolled high blood pressure.</dd>\n<dt>•</dt>\n<dd>severe liver problems.</dd>\n<dt>•</dt>\n<dd>hemiplegic migraines or basilar migraines. If you are not sure if you have these types of migraines, ask your healthcare provider.</dd>\n<dt>•</dt>\n<dd>had a stroke, transient ischemic attacks (TIAs), or problems with your blood circulation.</dd>\n<dt>•</dt>\n<dd>taken any of the following medicines in the last 24 hours:</dd>\n<dt> </dt>\n<dd>o almotriptan (AXERT)\t o eletriptan (RELPAX)</dd>\n<dt> </dt>\n<dd>o frovatriptan (FROVA)\t o naratriptan (AMERGE)</dd>\n<dt> </dt>\n<dd>o rizatriptan (MAXALT, MAXALT-MLT) o sumatriptan and naproxen (TREXIMET)</dd>\n<dt> </dt>\n<dd>o ergotamines (CAFERGOT, ERGOMAR, MIGERGOT) o dihydroergotamine (D.H.E. 45, MIGRANAL)</dd>\n<dt> </dt>\n<dd>Ask your healthcare provider if you are not sure if your medicine is listed above.</dd>\n<dt>•</dt>\n<dd>an allergy to sumatriptan or any of the ingredients in sumatriptan injection. See the end of this leaflet for a complete list of ingredients in sumatriptan injection.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Before taking sumatriptan injectiontell your healthcare provider about all of your medical conditions, including if you:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>have high blood pressure</dd>\n<dt>•</dt>\n<dd>have high cholesterol</dd>\n<dt>•</dt>\n<dd>have diabetes</dd>\n<dt>•</dt>\n<dd>smoke</dd>\n<dt>•</dt>\n<dd>are overweight</dd>\n<dt>•</dt>\n<dd>have heart problems or family history of heart problems or stroke</dd>\n<dt>•</dt>\n<dd>have kidney problems</dd>\n<dt>•</dt>\n<dd>have liver problems</dd>\n<dt>•</dt>\n<dd>are allergic to latex</dd>\n<dt>•</dt>\n<dd>have had epilepsy or seizures</dd>\n<dt>•</dt>\n<dd>are not using effective birth control</dd>\n<dt>•</dt>\n<dd>are pregnant or plan to become pregnant. It is not known if sumatriptan injection can harm your unborn baby.</dd>\n<dt>•</dt>\n<dd>are breastfeeding or plan to breastfeed. Sumatriptan passes into your breast milk. It is not known if this can harm your baby. Talk with your healthcare provider about the best way to feed your baby if you take sumatriptan injection.</dd>\n</dl>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p>\n<p>Sumatriptan injection and certain other medicines can affect each other, causing serious side effects.</p>\n<p>\n<span class=\"Bold\">Especially tell your healthcare provider if</span> you take antidepressant medicines called:</p>\n<dl>\n<dt>•</dt>\n<dd>selective serotonin reuptake inhibitors (SSRIs)</dd>\n<dt>•</dt>\n<dd>serotonin norepinephrine reuptake inhibitors (SNRIs)</dd>\n<dt>•</dt>\n<dd>tricyclic antidepressants (TCAs)</dd>\n<dt>•</dt>\n<dd>monoamine oxidase inhibitors (MAOIs)</dd>\n</dl>\n<p>Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure.</p>\n<p>Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I take sumatriptan injection?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Certain people should take their first dose of sumatriptan injection in their healthcare provider’s office or in another medical setting. Ask your healthcare provider if you should take your first dose in a medical setting.</dd>\n<dt>•</dt>\n<dd>Use sumatriptan injection exactly as your healthcare provider tells you to use it.</dd>\n<dt>•</dt>\n<dd>Your healthcare provider may change your dose. Do not change your dose without first talking with your healthcare provider.</dd>\n<dt>•</dt>\n<dd>For adults, the usual dose is a single injection given just below the skin.</dd>\n<dt>•</dt>\n<dd>You should give an injection as soon as the symptoms of your headache start, but it may be given at any time during a migraine or cluster headache attack.</dd>\n<dt>•</dt>\n<dd>If you did not get any relief after the first injection, do not give a second injection without first talking with your healthcare provider. </dd>\n<dt>•</dt>\n<dd>If your headache comes back or you only get some relief after your first injection, you can take a second injection 1 hour after the first injection, but not sooner.</dd>\n<dt>•</dt>\n<dd>Do not take more than 12 mg in a 24-hour period.</dd>\n<dt>•</dt>\n<dd>If you use too much sumatriptan injection, call your healthcare provider or go to the nearest hospital emergency room right away.</dd>\n<dt>•</dt>\n<dd>You should write down when you have headaches and when you take sumatriptan injection so you can talk with your healthcare provider about how sumatriptan injection is working for you.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What should I avoid while taking sumatriptan injection?</span>\n</p>\n<p>Sumatriptan injection can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery, or do anything where you need to be alert.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of sumatriptan injection?</span>\n</p>\n<p>\n<span class=\"Bold\">Sumatriptan injection may cause serious side effects.</span> See “What is the most important information I should know about sumatriptan injection?”</p>\n<p>These serious side effects include:</p>\n<dl>\n<dt>•</dt>\n<dd>changes in color or sensation in your fingers and toes (Raynaud’s syndrome)</dd>\n<dt>•</dt>\n<dd>stomach and intestinal problems (gastrointestinal and colonic ischemic events). Symptoms of gastrointestinal and colonic ischemic events include:</dd>\n<dt> </dt>\n<dd>o sudden or severe stomach pain\t o nausea or vomiting</dd>\n<dt> </dt>\n<dd>o stomach pain after meals\t o constipation or diarrhea</dd>\n<dt> </dt>\n<dd>o weight loss\t o bloody diarrhea</dd>\n<dt> </dt>\n<dd>o fever</dd>\n<dt>•</dt>\n<dd>problems with blood circulation to your legs and feet (peripheral vascular ischemia). Symptoms of peripheral vascular ischemia include:</dd>\n<dt>o</dt>\n<dd>cramping and pain in your legs or hips</dd>\n<dt>o</dt>\n<dd>feeling of heaviness or tightness in your leg muscles</dd>\n<dt>o</dt>\n<dd>burning or aching pain in your feet or toes while resting</dd>\n<dt>o</dt>\n<dd>numbness, tingling, or weakness in your legs</dd>\n<dt>o</dt>\n<dd>cold feeling or color changes in 1 or both legs or feet</dd>\n<dt>•</dt>\n<dd>medication overuse headaches. Some people who use too many sumatriptan injection may have worse headaches (medication overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with sumatriptan injection.</dd>\n<dt>•</dt>\n<dd>serotonin syndrome. Serotonin syndrome is a rare but serious problem that can happen in people using sumatriptan injection, especially if sumatriptan injection is used with anti‑depressant medicines called SSRIs or SNRIs.</dd>\n<dt>•</dt>\n<dd>Call your healthcare provider right away if you have any of the following symptoms of serotonin syndrome:</dd>\n<dt>o</dt>\n<dd>mental changes such as seeing things that are not there (hallucinations), agitation, or coma</dd>\n<dt>o</dt>\n<dd>fast heartbeat</dd>\n<dt>o</dt>\n<dd>changes in blood pressure</dd>\n<dt>o</dt>\n<dd>high body temperature</dd>\n<dt>o</dt>\n<dd>tight muscles</dd>\n<dt>o</dt>\n<dd>trouble walking</dd>\n<dt>•</dt>\n<dd>hives (itchy bumps); swelling of your tongue, mouth or throat.</dd>\n<dt>•</dt>\n<dd>seizures. Seizures have happened in people taking sumatriptan injection who have never had seizures before. Talk with your healthcare provider about your chance of having seizures while you take sumatriptan injection.</dd>\n</dl>\n<p>The most common side effects of sumatriptan injection include:</p>\n<dl>\n<dt>•</dt>\n<dd>pain or redness at your injection site</dd>\n<dt>•</dt>\n<dd>tingling or numbness in your fingers or toes</dd>\n<dt>•</dt>\n<dd>dizziness</dd>\n<dt>•</dt>\n<dd>warm, hot, burning feeling to your face (flushing)</dd>\n<dt>•</dt>\n<dd>discomfort or stiffness in your neck</dd>\n<dt>•</dt>\n<dd>feeling weak, drowsy, or tired</dd>\n</dl>\n<p>Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</p>\n<p>These are not all the possible side effects of sumatriptan injection. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store sumatriptan injection?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Store sumatriptan injection at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F).</dd>\n<dt>•</dt>\n<dd>Store your medicine away from light.</dd>\n<dt>•</dt>\n<dd>Keep your medicine in the packaging or carrying case provided with it.</dd>\n</dl>\n<p>\n<span class=\"Bold\">Keep sumatriptan injection and all medicines out of the reach of children.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of sumatriptan injection</span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use sumatriptan injection for a condition for which it was not prescribed. Do not give sumatriptan injection to other people, even if they have the same symptoms you have. It may harm them.</p>\n<p>This Patient Information leaflet summarizes the most important information about sumatriptan injection. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about sumatriptan injection that is written for healthcare professionals.</p>\n<p>For more information, contact Baxter at 1-877-725-2747</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredientsinsumatriptan injection?</span>\n</p>\n<p>Active ingredient: sumatriptan succinate</p>\n<p>Inactive ingredients: sodium chloride, USP and water for injection, USP</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">Manufactured for:</p>\n<p>\n<span class=\"Bold\">Baxter Healthcare Corporation</span>\n</p>\n<p>Deerfield, IL 60015 USA</p>\n<p>Manufactured by: </p>\n<p>\n<span class=\"Bold\">Baxter Pharmaceuticals India Private Ltd</span>\n</p>\n<p>Ahmedabad 382213, India</p>\n<p>2021-10-06</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Patient Information has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Patient Information has been approved by the U.S. Food and Drug Administration." }

The brand names mentioned in this document are the trademarks of their respective owners.

{ "type": "p", "children": [], "text": "The brand names mentioned in this document are the trademarks of their respective owners." }

NDC 36000-289-01 Rx Only

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Sumatriptan Injection, USP

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6 mg/0.5 mL

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For subcutaneous injection only

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0.5 mL Single-dose Vial

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Baxter

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Manufactured for:

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Baxter Healthcare Corporation

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Deerfield, IL 60015 USA

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NDC 36000-289-05 Rx Only

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Sumatriptan Injection, USP

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6 mg/0.5 mL

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For subcutaneous injection only

{ "type": "p", "children": [], "text": "\nFor subcutaneous injection only\n" }

5 x 0.5 mL Single-dose Vials

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Baxter

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Manufactured for:

{ "type": "p", "children": [], "text": "Manufactured for:" }

Baxter Healthcare Corporation

{ "type": "p", "children": [], "text": "Baxter Healthcare Corporation" }

Deerfield, IL 60015 USA

{ "type": "p", "children": [], "text": "Deerfield, IL 60015 USA" }

NDC 36000-289-10 Rx Only

{ "type": "p", "children": [], "text": "\nNDC 36000-289-10 Rx Only" }

Sumatriptan Injection, USP

{ "type": "p", "children": [], "text": "Sumatriptan Injection, USP" }

6 mg/0.5 mL

{ "type": "p", "children": [], "text": "6 mg/0.5 mL" }

For subcutaneous injection only

{ "type": "p", "children": [], "text": "\nFor subcutaneous injection only\n" }

10 x 0.5 mL Single-dose Vials

{ "type": "p", "children": [], "text": "\n10 x 0.5 mL Single-dose Vials\n" }

Baxter

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Manufactured for:

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Baxter Healthcare Corporation

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Deerfield, IL 60015 USA

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NDC 36000-289-25 Rx Only

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Sumatriptan Injection, USP

{ "type": "p", "children": [], "text": "Sumatriptan Injection, USP" }

6 mg/0.5 mL

{ "type": "p", "children": [], "text": "6 mg/0.5 mL" }

For subcutaneous injection only

{ "type": "p", "children": [], "text": "\nFor subcutaneous injection only\n" }

25 x 0.5 mL Single-dose Vials

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Baxter

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Manufactured for:

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Baxter Healthcare Corporation

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Deerfield, IL 60015 USA

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Limitations of Use

The recommended dosage of ONZETRA is 22 mg of sumatriptan nasal powder (2 nosepieces), administered using the Xsail breath-powered delivery device. If the migraine has not resolved by 2 hours after taking ONZETRA Xsail, or returns after a transient improvement, a second dose of 22 mg may be administered at least 2 hours after the first dose. The maximum recommended dose that may be given in 24 hours is two doses of ONZETRA Xsail (44 mg/4 nosepieces) or one dose of ONZETRA Xsail and one dose of another sumatriptan product, separated by at least 2 hours. The safety of treating an average of more than 4 headaches in a 30 day period has not been established.

The recommended dose of 22 mg is administered by using one 11 mg nosepiece in each nostril [see Patient Counseling Information (17)]. For administration of ONZETRA Xsail, the patient removes the clear device cap from the reusable delivery device, then removes a disposable nosepiece from its foil pouch and clicks the nosepiece into the device body. The patient then fully presses and promptly releases the white piercing button on the device body to pierce the capsule inside the nosepiece. The white piercing button should only be pressed once and released prior to administration to each nostril. The nosepiece is then inserted into the nostril so that it makes a tight seal. Keeping the nosepiece in the nose, the device is rotated to place the mouthpiece into the mouth. The patient blows forcefully through the mouthpiece to deliver the sumatriptan powder into the nasal cavity. Vibration (e.g., a rattling noise) may occur, and indicates that the patient is blowing forcefully, as directed. Once the medication in the first nosepiece has been administered, the patient removes and discards the nosepiece. The same process must then be repeated using a second 11 mg nosepiece into the other nostril to administer the remainder of the total recommended 22 mg dose [see Patient Counseling Information (17)].

ONZETRA Xsail is supplied as a disposable nosepiece containing a capsule and a reusable delivery device body. Each capsule contains 11 mg sumatriptan base (equivalent to 15.4 mg of sumatriptan succinate nasal powder) in a clear, hypromellose capsule with 825 printed on one side.

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ONZETRA Xsail is contraindicated in patients with:

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{ "type": "ul", "children": [ "Ischemic coronary artery disease (CAD) (e.g., angina pectoris, history of myocardial infarction, or silent ischemia) or coronary artery vasospasm, including Prinzmetal's angina or in patients with other significant underlying cardiovascular diseases [see Warnings and Precautions (5.1)].\n", "Wolff-Parkinson-White Syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.2)].\n", "History of stroke, transient ischemic attack (TIA), or history of hemiplegic or basilar migraine because these patients are at a higher risk of stroke [see Warnings and Precautions (5.4)].\n", "Peripheral vascular disease [see Warnings and Precautions (5.5)].\n", "Ischemic bowel disease [see Warnings and Precautions (5.5)].\n", "Uncontrolled hypertension [see Warnings and Precautions (5.8)].\n", "Recent use (i.e., within 24 hours) of ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide), or another 5-hydroxytryptamine1 (5-HT1) agonist [see Drug Interactions (7.1 and 7.3)].\n", "Concurrent administration of an MAO-A inhibitor or recent use (within 2 weeks) of an MAO-A inhibitor [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)].\n", "Hypersensitivity to sumatriptan (angioedema and anaphylaxis seen) [see Warnings and Precautions (5.9)].\n", "Severe hepatic impairment [see Clinical Pharmacology (12.3)]\n" ], "text": "" }

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-HT1 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.

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 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.

Sensations of tightness, pain, pressure, and heaviness in the chest, throat, neck, and jaw commonly occur after treatment with 5-HT1 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.

Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have occurred in patients treated with 5-HT1 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-HT1 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-HT1 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-HT1 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-HT1 agonists including sumatriptan. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1 agonists have not been clearly established.

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.

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.

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-HT1 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.

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.

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.

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.

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 1: Adverse Reactions Reported by at Least 2% of Patients in 2 Controlled Migraine Trials </span> </caption> <col align="left" valign="top" width="34%"/> <col align="center" valign="top" width="33%"/> <col align="center" valign="top" width="33%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule" colspan="2">Percent of Patients Reporting</th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule" valign="middle">Adverse Reaction</th><th align="center" class="Rrule">ONZETRA<br/>N=151</th><th align="center" class="Rrule">Placebo<br/>N=150</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Limited examinations of the nose and throat did not reveal any clinically noticeable injury in these patients.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Abnormal Taste</td><td align="center" class="Rrule">20</td><td align="center" class="Rrule">3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Nasal Discomfort</td><td align="center" class="Rrule">11<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></td><td align="center" class="Rrule">1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Rhinorrhea</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">2</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Rhinitis</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">0</td> </tr> </tbody> </table></div>

There is insufficient data with ONZETRA Xsail to assess the impact of age, gender, and race on adverse effects.

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.

Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine containing or ergot-type medications (like dihydroergotamine or methysergide) and ONZETRA Xsail within 24 hours of each other is contraindicated.

MAO-A inhibitors increase systemic exposure by up to 7-fold. Therefore, the use of ONZETRA Xsail in patients receiving MAO-A inhibitors is contraindicated [see Clinical Pharmacology (12.3)].

Because their vasospastic effects may be additive, co-administration of ONZETRA Xsail and other 5-HT1 agonists (e.g., triptans) within 24 hours of each other is contraindicated.

Cases of serotonin syndrome have been reported during co-administration of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7)].

Risk Summary

Data from a prospective pregnancy exposure registry and epidemiological studies of pregnant women have not detected an increased frequency of birth defects or a consistent pattern of birth defects among women exposed to sumatriptan compared with the general population (see Data). In developmental toxicity studies in rats and rabbits, oral administration of sumatriptan to pregnant animals was associated with embryolethality, fetal abnormalities, and pup mortality. When administered by the intravenous route to pregnant rabbits, sumatriptan was embryolethal (see Data).

In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of major birth defects among deliveries to women with migraine ranged from 2.2% to 2.9%, and the reported rate of miscarriage was 17%, which were similar to rates reported in women without migraine.

Clinical Considerations

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

Data

Human Data: The Sumatriptan/Naratriptan/Treximet (sumatriptan and naproxen sodium) Pregnancy Registry, a population-based international prospective study, collected data for sumatriptan from January 1996 to September 2012. The Registry documented outcomes of 626 infants and fetuses exposed to sumatriptan during pregnancy (528 with earliest exposure during the first trimester, 78 during the second trimester, 16 during the third trimester, and 4 unknown). The occurrence of major birth defects (excluding fetal deaths and induced abortions without reported defects and all spontaneous pregnancy losses) during first-trimester exposure to sumatriptan was 4.2% (20/478 [95% CI: 2.6% to 6.5%]) and during any trimester of exposure was 4.2% (24/576 [95% CI: 2.7% to 6.2%]). The sample size in this study had 80% power to detect at least a 1.73- to 1.91-fold increase in the rate of major malformations. The number of exposed pregnancy outcomes accumulated during the registry was insufficient to support definitive conclusions about overall malformation risk or to support comparisons of the frequencies of specific birth defects. Of the 20 infants with reported birth defects after exposure to sumatriptan in the first trimester, 4 infants had ventricular septal defects, including one infant who was exposed to both sumatriptan and naratriptan, and 3 infants had pyloric stenosis. No other birth defect was reported for more than 2 infants in this group.

In a study using data from the Swedish Medical Birth Register, live births to women who reported using triptans or ergots during pregnancy were compared with those of women who did not. Of the 2,257 births with first-trimester exposure to sumatriptan, 107 infants were born with malformations (relative risk 0.99 [95% CI: 0.91 to 1.21]). A study using linked data from the Medical Birth Registry of Norway to the Norwegian Prescription Database compared pregnancy outcomes in women who redeemed prescriptions for triptans during pregnancy, as well as a migraine disease comparison group who redeemed prescriptions for sumatriptan before pregnancy only, compared with a population control group. Of the 415 women who redeemed prescriptions for sumatriptan during the first trimester, 15 had infants with major congenital malformations (OR 1.16 [95% CI: 0.69 to 1.94]) while for the 364 women who redeemed prescriptions for sumatriptan before, but not during, pregnancy, 20 had infants with major congenital malformations (OR 1.83 [95% CI: 1.17 to 2.88]), each compared with the population comparison group. Additional smaller observational studies evaluating use of sumatriptan during pregnancy have not suggested an increased risk of teratogenicity.

Animal Data: Oral administration of sumatriptan to pregnant rats during the period of organogenesis resulted in an increased incidence of fetal blood vessel (cervicothoracic and umbilical) abnormalities. The highest no-effect dose for embryofetal developmental toxicity in rats was 60 mg/kg/day. Oral administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in increased incidences of embryolethality and fetal cervicothoracic vascular and skeletal abnormalities. Intravenous administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in an increased incidence of embryolethality. The highest oral and intravenous no-effect doses for developmental toxicity in rabbits were 15 and 0.75 mg/kg/day, respectively.

Oral administration of sumatriptan to rats prior to and throughout gestation resulted in embryofetal toxicity (decreased body weight, decreased ossification, increased incidence of skeletal abnormalities). The highest no-effect dose was 50 mg/kg/day. In offspring of pregnant rats treated orally with sumatriptan during organogenesis, there was a decrease in pup survival. The highest no-effect dose for this effect was 60 mg/kg/day. Oral treatment of pregnant rats with sumatriptan during the latter part of gestation and throughout lactation resulted in a decrease in pup survival. The highest no-effect dose for this finding was 100 mg/kg/day.

Risk Summary

Sumatriptan is excreted in human milk following subcutaneous administration (see Data). There is no information regarding sumatriptan concentrations in milk from lactating women following administration of ONZETRA Xsail. There are no data on the effects of sumatriptan on the breastfed infant or the effects of sumatriptan on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ONZETRA Xsail and any potential adverse effects on the breastfed infant from sumatriptan or from the underlying maternal condition.

Clinical Considerations

Infant exposure to sumatriptan can be minimized by avoiding breastfeeding for 12 hours after treatment with ONZETRA Xsail.

Data

Following subcutaneous administration of a 6-mg dose of sumatriptan injection in 5 lactating volunteers, sumatriptan was present in milk.

Safety and effectiveness has not been established in pediatric patients younger than 18 years of age.

Two controlled clinical trials evaluated sumatriptan nasal spray (5 to 20 mg) in 1,248 adolescent migraineurs aged 12 to 17 years who treated a single attack. The trials did not establish the efficacy of sumatriptan nasal spray compared with placebo in the treatment of migraine in adolescents. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults.

Five controlled clinical trials (2 single-attack studies, 3 multiple-attack studies) evaluating oral sumatriptan (25 to 100 mg) in pediatric patients aged 12 to 17 years enrolled a total of 701 adolescent migraineurs. These studies did not establish the efficacy of oral sumatriptan compared to placebo in the treatment of migraine in adolescents. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults. The frequency of all adverse reactions in these patients appeared to be both dose- and age-dependent, with younger patients reporting reactions more commonly than older adolescents.

Postmarketing experience documents that serious adverse reactions have occurred in the pediatric population after use of subcutaneous, oral, and/or intranasal sumatriptan. These reports include reactions similar in nature to those reported rarely in adults, including stroke, visual loss, and death. A myocardial infarction has been reported in a 14-year-old male following the use of oral sumatriptan; clinical signs occurred within 1 day of drug administration. Clinical data to determine the frequency of serious adverse reactions in pediatric patients who might receive subcutaneous, oral, or nasal sumatriptan are not presently available.

Clinical trials of ONZETRA Xsail did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience with subcutaneous, oral, and liquid nasal spray sumatriptan has not identified differences in responses between the elderly and younger patients. In general, treatment for an elderly patient should be cautious, reflecting the greater frequency of decreased or abnormal hepatic function, renal function, or cardiac function, more pronounced blood pressure increases, higher risks for unrecognized CAD, and/or concomitant disease or other drug therapy.

A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving ONZETRA Xsail [see Warnings and Precautions (5.1)].

The clearance of oral sumatriptan was reduced in patients with moderate hepatic impairment [see Clinical Pharmacology (12.3)]. Similar changes can be expected following intranasal administration. The effect of severe hepatic impairment was NOT evaluated using oral formulation. The use of ONZETRA Xsail in patients with severe hepatic impairment is contraindicated [see Contraindications (4)].

In clinical trials, the highest single doses of sumatriptan nasal spray administered without significant reactions were 40 mg to 12 volunteers and 40 mg to 85 subjects with migraine, which is twice the highest single recommended dose. In addition, 12 volunteers were administered a total daily dose of 60 mg (20 mg 3 times daily) for 3.5 days without significant adverse reactions.

{ "type": "p", "children": [], "text": "In clinical trials, the highest single doses of sumatriptan nasal spray administered without significant reactions were 40 mg to 12 volunteers and 40 mg to 85 subjects with migraine, which is twice the highest single recommended dose. In addition, 12 volunteers were administered a total daily dose of 60 mg (20 mg 3 times daily) for 3.5 days without significant adverse reactions." }

Overdose in animals has been fatal and has been heralded by convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation, and lacrimation.

{ "type": "p", "children": [], "text": "Overdose in animals has been fatal and has been heralded by convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation, and lacrimation. " }

The elimination half-life of ONZETRA Xsail is about 3 hours [see Clinical Pharmacology (12.3)], and therefore monitoring of patients after overdose with ONZETRA Xsail should continue for at least 15 hours or while symptoms persist.

{ "type": "p", "children": [], "text": "The elimination half-life of ONZETRA Xsail is about 3 hours [see Clinical Pharmacology (12.3)], and therefore monitoring of patients after overdose with ONZETRA Xsail should continue for at least 15 hours or while symptoms persist. " }

It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan.

{ "type": "p", "children": [], "text": "It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan. " }

ONZETRA Xsail (sumatriptan nasal powder) uses a disposable, single use nosepiece which is attached by the patient to a delivery device body which has a mouthpiece and a piercing mechanism. The nosepiece contains a hypromellose capsule filled with 11 mg sumatriptan base (as 15.4 mg of sumatriptan succinate) in a dry powder form. Two nosepieces comprise a single 22 mg dose. ONZETRA is for nasal administration with the Xsail device only.

{ "type": "p", "children": [], "text": "ONZETRA Xsail (sumatriptan nasal powder) uses a disposable, single use nosepiece which is attached by the patient to a delivery device body which has a mouthpiece and a piercing mechanism. The nosepiece contains a hypromellose capsule filled with 11 mg sumatriptan base (as 15.4 mg of sumatriptan succinate) in a dry powder form. Two nosepieces comprise a single 22 mg dose. ONZETRA is for nasal administration with the Xsail device only. " }

The active component of ONZETRA Xsail is sumatriptan, a selective 5-hydroxy-tryptamine receptor subtype 1 (5-HT1) agonist (triptan), as the succinate salt. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1), and it has the following structure:

{ "type": "p", "children": [], "text": "The active component of ONZETRA Xsail is sumatriptan, a selective 5-hydroxy-tryptamine receptor subtype 1 (5-HT1) agonist (triptan), as the succinate salt. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1), and it has the following structure:" }

The empirical formula is C14H21N3O2S ∙ C4H6O4, representing a molecular weight of 413.5.

{ "type": "p", "children": [], "text": "The empirical formula is C14H21N3O2S ∙ C4H6O4, representing a molecular weight of 413.5." }

Sumatriptan succinate is a white to off-white powder that is readily soluble in water and in saline.

{ "type": "p", "children": [], "text": "Sumatriptan succinate is a white to off-white powder that is readily soluble in water and in saline." }

The ONZETRA Xsail breath-powered delivery device is used to deliver the dry powder contained in the disposable nosepiece (in a capsule) into the nostril using breath exhaled into the device. The Xsail delivery device has a flexible mouthpiece to adjust to individual anatomic variations. Under standardized in vitro testing, the Xsail device delivers a mean of 10 mg sumatriptan per nosepiece when tested at a flow rate of 30 L/min for 4 seconds (2 L total). The amount of sumatriptan delivered to the nasal cavity will depend on patient factors such as expiratory flow. Delivered dose was measured in patients with migraine headache treated in clinical trials to evaluate the efficacy of the product. In these trials, each nosepiece delivered an average dose of 7.5-8.1 mg, providing a total dose of 15-16.2 mg per treatment episode from two nosepieces.

{ "type": "p", "children": [], "text": "The ONZETRA Xsail breath-powered delivery device is used to deliver the dry powder contained in the disposable nosepiece (in a capsule) into the nostril using breath exhaled into the device. The Xsail delivery device has a flexible mouthpiece to adjust to individual anatomic variations. Under standardized in vitro testing, the Xsail device delivers a mean of 10 mg sumatriptan per nosepiece when tested at a flow rate of 30 L/min for 4 seconds (2 L total). The amount of sumatriptan delivered to the nasal cavity will depend on patient factors such as expiratory flow. Delivered dose was measured in patients with migraine headache treated in clinical trials to evaluate the efficacy of the product. In these trials, each nosepiece delivered an average dose of 7.5-8.1 mg, providing a total dose of 15-16.2 mg per treatment episode from two nosepieces. " }

Sumatriptan binds with high affinity to human cloned 5-HT1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine headache through agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

Blood Pressure

Significant elevation in blood pressure, including hypertensive crisis, has been reported in patients treated with sumatriptan, with and without a history of hypertension [see Warnings and Precautions (5.8)].

Peripheral (Small) Arteries

In healthy volunteers (N = 18), a trial evaluating the effects of sumatriptan injection on peripheral (small vessel) arterial reactivity failed to detect a clinically significant increase in peripheral resistance.

Heart Rate

Transient increases in blood pressure observed in some patients in clinical studies carried out during development of sumatriptan as a treatment for migraine were not accompanied by any clinically significant changes in heart rate.

Absorption and Bioavailability

The mean maximum concentration (Cmax) following a 22 mg nasal dose of ONZETRA Xsail was 21 ng/mL (range: 9 to 61 ng/mL), and the AUC0-∞ was 65 ng∙hr/ml (range: 40 to 107 ng/mL). Peak plasma concentration (Tmax) was achieved on average 45 minutes (range: 10 minutes to 2 hours) following ONZETRA Xsail administration. The bioavailability of ONZETRA relative to subcutaneous injection was approximately 19%, primarily due to pre-systemic metabolism and partly due to incomplete absorption. Sumatriptan bioavailability following liquid nasal spray administration is 14%, similar to that after oral administration (15%).

Distribution

Protein binding of sumatriptan, determined by equilibrium dialysis over the concentration range of 10 to 1000 ng/mL, is approximately 14% to 21%. The effect of sumatriptan on the protein binding of other drugs has not been evaluated. The apparent volume of distribution is 2.7 L/kg.

Metabolism

In vitro studies with human microsomes suggest that sumatriptan is metabolized by MAO (predominately A isoenzyme). Most of a radiolabeled dose of sumatriptan excreted in the urine is the major metabolite indole acetic acid (IAA) or the IAA glucuronide, both of which are inactive.

Elimination

The elimination half-life of sumatriptan administered as a nasal powder by the Xsail device is approximately 3 hours, similar to the half-life seen with sumatriptan nasal spray. Only 3% of a nasal spray dose is excreted in the urine as unchanged sumatriptan; 42% of a nasal spray dose is excreted as the major metabolite, the indole acetic acid analogue of sumatriptan. The total plasma clearance of the nasal spray is approximately 1200 mL/min.

Specific Populations

Age

The pharmacokinetics of oral sumatriptan in the elderly (mean age: 72 years, 2 males and 4 females) and in patients with migraine (mean age: 38 years, 25 males and 155 females) were similar to that in healthy male subjects (mean age: 30 years). Intranasal sumatriptan has not been evaluated for age differences.

Race

The systemic clearance and Cmax of subcutaneous sumatriptan were similar in black (n=34) and Caucasian (n=38) healthy male subjects. Intranasal sumatriptan has not been evaluated for race differences.

Renal Impairment

The effect of renal impairment on the pharmacokinetics of sumatriptan has not been examined.

Hepatic Impairment

The effect of mild hepatic disease on the pharmacokinetics of sumatriptan has not been evaluated. Following oral administration, an approximately 70% increase in Cmax and AUC was observed in one small trial of patients with moderate liver impairment (n=8) matched for sex, age, and weight with healthy subjects (n=8). Similar changes can be expected following intranasal administration.

The pharmacokinetics of sumatriptan in patients with severe hepatic impairment has not been studied [see Contraindications (4)].

Drug Interaction Studies

Monoamine Oxidase-A Inhibitors

Treatment with MAO-A inhibitors generally leads to an increase of sumatriptan plasma levels [see Contraindications (4) and Drug Interactions (7.2)]. MAO inhibitors interaction studies have not been performed with intranasal sumatriptan.

Due to gut and hepatic metabolic first-pass effects, the increase of systemic exposure after co-administration of an MAO-A inhibitor with oral sumatriptan is greater than after co-administration of the MAO inhibitors with subcutaneous sumatriptan. The effects of an MAO inhibitor on systemic exposure after intranasal sumatriptan would be expected to be greater than the effect after subcutaneous sumatriptan but smaller than the effect after oral sumatriptan because only swallowed drug would be subject to first-pass effects.

In a trial of 14 healthy females, pretreatment with an MAO-A inhibitor decreased the clearance of subcutaneous sumatriptan, resulting in a 2-fold increase in the area under the sumatriptan plasma concentration-time curve (AUC), corresponding to a 40% increase in elimination half-life.

A small study evaluating the effect of pretreatment with an MAO-A inhibitor on the bioavailability from a 25 mg oral sumatriptan tablet resulted in an approximately 7-fold increase in systemic exposure.

Xylometazoline

An in vivo drug interaction trial indicated that 3 drops of xylometazoline (0.1% w/v), a decongestant, administered 15 minutes prior to a 20 mg nasal spray dose of sumatriptan did not alter the pharmacokinetics of sumatriptan.

Carcinogenesis

In carcinogenicity studies in mouse and rat in which sumatriptan was administered orally for 78 weeks and 104 weeks, respectively, there was no evidence in either species of an increase in tumors related to sumatriptan administration.

Carcinogenicity studies of sumatriptan using the nasal route have not been conducted.

Mutagenesis

Sumatriptan was negative in in vitro (bacterial reverse mutation [Ames], gene cell mutation in Chinese hamster V79/HGPRT, chromosomal aberration in human lymphocytes) and in vivo (rat micronucleus) assays.

Impairment of Fertility

When sumatriptan (5, 50, or 500 mg/kg/day) was administered orally to male and female rats prior to and throughout the mating period, there was a treatment-related decrease in fertility secondary to a decrease in mating in animals treated with doses greater than 5 mg/kg/day. It is not clear whether this finding was due to an effect on males or females or both.

When sumatriptan was administered by subcutaneous injection to male and female rats prior to and throughout the mating period, there was no evidence of impaired fertility at doses of up to 60 mg/kg/day.

Fertility studies of sumatriptan using the intranasal route have not been conducted.

Corneal Opacities

Dogs receiving oral sumatriptan developed corneal opacities and defects in the corneal epithelium. Corneal opacities were seen at the lowest dose tested, 2 mg/kg/day, and were present after 1 month of treatment. Defects in the corneal epithelium were noted in a 60-week study. Earlier examinations for these toxicities were not conducted, and no-effect doses were not established.

The efficacy of ONZETRA Xsail for the acute treatment of migraine with or without aura was established in a multicenter, randomized, double-blind, placebo-controlled study (Study 1).

{ "type": "p", "children": [], "text": "The efficacy of ONZETRA Xsail for the acute treatment of migraine with or without aura was established in a multicenter, randomized, double-blind, placebo-controlled study (Study 1). " }

Migraineurs enrolled in Study 1 were primarily female (84%) and Caucasian (86%), with a mean age of 42 years (range of 19 to 64). Patients were instructed to treat a moderate to severe migraine headache. Additional medications were allowed as rescue therapy beginning 2 hours after the initial treatment.

{ "type": "p", "children": [], "text": "Migraineurs enrolled in Study 1 were primarily female (84%) and Caucasian (86%), with a mean age of 42 years (range of 19 to 64). Patients were instructed to treat a moderate to severe migraine headache. Additional medications were allowed as rescue therapy beginning 2 hours after the initial treatment." }

In Study 1, the proportion of patients who had headache relief defined as a reduction from moderate or severe pain to mild or no pain was assessed at 15, 30, 60, 90 minutes and 2, 24 and 48 hours after treatment with study drug. Associated symptoms of nausea, photophobia, and phonophobia were assessed as secondary endpoints. The proportion of patients who had no headache at 2 hours (120 minutes) was also assessed.

{ "type": "p", "children": [], "text": "In Study 1, the proportion of patients who had headache relief defined as a reduction from moderate or severe pain to mild or no pain was assessed at 15, 30, 60, 90 minutes and 2, 24 and 48 hours after treatment with study drug. Associated symptoms of nausea, photophobia, and phonophobia were assessed as secondary endpoints. The proportion of patients who had no headache at 2 hours (120 minutes) was also assessed. " }

The percentage of patients achieving headache relief 2 hours after treatment was significantly greater in the ONZETRA Xsail 22 mg group compared to those who received placebo (see Table 2 and Figure 1). For patients with migraine-associated nausea, photophobia, and phonophobia at baseline, there was a lower incidence of these symptoms at 2 hours following administration of ONZETRA Xsail compared with placebo.

{ "type": "p", "children": [], "text": "The percentage of patients achieving headache relief 2 hours after treatment was significantly greater in the ONZETRA Xsail 22 mg group compared to those who received placebo (see Table 2 and Figure 1). For patients with migraine-associated nausea, photophobia, and phonophobia at baseline, there was a lower incidence of these symptoms at 2 hours following administration of ONZETRA Xsail compared with placebo. " }

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 2: Percentage of Patients With Headache Relief (Primary Efficacy Endpoint), with No Headache, No Nausea, No Photophobia, and No Phonophobia 2 hours Post Treatment with ONZETRA Xsail (Study 1)</span> </caption> <col align="left" valign="top" width="34%"/> <col align="center" valign="top" width="33%"/> <col align="center" valign="top" width="33%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">2 hours post treatment</th><th align="center" class="Rrule">ONZETRA 22 mg (n=108)</th><th align="center" class="Rrule">Placebo (n=104)</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd> <span class="Italics">p</span>&lt;0.05 versus placebo</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Headache Relief</td><td align="center" class="Rrule">68%<a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a></td><td align="center" class="Rrule">45%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">No Headache</td><td align="center" class="Rrule">34% <a class="Sup" href="#footnote-2">*</a></td><td align="center" class="Rrule">17%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">No Nausea</td><td align="center" class="Rrule">82%</td><td align="center" class="Rrule">79%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">No Photophobia</td><td align="center" class="Rrule">52%</td><td align="center" class="Rrule">40%</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">No Phonophobia</td><td align="center" class="Rrule">68%</td><td align="center" class="Rrule">56%</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"90%\">\n<caption>\n<span>Table 2: Percentage of Patients With Headache Relief (Primary Efficacy Endpoint), with No Headache, No Nausea, No Photophobia, and No Phonophobia 2 hours Post Treatment with ONZETRA Xsail (Study 1)</span>\n</caption>\n<col align=\"left\" valign=\"top\" width=\"34%\"/>\n<col align=\"center\" valign=\"top\" width=\"33%\"/>\n<col align=\"center\" valign=\"top\" width=\"33%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\" class=\"Lrule Rrule\">2 hours post treatment</th><th align=\"center\" class=\"Rrule\">ONZETRA 22 mg (n=108)</th><th align=\"center\" class=\"Rrule\">Placebo (n=104)</th>\n</tr>\n</thead>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"3\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-2\" name=\"footnote-2\">*</a>\n</dt>\n<dd>\n<span class=\"Italics\">p</span>&lt;0.05 versus placebo</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\">Headache Relief</td><td align=\"center\" class=\"Rrule\">68%<a class=\"Sup\" href=\"#footnote-2\" name=\"footnote-reference-2\">*</a></td><td align=\"center\" class=\"Rrule\">45%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">No Headache</td><td align=\"center\" class=\"Rrule\">34% <a class=\"Sup\" href=\"#footnote-2\">*</a></td><td align=\"center\" class=\"Rrule\">17%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">No Nausea</td><td align=\"center\" class=\"Rrule\">82%</td><td align=\"center\" class=\"Rrule\">79%</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">No Photophobia</td><td align=\"center\" class=\"Rrule\">52%</td><td align=\"center\" class=\"Rrule\">40%</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\">No Phonophobia</td><td align=\"center\" class=\"Rrule\">68%</td><td align=\"center\" class=\"Rrule\">56%</td>\n</tr>\n</tbody>\n</table></div>" }

Figure 1: Percentage of Patients with Headache Relief within 2 Hours with ONZETRA Xsail

{ "type": "p", "children": [], "text": "\nFigure 1: Percentage of Patients with Headache Relief within 2 Hours with ONZETRA Xsail \n" }

The efficacy of ONZETRA Xsail was unaffected by presence of aura; duration of headache prior to treatment; gender, age, or weight of the subject; or concomitant use of common migraine prophylactic drugs (e.g., beta-blockers, calcium channel blockers, tricyclic antidepressants). There was insufficient data to assess the impact of race on efficacy.

{ "type": "p", "children": [], "text": "The efficacy of ONZETRA Xsail was unaffected by presence of aura; duration of headache prior to treatment; gender, age, or weight of the subject; or concomitant use of common migraine prophylactic drugs (e.g., beta-blockers, calcium channel blockers, tricyclic antidepressants). There was insufficient data to assess the impact of race on efficacy." }

ONZETRA Xsail is supplied as a disposable nosepiece containing a capsule and a reusable breath-powered delivery device body. Each capsule contains 11 mg sumatriptan base (equivalent to 15.4 mg of sumatriptan succinate nasal powder) in a clear, hypromellose capsule with 825 printed on one side.

ONZETRA Xsail is available in kits containing 8 doses.

The following table provides a description of the packaging configurations:

<div class="scrollingtable"><table width="90%"> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="60%"/> <col align="center" valign="top" width="20%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule">Description</th><th align="center" class="Rrule">Contents</th><th align="center" class="Rrule">NDC Code</th> </tr> </thead> <tbody> <tr class="First Last"> <td align="center" class="Lrule Rrule">8 Dose Kit</td><td align="center" class="Rrule">8 pouches containing 2 nosepieces (22 mg sumatriptan) per pouch. <br/>Each nosepiece contains 11 mg sumatriptan<br/>2 breath-powered delivery system bodies</td><td align="center" class="Rrule">42847-311-08</td> </tr> </tbody> </table></div>

Store at room temperature between 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C to 30°C (59°F to 86°F). Do not store in the refrigerator or freezer. Use nosepiece immediately after removing from foil pouch.

Risk of Myocardial Ischemia and/or Infarction, Prinzmetal's Angina, Other Vasospasm-Related Events, Arrhythmias, and Cerebrovascular Events

Inform patients that triptan medications, including ONZETRA Xsail, may cause serious cardiovascular side effects such as myocardial infarction or stroke, which may result in hospitalization and even death. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, irregular heartbeat, significant rise in blood pressure, weakness, and slurring of speech and should ask for medical advice if any indicative signs or symptoms are observed. Apprise patients of the importance of this follow-up [see Warnings and Precautions (5.1, 5.2, 5.3, 5.4, and 5.5)].

Hypersensitivity Reactions

Inform patients that anaphylactic reactions 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 [see Warnings and Precautions (5.9)].

Concomitant Use with Other Triptans and Ergot Medications

Inform patients that use of ONZETRA Xsail within 24 hours of another triptan or an ergot-type medication (including dihydroergotamine or methysergide) is contraindicated [see Contraindications (4) and Drug Interactions (7.1, 7.3)].

Serotonin Syndrome

Caution patients about the risk of serotonin syndrome with the use of ONZETRA Xsail or other triptans, particularly during combined use with SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7) and Drug Interactions (7.4)].

Medication Overuse Headache

Inform patients that use of acute migraine drugs for 10 or more days per month may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6)].

Pregnancy

Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant [see Use in Specific Populations (8.1)].

Nursing Mothers

Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.2)].

Ability To Perform Complex Tasks

Treatment with sumatriptan may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks during migraine attacks and after administration of ONZETRA Xsail.

Local Irritation

Inform patients that they may experience local irritation of their nose and throat. The symptoms will generally resolve in less than 2 hours.

How to Use ONZETRA Xsail with the breath powered device

Provide patients with instructions on the proper use of ONZETRA Xsail with the breath powered device.

Advise patients that use of the breath powered device is for ONZETRA Xsail only. No other product or substance is approved for use in the breath powered device.

Advise patients to remove a disposable nosepiece from the foil pouch, remove the clear device cap from the reusable device, and click the nosepiece into the device body.

Advise the patient to fully press and release the white piercing button on the device body to pierce the capsule inside the nosepiece. Instruct the patient to press the white piercing button only once.

Advise the patient to insert the nosepiece into the nostril so that it makes a tight seal. The device is then rotated and the mouthpiece inserted between the lips.

Instruct the patient to blow forcefully through the mouthpiece to deliver the sumatriptan powder into the nasal cavity. Vibration (e.g., a rattling noise) may occur, and indicates that the patient is blowing forcefully, as directed.

Advise the patient to remove and discard the nosepiece in the trash once the medication has been administered.

Instruct the patient to follow the same process using a second nosepiece in the other nostril to administer the remainder of the total recommended dose.

ONZETRA and Xsail are registered trademarks of Currax™ Pharmaceuticals LLC in the United States and other countries

{ "type": "p", "children": [], "text": "ONZETRA and Xsail are registered trademarks of Currax™ Pharmaceuticals LLC in the United States and other countries" }

Distributed by:Currax™ Pharmaceuticals LLCBrentwood, TN 37027

{ "type": "p", "children": [], "text": "Distributed by:Currax™ Pharmaceuticals LLCBrentwood, TN 37027" }

©2024 Currax™ Pharmaceuticals LLC All rights reserved

{ "type": "p", "children": [], "text": "©2024 Currax™ Pharmaceuticals LLC All rights reserved" }

Read this Patient Information before you start using ONZETRA Xsail and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment.

{ "type": "p", "children": [], "text": "Read this Patient Information before you start using ONZETRA Xsail and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment. " }

What is the most important information I should know about ONZETRA Xsail?

{ "type": "p", "children": [], "text": "\nWhat is the most important information I should know about ONZETRA Xsail? \n" }

ONZETRA Xsail can cause serious side effects, including:

{ "type": "p", "children": [], "text": "\nONZETRA Xsail can cause serious side effects, including: \n" }

Heart attack and other heart problems. Heart problems may lead to death.

{ "type": "p", "children": [], "text": "\nHeart attack and other heart problems. Heart problems may lead to death. \n" }

Stop taking ONZETRA Xsail and get emergency medical help right away if you have any of the following symptoms of a heart attack:

{ "type": "p", "children": [], "text": "\nStop taking ONZETRA Xsail and get emergency medical help right away if you have any of the following symptoms of a heart attack: \n" }

{ "type": "ul", "children": [ "discomfort in the center of your chest that lasts for more than a few minutes, or that 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" ], "text": "" }

ONZETRA Xsail is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. You have a higher risk for heart disease if you:

{ "type": "p", "children": [], "text": "ONZETRA Xsail is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. You have a higher risk for heart disease if you: " }

{ "type": "ul", "children": [ "have high blood pressure ", "have high cholesterol levels ", "smoke ", "are overweight ", "have diabetes ", "have a family history of heart disease " ], "text": "" }

What is ONZETRA Xsail?

{ "type": "p", "children": [], "text": "\nWhat is ONZETRA Xsail? \n" }

ONZETRA Xsail is a prescription medicine used to treat acute migraine headaches with or without aura in adults.

{ "type": "p", "children": [], "text": "ONZETRA Xsail is a prescription medicine used to treat acute migraine headaches with or without aura in adults. " }

ONZETRA Xsail is not used to treat other types of headaches such as hemiplegic migraines (that make you unable to move on one side of your body) or basilar migraines (rare form of migraine with aura).

{ "type": "p", "children": [], "text": "ONZETRA Xsail is not used to treat other types of headaches such as hemiplegic migraines (that make you unable to move on one side of your body) or basilar migraines (rare form of migraine with aura). " }

ONZETRA Xsail is not used to prevent or decrease the number of migraine headaches you have.

{ "type": "p", "children": [], "text": "ONZETRA Xsail is not used to prevent or decrease the number of migraine headaches you have. " }

It is not known if ONZETRA Xsail is safe and effective to treat cluster headaches.

{ "type": "p", "children": [], "text": "It is not known if ONZETRA Xsail is safe and effective to treat cluster headaches. " }

It is not known if ONZETRA Xsail is safe and effective in children under 18 years of age.

{ "type": "p", "children": [], "text": "It is not known if ONZETRA Xsail is safe and effective in children under 18 years of age. " }

Who should not use ONZETRA Xsail?

{ "type": "p", "children": [], "text": "\nWho should not use ONZETRA Xsail? \n" }

Do not use ONZETRA Xsail if you have:

{ "type": "p", "children": [], "text": "\nDo not use ONZETRA Xsail if you have:\n" }

{ "type": "ul", "children": [ "an allergy to sumatriptan", "heart problems or history of heart problems", "narrowing of blood vessels to your legs, arms, stomach or kidney (peripheral vascular disease)", "uncontrolled high blood pressure ", "severe liver problems ", "hemiplegic migraines or basilar migraines. If you are not sure if you have these types of migraines, ask your healthcare provider.", "had a stroke, transient ischemic attacks (TIAs) or problems with your blood circulation ", "taken any of the following medicines in the last 24 hours: \t\t\t\t\t\t\t\nalmotriptan (AXERT®)\neletriptan (RELPAX®)\nfrovatriptan (FROVA®)\nnaratriptan (AMERGE®)\nrizatriptan (MAXALT®, MAXALT-MLT®)\nzolmitriptan (ZOMIG®, ZOMIG-ZMT®, ZOMIG® NASAL SPRAY)\nsumatriptan (IMITREX®, IMITREX® NASAL SPRAY, IMITREX® INJECTION)\nsumatriptan and naproxen (TREXIMET®)\nsumatriptan (SUMAVEL® DOSE PRO® INJECTION)\nsumatriptan (ALSUMA®)\nsumatriptan (ZECUITY® TRANSDERMAL PATCH)\nergotamines (CAFERGOT®, ERGOMAR®, MIGERGOT®)\ndihydroergotamine (D.H.E. 45®, MIGRANAL®)Ask your healthcare provider if you are not sure if your medicine is listed above. \n\n" ], "text": "" }

What should I tell my healthcare provider before taking ONZETRA Xsail?

{ "type": "p", "children": [], "text": "\nWhat should I tell my healthcare provider before taking ONZETRA Xsail? \n" }

Before you use ONZETRA Xsail, tell your healthcare provider about all of your medical conditions, including if you:

{ "type": "p", "children": [], "text": "Before you use ONZETRA Xsail, tell your healthcare provider about all of your medical conditions, including if you: " }

{ "type": "ul", "children": [ "have high blood pressure ", "have high cholesterol ", "have diabetes ", "smoke ", "are overweight ", "have heart problems or a family history of heart problems or stroke ", "have kidney problems ", "have liver problems ", "have had epilepsy or seizures ", "are not using effective birth control ", "are pregnant or plan to become pregnant. It is not known if ONZETRA Xsail can harm your unborn baby.", "are breastfeeding or plan to breastfeed. ONZETRA Xsail passes into your breast milk. It is not known if this can harm your baby. Talk with your healthcare provider about the best way to feed your baby if you use ONZETRA Xsail. " ], "text": "" }

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements.

{ "type": "p", "children": [], "text": "\nTell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements. " }

ONZETRA Xsail and certain other medicines can affect each other, causing serious side effects.

{ "type": "p", "children": [], "text": "ONZETRA Xsail and certain other medicines can affect each other, causing serious side effects. " }

Especially tell your healthcare provider if you take anti-depressant medicines called:

{ "type": "p", "children": [], "text": "\nEspecially tell your healthcare provider if you take anti-depressant medicines called: " }

{ "type": "ul", "children": [ "selective serotonin reuptake inhibitors (SSRIs) ", "serotonin norepinephrine reuptake inhibitors (SNRIs) ", "tricyclic antidepressants (TCAs)", "monoamine oxidase inhibitors (MAOIs) " ], "text": "" }

Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure.

{ "type": "p", "children": [], "text": "Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure. " }

Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.

{ "type": "p", "children": [], "text": "Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine. " }

How should I use ONZETRA Xsail?

{ "type": "p", "children": [], "text": "\nHow should I use ONZETRA Xsail? \n" }

Before using ONZETRA Xsail, read the Patient Instructions for Use.

{ "type": "p", "children": [], "text": "\nBefore using ONZETRA Xsail, read the Patient Instructions for Use.\n" }

{ "type": "ul", "children": [ "Certain people should use their first dose of ONZETRA Xsail in their healthcare provider's office or in another medical setting. Ask your healthcare provider if you should use your first dose in a medical setting.", "Use ONZETRA Xsail exactly as your healthcare provider tells you to use it. ", "Use a full dose (2 nosepieces) to treat your headache. ", "If you do not get any relief after your first full dose, do not use a second dose without first talking with your healthcare provider.", "If your headache comes back after the first full dose or you only get some relief from your headache, you can use a second full dose 2 hours after the first full dose. ", "Do not take more than a total of 44 mg (two full doses) of ONZETRA Xsail in a 24-hour period. ", "It is not known how using ONZETRA Xsail for a long time affects the nose and throat. ", "If you use too much ONZETRA Xsail, call your healthcare provider or go to the nearest hospital emergency room right away. ", "You should write down when you have headaches and when you take ONZETRA Xsail so you can talk with your healthcare provider about how ONZETRA Xsail is working for you. " ], "text": "" }

What should I avoid while taking ONZETRA Xsail?

{ "type": "p", "children": [], "text": "\nWhat should I avoid while taking ONZETRA Xsail? \n" }

ONZETRA Xsail can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery or do anything where you need to be alert.

{ "type": "p", "children": [], "text": "ONZETRA Xsail can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery or do anything where you need to be alert. " }

What are the possible side effects of ONZETRA Xsail?

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects of ONZETRA Xsail?\n" }

ONZETRA Xsail may cause serious side effects. See "What is the most important information I should know about ONZETRA Xsail?"

{ "type": "p", "children": [], "text": "\nONZETRA Xsail may cause serious side effects. See \"What is the most important information I should know about ONZETRA Xsail?\"" }

These serious side effects include:

{ "type": "p", "children": [], "text": "These serious side effects include: " }

{ "type": "ul", "children": [ "changes in color or sensation in your fingers and toes (Raynaud's syndrome)", "stomach and intestinal problems (gastrointestinal and colonic ischemic events). Symptoms of gastrointestinal and colonic ischemic events include: \t\t\t\t\t\t\t\nsudden or severe stomach pain\nstomach pain after meals\nweight loss\nnausea or vomiting\nconstipation or diarrhea \nbloody diarrhea\nfever\n\n", "problems with blood circulation to your legs and feet (peripheral vascular ischemia). Symptoms of peripheral vascular ischemia include: \t\t\t\t\t\t\t\ncramping and pain in your legs or hips \nfeeling of heaviness or tightness in your leg muscles \nburning or aching pain in your feet or toes while resting\nnumbness, tingling or weakness in your legs\ncold feeling or color changes in 1 or both legs or feet\n\n", "hives (itchy bumps); swelling of your tongue, mouth or throat ", "medication overuse headaches. Some people who use too much sumatriptan may have worse headaches (medication overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with ONZETRA Xsail.", "serotonin syndrome. Serotonin syndrome is a rare but serious problem that can happen in people using ONZETRA Xsail, especially if ONZETRA Xsail is used with anti-depressant medications called SSRIs or SNRIs. Call your healthcare provider right away if you have any of the following symptoms of serotonin syndrome: \t\t\t\t\t\t\t\nMental changes such as seeing things that are not there (hallucinations), agitation, or coma\nFast heartbeat\nChanges in blood pressure\nHigh body temperature\nTight muscles\nTrouble walking\n\n", "seizures. Seizures have happened in people taking sumatriptan who have never had seizures before. Talk with your healthcare provider about your chance of having seizures while you take ONZETRA Xsail." ], "text": "" }

The most common side effects of ONZETRA Xsail include:

{ "type": "p", "children": [], "text": "The most common side effects of ONZETRA Xsail include: " }

{ "type": "ul", "children": [ "unusual or bad taste in your mouth ", "discomfort of your throat or nose ", "runny nose, stuffy nose, and/or postnasal drip" ], "text": "" }

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

{ "type": "p", "children": [], "text": "Tell your healthcare provider if you have any side effect that bothers you or that does not go away. " }

These are not all the possible side effects of ONZETRA Xsail. For more information, ask your healthcare provider or pharmacist.

{ "type": "p", "children": [], "text": "These are not all the possible side effects of ONZETRA Xsail. For more information, ask your healthcare provider or pharmacist. " }

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

{ "type": "p", "children": [], "text": "Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. " }

How should I store ONZETRA Xsail?

{ "type": "p", "children": [], "text": "\nHow should I store ONZETRA Xsail?\n" }

{ "type": "ul", "children": [ "Store at room temperature, between 68°F to 77°F (20°C to 25°C). ", "Do not store in the refrigerator or freezer." ], "text": "" }

Keep ONZETRA Xsail and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep ONZETRA Xsail and all medicines out of the reach of children. \n" }

General information about the safe and effective use of ONZETRA Xsail.

{ "type": "p", "children": [], "text": "\nGeneral information about the safe and effective use of ONZETRA Xsail. \n" }

{ "type": "ul", "children": [ "ONZETRA Xsail is to be used only with the Xsail breath-powered device.", "Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. ", "Do not use ONZETRA Xsail for a condition for which it was not prescribed. ", "Do not give ONZETRA Xsail to other people, even if they have the same symptoms you have. It may harm them. " ], "text": "" }

This Patient Information leaflet summarizes the most important information about ONZETRA Xsail. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about ONZETRA Xsail that is written for healthcare professionals.

{ "type": "p", "children": [], "text": "This Patient Information leaflet summarizes the most important information about ONZETRA Xsail. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about ONZETRA Xsail that is written for healthcare professionals. " }

For more information, go to www.ONZETRA.com or call 1-800-793-2145.

{ "type": "p", "children": [], "text": "For more information, go to www.ONZETRA.com or call 1-800-793-2145." }

What are the ingredients in ONZETRA Xsail?

{ "type": "p", "children": [], "text": "\nWhat are the ingredients in ONZETRA Xsail?\n" }

{ "type": "ul", "children": [ "Active ingredient: sumatriptan succinate", "Inactive ingredient: hypromellose (capsule)" ], "text": "" }

This Patient Information has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Patient Information has been approved by the U.S. Food and Drug Administration." }

Revised: 01/2024

{ "type": "p", "children": [], "text": "Revised: 01/2024" }

Read these Instructions for Use which come with ONZETRA® Xsail® before you start using it and each time you get a refill. Follow these instructions each time you use ONZETRA Xsail.

{ "type": "p", "children": [], "text": "Read these Instructions for Use which come with ONZETRA® Xsail® before you start using it and each time you get a refill. Follow these instructions each time you use ONZETRA Xsail. " }

These Instructions for Use have been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "These Instructions for Use have been approved by the U.S. Food and Drug Administration." }

ONZETRA and Xsail are registered trademarks of Currax™ Pharmaceuticals LLC in the United States and other countries. The other brands listed are trademarks of their respective owners and are not trademarks of Currax™ Pharmaceuticals LLC. The makers of these brands are not affiliated with and do not endorse Currax™ Pharmaceuticals LLC or its products.

{ "type": "p", "children": [], "text": "ONZETRA and Xsail are registered trademarks of Currax™ Pharmaceuticals LLC in the United States and other countries. The other brands listed are trademarks of their respective owners and are not trademarks of Currax™ Pharmaceuticals LLC. The makers of these brands are not affiliated with and do not endorse Currax™ Pharmaceuticals LLC or its products." }

U.S. Patent Nos, 6,715,485; 7,975,690; 8,047,202; 8,327,844; 8,550,073; 8,555,877; 8,590,530; 8,875,704; 8,899,229; 8,978,647; 9,108,015; 9,119,932

{ "type": "p", "children": [], "text": "U.S. Patent Nos, 6,715,485; 7,975,690; 8,047,202; 8,327,844; 8,550,073; 8,555,877; 8,590,530; 8,875,704; 8,899,229; 8,978,647; 9,108,015; 9,119,932" }

Distributed by:Currax™ Pharmaceuticals LLCBrentwood, TN 37027 1-800-793-2145 Issued January 2024

{ "type": "p", "children": [], "text": "Distributed by:Currax™ Pharmaceuticals LLCBrentwood, TN 37027\n1-800-793-2145\nIssued January 2024" }

ONZ-LC103.01

{ "type": "p", "children": [], "text": "ONZ-LC103.01" }

© 2024 Currax™ Pharmaceuticals LLC. All rights reserved

{ "type": "p", "children": [], "text": "© 2024 Currax™ Pharmaceuticals LLC. All rights reserved" }

NDC 42847-311-08

{ "type": "p", "children": [], "text": "NDC 42847-311-08" }

ONZETRA® Xsail® (sumatriptan nasal powder)11 mg per nosepiece

{ "type": "p", "children": [], "text": "ONZETRA® Xsail®\n(sumatriptan nasal powder)11 mg per nosepiece" }

Rx OnlyFor Intranasal Use Only

{ "type": "p", "children": [], "text": "Rx OnlyFor Intranasal Use Only" }

PLEASE READ INSTRUCTIONS FOR USE.

{ "type": "p", "children": [], "text": "PLEASE READ INSTRUCTIONS FOR USE." }

FOR USE WITH XSAIL® INTRANASAL DEVICE ONLY

{ "type": "p", "children": [], "text": "FOR USE WITH XSAIL®\nINTRANASAL DEVICE ONLY" }

TheBreath Powered® intranasal medicationdelivery system

{ "type": "p", "children": [], "text": "TheBreath Powered®\nintranasal medicationdelivery system" }

Sumatriptan tablets are indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use:

{ "type": "p", "children": [], "text": "Sumatriptan tablets are indicated for the acute treatment of migraine with or without aura in adults. \n \n\n Limitations of Use:\n \n" }

{ "type": "ul", "children": [ "Use only if a clear diagnosis of migraine headache has been established. If a patient has no response to the first migraine attack treated with sumatriptan tablets, reconsider the diagnosis of migraine before sumatriptan tablets are administered to treat any subsequent attacks.", "Sumatriptan tablets are not indicated for the prevention of migraine attacks.", "Safety and effectiveness of sumatriptan tablets have not been established for cluster headache." ], "text": "" }

The recommended dose of sumatriptan tablets is 25 mg, 50 mg, or 100 mg. Doses of 50 mg and 100 mg may provide a greater effect than the 25 mg dose, but doses of 100 mg may not provide a greater effect than the 50 mg dose. Higher doses may have a greater risk of adverse reactions [see Clinical Studies (14)] . If the migraine has not resolved by 2 hours after taking sumatriptan tablets, or returns after a transient improvement, a second dose may be administered at least 2 hours after the first dose. The maximum daily dose is 200 mg in a 24-hour period. Use after Sumatriptan Injection If the migraine returns following an initial treatment with sumatriptan injection, additional single sumatriptan tablets (up to 100 mg/day) may be given with an interval of at least 2 hours between tablet doses. The safety of treating an average of more than 4 headaches in a 30-day period has not been established.

If treatment is deemed advisable in the presence of mild to moderate hepatic impairment, the maximum single dose should not exceed 50 mg [see  Use in Specific Populations (8.6), Clinical Pharmacology (12.3)] .

100 mg Tablets:White to off-white, capsule shaped, biconvex uncoated tablets, debossed with ‘C’ on one side and ‘34’ on other side. Each tablet contains 140 mg of sumatriptan succinate USP equivalent to 100 mg of sumatriptan.

{ "type": "p", "children": [], "text": "\n100 mg Tablets:White to off-white, capsule shaped, biconvex uncoated tablets, debossed with ‘C’ on one side and ‘34’ on other side. Each tablet contains 140 mg of sumatriptan succinate USP equivalent to 100 mg of sumatriptan.\n " }

Sumatriptan tablets are contraindicated in patients with: 

{ "type": "p", "children": [], "text": "Sumatriptan tablets are contraindicated in patients with: " }

{ "type": "ul", "children": [ "Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetal’s angina\n \n [see\n \n Warnings and Precautions (5.1)]\n \n \n", "Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders\n \n [see\n \n Warnings and Precautions (5.2)]\n \n \n", "History of stroke or transient ischemic attack (TIA) or history of hemiplegic or basilar migraine because these patients are at a higher risk of stroke\n \n [see\n \n Warnings and Precautions (5.4)]\n \n \n", "Peripheral vascular disease\n \n [see Warnings and Precautions (5.5)]\n \n \n", "Ischemic bowel disease\n \n [see Warnings and Precautions (5.5)]\n \n \n", "Uncontrolled hypertension\n \n [see Warnings and Precautions (5.8)]\n \n \n", "Recent use (i.e., within 24 hours) of ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide), or another 5-hydroxytryptamine\n \n 1(5-HT\n \n 1) agonist\n \n [see \n \n Drug Interactions (7.1, \n \n 7.3)]\n \n \n", "Concurrent administration of a monoamine oxidase (MAO)-A inhibitor or recent (within 2 weeks) use of an MAO-A inhibitor\n \n [see \n \n Drug Interactions (7.2),\n \n Clinical Pharmacology (12.3)]\n \n \n", "Hypersensitivity to sumatriptan tablets (angioedema and anaphylaxis seen)\n \n [see\n \n Warnings and Precautions (5.9)]\n \n \n", "Severe hepatic impairment\n \n [see\n \n Use in Specific Populations (8.6), \n \n Clinical Pharmacology (12.3)]\n \n \n" ], "text": "" }

The use of sumatriptan tablets are 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 tablets. Some of these reactions occurred in patients without known CAD. Sumatriptan tablets may cause coronary artery vasospasm (Prinzmetal’s angina), even in patients without a history of CAD. Perform a cardiovascular evaluation in triptan-naive patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving sumatriptan tablets. If there is evidence of CAD or coronary artery vasospasm, sumatriptan tablets are contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of sumatriptan tablets in a medically supervised setting and performing an electrocardiogram (ECG) immediately following administration of sumatriptan tablets. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of sumatriptan tablets.

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 1agonists. Discontinue sumatriptan tablets if these disturbances occur. Sumatriptan tablets are contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

Sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw commonly occur after treatment with sumatriptan tablets and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of sumatriptan tablets is contraindicated in patients with CAD and those with Prinzmetal’s variant angina.

Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT 1agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT 1agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). Discontinue sumatriptan tablets 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. Sumatriptan tablets are contraindicated in patients with a history of stroke or TIA.

Sumatriptan tablets 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 non-coronary vasospasm reaction following the use of any 5-HT 1agonist, rule out a vasospastic reaction before receiving additional sumatriptan tablets. Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT 1agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT 1agonists has not been clearly established.

Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or combination 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.

Serotonin syndrome may occur with sumatriptan tablets, 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 aberrations (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 sumatriptan tablets if serotonin syndrome is suspected.

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 1agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with sumatriptan. Sumatriptan tablets are contraindicated in patients with uncontrolled hypertension.

Anaphylactic/anaphylactoid reactions 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. Sumatriptan tablets are contraindicated in patients with a history of hypersensitivity reaction to sumatriptan.

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. Sumatriptan tablets should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with 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 placebo-controlled clinical trials in patients who took at least 1 dose of study drug. Only treatment-emergent adverse reactions that occurred at a frequency of 2% or more in any group treated with sumatriptan tablets and that occurred at a frequency greater than the placebo group are included in Table 1.

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <caption> <span>Table 1. Adverse Reactions Reported by at Least 2% of Patients Treated with Sumatriptan Tablets and at a Greater Frequency than Placebo </span> </caption> <col width="32.18%"/> <col width="16.94%"/> <col width="17.02%"/> <col width="17.02%"/> <col width="16.84%"/> <tbody class="Headless"> <tr class="Botrule First"> <td class="Lrule Rrule" rowspan="2" valign="bottom"><span class="Bold">Adverse Reaction</span> <br/> </td><td align="center" class="Rrule" colspan="4" valign="top"><span class="Bold">Percent of Patients Reporting</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="bottom"><span class="Bold">Sumatriptan Tablets</span> <br/> <span class="Bold">25 mg</span> <br/> <span class="Bold">(n = 417)</span> <br/> </td><td align="center" class="Rrule" valign="bottom"><span class="Bold">Sumatriptan Tablets</span> <br/> <span class="Bold">50 mg</span> <br/> <span class="Bold">(n = 771)</span> <br/> </td><td align="center" class="Rrule" valign="bottom"><span class="Bold">Sumatriptan Tablets</span> <br/> <span class="Bold">100 mg</span> <br/> <span class="Bold">(n = 437)</span> <br/> </td><td align="center" class="Rrule" valign="bottom"><span class="Bold">Placebo</span> <br/> <span class="Bold">(n = 309)</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Atypical sensations <br/>    Paresthesia (all types) <br/>    Sensation warm/cold <br/> </td><td align="center" class="Rrule" valign="top">5 <br/> 3 <br/> 3 <br/> </td><td align="center" class="Rrule" valign="top">6 <br/> 5 <br/> 2 <br/> </td><td align="center" class="Rrule" valign="top">6 <br/> 3 <br/> 3 <br/> </td><td align="center" class="Rrule" valign="top">4 <br/> 2 <br/> 2 <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Pain and other pressure sensations <br/> </td><td align="center" class="Rrule" valign="top">6 <br/> </td><td align="center" class="Rrule" valign="top">6 <br/> </td><td align="center" class="Rrule" valign="top">8 <br/> </td><td align="center" class="Rrule" valign="top">4 <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">   Chest - pain/tightness/ pressure and/or heaviness <br/> </td><td align="center" class="Rrule" valign="top">1 <br/> </td><td align="center" class="Rrule" valign="top">2 <br/> </td><td align="center" class="Rrule" valign="top">2 <br/> </td><td align="center" class="Rrule" valign="top">1 <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">   Neck/throat/jaw - pain/ tightness/pressure <br/> </td><td align="center" class="Rrule" valign="top">&lt;1 <br/> </td><td align="center" class="Rrule" valign="top">2 <br/> </td><td align="center" class="Rrule" valign="top">3 <br/> </td><td align="center" class="Rrule" valign="top">&lt;1 <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">   Pain - location specified <br/> </td><td align="center" class="Rrule" valign="top">2 <br/> </td><td align="center" class="Rrule" valign="top">1 <br/> </td><td align="center" class="Rrule" valign="top">1 <br/> </td><td align="center" class="Rrule" valign="top">1 <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">   Other - pressure/tightness/ heaviness <br/> </td><td align="center" class="Rrule" valign="top">1 <br/> </td><td align="center" class="Rrule" valign="top">1 <br/> </td><td align="center" class="Rrule" valign="top">3 <br/> </td><td align="center" class="Rrule" valign="top">2 <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Neurological <br/>    Vertigo <br/> </td><td align="center" class="Rrule" valign="middle">  <br/> &lt;1 <br/> </td><td align="center" class="Rrule" valign="middle">  <br/> &lt;1 <br/> </td><td align="center" class="Rrule" valign="middle">  <br/> 2 <br/> </td><td align="center" class="Rrule" valign="middle">  <br/> &lt;1 <br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top">Other <br/>    Malaise/fatigue <br/> </td><td align="center" class="Rrule" valign="middle">  <br/> 2 <br/> </td><td align="center" class="Rrule" valign="middle">  <br/> 2 <br/> </td><td align="center" class="Rrule" valign="middle">  <br/> 3 <br/> </td><td align="center" class="Rrule" valign="middle">  <br/> &lt;1 <br/> </td> </tr> </tbody> </table></div>

The incidence of adverse reactions in controlled clinical trials was not affected by gender or age of the patients. There were insufficient data to assess the impact of race on the incidence of adverse reactions.

The following adverse reactions have been identified during postapproval use of sumatriptan tablets, sumatriptan nasal spray, and sumatriptan injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to sumatriptan or a combination of these factors. Cardiovascular Hypotension, palpitations. Neurological Dystonia, tremor.

Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and sumatriptan tablets within 24 hours of each other is contraindicated.

MAO-A inhibitors increase systemic exposure by 7-fold. Therefore, the use of sumatriptan tablets in patients receiving MAO-A inhibitors is contraindicated [see Clinical Pharmacology (12.3)] .

Because their vasospastic effects may be additive, co-administration of sumatriptan tablets and other 5-HT 1agonists (e.g., triptans) within 24 hours of each other is contraindicated.

Cases of serotonin syndrome have been reported during co-administration of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7)] .

Risk Summary

Data from a prospective pregnancy exposure registry and epidemiological studies of pregnant women have not detected an increased frequency of birth defects or a consistent pattern of birth defects among women exposed to sumatriptan compared with the general population (see Data). In developmental toxicity studies in rats and rabbits, oral administration of sumatriptan to pregnant animals was associated with embryolethality, fetal abnormalities, and pup mortality. When administered by the intravenous route to pregnant rabbits, sumatriptan was embryolethal (see Data).

In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of major birth defects among deliveries to women with migraine ranged from 2.2% to 2.9% and the reported rate of miscarriage was 17%, which were similar to rates reported in women without migraine.

Clinical Considerations

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.

Data

Human Data:The Sumatriptan/Naratriptan/Treximet (sumatriptan and naproxen sodium) Pregnancy Registry, a population-based international prospective study, collected data for sumatriptan from January 1996 to September 2012. The Registry documented outcomes of 626 infants and fetuses exposed to sumatriptan during pregnancy (528 with earliest exposure during the first trimester, 78 during the second trimester, 16 during the third trimester, and 4 unknown). The occurrence of major birth defects (excluding fetal deaths and induced abortions without reported defects and all spontaneous pregnancy losses) during first-trimester exposure to sumatriptan was 4.2% (20/478 [95% CI: 2.6% to 6.5%]) and during any trimester of exposure was 4.2% (24/576 [95% CI: 2.7% to 6.2%]). The sample size in this study had 80% power to detect at least a 1.73- to 1.91-fold increase in the rate of major malformations. The number of exposed pregnancy outcomes accumulated during the registry was insufficient to support definitive conclusions about overall malformation risk or for making comparisons of the frequencies of specific birth defects. Of the 20 infants with reported birth defects after exposure to sumatriptan in the first trimester, 4 infants had ventricular septal defects, including one infant who was exposed to both sumatriptan and naratriptan, and 3 infants had pyloric stenosis. No other birth defect was reported for more than 2 infants in this group.

In a study using data from the Swedish Medical Birth Register, live births to women who reported using triptans or ergots during pregnancy were compared with those of women who did not. Of the 2,257 births with first-trimester exposure to sumatriptan, 107 infants were born with malformations (relative risk 0.99 [95% CI: 0.91 to 1.21]). A study using linked data from the Medical Birth Registry of Norway to the Norwegian Prescription Database compared pregnancy outcomes in women who redeemed prescriptions for triptans during pregnancy, as well as a migraine disease comparison group who redeemed prescriptions for sumatriptan before pregnancy only, compared with a population control group. Of the 415 women who redeemed prescriptions for sumatriptan during the first trimester, 15 had infants with major congenital malformations (OR 1.16 [95% CI: 0.69 to 1.94]) while for the 364 women who redeemed prescriptions for sumatriptan before, but not during, pregnancy, 20 had infants with major congenital malformations (OR 1.83 [95% CI: 1.17 to 2.88]), each compared with the population comparison group. Additional smaller observational studies evaluating use of sumatriptan during pregnancy have not suggested an increased risk of teratogenicity.

Animal Data:Oral administration of sumatriptan to pregnant rats during the period of organogenesis resulted in an increased incidence of fetal blood vessel (cervicothoracic and umbilical) abnormalities. The highest no-effect dose for embryofetal developmental toxicity in rats was 60 mg/kg/day, or approximately 3 times the maximum recommended human dose (MRHD) of 200 mg/day on a mg/m 2basis. Oral administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in increased incidences of embryolethality and fetal cervicothoracic vascular and skeletal abnormalities. Intravenous administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in an increased incidence of embryolethality. The highest oral and intravenous no-effect doses for developmental toxicity in rabbits were 15 (approximately 2 times the MRHD on a mg/m 2basis) and 0.75 mg/kg/day, respectively.

Oral administration of sumatriptan to rats prior to and throughout gestation resulted in embryofetal toxicity (decreased body weight, decreased ossification, increased incidence of skeletal abnormalities). The highest no-effect dose was 50 mg/kg/day, or approximately 2 times the MRHD on a mg/m 2basis. In offspring of pregnant rats treated orally with sumatriptan during organogenesis, there was a decrease in pup survival. The highest no-effect dose for this effect was 60 mg/kg/day, or approximately 3 times the MRHD on a mg/m 2basis. Oral treatment of pregnant rats with sumatriptan during the latter part of gestation and throughout lactation resulted in a decrease in pup survival. The highest no-effect dose for this finding was 100 mg/kg/day, or approximately 5 times the MRHD on a mg/m 2basis.

Risk Summary

Sumatriptan is excreted in human milk following subcutaneous administration (see Data). There is no information regarding sumatriptan concentrations in milk from lactating women following administration of sumatriptan tablets. There are no data on the effects of sumatriptan on the breastfed infant or the effects of sumatriptan on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for sumatriptan tablets and any potential adverse effects on the breastfed infant from sumatriptan or from the underlying maternal condition.

Clinical Considerations

Infant exposure to sumatriptan can be minimized by avoiding breastfeeding for 12 hours after treatment with sumatriptan tablets.

Data

Following subcutaneous administration of a 6 mg dose of sumatriptan injection in 5 lactating volunteers, sumatriptan was present in milk.

Safety and effectiveness in pediatric patients have not been established. Sumatriptan tablets are not recommended for use in patients younger than 18 years of age. Two controlled clinical trials evaluated sumatriptan nasal spray (5 to 20 mg) in 1,248 adolescent migraineurs aged 12 to 17 years who treated a single attack. The trials did not establish the efficacy of sumatriptan nasal spray compared with placebo in the treatment of migraine in adolescents. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults. Five controlled clinical trials (2 single-attack trials, 3 multiple-attack trials) evaluating oral sumatriptan (25 to 100 mg) in pediatric patients aged 12 to 17 years enrolled a total of 701 adolescent migraineurs. These trials did not establish the efficacy of oral sumatriptan compared with placebo in the treatment of migraine in adolescents. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults. The frequency of all adverse reactions in these patients appeared to be both dose- and age-dependent, with younger patients reporting reactions more commonly than older adolescents. Postmarketing experience documents that serious adverse reactions have occurred in the pediatric population after use of subcutaneous, oral, and/or intranasal sumatriptan. These reports include reactions similar in nature to those reported rarely in adults, including stroke, visual loss, and death. A myocardial infarction has been reported in a 14-year-old male following the use of oral sumatriptan; clinical signs occurred within 1 day of drug administration. Clinical data to determine the frequency of serious adverse reactions in pediatric patients who might receive subcutaneous, oral, or intranasal sumatriptan are not presently available.

Clinical trials of sumatriptan tablets did not include sufficient numbers of patients aged   65 and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving sumatriptan tablets [see Warnings and Precautions (5.1)] .

The maximum single dose in patients with mild to moderate hepatic impairment should not exceed 50 mg. Sumatriptan tablets are contraindicated in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)] .

Patients in clinical trials (N = 670) received single oral doses of 140 to 300 mg without significant adverse reactions. Volunteers (N = 174) received single oral doses of 140 to 400 mg without serious adverse reactions. Overdose in animals has been fatal and has been heralded by convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation, and lacrimation. The elimination half-life of sumatriptan is approximately 2.5 hours [see Clinical Pharmacology (12.3)] , and therefore monitoring of patients after overdose with sumatriptan tablets should continue for at least 12 hours or while symptoms or signs persist. It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan.

{ "type": "p", "children": [], "text": "Patients in clinical trials (N = 670) received single oral doses of 140 to 300 mg without significant adverse reactions. Volunteers (N = 174) received single oral doses of 140 to 400 mg without serious adverse reactions. \n \n Overdose in animals has been fatal and has been heralded by convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation, and lacrimation. \n \n The elimination half-life of sumatriptan is approximately 2.5 hours\n \n [see\n \n Clinical Pharmacology (12.3)]\n \n , and therefore monitoring of patients after overdose with sumatriptan tablets should continue for at least 12 hours or while symptoms or signs persist. \n \n It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan.\n\n " }

Sumatriptan tablets, USP contain sumatriptan succinate, a selective 5-HT 1B/1Dreceptor agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole­-5-methanesulfonamide succinate (1:1), and it has the following structure:

{ "type": "p", "children": [], "text": "Sumatriptan tablets, USP contain sumatriptan succinate, a selective 5-HT\n \n 1B/1Dreceptor agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole­-5-methanesulfonamide succinate (1:1), and it has the following structure:\n\n " }

The molecular formula is C 14H 21N 3O 2S•C 4H 6O 4, representing a molecular weight of 413.5. Sumatriptan succinate USP is a white to off-white powder that is readily soluble in water and in saline. Each sumatriptan tablet, USP for oral administration contains 35 mg, 70 mg, or 140 mg of sumatriptan succinate USP equivalent to 25 mg, 50 mg, or 100 mg of sumatriptan, respectively. Each tablet also contains the inactive ingredients croscarmellose sodium, dibasic calcium phosphate anhydrous, magnesium stearate, microcrystalline cellulose, polysorbate 80, and sodium bicarbonate.

{ "type": "p", "children": [], "text": "The molecular formula is C\n \n 14H\n \n 21N\n \n 3O\n \n 2S•C\n \n 4H\n \n 6O\n \n 4, representing a molecular weight of 413.5. Sumatriptan succinate USP is a white to off-white powder that is readily soluble in water and in saline. \n \n Each sumatriptan tablet, USP for oral administration contains 35 mg, 70 mg, or 140 mg of sumatriptan succinate USP equivalent to 25 mg, 50 mg, or 100 mg of sumatriptan, respectively. Each tablet also contains the inactive ingredients croscarmellose sodium, dibasic calcium phosphate anhydrous, magnesium stearate, microcrystalline cellulose, polysorbate 80, and sodium bicarbonate.\n\n " }

Sumatriptan binds with high affinity to human cloned 5-HT 1B/1Dreceptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine headache through agonist effects at the 5-HT 1B/1Dreceptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

Blood Pressure Significant elevation in blood pressure, including hypertensive crisis, has been reported in patients with and without a history of hypertension [see Warnings and Precautions (5.8)] . Peripheral (Small) Arteries In healthy volunteers (N = 18), a trial evaluating the effects of sumatriptan on peripheral (small vessel) arterial reactivity failed to detect a clinically significant increase in peripheral resistance. Heart Rate Transient increases in blood pressure observed in some patients in clinical trials carried out during sumatriptan’s development as a treatment for migraine were not accompanied by any clinically significant changes in heart rate.

Absorption The mean maximum concentration following oral dosing with 25 mg is 18 ng/mL (range: 7 to 47 ng/mL) and 51 ng/mL (range: 28 to 100 ng/mL) following oral dosing with 100 mg of sumatriptan. This compares with a C maxof 5 and 16 ng/mL following dosing with a 5 and 20 mg intranasal dose, respectively. The mean C maxfollowing a 6 mg subcutaneous injection is 71 ng/mL (range: 49 to 110 ng/mL). The bioavailability is approximately 15%, primarily due to presystemic metabolism and partly due to incomplete absorption. The C maxis similar during a migraine attack and during a migraine-free period, but the T maxis slightly later during the attack, approximately 2.5 hours compared with 2 hours. When given as a single dose, sumatriptan displays dose proportionality in its extent of absorption (area under the curve [AUC]) over the dose range of 25 to 200 mg, but the C maxafter 100 mg is approximately 25% less than expected (based on the 25 mg dose). Effect of Food:A food effect trial involving administration of sumatriptan tablets 100 mg to healthy volunteers under fasting conditions and with a high-fat meal indicated that the C maxand AUC were increased by 15% and 12%, respectively, when administered in the fed state. Distribution Protein binding, determined by equilibrium dialysis over the concentration range of 10 to 1,000 ng/mL is low, approximately 14% to 21%. The effect of sumatriptan on the protein binding of other drugs has not been evaluated. The apparent volume of distribution is 2.7 L/kg. Metabolism In vitrostudies with human microsomes suggest that sumatriptan is metabolized by MAO, predominantly the A isoenzyme. Most of a radiolabeled dose of sumatriptan excreted in the urine is the major metabolite indole acetic acid (IAA) or the IAA glucuronide, both of which are inactive. Elimination The elimination half-life of sumatriptan is approximately 2.5 hours. Radiolabeled 14C-sumatriptan administered orally is largely renally excreted (about 60%) with about 40% found in the feces. Most of the radiolabeled compound excreted in the urine is the major metabolite, IAA, which is inactive, or the IAA glucuronide. Only 3% of the dose can be recovered as unchanged sumatriptan. Specific Populations Age:The pharmacokinetics of sumatriptan in the elderly (mean age: 72 years, 2 males and 4 females) and in subjects with migraine (mean age: 38 years, 25 males and 155 females) were similar to that in healthy male subjects (mean age: 30 years). Patients with Renal Impairment: The effect of renal impairment on the pharmacokinetics of sumatriptan has not been examined. Patients with Hepatic Impairment: The liver plays an important role in the presystemic clearance of orally administered sumatriptan. Accordingly, the bioavailability of sumatriptan following oral administration may be markedly increased in patients with liver disease. In one small trial of patients with moderate liver impairment (n = 8) matched for sex, age, and weight with healthy subjects (n = 8), the hepatically-impaired patients had an approximately 70% increase in AUC and C maxand a T max40 minutes earlier compared with the healthy subjects. The pharmacokinetics of sumatriptan in patients with severe hepatic impairment has not been studied. The use of sumatriptan tablets in this population is contraindicated [see  Contraindications (4), Use in Specific Populations (8.6)] . Male and Female Patients: In a trial comparing females to males, no pharmacokinetic differences were observed between genders for AUC, C max, T max, and half-life. Racial Groups: The systemic clearance and C maxof subcutaneous sumatriptan were similar in black (n = 34) and Caucasian (n = 38) healthy male subjects. Oral sumatriptan has not been evaluated for race differences. Drug Interaction Studies Monoamine Oxidase-A Inhibitors: Treatment with MAO-A inhibitors generally leads to an increase of sumatriptan plasma levels [see  Contraindications (4), Drug Interactions (7.2)] . Due to gut and hepatic metabolic first-pass effects, the increase of systemic exposure after co-administration of an MAO-A inhibitor with oral sumatriptan is greater than after co-­administration of the MAO inhibitors with subcutaneous sumatriptan. In a trial of 14 healthy females, pretreatment with an MAO-A inhibitor decreased the clearance of subcutaneous sumatriptan, resulting in a 2-fold increase in the area under the sumatriptan plasma concentration-time curve (AUC), corresponding to a 40% increase in elimination half-life. A small trial evaluating the effect of pretreatment with an MAO-A inhibitor on the bioavailability from a 25 mg oral sumatriptan tablet resulted in an approximately 7-fold increase in systemic exposure. Alcohol: Alcohol consumed 30 minutes prior to sumatriptan ingestion had no effect on the pharmacokinetics of sumatriptan.

Carcinogenesis In carcinogenicity studies in mouse and rat, sumatriptan was administered orally for 78 and 104 weeks, respectively, at doses up to 160 mg/kg/day (the high dose in rat was reduced from 360 mg/kg/day during Week 21). There was no evidence in either species of an increase in tumors related to sumatriptan administration. Plasma exposures (AUC) at the highest doses tested were 20 and 8 times that in humans at the maximum recommended human dose (MRHD) of 200 mg/day. Mutagenesis Sumatriptan was negative in in vitro(bacterial reverse mutation [Ames], gene cell mutation in Chinese hamster V79/HGPRT, chromosomal aberration in human lymphocytes) and in vivo(rat micronucleus) assays. Impairment of Fertility When sumatriptan (5, 50, 500 mg/kg/day) was administered orally to male and female rats prior to and throughout the mating period, there was a treatment-related decrease in fertility secondary to a decrease in mating in animals treated with doses greater than   5 mg/kg/day (less than the MRHD on a mg/m 2basis). It is not clear whether this finding was due to an effect on males or females or both. When sumatriptan was administered by subcutaneous injection to male and female rats prior to and throughout the mating period, there was no evidence of impaired fertility at doses up to 60 mg/kg/day.

Corneal Opacities Dogs receiving oral sumatriptan developed corneal opacities and defects in the corneal epithelium. Corneal opacities were seen at the lowest dose tested, 2 mg/kg/day, and were present after 1 month of treatment. Defects in the corneal epithelium were noted in a 60-week study. Earlier examinations for these toxicities were not conducted and no-effect doses were not established. Plasma exposure at the lowest dose tested was approximately 2 times that in humans at the MRHD.

The efficacy of sumatriptan tablets in the acute treatment of migraine headaches was demonstrated in 3, randomized, double-blind, placebo-controlled trials. Patients enrolled in these 3 trials were predominately female (87%) and Caucasian (97%), with a mean age of 40 years (range: 18 to 65 years). Patients were instructed to treat a moderate to severe headache. Headache response, defined as a reduction in headache severity from moderate or severe pain to mild or no pain, was assessed up to 4 hours after dosing. Associated symptoms such as nausea, photophobia, and phonophobia were also assessed. Maintenance of response was assessed for up to 24 hours postdose. A second dose of sumatriptan tablets or other medication was allowed 4 to   24 hours after the initial treatment for recurrent headache. Acetaminophen was offered to patients in Trials 2 and 3 beginning at 2 hours after initial treatment if the migraine pain had not improved or had worsened. Additional medications were allowed 4 to 24 hours after the initial treatment for recurrent headache or as rescue in all 3 trials. The frequency and time to use of these additional treatments were also determined. In all trials, doses of 25, 50, and 100 mg were compared with placebo in the treatment of migraine attacks. In 1 trial, doses of 25, 50, and 100 mg were also compared with each other. In all 3 trials, the percentage of patients achieving headache response 2 and 4 hours after treatment was significantly greater among patients receiving sumatriptan tablets at all doses compared with those who received placebo. In 1 of the 3 trials, there was a statistically significant greater percentage of patients with headache response at 2 and 4 hours in the 50 mg or 100 mg group when compared with the 25 mg dose groups. There were no statistically significant differences between the 50 mg and 100 mg dose groups in any trial. The results from the 3 controlled clinical trials are summarized in Table 2.

{ "type": "p", "children": [], "text": "The efficacy of sumatriptan tablets in the acute treatment of migraine headaches was demonstrated in 3, randomized, double-blind, placebo-controlled trials. Patients enrolled in these 3 trials were predominately female (87%) and Caucasian (97%), with a mean age of 40 years (range: 18 to 65 years). Patients were instructed to treat a moderate to severe headache. Headache response, defined as a reduction in headache severity from moderate or severe pain to mild or no pain, was assessed up to 4 hours after dosing. Associated symptoms such as nausea, photophobia, and phonophobia were also assessed. Maintenance of response was assessed for up to 24 hours postdose. A second dose of sumatriptan tablets or other medication was allowed 4 to   24 hours after the initial treatment for recurrent headache. Acetaminophen was offered to patients in Trials 2 and 3 beginning at 2 hours after initial treatment if the migraine pain had not improved or had worsened. Additional medications were allowed 4 to 24 hours after the initial treatment for recurrent headache or as rescue in all 3 trials. The frequency and time to use of these additional treatments were also determined. In all trials, doses of 25, 50, and 100 mg were compared with placebo in the treatment of migraine attacks. In 1 trial, doses of 25, 50, and 100 mg were also compared with each other. \n \n In all 3 trials, the percentage of patients achieving headache response 2 and 4 hours after treatment was significantly greater among patients receiving sumatriptan tablets at all doses compared with those who received placebo. In 1 of the 3 trials, there was a statistically significant greater percentage of patients with headache response at 2 and 4 hours in the 50 mg or 100 mg group when compared with the 25 mg dose groups. There were no statistically significant differences between the 50 mg and 100 mg dose groups in any trial. The results from the 3 controlled clinical trials are summarized in Table 2.\n " }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <caption> <span>Table 2. Percentage of Patients with Headache Response (Mild or No Headache) 2 and 4 Hours following Treatment </span> </caption> <col width="16.62%"/> <col width="22%"/> <col width="22.04%"/> <col width="22.06%"/> <col width="17.26%"/> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" valign="bottom">  <br/> </td><td align="center" class="Rrule" valign="bottom"><span class="Bold">Sumatriptan Tablets</span> <br/> <span class="Bold">25 mg</span> <br/> <span class="Bold">2 h       4 h</span> <br/> </td><td align="center" class="Rrule" valign="bottom"><span class="Bold">Sumatriptan Tablets</span> <br/> <span class="Bold">50 mg</span> <br/> <span class="Bold">2 h      4 h</span> <br/> </td><td align="center" class="Rrule" valign="bottom"><span class="Bold">Sumatriptan Tablets</span> <br/> <span class="Bold">100 mg</span> <br/> <span class="Bold">2 h      4 h</span> <br/> </td><td align="center" class="Rrule" valign="bottom"><span class="Bold">Placebo</span> <br/> <span class="Bold">2 h      4 h</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Trial 1 <br/> </td><td align="center" class="Rrule" valign="middle">52% <span class="Sup">a</span>      67% <span class="Sup">a</span> <br/> (n = 298) <br/> </td><td align="center" class="Rrule" valign="middle">61% <span class="Sup">a,b</span>      78% <span class="Sup">a,b</span> <br/> (n = 296) <br/> </td><td align="center" class="Rrule" valign="middle">62% <span class="Sup">a,b</span>      79% <span class="Sup">a,b</span> <br/> (n = 296) <br/> </td><td align="center" class="Rrule" valign="middle">27%     38% <br/> (n = 94) <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Trial 2 <br/> </td><td align="center" class="Rrule" valign="middle">52% <span class="Sup">a</span>      70% <span class="Sup">a</span> <br/> (n = 66) <br/> </td><td align="center" class="Rrule" valign="middle">50% <span class="Sup">a</span>      68% <span class="Sup">a</span> <br/> (n = 62) <br/> </td><td align="center" class="Rrule" valign="middle">56% <span class="Sup">a</span>      71% <span class="Sup">a</span> <br/> (n = 66) <br/> </td><td align="center" class="Rrule" valign="middle">26%     38% <br/> (n = 65) <br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="middle">Trial 3 <br/> </td><td align="center" class="Rrule" valign="middle">52% <span class="Sup">a</span>      65% <span class="Sup">a</span> <br/> (n = 48) <br/> </td><td align="center" class="Rrule" valign="middle">54% <span class="Sup">a</span>      72% <span class="Sup">a</span> <br/> (n = 46) <br/> </td><td align="center" class="Rrule" valign="middle">57% <span class="Sup">a</span>      78% <span class="Sup">a</span> <br/> (n = 46) <br/> </td><td align="center" class="Rrule" valign="middle">17%     19% <br/> (n = 47) <br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"100%\">\n<caption>\n<span>Table 2. Percentage of Patients with Headache Response (Mild or No Headache) 2 and 4 Hours following Treatment </span>\n</caption>\n<col width=\"16.62%\"/>\n<col width=\"22%\"/>\n<col width=\"22.04%\"/>\n<col width=\"22.06%\"/>\n<col width=\"17.26%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"bottom\">  \n <br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"bottom\"><span class=\"Bold\">Sumatriptan Tablets</span>\n<br/>\n<span class=\"Bold\">25 mg</span>\n<br/>\n<span class=\"Bold\">2 h       4 h</span>\n<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"bottom\"><span class=\"Bold\">Sumatriptan Tablets</span>\n<br/>\n<span class=\"Bold\">50 mg</span>\n<br/>\n<span class=\"Bold\">2 h      4 h</span>\n<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"bottom\"><span class=\"Bold\">Sumatriptan Tablets</span>\n<br/>\n<span class=\"Bold\">100 mg</span>\n<br/>\n<span class=\"Bold\">2 h      4 h</span>\n<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"bottom\"><span class=\"Bold\">Placebo</span>\n<br/>\n<span class=\"Bold\">2 h      4 h</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\">Trial 1 \n <br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">52%\n \n <span class=\"Sup\">a</span>      67%\n \n <span class=\"Sup\">a</span>\n<br/> (n = 298) \n <br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">61%\n \n <span class=\"Sup\">a,b</span>      78%\n \n <span class=\"Sup\">a,b</span>\n<br/> (n = 296) \n <br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">62%\n \n <span class=\"Sup\">a,b</span>      79%\n \n <span class=\"Sup\">a,b</span>\n<br/> (n = 296) \n <br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">27%     38% \n <br/> (n = 94) \n <br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\">Trial 2 \n <br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">52%\n \n <span class=\"Sup\">a</span>      70%\n \n <span class=\"Sup\">a</span>\n<br/> (n = 66) \n <br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">50%\n \n <span class=\"Sup\">a</span>      68%\n \n <span class=\"Sup\">a</span>\n<br/> (n = 62) \n <br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">56%\n \n <span class=\"Sup\">a</span>      71%\n \n <span class=\"Sup\">a</span>\n<br/> (n = 66) \n <br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">26%     38% \n <br/> (n = 65) \n <br/>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule\" valign=\"middle\">Trial 3 \n <br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">52%\n \n <span class=\"Sup\">a</span>      65%\n \n <span class=\"Sup\">a</span>\n<br/> (n = 48) \n <br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">54%\n \n <span class=\"Sup\">a</span>      72%\n \n <span class=\"Sup\">a</span>\n<br/> (n = 46) \n <br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">57%\n \n <span class=\"Sup\">a</span>      78%\n \n <span class=\"Sup\">a</span>\n<br/> (n = 46) \n <br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">17%     19% \n <br/> (n = 47) \n <br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

a P<0.05 in comparison with placebo.

{ "type": "p", "children": [], "text": "\na P<0.05 in comparison with placebo.\n\n " }

bP<0.05 in comparison with 25 mg. The estimated probability of achieving an initial headache response over the 4 hours following treatment in pooled Trials 1, 2, and 3 is depicted in Figure 1. Figure 1. Estimated Probability of Achieving Initial Headache Response within 4 Hours of Treatment in Pooled Trials 1, 2, and 3 a

{ "type": "p", "children": [], "text": "\nbP<0.05 in comparison with 25 mg. \n \n The estimated probability of achieving an initial headache response over the 4 hours following treatment in pooled Trials 1, 2, and 3 is depicted in Figure 1. \n \n\n Figure 1. Estimated Probability of Achieving Initial Headache Response within 4 Hours of Treatment in Pooled Trials 1, 2, and 3\n \n a\n" }

aThe figure shows the probability over time of obtaining headache response (no or mild pain) following treatment with oral sumatriptan. The averages displayed are based on pooled data from the 3 clinical controlled trials providing evidence of efficacy. Kaplan-Meier plot with patients not achieving response and/or taking rescue within 240 minutes censored to 240 minutes. For patients with migraine-associated nausea, photophobia, and/or phonophobia at baseline, there was a lower incidence of these symptoms at 2 hours (Trial 1) and at 4 hours (Trials 1, 2, and 3) following administration of sumatriptan tablets compared with placebo. As early as 2 hours in Trials 2 and 3, or as early as 4 hours in Trial 1, through 24 hours following the initial dose of study treatment, patients were allowed to use additional treatment for pain relief in the form of a second dose of study treatment or other medication. The estimated probability of patients taking a second dose or other medication for migraine over the 24 hours following the initial dose of study treatment is summarized in Figure 2. Figure 2. The Estimated Probability of Patients Taking a Second Dose of Sumatriptan Tablets or Other Medication to Treat Migraine over the 24 Hours following the Initial Dose of Study Treatment in Pooled Trials 1, 2, and 3 a

{ "type": "p", "children": [], "text": "\naThe figure shows the probability over time of obtaining headache response (no or mild pain) following treatment with oral sumatriptan. The averages displayed are based on pooled data from the 3 clinical controlled trials providing evidence of efficacy. Kaplan-Meier plot with patients not achieving response and/or taking rescue within 240 minutes censored to 240 minutes. \n \n For patients with migraine-associated nausea, photophobia, and/or phonophobia at baseline, there was a lower incidence of these symptoms at 2 hours (Trial 1) and at 4 hours (Trials 1, 2, and 3) following administration of sumatriptan tablets compared with placebo. \n \n As early as 2 hours in Trials 2 and 3, or as early as 4 hours in Trial 1, through 24 hours following the initial dose of study treatment, patients were allowed to use additional treatment for pain relief in the form of a second dose of study treatment or other medication. The estimated probability of patients taking a second dose or other medication for migraine over the 24 hours following the initial dose of study treatment is summarized in Figure 2. \n \n\n Figure 2. The Estimated Probability of Patients Taking a Second Dose of Sumatriptan Tablets or Other Medication to Treat Migraine over the 24 Hours following the Initial Dose of Study Treatment in Pooled Trials 1, 2, and 3\n \n a\n" }

aKaplan-Meier plot based on data obtained in the 3 clinical controlled trials providing evidence of efficacy with patients not using additional treatments censored to 24 hours. Plot also includes patients who had no response to the initial dose. No remedication was allowed within 2 hours postdose. There is evidence that doses above 50 mg do not provide a greater effect than 50 mg. There was no evidence to suggest that treatment with sumatriptan tablets was associated with an increase in the severity of recurrent headaches. The efficacy of sumatriptan tablets was unaffected by presence of aura; duration of headache prior to treatment; gender, age, or weight of the subject; relationship to menses; or concomitant use of common migraine prophylactic drugs (e.g., beta-blockers, calcium channel blockers, tricyclic antidepressants). There were insufficient data to assess the impact of race on efficacy.

{ "type": "p", "children": [], "text": "\naKaplan-Meier plot based on data obtained in the 3 clinical controlled trials providing evidence of efficacy with patients not using additional treatments censored to 24 hours. Plot also includes patients who had no response to the initial dose. No remedication was allowed within 2 hours postdose. \n \n There is evidence that doses above 50 mg do not provide a greater effect than 50 mg. There was no evidence to suggest that treatment with sumatriptan tablets was associated with an increase in the severity of recurrent headaches. The efficacy of sumatriptan tablets was unaffected by presence of aura; duration of headache prior to treatment; gender, age, or weight of the subject; relationship to menses; or concomitant use of common migraine prophylactic drugs (e.g., beta-blockers, calcium channel blockers, tricyclic antidepressants). There were insufficient data to assess the impact of race on efficacy.\n\n " }

Sumatriptan Tablets USP, 100 mg of sumatriptan (base) as the succinate.

{ "type": "p", "children": [], "text": "Sumatriptan Tablets USP, 100 mg of sumatriptan (base) as the succinate." }

Sumatriptan Tablets USP, 100 mg are white to off-white, capsule shaped, biconvex uncoated tablets, debossed with ‘C’ on one side and ‘34’ on other side.

{ "type": "p", "children": [], "text": "Sumatriptan Tablets USP, 100 mg are white to off-white, capsule shaped, biconvex uncoated tablets, debossed with ‘C’ on one side and ‘34’ on other side." }

NDC: 70518-1184-00

{ "type": "p", "children": [], "text": "NDC: 70518-1184-00" }

PACKAGING: 1 in 1 CARTON. 9 in 1 BLISTER PACK TYPE 0

{ "type": "p", "children": [], "text": "PACKAGING: 1 in 1 CARTON. 9 in 1 BLISTER PACK TYPE 0" }

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]." }

Repackaged and Distributed By:

{ "type": "p", "children": [], "text": "Repackaged and Distributed By:" }

Remedy Repack, Inc.

{ "type": "p", "children": [], "text": "Remedy Repack, Inc." }

625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

{ "type": "p", "children": [], "text": "625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762" }

Advise the patient to read the FDA-approved patient labeling ( Patient Information). Risk of Myocardial Ischemia and/or Infarction, Prinzmetal’s Angina, Other Vasospasm-Related Events, Arrhythmias, and Cerebrovascular Events Inform patients that sumatriptan tablets may cause serious cardiovascular side effects such as myocardial infarction or stroke. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, irregular heartbeat, significant rise in blood pressure, weakness, and slurring of speech, and should ask for medical advice if any indicative sign or symptoms are observed. Apprise patients of the importance of this follow-up [see Warnings and Precautions (5.1, 5.2, 5.4, 5.5, 5.8)] . Anaphylactic/Anaphylactoid Reactions Inform patients that anaphylactic/anaphylactoid reactions have occurred in patients receiving sumatriptan tablets. 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 [see Contraindications (4), Warnings and Precautions (5.9)] . Concomitant Use with Other Triptans or Ergot Medications Inform patients that use of sumatriptan tablets within 24 hours of another triptan or an ergot-type medication (including dihydroergotamine or methysergide) is contraindicated [see Contraindications (4), Drug Interactions (7.1, 7.3)] . Serotonin Syndrome Caution patients about the risk of serotonin syndrome with the use of sumatriptan tablets or other triptans, particularly during combined use with SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7), Drug Interactions (7.4)]. Medication Overuse Headache Inform patients that use of acute migraine drugs for 10 or more days per month may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6)] . Pregnancy Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant [see Use in Specific Populations (8.1)] . Lactation Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.2)] . Ability to Perform Complex Tasks Treatment with sumatriptan tablets may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks after administration of sumatriptan tablets.

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling ( \n Patient Information).\n \n\nRisk of Myocardial Ischemia and/or Infarction, Prinzmetal’s Angina, Other Vasospasm-Related Events, Arrhythmias, and Cerebrovascular Events \n\n\nInform patients that sumatriptan tablets may cause serious cardiovascular side effects such as myocardial infarction or stroke. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, irregular heartbeat, significant rise in blood pressure, weakness, and slurring of speech, and should ask for medical advice if any indicative sign or symptoms are observed. Apprise patients of the importance of this follow-up \n [see \n Warnings and Precautions (5.1, \n 5.2, \n 5.4, \n 5.5, \n 5.8)] \n .\n \n\nAnaphylactic/Anaphylactoid Reactions \n\n\nInform patients that anaphylactic/anaphylactoid reactions have occurred in patients receiving sumatriptan tablets. 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 \n [see \n Contraindications (4), \n Warnings and Precautions (5.9)] \n .\n \n\nConcomitant Use with Other Triptans or Ergot Medications \n\n\nInform patients that use of sumatriptan tablets within 24 hours of another triptan or an ergot-type medication (including dihydroergotamine or methysergide) is contraindicated \n [see \n Contraindications (4), \n Drug Interactions (7.1, \n 7.3)] \n .\n \n\nSerotonin Syndrome \n\n\nCaution patients about the risk of serotonin syndrome with the use of sumatriptan tablets or other triptans, particularly during combined use with SSRIs, SNRIs, TCAs, and MAO inhibitors \n [see \n Warnings and Precautions (5.7), \n Drug Interactions (7.4)]. \n \n\n\nMedication Overuse Headache \n\n\nInform patients that use of acute migraine drugs for 10 or more days per month may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) \n [see \n Warnings and Precautions (5.6)] \n .\n \n\nPregnancy \n\n\nAdvise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant \n [see \n Use in Specific Populations (8.1)] \n .\n \n\nLactation \n\n\nAdvise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed \n [see \n Use in Specific Populations (8.2)] \n .\n \n\nAbility to Perform Complex Tasks \n\n\nTreatment with sumatriptan tablets may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks after administration of sumatriptan tablets.\n \n" }

Repackaged By / Distributed By: RemedyRepack Inc.

{ "type": "p", "children": [], "text": "Repackaged By / Distributed By: RemedyRepack Inc." }

625 Kolter Drive, Indiana, PA 15701

{ "type": "p", "children": [], "text": "625 Kolter Drive, Indiana, PA 15701" }

(724) 465-8762

{ "type": "p", "children": [], "text": "(724) 465-8762" }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="636.804"> <colgroup> <col width="100%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" valign="top"><span class="Bold">Patient Information</span> <br/> <span class="Bold">Sumatriptan Tablets, USP</span> <br/> <span class="Bold">[Sumatriptan (soo ma TRIP tan)]</span> <br/> <span class="Bold"></span></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">What is the most important information I should know about sumatriptan tablets?</span> <br/> <span class="Bold"></span> <br/> <span class="Bold">Sumatriptan tablets can cause serious side effects, including: </span> <br/> <br/> <span class="Bold">Heart attack and other heart problems. Heart problems may lead to death. </span> <br/> <br/> <span class="Bold">Stop taking Sumatriptan tablets and get emergency medical help right away if you have any of the following symptoms of a heart attack:</span> <br/> <ul class="Disc"> <li>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</li> <li>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</li> <li>pain or discomfort in your arms, back, neck, jaw, or stomach</li> <li>shortness of breath with or without chest discomfort</li> <li>breaking out in a cold sweat</li> <li>nausea or vomiting</li> <li>feeling lightheaded</li> </ul> Sumatriptan tablets are not for people with risk factors for heart disease unless a heart exam is done and shows no problem. You have a higher risk for heart disease if you: <ul class="Disc"> <li>have high blood pressure</li> <li>have high cholesterol levels</li> <li>smoke</li> <li>are overweight</li> <li>have diabetes</li> <li>have a family history of heart disease</li> </ul> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">What are sumatriptan tablets?</span> <br/> <br/> Sumatriptan tablets are a prescription medicine used to treat acute migraine headaches with or without aura in adults. <br/> <br/> Sumatriptan tablets are not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines. <br/> <br/> Sumatriptan tablets are not used to prevent or decrease the number of migraine headaches you have. <br/> <br/> It is not known if sumatriptan tablets are safe and effective to treat cluster headaches. <br/> <br/> It is not known if sumatriptan tablets are safe and effective in children under 18 years of age. </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top"><span class="Bold">Do not take sumatriptan tablets if you have:</span> <br/> <ul class="Disc"> <li>heart problems or a history of heart problems</li> <li>narrowing of blood vessels to your legs, arms, stomach, or kidneys (peripheral vascular disease)</li> <li>uncontrolled high blood pressure</li> <li>severe liver problems</li> <li>hemiplegic migraines or basilar migraines. If you are not sure if you have these types of migraines, ask your healthcare provider.</li> <li>had a stroke, transient ischemic attacks (TIAs), or problems with your blood circulation</li> <li>taken any of the following medicines in the last 24 hours: <ul class="Disc"> <li>almotriptan (AXERT)</li> <li>eletriptan (RELPAX)</li> <li>frovatriptan (FROVA)</li> <li>naratriptan (AMERGE)</li> <li>rizatriptan (MAXALT, MAXALT-MLT)</li> <li>sumatriptan and naproxen (TREXIMET)</li> <li>ergotamines (CAFERGOT, ERGOMAR, MIGERGOT)</li> <li>dihydroergotamine (D.H.E. 45, MIGRANAL)</li> </ul> </li> </ul> Ask your healthcare provider if you are not sure if your medicine is listed above. <ul class="Disc"> <li>an allergy to sumatriptan or any of the ingredients in sumatriptan tablets. See the end of this leaflet for a complete list of ingredients in sumatriptan tablets.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">Before you take sumatriptan tablets, tell your healthcare provider about all of your medical conditions, including if you:</span> <ul class="Disc"> <li>have high blood pressure.</li> <li>have high cholesterol.</li> <li>have diabetes.</li> <li>smoke.</li> <li>are overweight.</li> <li>have heart problems or family history of heart problems or stroke.</li> <li>have kidney problems.</li> <li>have liver problems.</li> <li>have had epilepsy or seizures.</li> <li>are not using effective birth control.</li> <li>are pregnant or plan to become pregnant. It is not known if sumatriptan can harm your unborn baby.</li> <li>are breastfeeding or plan to breastfeed. Sumatriptan passes into your breast milk. It is not known if this can harm your baby. Talk with your healthcare provider about the best way to feed your baby if you take sumatriptan tablets.</li> </ul> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span>including prescription and over-the-counter medicines, vitamins, and herbal supplements. <br/> <br/> Sumatriptan tablets and certain other medicines can affect each other, causing serious side effects. <br/> <br/> <span class="Bold">Especially tell your healthcare provider if</span>you take antidepressant medicines called: <ul class="Disc"> <li>selective serotonin reuptake inhibitors (SSRIs)</li> <li>serotonin norepinephrine reuptake inhibitors (SNRIs)</li> <li>tricyclic antidepressants (TCAs)</li> <li>monoamine oxidase inhibitors (MAOIs)</li> </ul> Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure. <br/> <br/> Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine. </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top"><span class="Bold">How should I take</span><span class="Bold">sumatriptan tablets?</span> <ul class="Disc"> <li>Certain people should take their first dose of sumatriptan tablets in their healthcare provider’s office or in another medical setting. Ask your healthcare provider if you should take your first dose in a medical setting.</li> <li>Take sumatriptan tablets exactly as your healthcare provider tells you to take them.</li> <li>Your healthcare provider may change your dose. Do not change your dose without first talking to your healthcare provider.</li> <li>Take sumatriptan tablets whole with water or other liquids.</li> <li>If you do not get any relief after your first tablet, do not take a second tablet without first talking with your healthcare provider.</li> <li>If your headache comes back or you only get some relief from your headache, you can take a second tablet 2 hours after the first tablet.</li> <li>Do not take more than 200 mg of sumatriptan tablets in a 24-hour period.</li> <li>If you take too much sumatriptan, call your healthcare provider or go to the nearest hospital emergency room right away.</li> <li>You should write down when you have headaches and when you take sumatriptan tablets so you can talk with your healthcare provider about how sumatriptan tablets are working for you.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">What should I avoid while taking sumatriptan tablets?</span> <br/> <br/> Sumatriptan tablets can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery, or do anything where you need to be alert. </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">What are the possible side effects of sumatriptan tablets? </span> <br/> <br/> <span class="Bold">Sumatriptan tablets may cause serious side effects.</span>See “ <span class="Bold">What is the most important information I should know about sumatriptan tablets?</span>” <br/> <br/> These serious side effects include: <ul class="Disc"> <li>changes in color or sensation in your fingers and toes (Raynaud’s syndrome)</li> <li>stomach and intestinal problems (gastrointestinal and colonic ischemic events).</li> </ul> Symptoms of gastrointestinal and colonic ischemic events include: <br/> • sudden or severe stomach pain <br/> • stomach pain after meals <br/> • weight loss <br/> • nausea or vomiting <br/> • constipation or diarrhea <br/> • bloody diarrhea <br/> • fever <ul class="Disc"> <li>problems with blood circulation to your legs and feet (peripheral vascular ischemia). Symptoms of peripheral vascular ischemia include: <ul class="Disc"> <li>cramping and pain in your legs or hips</li> <li>feeling of heaviness or tightness in your leg muscles</li> <li>burning or aching pain in your feet or toes while resting</li> <li>numbness, tingling, or weakness in your legs</li> <li>cold feeling or color changes in 1 or both legs or feet</li> </ul> </li> <li>medication overuse headaches. Some people who use too many sumatriptan tablets may have worse headaches (medication overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with sumatriptan tablets.</li> <li>serotonin syndrome. Serotonin syndrome is a rare but serious problem that can happen in people using sumatriptan tablets, especially if sumatriptan tablets are used with anti-depressant medicines called SSRIs or SNRIs.</li> </ul> Call your healthcare provider right away if you have any of the following symptoms of serotonin syndrome: <br/> • mental changes such as seeing things that are not there (hallucinations), agitation, or coma <br/> • fast heartbeat <br/> • changes in blood pressure <br/> • high body temperature <br/> • tight muscles <br/> • trouble walking <ul class="Disc"> <li>hives (itchy bumps); swelling of your tongue, mouth, or throat.</li> <li>seizures. Seizures have happened in people taking sumatriptan tablets who have never had seizures before. Talk with your healthcare provider about your chance of having seizures while you take sumatriptan tablets.</li> </ul> The most common side effects of sumatriptan tablets include: <ul class="Disc"> <li>tingling or numbness in your fingers or toes</li> <li>warm or cold feeling</li> <li>feeling weak, drowsy, or tired</li> <li>pain, discomfort, or stiffness in your neck, throat, jaw, or chest</li> <li>dizziness</li> </ul> Tell your healthcare provider if you have any side effect that bothers you or that does not go away. <br/> <br/> These are not all the possible side effects of sumatriptan tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">How should I store</span><span class="Bold">sumatriptan tablets?</span> <br/> <br/> Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). <br/> <br/> <span class="Bold">Keep</span><span class="Bold">sumatriptan tablets and all medicines out of the reach of children.</span></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">General information about the safe and effective use of</span><span class="Bold">sumatriptan tablets.</span> <br/> <br/> Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use sumatriptan tablets for a condition for which it was not prescribed. Do not give sumatriptan tablets to other people, even if they have the same symptoms you have. They may harm them. <br/> <br/> This Patient Information leaflet summarizes the most important information about sumatriptan tablets. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about sumatriptan tablets that is written for healthcare professionals. <br/> <br/> For more information, call Aurobindo Pharma USA, Inc. at 1-866-850-2876. </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">What are the ingredients in sumatriptan tablets?</span> <br/> <br/> Active ingredient: sumatriptan succinate <br/> <br/> Inactive ingredients: croscarmellose sodium, dibasic calcium phosphate anhydrous, magnesium stearate, microcrystalline cellulose, polysorbate 80, and sodium bicarbonate. </td> </tr> <tr class="Last"> <td align="justify" class="Lrule Rrule" valign="top">All brands listed are the trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited. <br/> <p class="First">Repackaged and Distributed By:</p> <p>Remedy Repack, Inc.</p> <p>625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"636.804\">\n<colgroup>\n<col width=\"100%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">Patient Information</span>\n<br/>\n<span class=\"Bold\">Sumatriptan Tablets, USP</span>\n<br/>\n<span class=\"Bold\">[Sumatriptan (soo ma TRIP tan)]</span>\n<br/>\n<span class=\"Bold\"></span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">What is the most important information I should know about sumatriptan tablets?</span>\n<br/>\n<span class=\"Bold\"></span>\n<br/>\n<span class=\"Bold\">Sumatriptan tablets can cause serious side effects, including: </span>\n<br/>\n<br/>\n<span class=\"Bold\">Heart attack and other heart problems. Heart problems may lead to death. </span>\n<br/>\n<br/>\n<span class=\"Bold\">Stop taking Sumatriptan tablets and get emergency medical help right away if you have any of the following symptoms of a heart attack:</span>\n<br/>\n<ul class=\"Disc\">\n<li>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</li>\n<li>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</li>\n<li>pain or discomfort in your arms, back, neck, jaw, or stomach</li>\n<li>shortness of breath with or without chest discomfort</li>\n<li>breaking out in a cold sweat</li>\n<li>nausea or vomiting</li>\n<li>feeling lightheaded</li>\n</ul>\n\t\t\tSumatriptan tablets are not for people with risk factors for heart disease unless a heart exam is done and shows no problem. You have a higher risk for heart disease if you:\n\n\t\t\t\n <ul class=\"Disc\">\n<li>have high blood pressure</li>\n<li>have high cholesterol levels</li>\n<li>smoke</li>\n<li>are overweight</li>\n<li>have diabetes</li>\n<li>have a family history of heart disease</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">What are sumatriptan tablets?</span>\n<br/>\n<br/>\n\t\t\tSumatriptan tablets are a prescription medicine used to treat acute migraine headaches with or without aura in adults.\n <br/>\n<br/>\n\t\t\tSumatriptan tablets are not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines.\n <br/>\n<br/>\n\t\t\tSumatriptan tablets are not used to prevent or decrease the number of migraine headaches you have.\n <br/>\n<br/>\n\t\t\tIt is not known if sumatriptan tablets are safe and effective to treat cluster headaches.\n <br/>\n<br/>\n\t\t\tIt is not known if sumatriptan tablets are safe and effective in children under 18 years of age.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">Do not take sumatriptan tablets if you have:</span>\n<br/>\n<ul class=\"Disc\">\n<li>heart problems or a history of heart problems</li>\n<li>narrowing of blood vessels to your legs, arms, stomach, or kidneys (peripheral vascular disease)</li>\n<li>uncontrolled high blood pressure</li>\n<li>severe liver problems</li>\n<li>hemiplegic migraines or basilar migraines. If you are not sure if you have these types of migraines, ask your healthcare provider.</li>\n<li>had a stroke, transient ischemic attacks (TIAs), or problems with your blood circulation</li>\n<li>taken any of the following medicines in the last 24 hours:\n\t\t\t\t\n <ul class=\"Disc\">\n<li>almotriptan (AXERT)</li>\n<li>eletriptan (RELPAX)</li>\n<li>frovatriptan (FROVA)</li>\n<li>naratriptan (AMERGE)</li>\n<li>rizatriptan (MAXALT, MAXALT-MLT)</li>\n<li>sumatriptan and naproxen (TREXIMET)</li>\n<li>ergotamines (CAFERGOT, ERGOMAR, MIGERGOT)</li>\n<li>dihydroergotamine (D.H.E. 45, MIGRANAL)</li>\n</ul>\n</li>\n</ul>\n\t\t\t Ask your healthcare provider if you are not sure if your medicine is listed above.\n\n\t\t\t\n <ul class=\"Disc\">\n<li>an allergy to sumatriptan or any of the ingredients in sumatriptan tablets. See the end of this leaflet for a complete list of ingredients in sumatriptan tablets.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">Before you take sumatriptan tablets, tell your healthcare provider about all of your medical conditions, including if you:</span>\n<ul class=\"Disc\">\n<li>have high blood pressure.</li>\n<li>have high cholesterol.</li>\n<li>have diabetes.</li>\n<li>smoke.</li>\n<li>are overweight.</li>\n<li>have heart problems or family history of heart problems or stroke.</li>\n<li>have kidney problems.</li>\n<li>have liver problems.</li>\n<li>have had epilepsy or seizures.</li>\n<li>are not using effective birth control.</li>\n<li>are pregnant or plan to become pregnant. It is not known if sumatriptan can harm your unborn baby.</li>\n<li>are breastfeeding or plan to breastfeed. Sumatriptan passes into your breast milk. It is not known if this can harm your baby. Talk with your healthcare provider about the best way to feed your baby if you take sumatriptan tablets.</li>\n</ul>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span>including prescription and over-the-counter medicines, vitamins, and herbal supplements.\n <br/>\n<br/>\n\t\t\tSumatriptan tablets and certain other medicines can affect each other, causing serious side effects.\n <br/>\n<br/>\n<span class=\"Bold\">Especially tell your healthcare provider if</span>you take antidepressant medicines called:\n\n\t\t\t\n <ul class=\"Disc\">\n<li>selective serotonin reuptake inhibitors (SSRIs)</li>\n<li>serotonin norepinephrine reuptake inhibitors (SNRIs)</li>\n<li>tricyclic antidepressants (TCAs)</li>\n<li>monoamine oxidase inhibitors (MAOIs)</li>\n</ul>\n\t\t\tAsk your healthcare provider or pharmacist for a list of these medicines if you are not sure.\n <br/>\n<br/>\n\t\t\tKnow the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">How should I take</span><span class=\"Bold\">sumatriptan tablets?</span>\n<ul class=\"Disc\">\n<li>Certain people should take their first dose of sumatriptan tablets in their healthcare provider’s office or in another medical setting. Ask your healthcare provider if you should take your first dose in a medical setting.</li>\n<li>Take sumatriptan tablets exactly as your healthcare provider tells you to take them.</li>\n<li>Your healthcare provider may change your dose. Do not change your dose without first talking to your healthcare provider.</li>\n<li>Take sumatriptan tablets whole with water or other liquids.</li>\n<li>If you do not get any relief after your first tablet, do not take a second tablet without first talking with your healthcare provider.</li>\n<li>If your headache comes back or you only get some relief from your headache, you can take a second tablet 2 hours after the first tablet.</li>\n<li>Do not take more than 200 mg of sumatriptan tablets in a 24-hour period.</li>\n<li>If you take too much sumatriptan, call your healthcare provider or go to the nearest hospital emergency room right away.</li>\n<li>You should write down when you have headaches and when you take sumatriptan tablets so you can talk with your healthcare provider about how sumatriptan tablets are working for you.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">What should I avoid while taking sumatriptan tablets?</span>\n<br/>\n<br/>\n\t\t\tSumatriptan tablets can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery, or do anything where you need to be alert.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">What are the possible side effects of sumatriptan tablets? </span>\n<br/>\n<br/>\n<span class=\"Bold\">Sumatriptan tablets may cause serious side effects.</span>See “ \n <span class=\"Bold\">What is the most important information I should know about sumatriptan tablets?</span>”\n <br/>\n<br/>\n\t\t\tThese serious side effects include:\n\t\t\t\n <ul class=\"Disc\">\n<li>changes in color or sensation in your fingers and toes (Raynaud’s syndrome)</li>\n<li>stomach and intestinal problems (gastrointestinal and colonic ischemic events).</li>\n</ul>\n\t\t\tSymptoms of gastrointestinal and colonic ischemic events include:\n <br/>\n\t\t\t • sudden or severe stomach pain\n <br/>\n\t\t\t • stomach pain after meals\n <br/>\n\t\t\t • weight loss\n <br/>\n\t\t\t • nausea or vomiting\n <br/>\n\t\t\t • constipation or diarrhea\n <br/>\n\t\t\t • bloody diarrhea\n <br/>\n\t\t\t • fever\n\t\t\t\n <ul class=\"Disc\">\n<li>problems with blood circulation to your legs and feet (peripheral vascular ischemia). Symptoms of peripheral vascular ischemia include:\n\t\t\t\t\n <ul class=\"Disc\">\n<li>cramping and pain in your legs or hips</li>\n<li>feeling of heaviness or tightness in your leg muscles</li>\n<li>burning or aching pain in your feet or toes while resting</li>\n<li>numbness, tingling, or weakness in your legs</li>\n<li>cold feeling or color changes in 1 or both legs or feet</li>\n</ul>\n</li>\n<li>medication overuse headaches. Some people who use too many sumatriptan tablets may have worse headaches (medication overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with sumatriptan tablets.</li>\n<li>serotonin syndrome. Serotonin syndrome is a rare but serious problem that can happen in people using sumatriptan tablets, especially if sumatriptan tablets are used with anti-depressant medicines called SSRIs or SNRIs.</li>\n</ul>\n\t\t\tCall your healthcare provider right away if you have any of the following symptoms of serotonin syndrome:\n <br/>\n\t\t\t • mental changes such as seeing things that are not there (hallucinations), agitation, or coma\n <br/>\n\t\t\t • fast heartbeat\n <br/>\n\t\t\t • changes in blood pressure\n <br/>\n\t\t\t • high body temperature\n <br/>\n\t\t\t • tight muscles\n <br/>\n\t\t\t • trouble walking\n\t\t\t\n <ul class=\"Disc\">\n<li>hives (itchy bumps); swelling of your tongue, mouth, or throat.</li>\n<li>seizures. Seizures have happened in people taking sumatriptan tablets who have never had seizures before. Talk with your healthcare provider about your chance of having seizures while you take sumatriptan tablets.</li>\n</ul>\n\t\t\tThe most common side effects of sumatriptan tablets include:\n\n\t\t\t\n <ul class=\"Disc\">\n<li>tingling or numbness in your fingers or toes</li>\n<li>warm or cold feeling</li>\n<li>feeling weak, drowsy, or tired</li>\n<li>pain, discomfort, or stiffness in your neck, throat, jaw, or chest</li>\n<li>dizziness</li>\n</ul>\n\t\t\tTell your healthcare provider if you have any side effect that bothers you or that does not go away.\n <br/>\n<br/>\n\t\t\tThese are not all the possible side effects of sumatriptan tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">How should I store</span><span class=\"Bold\">sumatriptan tablets?</span>\n<br/>\n<br/>\n\t\t\tStore at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).\n <br/>\n<br/>\n<span class=\"Bold\">Keep</span><span class=\"Bold\">sumatriptan tablets and all medicines out of the reach of children.</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">General information about the safe and effective use of</span><span class=\"Bold\">sumatriptan tablets.</span>\n<br/>\n<br/>\n\t\t\tMedicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use sumatriptan tablets for a condition for which it was not prescribed. Do not give sumatriptan tablets to other people, even if they have the same symptoms you have. They may harm them.\n <br/>\n<br/>\n\t\t\tThis Patient Information leaflet summarizes the most important information about sumatriptan tablets. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about sumatriptan tablets that is written for healthcare professionals.\n <br/>\n<br/>\n\t\t\tFor more information, call Aurobindo Pharma USA, Inc. at 1-866-850-2876.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">What are the ingredients in sumatriptan tablets?</span>\n<br/>\n<br/>\n\t\t\tActive ingredient: sumatriptan succinate\n <br/>\n<br/>\n\t\t\tInactive ingredients: croscarmellose sodium, dibasic calcium phosphate anhydrous, magnesium stearate, microcrystalline cellulose, polysorbate 80, and sodium bicarbonate.\n </td>\n</tr>\n<tr class=\"Last\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\">All brands listed are the trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited.\n <br/>\n<p class=\"First\">Repackaged and Distributed By:</p>\n<p>Remedy Repack, Inc.</p>\n<p>625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 08/2021

{ "type": "p", "children": [], "text": "This Patient Information has been approved by the U.S. Food and Drug Administration.\n \n\nRevised: 08/2021\n " }

DRUG: Sumatriptan

{ "type": "p", "children": [], "text": "DRUG: Sumatriptan" }

GENERIC: Sumatriptan Succinate

{ "type": "p", "children": [], "text": "GENERIC: Sumatriptan Succinate" }

DOSAGE: TABLET

{ "type": "p", "children": [], "text": "DOSAGE: TABLET" }

ADMINSTRATION: ORAL

{ "type": "p", "children": [], "text": "ADMINSTRATION: ORAL" }

NDC: 70518-1184-0

{ "type": "p", "children": [], "text": "NDC: 70518-1184-0" }

COLOR: white

{ "type": "p", "children": [], "text": "COLOR: white" }

SHAPE: CAPSULE

{ "type": "p", "children": [], "text": "SHAPE: CAPSULE" }

SCORE: No score

{ "type": "p", "children": [], "text": "SCORE: No score" }

SIZE: 12 mm

{ "type": "p", "children": [], "text": "SIZE: 12 mm" }

IMPRINT: C;34

{ "type": "p", "children": [], "text": "IMPRINT: C;34" }

PACKAGING: 9 in 1 BLISTER PACK

{ "type": "p", "children": [], "text": "PACKAGING: 9 in 1 BLISTER PACK" }

OUTER PACKAGING: 1 in 1 CARTON

{ "type": "p", "children": [], "text": "OUTER PACKAGING: 1 in 1 CARTON" }

ACTIVE INGREDIENT(S):

{ "type": "p", "children": [], "text": "ACTIVE INGREDIENT(S):" }

{ "type": "ul", "children": [ "SUMATRIPTAN SUCCINATE 100mg in 1" ], "text": "" }

INACTIVE INGREDIENT(S):

{ "type": "p", "children": [], "text": "INACTIVE INGREDIENT(S):" }

{ "type": "ul", "children": [ "CROSCARMELLOSE SODIUM", "CALCIUM PHOSPHATE, DIBASIC, ANHYDROUS", "MAGNESIUM STEARATE", "MICROCRYSTALLINE CELLULOSE", "POLYSORBATE 80", "SODIUM BICARBONATE" ], "text": "" }

Sumatriptan injection is indicated in adults for (1) the acute treatment of migraine, with or without aura, and (2) the acute treatment of cluster headache. Limitations of Use:

{ "type": "p", "children": [], "text": "Sumatriptan injection is indicated in adults for (1) the acute treatment of migraine, with or without aura, and (2) the acute treatment of cluster headache.\n\n Limitations of Use:\n\n\n" }

{ "type": "ul", "children": [ "Use only if a clear diagnosis of migraine or cluster headache has been established. If a patient has no response to the first migraine or cluster headache attack treated with sumatriptan injection, reconsider the diagnosis before sumatriptan injection is administered to treat any subsequent attacks.", "Sumatriptan injection is not indicated for the prevention of migraine or cluster headache attacks." ], "text": "" }

The maximum single recommended adult dose of sumatriptan injection for the acute treatment of migraine or cluster headache is 6 mg injected subcutaneously. For the treatment of migraine, if side effects are dose limiting, the lower doses (1 mg to 5 mg) may be used [see Clinical Studies (14.1)]. For the treatment of cluster headache, the efficacy of lower doses has not been established.

The maximum cumulative dose that may be given in 24 hours is 12 mg, two 6 mg injections separated by at least 1 hour. A second 6 mg dose should only be considered if some response to a first injection was observed.

In patients receiving doses other than 4 mg or 6 mg, use the 6 mg single-dose vial. Visually inspect the vial for particulate matter and discoloration before administration. Do not use if particulates and discolorations are noted.

{ "type": "ul", "children": [ "Injection: 6 mg single-dose vial. Each 0.5 mL injection contains 8.4 mg of sumatriptan succinate equivalent to 6 mg of sumatriptan." ], "text": "" }

Sumatriptan injection is contraindicated in patients with:

{ "type": "p", "children": [], "text": "Sumatriptan injection is contraindicated in patients with:\n\n" }

{ "type": "ul", "children": [ "Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetal’s angina [see Warnings and Precautions (5.1)]. ", "Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.2)]. ", "History of stroke or transient ischemic attack (TIA) or history of hemiplegic or basilar migraine because these patients are at a higher risk of stroke [see Warnings and Precautions (5.4)]. ", "Peripheral vascular disease [see Warnings and Precautions (5.5)]. ", "Ischemic bowel disease [see Warnings and Precautions (5.5)]. ", "Uncontrolled hypertension [see Warnings and Precautions (5.8)]. ", "Recent use (i.e., within 24 hours) of ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide), or another 5-hydroxytryptamine1 (5-HT1) agonist [see Drug Interactions (7.1, 7.3)]. ", "Concurrent administration of a monoamine oxidase (MAO)-A inhibitor or recent (within 2 weeks) use of an MAO-A inhibitor [see Drug Interactions (7.2), Clinical Pharmacology (12.3)].", "Hypersensitivity to sumatriptan (angioedema and anaphylaxis seen) [see Warnings and Precautions (5.9)]. ", "Severe hepatic impairment [see Clinical Pharmacology (12.3)]." ], "text": "" }

The use of sumatriptan injection 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 injection. Some of these reactions occurred in patients without known CAD. Sumatriptan injection may cause coronary artery vasospasm (Prinzmetal’s angina), even in patients without a history of CAD. Perform a cardiovascular evaluation in triptan-naive patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving sumatriptan injection. If there is evidence of CAD or coronary artery vasospasm, sumatriptan injection is contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of sumatriptan injection in a medically supervised setting and performing an electrocardiogram (ECG) immediately following administration of sumatriptan injection. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of sumatriptan injection.

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 sumatriptan injection if these disturbances occur. Sumatriptan injection is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

Sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw commonly occur after treatment with sumatriptan injection and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of sumatriptan injection is contraindicated in patients with CAD and those with Prinzmetal’s variant angina.

Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). Discontinue sumatriptan injection if a cerebrovascular event occurs. Before treating headaches in patients not previously diagnosed with migraine or cluster headache or in patients who present with atypical symptoms, exclude other potentially serious neurological conditions. Sumatriptan injection is contraindicated in patients with a history of stroke or TIA.

Sumatriptan injection 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 non-coronary vasospasm reaction following the use of any 5-HT1 agonist, rule out a vasospastic reaction before receiving additional injections of sumatriptan. Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1 agonists has not been clearly established.

Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or combination 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.

Serotonin syndrome may occur with sumatriptan injection, particularly during coadministration 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 aberrations (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 sumatriptan injection if serotonin syndrome is suspected.

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-HT1 agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with sumatriptan. Sumatriptan injection is contraindicated in patients with uncontrolled hypertension.

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. Sumatriptan injection is contraindicated in patients with a history of hypersensitivity reaction to sumatriptan.

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. Sumatriptan injection should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Migraine Headache

Table 1 lists adverse reactions that occurred in 2 U.S. placebo-controlled clinical trials in patients with migraines (Studies 2 and 3) following either a single 6 mg dose of sumatriptan injection or placebo. Only reactions that occurred at a frequency of 2% or more in groups treated with sumatriptan injection 6 mg and that occurred at a frequency greater than the placebo group are included in Table 1.

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <caption> <span>Table 1. Adverse Reactions in Pooled Placebo-Controlled Trials in Patients with Migraine (Studies 2 and 3) </span> </caption> <colgroup> <col width="39.08%"/> <col width="27.6%"/> <col width="33.32%"/> </colgroup> <tfoot> <tr class="First Last"> <td colspan="3"><span class="Sup">a</span> Includes injection site pain, stinging/burning, swelling, erythema, bruising, bleeding.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" valign="middle"><span class="Bold">Adverse Reaction</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Sumatriptan Injection</span> <br/> <span class="Bold">6 mg Subcutaneous</span> <br/> <span class="Bold">(n = 547)</span> <br/> <span class="Bold">%</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Placebo</span> <br/> <span class="Bold">(n = 370)</span> <br/> <span class="Bold">%</span> <br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Atypical sensations<br/> </td><td align="center" class="Rrule" valign="middle">42<br/> </td><td align="center" class="Rrule" valign="middle">9<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Tingling<br/> </td><td align="center" class="Rrule" valign="middle">14<br/> </td><td align="center" class="Rrule" valign="middle">3<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Warm/hot sensation<br/> </td><td align="center" class="Rrule" valign="middle">11<br/> </td><td align="center" class="Rrule" valign="middle">4<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Burning sensation<br/> </td><td align="center" class="Rrule" valign="middle">7<br/> </td><td align="center" class="Rrule" valign="middle">&lt;1<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Feeling of heaviness<br/> </td><td align="center" class="Rrule" valign="middle">7<br/> </td><td align="center" class="Rrule" valign="middle">1<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Pressure sensation<br/> </td><td align="center" class="Rrule" valign="middle">7<br/> </td><td align="center" class="Rrule" valign="middle">2<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Feeling of tightness<br/> </td><td align="center" class="Rrule" valign="middle">5<br/> </td><td align="center" class="Rrule" valign="middle">&lt;1<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Numbness<br/> </td><td align="center" class="Rrule" valign="middle">5<br/> </td><td align="center" class="Rrule" valign="middle">2<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Feeling strange<br/> </td><td align="center" class="Rrule" valign="middle">2<br/> </td><td align="center" class="Rrule" valign="middle">&lt;1<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Tight feeling in head<br/> </td><td align="center" class="Rrule" valign="middle">2<br/> </td><td align="center" class="Rrule" valign="middle">&lt;1<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Cardiovascular<br/> </td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Flushing<br/> </td><td align="center" class="Rrule" valign="middle">7<br/> </td><td align="center" class="Rrule" valign="middle">2<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Chest discomfort<br/> </td><td align="center" class="Rrule" valign="middle">5<br/> </td><td align="center" class="Rrule" valign="middle">1<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Tightness in chest<br/> </td><td align="center" class="Rrule" valign="middle">3<br/> </td><td align="center" class="Rrule" valign="middle">&lt;1<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Pressure in chest<br/> </td><td align="center" class="Rrule" valign="middle">2<br/> </td><td align="center" class="Rrule" valign="middle">&lt;1<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Ear, nose, and throat<br/> </td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Throat discomfort<br/> </td><td align="center" class="Rrule" valign="middle">3<br/> </td><td align="center" class="Rrule" valign="middle">&lt;1<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Discomfort: nasal cavity/sinuses<br/> </td><td align="center" class="Rrule" valign="middle">2<br/> </td><td align="center" class="Rrule" valign="middle">&lt;1<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Injection site reaction<span class="Sup">a</span> <br/> </td><td align="center" class="Rrule" valign="middle">59<br/> </td><td align="center" class="Rrule" valign="middle">24<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Miscellaneous<br/> </td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Jaw discomfort<br/> </td><td align="center" class="Rrule" valign="middle">2<br/> </td><td align="center" class="Rrule" valign="middle">0<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Musculoskeletal <br/> </td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Weakness <br/> </td><td align="center" class="Rrule" valign="middle">5<br/> </td><td align="center" class="Rrule" valign="middle">&lt;1<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Neck pain/stiffness<br/> </td><td align="center" class="Rrule" valign="middle">5<br/> </td><td align="center" class="Rrule" valign="middle">&lt;1<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Myalgia<br/> </td><td align="center" class="Rrule" valign="middle">2<br/> </td><td align="center" class="Rrule" valign="middle">&lt;1<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Neurological <br/> </td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Dizziness/vertigo<br/> </td><td align="center" class="Rrule" valign="middle">12<br/> </td><td align="center" class="Rrule" valign="middle">4<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Drowsiness/sedation <br/> </td><td align="center" class="Rrule" valign="middle">3<br/> </td><td align="center" class="Rrule" valign="middle">2<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">    Headache<br/> </td><td align="center" class="Rrule" valign="middle">2<br/> </td><td align="center" class="Rrule" valign="middle">&lt;1<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="middle">Skin <br/> </td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td> </tr> <tr class="Last"> <td align="justify" class="Lrule Rrule" valign="middle">    Sweating<br/> </td><td align="center" class="Rrule" valign="middle">2<br/> </td><td align="center" class="Rrule" valign="middle">1<br/> </td> </tr> </tbody> </table></div>

The incidence of adverse reactions in controlled clinical trials was not affected by gender or age of the patients. There were insufficient data to assess the impact of race on the incidence of adverse reactions.

Cluster Headache

In the controlled clinical trials assessing the efficacy of sumatriptan injection as a treatment for cluster headache (Studies 4 and 5), no new significant adverse reactions were detected that had not already been identified in trials of sumatriptan in patients with migraine.

Overall, the frequency of adverse reactions reported in the trials of cluster headache was generally lower than in the migraine trials. Exceptions include reports of paresthesia (5% sumatriptan injection, 0% placebo), nausea and vomiting (4% sumatriptan injection, 0% placebo), and bronchospasm (1% sumatriptan injection, 0% placebo).

The following adverse reactions have been identified during postapproval use of sumatriptan tablets, sumatriptan nasal spray, and sumatriptan injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular Hypotension, palpitations. Neurological Dystonia, tremor.

Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and sumatriptan injection within 24 hours of each other is contraindicated.

MAO-A inhibitors increase systemic exposure by 2-fold. Therefore, the use of sumatriptan injection in patients receiving MAO-A inhibitors is contraindicated [see Clinical Pharmacology (12.3)].

Because their vasospastic effects may be additive, coadministration of sumatriptan injection and other 5-HT1 agonists (e.g., triptans) within 24 hours of each other is contraindicated.

Cases of serotonin syndrome have been reported during coadministration of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7)].

Risk Summary Data from a prospective pregnancy exposure registry and epidemiological studies of pregnant women have not detected an increased frequency of birth defects or a consistent pattern of birth defects among women exposed to sumatriptan compared with the general population (see Data). In developmental toxicity studies in rats and rabbits, oral administration of sumatriptan to pregnant animals was associated with embryolethality, fetal abnormalities, and pup mortality. When administered by the intravenous route to pregnant rabbits, sumatriptan was embryolethal (see Data). In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of major birth defects among deliveries to women with migraine ranged from 2.2% to 2.9% and the reported rate of miscarriage was 17%, which were similar to rates reported in women without migraine. Clinical Considerations 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. Data Human Data The Sumatriptan/Naratriptan/TREXIMET (sumatriptan and naproxen sodium) Pregnancy Registry, a population-based international prospective study, collected data for sumatriptan from January 1996 to September 2012. The Registry documented outcomes of 626 infants and fetuses exposed to sumatriptan during pregnancy (528 with earliest exposure during the first trimester, 78 during the second trimester, 16 during the third trimester, and 4 unknown). The occurrence of major birth defects (excluding fetal deaths and induced abortions without reported defects and all spontaneous pregnancy losses) during first-trimester exposure to sumatriptan was 4.2% (20/478 [95% CI: 2.6% to 6.5%]) and during any trimester of exposure was 4.2% (24/576 [95% CI: 2.7% to 6.2%]). The sample size in this study had 80% power to detect at least a 1.73- to 1.91-fold increase in the rate of major malformations. The number of exposed pregnancy outcomes accumulated during the registry was insufficient to support definitive conclusions about overall malformation risk or for making comparisons of the frequencies of specific birth defects. Of the 20 infants with reported birth defects after exposure to sumatriptan in the first trimester, 4 infants had ventricular septal defects, including one infant who was exposed to both sumatriptan and naratriptan, and 3 infants had pyloric stenosis. No other birth defect was reported for more than 2 infants in this group. In a study using data from the Swedish Medical Birth Register, live births to women who reported using triptans or ergots during pregnancy were compared with those of women who did not. Of the 2,257 births with first-trimester exposure to sumatriptan, 107 infants were born with malformations (relative risk 0.99 [95% CI: 0.91 to 1.21]). A study using linked data from the Medical Birth Registry of Norway to the Norwegian Prescription Database compared pregnancy outcomes in women who redeemed prescriptions for triptans during pregnancy, as well as a migraine disease comparison group who redeemed prescriptions for sumatriptan before pregnancy only, compared with a population control group. Of the 415 women who redeemed prescriptions for sumatriptan during the first trimester, 15 had infants with major congenital malformations (OR 1.16 [95% CI: 0.69 to 1.94]) while for the 364 women who redeemed prescriptions for sumatriptan before, but not during, pregnancy, 20 had infants with major congenital malformations (OR 1.83 [95% CI: 1.17 to 2.88]), each compared with the population comparison group. Additional smaller observational studies evaluating use of sumatriptan during pregnancy have not suggested an increased risk of teratogenicity. Animal Data Oral administration of sumatriptan to pregnant rats during the period of organogenesis resulted in an increased incidence of fetal blood vessel (cervicothoracic and umbilical) abnormalities. The highest no-effect dose for embryofetal developmental toxicity in rats was 60 mg/kg/day. Oral administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in increased incidences of embryolethality and fetal cervicothoracic vascular and skeletal abnormalities. Intravenous administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in an increased incidence of embryolethality. The highest oral and intravenous no-effect doses for developmental toxicity in rabbits were 15 and 0.75 mg/kg/day, respectively. Oral administration of sumatriptan to rats prior to and throughout gestation resulted in embryofetal toxicity (decreased body weight, decreased ossification, increased incidence of skeletal abnormalities). The highest no-effect dose was 50 mg/kg/day. In offspring of pregnant rats treated orally with sumatriptan during organogenesis, there was a decrease in pup survival. The highest no-effect dose for this effect was 60 mg/kg/day. Oral treatment of pregnant rats with sumatriptan during the latter part of gestation and throughout lactation resulted in a decrease in pup survival. The highest no-effect dose for this finding was 100 mg/kg/day.

Risk Summary Sumatriptan is excreted in human milk following subcutaneous administration (see Data). There are no data on the effects of sumatriptan on the breastfed infant or the effects of sumatriptan on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for sumatriptan injection and any potential adverse effects on the breastfed infant from sumatriptan or from the underlying maternal condition. Clinical Considerations Infant exposure to sumatriptan can be minimized by avoiding breastfeeding for 12 hours after treatment with sumatriptan injection. Data Following subcutaneous administration of a 6 mg dose of sumatriptan injection in 5 lactating volunteers, sumatriptan was present in milk.

Safety and effectiveness in pediatric patients have not been established. Sumatriptan injection is not recommended for use in patients younger than 18 years of age. Two controlled clinical trials evaluated sumatriptan nasal spray (5 to 20 mg) in 1,248 pediatric migraineurs aged 12 to 17 years who treated a single attack. The trials did not establish the efficacy of sumatriptan nasal spray compared with placebo in the treatment of migraine in pediatric patients. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults. Five controlled clinical trials (2 single-attack trials, 3 multiple-attack trials) evaluating oral sumatriptan (25 to 100 mg) in pediatric patients aged 12 to 17 years enrolled a total of 701 pediatric migraineurs. These trials did not establish the efficacy of oral sumatriptan compared with placebo in the treatment of migraine in pediatric patients. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults. The frequency of all adverse reactions in these patients appeared to be both dose- and age-dependent, with younger patients reporting reactions more commonly than older pediatric patients. Postmarketing experience documents that serious adverse reactions have occurred in the pediatric population after use of subcutaneous, oral, and/or intranasal sumatriptan. These reports include reactions similar in nature to those reported rarely in adults, including stroke, visual loss, and death. A myocardial infarction has been reported in a 14-year-old male following the use of oral sumatriptan; clinical signs occurred within 1 day of drug administration. Clinical data to determine the frequency of serious adverse reactions in pediatric patients who might receive subcutaneous, oral, or intranasal sumatriptan are not presently available.

Clinical trials of sumatriptan injection did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving sumatriptan injection [see Warnings and Precautions (5.1)].

Coronary vasospasm was observed after intravenous administration of sumatriptan injection [see Contraindications (4)]. Overdoses would be expected from animal data (dogs at 0.1 g/kg, rats at 2 g/kg) to possibly cause convulsions, tremor, inactivity, erythema of the extremities, reduced respiratory rate, cyanosis, ataxia, mydriasis, injection site reactions (desquamation, hair loss, and scab formation), and paralysis. The elimination half-life of sumatriptan is about 2 hours [see Clinical Pharmacology (12.3)]; therefore, monitoring of patients after overdose with sumatriptan injection should continue for at least 10 hours or while symptoms or signs persist. It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan.

{ "type": "p", "children": [], "text": "Coronary vasospasm was observed after intravenous administration of sumatriptan injection [see Contraindications (4)]. Overdoses would be expected from animal data (dogs at 0.1 g/kg, rats at 2 g/kg) to possibly cause convulsions, tremor, inactivity, erythema of the extremities, reduced respiratory rate, cyanosis, ataxia, mydriasis, injection site reactions (desquamation, hair loss, and scab formation), and paralysis.\n The elimination half-life of sumatriptan is about 2 hours [see Clinical Pharmacology (12.3)]; therefore, monitoring of patients after overdose with sumatriptan injection should continue for at least 10 hours or while symptoms or signs persist.\n It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan." }

Sumatriptan Injection USP contains sumatriptan succinate, a selective 5-HT1B/1D receptor agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1), and it has the following structure:

{ "type": "p", "children": [], "text": " Sumatriptan Injection USP contains sumatriptan succinate, a selective 5-HT1B/1D receptor agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1), and it has the following structure:" }

The molecular formula is C14H21N3O2S•C4H6O4, representing a molecular weight of 413.5. Sumatriptan succinate USP is a white or almost white powder that is readily soluble in water and in saline. Sumatriptan injection USP is a clear, colorless to pale yellow, sterile, nonpyrogenic solution for subcutaneous injection. Each 0.5 mL of sumatriptan injection USP 12 mg/mL solution contains 8.4 mg of sumatriptan succinate equivalent to 6 mg of sumatriptan and 3.5 mg of sodium chloride, USP in Water for Injection, USP. The pH range of the solution is approximately 4.2 to 5.3. The osmolality of the injection is 291 mOsmol.

{ "type": "p", "children": [], "text": "The molecular formula is C14H21N3O2S•C4H6O4, representing a molecular weight of 413.5. Sumatriptan succinate USP is a white or almost white powder that is readily soluble in water and in saline.\n Sumatriptan injection USP is a clear, colorless to pale yellow, sterile, nonpyrogenic solution for subcutaneous injection. Each 0.5 mL of sumatriptan injection USP 12 mg/mL solution contains 8.4 mg of sumatriptan succinate equivalent to 6 mg of sumatriptan and 3.5 mg of sodium chloride, USP in Water for Injection, USP. The pH range of the solution is approximately 4.2 to 5.3. The osmolality of the injection is 291 mOsmol." }

Sumatriptan binds with high affinity to human cloned 5-HT1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine and cluster headaches through agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

Blood Pressure Significant elevation in blood pressure, including hypertensive crisis, has been reported in patients with and without a history of hypertension [see Warnings and Precautions (5.8)]. Peripheral (Small) Arteries In healthy volunteers (N = 18), a trial evaluating the effects of sumatriptan on peripheral (small vessel) arterial reactivity failed to detect a clinically significant increase in peripheral resistance. Heart Rate Transient increases in blood pressure observed in some patients in clinical trials carried out during sumatriptan’s development as a treatment for migraine were not accompanied by any clinically significant changes in heart rate.

Absorption The bioavailability of sumatriptan via subcutaneous site injection to 18 healthy male subjects was 97% ± 16% of that obtained following intravenous injection.

After a single 6 mg subcutaneous manual injection into the deltoid area of the arm in 18 healthy males (age: 24 ± 6 years, weight: 70 kg), the maximum serum concentration (Cmax) of sumatriptan was (mean ± standard deviation) 74 ± 15 ng/mL and the time to peak concentration (Tmax) was 12 minutes after injection (range: 5 to 20 minutes). In this trial, the same dose injected subcutaneously in the thigh gave a Cmax of 61 ± 15 ng/mL by manual injection versus 52 ± 15 ng/mL by autoinjector techniques. The Tmax or amount absorbed was not significantly altered by either the site or technique of injection.

Distribution 

Protein binding, determined by equilibrium dialysis over the concentration range of 10 to 1,000 ng/mL is low, approximately 14% to 21%. The effect of sumatriptan on the protein binding of other drugs has not been evaluated.

Following a 6 mg subcutaneous injection into the deltoid area of the arm in 9 males (mean age: 33 years, mean weight: 77 kg) the volume of distribution central compartment of sumatriptan was 50 ± 8 liters and the distribution half-life was 15 ± 2 minutes.

Metabolism 

In vitro studies with human microsomes suggest that sumatriptan is metabolized by MAO, predominantly the A isoenzyme. Most of a radiolabeled dose of sumatriptan excreted in the urine is the major metabolite indole acetic acid (IAA) or the IAA glucuronide, both of which are inactive.

Elimination 

After a single 6 mg subcutaneous dose, 22% ± 4% was excreted in the urine as unchanged sumatriptan and 38% ± 7% as the IAA metabolite.

Following a 6 mg subcutaneous injection into the deltoid area of the arm, the systemic clearance of sumatriptan was 1,194 ± 149 mL/min and the terminal half-life was 115 ± 19 minutes.

Specific Populations Age: The pharmacokinetics of sumatriptan in the elderly (mean age: 72 years, 2 males and 4 females) and in subjects with migraine (mean age: 38 years, 25 males and 155 females) were similar to that in healthy male subjects (mean age: 30 years). Patients with Hepatic Impairment: The effect of mild to moderate hepatic disease on the pharmacokinetics of subcutaneously administered sumatriptan has been evaluated. There were no significant differences in the pharmacokinetics of subcutaneously administered sumatriptan in moderately hepatically impaired subjects compared with healthy controls. The pharmacokinetics of subcutaneously administered sumatriptan in patients with severe hepatic impairment has not been studied. The use of sumatriptan injection in this population is contraindicated [see Contraindications (4)]. Racial Groups: The systemic clearance and Cmax of subcutaneous sumatriptan were similar in black (n = 34) and Caucasian (n = 38) healthy male subjects. Drug Interaction Studies Monoamine Oxidase-A Inhibitors: In a trial of 14 healthy females, pretreatment with an MAO-A inhibitor decreased the clearance of subcutaneous sumatriptan, resulting in a 2-fold increase in the area under the sumatriptan plasma concentration-time curve (AUC), corresponding to a 40% increase in elimination half-life.

Carcinogenesis 

In carcinogenicity studies in mouse and rat, sumatriptan was administered orally for 78 weeks and 104 weeks, respectively, at doses up to 160 mg/kg/day (the high dose in rat was reduced from 360 mg/kg/day during Week 21). The highest dose to mice and rats was approximately 130 and 260 times the single MRHD of 6 mg administered subcutaneously on a mg/m2 basis. There was no evidence in either species of an increase in tumors related to sumatriptan administration.

Mutagenesis 

Sumatriptan was negative in in vitro (bacterial reverse mutation [Ames], gene cell mutation in Chinese hamster V79/HGPRT, chromosomal aberration in human lymphocytes) and in vivo (rat micronucleus) assays.

Impairment of Fertility When sumatriptan (5, 50, 500 mg/kg/day) was administered orally to male and female rats prior to and throughout the mating period, there was a treatment-related decrease in fertility secondary to a decrease in mating in animals treated with doses greater than 5 mg/kg/day. It is not clear whether this finding was due to an effect on males or females or both. When sumatriptan was administered by subcutaneous injection to male and female rats prior to and throughout the mating period, there was no evidence of impaired fertility at doses up to 60 mg/kg/day.

Corneal Opacities Dogs receiving oral sumatriptan developed corneal opacities and defects in the corneal epithelium. Corneal opacities were seen at the lowest dose tested, 2 mg/kg/day, and were present after 1 month of treatment. Defects in the corneal epithelium were noted in a 60-week study. Earlier examinations for these toxicities were not conducted and no-effect doses were not established; however, the relative plasma exposure at the lowest dose tested was approximately 3 times the human exposure after a 6 mg subcutaneous dose.

In controlled clinical trials enrolling more than 1,000 patients during migraine attacks who were experiencing moderate or severe pain and 1 or more of the symptoms enumerated in Table 3, onset of relief began as early as 10 minutes following a 6 mg sumatriptan injection.  Lower doses of sumatriptan injection may also prove effective, although the proportion of patients obtaining adequate relief was decreased and the latency to that relief is greater with lower doses. In Study 1, 6 different doses of sumatriptan injection (n = 30 each group) were compared with placebo (n = 62) in a single-attack, parallel-group design; the dose-response relationship was found to be as shown in Table 2.

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <caption> <span>Table 2. Proportion of Patients with Migraine Relief and Incidence of Adverse Reactions by Time and by Dose of Sumatriptan Injection in Study 1  </span> </caption> <colgroup> <col width="16.64%"/> <col width="17.8%"/> <col width="18.72%"/> <col width="14.78%"/> <col width="13.48%"/> <col width="18.56%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" rowspan="2" valign="middle"><span class="Bold">Dose of</span> <br/> <span class="Bold">Sumatriptan Injection</span> <br/> </td><td align="center" class="Rrule" colspan="4" valign="middle"><span class="Bold">Percent Patients with Relief<span class="Sup">a</span></span> <br/> </td><td align="center" class="Rrule" rowspan="2" valign="middle"><span class="Bold">Adverse Reactions Incidence (%)</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle"><span class="Bold">at 10 Minutes</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">at 30 Minutes</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">at 1 Hour</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">at 2 Hours</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top">Placebo<br/> </td><td align="center" class="Rrule" valign="top">5<br/> </td><td align="center" class="Rrule" valign="top">15<br/> </td><td align="center" class="Rrule" valign="top">24<br/> </td><td align="center" class="Rrule" valign="top">21<br/> </td><td align="center" class="Rrule" valign="top">55<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top">1 mg<br/> </td><td align="center" class="Rrule" valign="top">10<br/> </td><td align="center" class="Rrule" valign="top">40<br/> </td><td align="center" class="Rrule" valign="top">43<br/> </td><td align="center" class="Rrule" valign="top">40<br/> </td><td align="center" class="Rrule" valign="top">63<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top">2 mg<br/> </td><td align="center" class="Rrule" valign="top">7<br/> </td><td align="center" class="Rrule" valign="top">23<br/> </td><td align="center" class="Rrule" valign="top">57<br/> </td><td align="center" class="Rrule" valign="top">43<br/> </td><td align="center" class="Rrule" valign="top">63<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top">3 mg<br/> </td><td align="center" class="Rrule" valign="top">17<br/> </td><td align="center" class="Rrule" valign="top">47<br/> </td><td align="center" class="Rrule" valign="top">57<br/> </td><td align="center" class="Rrule" valign="top">60<br/> </td><td align="center" class="Rrule" valign="top">77<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top">4 mg<br/> </td><td align="center" class="Rrule" valign="top">13<br/> </td><td align="center" class="Rrule" valign="top">37<br/> </td><td align="center" class="Rrule" valign="top">50<br/> </td><td align="center" class="Rrule" valign="top">57<br/> </td><td align="center" class="Rrule" valign="top">80<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top">6 mg<br/> </td><td align="center" class="Rrule" valign="top">10<br/> </td><td align="center" class="Rrule" valign="top">63<br/> </td><td align="center" class="Rrule" valign="top">73<br/> </td><td align="center" class="Rrule" valign="top">70<br/> </td><td align="center" class="Rrule" valign="top">83<br/> </td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule" valign="top">8 mg<br/> </td><td align="center" class="Rrule" valign="top">23<br/> </td><td align="center" class="Rrule" valign="top">57<br/> </td><td align="center" class="Rrule" valign="top">80<br/> </td><td align="center" class="Rrule" valign="top">83<br/> </td><td align="center" class="Rrule" valign="top">93<br/> </td> </tr> </tbody> </table></div>

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

In 2 randomized, placebo-controlled clinical trials of sumatriptan injection 6 mg in 1,104 patients with moderate or severe migraine pain (Studies 2 and 3), the onset of relief was less than 10 minutes. Headache relief, as defined by a reduction in pain from severe or moderately severe to mild or no headache, was achieved in 70% of the patients within 1 hour of a single 6 mg subcutaneous dose of sumatriptan injection. Approximately 82% and 65% of patients treated with sumatriptan injection 6 mg had headache relief and were pain free within 2 hours, respectively.   

Table 3 shows the 1- and 2-hour efficacy results for sumatriptan injection 6 mg in Studies 2 and 3. 

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <caption> <span>Table 3. Proportion of Patients with Pain Relief and Relief of Migraine Symptoms after 1 and 2 Hours of Treatment in Studies 2 and 3        </span> </caption> <colgroup> <col width="33.54%"/> <col width="11.98%"/> <col width="22.38%"/> <col width="11.58%"/> <col width="20.54%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" rowspan="2" valign="bottom"><span class="Bold"> <br/> <br/> 1-Hour Data</span> <br/> </td><td align="center" class="Rrule" colspan="2" valign="middle"><span class="Bold">Study 2</span> <br/> </td><td align="center" class="Rrule" colspan="2" valign="middle"><span class="Bold">Study 3</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle"><span class="Bold">Placebo</span> <br/> <span class="Bold">(n = 190)</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Sumatriptan </span><span class="Bold">6 mg</span> <br/> <span class="Bold">(n = 384)</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Placebo</span> <br/> <span class="Bold">(n = 180)</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Sumatriptan </span><span class="Bold">6 mg</span> <br/> <span class="Bold">(n = 350)</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">  Patients with pain relief (Grade 0/1)<br/> </td><td align="center" class="Rrule" valign="middle">18%<br/> </td><td align="center" class="Rrule" valign="middle">70%<span class="Sup">a</span> <br/> </td><td align="center" class="Rrule" valign="middle">26%<br/> </td><td align="center" class="Rrule" valign="middle">70%<span class="Sup">a</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">  Patients with no pain<br/> </td><td align="center" class="Rrule" valign="middle">5%<br/> </td><td align="center" class="Rrule" valign="middle">48%<span class="Sup">a</span> <br/> </td><td align="center" class="Rrule" valign="middle">13%<br/> </td><td align="center" class="Rrule" valign="middle">49%<span class="Sup">a</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">  Patients without nausea<br/> </td><td align="center" class="Rrule" valign="middle">48%<br/> </td><td align="center" class="Rrule" valign="middle">73%<span class="Sup">a</span> <br/> </td><td align="center" class="Rrule" valign="middle">50%<br/> </td><td align="center" class="Rrule" valign="middle">73%<span class="Sup">a</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">  Patients without photophobia<br/> </td><td align="center" class="Rrule" valign="middle">23%<br/> </td><td align="center" class="Rrule" valign="middle">56%<span class="Sup">a</span> <br/> </td><td align="center" class="Rrule" valign="middle">25%<br/> </td><td align="center" class="Rrule" valign="middle">58%<span class="Sup">a</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">  Patients with little or no clinical disability<span class="Sup">b</span> <br/> </td><td align="center" class="Rrule" valign="middle">34%<br/> </td><td align="center" class="Rrule" valign="middle">76%<span class="Sup">a</span> <br/> </td><td align="center" class="Rrule" valign="middle">34%<br/> </td><td align="center" class="Rrule" valign="middle">76%<span class="Sup">a</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" rowspan="2" valign="middle"><span class="Bold"> <br/> 2-Hour Data</span> <br/> </td><td align="center" class="Rrule" colspan="2" valign="middle"><span class="Bold">Study 2</span> <br/> </td><td align="center" class="Rrule" colspan="2" valign="middle"><span class="Bold">Study 3</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle"><span class="Bold">Placebo<span class="Sup">c</span></span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Sumatriptan </span><span class="Bold">6 mg<span class="Sup">d</span></span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Placebo<span class="Sup">c</span></span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Sumatriptan </span><span class="Bold">6 mg<span class="Sup">d</span></span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">  Patients with pain relief (Grade 0/1)<br/> </td><td align="center" class="Rrule" valign="middle">31% <br/> </td><td align="center" class="Rrule" valign="middle">81%<span class="Sup">a</span> <br/> </td><td align="center" class="Rrule" valign="middle">39% <br/> </td><td align="center" class="Rrule" valign="middle">82%<span class="Sup">a</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">  Patients with no pain<br/> </td><td align="center" class="Rrule" valign="middle">11%<br/> </td><td align="center" class="Rrule" valign="middle">63%<span class="Sup">a</span> <br/> </td><td align="center" class="Rrule" valign="middle">19%<br/> </td><td align="center" class="Rrule" valign="middle">65%<span class="Sup">a</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">  Patients without nausea<br/> </td><td align="center" class="Rrule" valign="middle">56%<br/> </td><td align="center" class="Rrule" valign="middle">82%<span class="Sup">a</span> <br/> </td><td align="center" class="Rrule" valign="middle">63%<br/> </td><td align="center" class="Rrule" valign="middle">81%<span class="Sup">a</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">  Patients without photophobia<br/> </td><td align="center" class="Rrule" valign="middle">31%<br/> </td><td align="center" class="Rrule" valign="middle">72%<span class="Sup">a</span> <br/> </td><td align="center" class="Rrule" valign="middle">35%<br/> </td><td align="center" class="Rrule" valign="middle">71%<span class="Sup">a</span> <br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="middle">  Patients with little or no clinical disability<span class="Sup">b</span> <br/> </td><td align="center" class="Rrule" valign="middle">42%<br/> </td><td align="center" class="Rrule" valign="middle">85%<span class="Sup">a</span> <br/> </td><td align="center" class="Rrule" valign="middle">49%<br/> </td><td align="center" class="Rrule" valign="middle">84%<span class="Sup">a</span> <br/> </td> </tr> </tbody> </table></div>

a  P<0.05 versus placebo. b A successful outcome in terms of clinical disability was defined prospectively as ability to work mildly impaired or ability to work and function normally. c Includes patients that may have received an additional placebo injection 1 hour after the initial injection. d Includes patients that may have received an additional 6 mg of sumatriptan injection 1 hour after the initial injection.

Sumatriptan injection also relieved photophobia, phonophobia (sound sensitivity), nausea, and vomiting associated with migraine attacks. The efficacy of sumatriptan injection was unaffected by whether or not the migraine was associated with aura, duration of attack, gender or age of the patient, or concomitant use of common migraine prophylactic drugs (e.g., beta-blockers).

The efficacy of sumatriptan injection in the acute treatment of cluster headache was demonstrated in 2 randomized, double-blind, placebo-controlled, 2-period crossover trials (Studies 4 and 5). Patients aged 21 to 65 years were enrolled and were instructed to treat a moderate to very severe headache within 10 minutes of onset. Headache relief was defined as a reduction in headache severity to mild or no pain. In both trials, the proportion of individuals gaining relief at 10 or 15 minutes was significantly greater among patients receiving 6 mg of sumatriptan injection compared with those who received placebo (see Table 4).

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <caption> <span>Table 4. Proportion of Patients with Cluster Headache Relief by Time in Studies 4 and 5 </span> </caption> <colgroup> <col width="29.12%"/> <col width="11.66%"/> <col width="25.08%"/> <col width="11.82%"/> <col width="22.32%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td class="Lrule Rrule" rowspan="2" valign="top"> <br/> </td><td align="center" class="Rrule" colspan="2" valign="middle"><span class="Bold">Study 4</span> <br/> </td><td align="center" class="Rrule" colspan="2" valign="middle"><span class="Bold">Study 5</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle"><span class="Bold">Placebo</span> <br/> <span class="Bold">(n = 39)</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Sumatriptan </span><span class="Bold">6 mg</span> <br/> <span class="Bold">(n = 39)</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Placebo</span> <br/> <span class="Bold">(n = 88)</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Sumatriptan </span><span class="Bold">6 mg</span> <br/> <span class="Bold">(n = 92)</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Patients with pain relief<br/>(no/mild) <br/> </td><td align="center" class="Rrule" valign="top"> <br/> </td><td align="center" class="Rrule" valign="top"> <br/> </td><td align="center" class="Rrule" valign="top"> <br/> </td><td align="center" class="Rrule" valign="top"> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">5 Minutes post-injection<br/> </td><td align="center" class="Rrule" valign="middle">8%<br/> </td><td align="center" class="Rrule" valign="middle">21%<br/> </td><td align="center" class="Rrule" valign="middle">7%<br/> </td><td align="center" class="Rrule" valign="middle">23%<span class="Sup">a</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">10 Minutes post-injection<br/> </td><td align="center" class="Rrule" valign="middle">10%<br/> </td><td align="center" class="Rrule" valign="middle">49%<span class="Sup">a</span> <br/> </td><td align="center" class="Rrule" valign="middle">25%<br/> </td><td align="center" class="Rrule" valign="middle">49%<span class="Sup">a</span> <br/> </td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule" valign="middle">15 Minutes post-injection<br/> </td><td align="center" class="Rrule" valign="middle">26%<br/> </td><td align="center" class="Rrule" valign="middle">74%<span class="Sup">a</span> <br/> </td><td align="center" class="Rrule" valign="middle">35%<br/> </td><td align="center" class="Rrule" valign="middle">75%<span class="Sup">a</span> <br/> </td> </tr> </tbody> </table></div>

 aP<0.05.

n = Number of headaches treated.

An estimate of the cumulative probability of a patient with a cluster headache obtaining relief after being treated with either sumatriptan injection or placebo is presented in Figure 1.

Figure 1. Time to Relief of Cluster Headache from Time of Injectiona

a The figure uses Kaplan-Meier (product limit) Survivorship Plot. Patients taking rescue medication were censored at 15 minutes. The plot was constructed with data from patients who either experienced relief or did not require (request) rescue medication within a period of 2 hours following treatment. As a consequence, the data in the plot are derived from only a subset of the 258 headaches treated (rescue medication was required in 52 of the 127 placebo-treated headaches and 18 of the 131 headaches treated with sumatriptan injection). Other data suggest that treatment with sumatriptan injection is not associated with an increase in early recurrence of headache and has little effect on the incidence of later-occurring headaches (i.e., those occurring after 2, but before 18 or 24 hours).

Sumatriptan Injection USP contains sumatriptan as sumatriptan succinate USP and is supplied as a clear, colorless to pale yellow, sterile, nonpyrogenic solution as follows: Sumatriptan Injection USP, 6 mg per 0.5 mLSingle-Dose Vials in a Carton of 5                                                                                   NDC 55150-173-01

{ "type": "p", "children": [], "text": "Sumatriptan Injection USP contains sumatriptan as sumatriptan succinate USP and is supplied as a clear, colorless to pale yellow, sterile, nonpyrogenic solution as follows:\n Sumatriptan Injection USP, 6 mg per 0.5 mLSingle-Dose Vials in a Carton of 5                                                                                   NDC 55150-173-01" }

Store between 2° and 30°C (36° and 86°F). Protect from light. The vial stopper is not made with natural rubber latex.

{ "type": "p", "children": [], "text": "Store between 2° and 30°C (36° and 86°F). Protect from light.\n The vial stopper is not made with natural rubber latex." }

Advise the patient to read the FDA-approved patient labeling (Patient Information).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Patient Information). " }

Risk of Myocardial Ischemia and/or Infarction, Prinzmetal’s Angina, Other Vasospasm-Related Events, Arrhythmias, and Cerebrovascular Events

{ "type": "p", "children": [], "text": "\nRisk of Myocardial Ischemia and/or Infarction, Prinzmetal’s Angina, Other Vasospasm-Related Events, Arrhythmias, and Cerebrovascular Events \n" }

Inform patients that sumatriptan injection may cause serious cardiovascular side effects such as myocardial infarction or stroke. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, irregular heartbeat, significant rise in blood pressure, weakness, and slurring of speech, and should ask for medical advice if any indicative sign or symptoms are observed. Apprise patients of the importance of this follow-up [see Warnings and Precautions (5.1, 5.2, 5.4, 5.5, 5.8)].

{ "type": "p", "children": [], "text": "Inform patients that sumatriptan injection may cause serious cardiovascular side effects such as myocardial infarction or stroke. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, irregular heartbeat, significant rise in blood pressure, weakness, and slurring of speech, and should ask for medical advice if any indicative sign or symptoms are observed. Apprise patients of the importance of this follow-up [see Warnings and Precautions (5.1, 5.2, 5.4, 5.5, 5.8)]." }

Hypersensitivity Reactions

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions \n" }

Inform patients that anaphylactic reactions have occurred in patients receiving sumatriptan injection. 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 [see Contraindications (4), Warnings and Precautions (5.9)]. Concomitant Use with Other Triptans or Ergot Medications

{ "type": "p", "children": [], "text": "Inform patients that anaphylactic reactions have occurred in patients receiving sumatriptan injection. 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 [see Contraindications (4), Warnings and Precautions (5.9)].\n\n Concomitant Use with Other Triptans or Ergot Medications\n" }

Inform patients that use of sumatriptan injection within 24 hours of another triptan or an ergot-type medication (including dihydroergotamine or methysergide) is contraindicated [see Contraindications (4), Drug Interactions (7.1, 7.3)]. Serotonin Syndrome

{ "type": "p", "children": [], "text": "Inform patients that use of sumatriptan injection within 24 hours of another triptan or an ergot-type medication (including dihydroergotamine or methysergide) is contraindicated [see Contraindications (4), Drug Interactions (7.1, 7.3)].\n\n Serotonin Syndrome \n" }

Caution patients about the risk of serotonin syndrome with the use of sumatriptan injection or other triptans, particularly during combined use with SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7), Drug Interactions (7.4)].  Medication Overuse Headache

{ "type": "p", "children": [], "text": "Caution patients about the risk of serotonin syndrome with the use of sumatriptan injection or other triptans, particularly during combined use with SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7), Drug Interactions (7.4)]. \n\n Medication Overuse Headache\n" }

Inform patients that use of acute migraine drugs for 10 or more days per month may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6)]. Pregnancy

{ "type": "p", "children": [], "text": "Inform patients that use of acute migraine drugs for 10 or more days per month may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6)].\n\n Pregnancy \n" }

Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant [see Use in Specific Populations (8.1)]. Lactation Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant [see Use in Specific Populations (8.1)].\n\n Lactation\n\n Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.2)]." }

Ability to Perform Complex Tasks

{ "type": "p", "children": [], "text": "\nAbility to Perform Complex Tasks\n" }

Treatment with sumatriptan injection may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks after administration of sumatriptan injection.

{ "type": "p", "children": [], "text": "Treatment with sumatriptan injection may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks after administration of sumatriptan injection." }

How to Use Sumatriptan Injection Instruct patients to read the Instructions for Use before starting therapy. Provide patients instruction on the proper use of sumatriptan injection if they are able to self-administer sumatriptan injection in medically unsupervised situations. Instruct patients on storage and disposal of the pen [see How Supplied/Storage and Handling (16)].

{ "type": "p", "children": [], "text": "\nHow to Use Sumatriptan Injection\n\n Instruct patients to read the Instructions for Use before starting therapy. Provide patients instruction on the proper use of sumatriptan injection if they are able to self-administer sumatriptan injection in medically unsupervised situations. Instruct patients on storage and disposal of the pen [see How Supplied/Storage and Handling (16)]." }

Inform patients that the injection is intended to be given subcutaneously and intramuscular or intravascular delivery should be avoided. Instruct patients to use injection sites with an adequate skin and subcutaneous thickness to accommodate the length of the needle. Distributed by: Eugia US LLC 279 Princeton-Hightstown Rd. E. Windsor, NJ 08520 Manufactured by: Eugia Pharma Specialities Limited Hyderabad - 500032 India

{ "type": "p", "children": [], "text": "Inform patients that the injection is intended to be given subcutaneously and intramuscular or intravascular delivery should be avoided. Instruct patients to use injection sites with an adequate skin and subcutaneous thickness to accommodate the length of the needle.\n Distributed by:\nEugia US LLC\n279 Princeton-Hightstown Rd. E. Windsor, NJ 08520\n Manufactured by:\nEugia Pharma Specialities Limited\nHyderabad - 500032 India" }

Sumatriptan (soo'' ma trip' tan) Injection USP What is the most important information I should know about sumatriptan? Sumatriptan can cause serious side effects, including: Heart attack and other heart problems. Heart problems may lead to death. Stop taking sumatriptan and get emergency medical help right away if you have any of the following symptoms of a heart attack:

{ "type": "p", "children": [], "text": "\nSumatriptan (soo'' ma trip' tan) Injection USP\n\n What is the most important information I should know about sumatriptan?\n Sumatriptan can cause serious side effects, including:\n\n Heart attack and other heart problems. Heart problems may lead to death.\n\n Stop taking sumatriptan and get emergency medical help right away if you have any of the following symptoms of a heart attack: \n\n" }

{ "type": "ul", "children": [ "discomfort in the center of your chest that lasts for more than a few minutes, or that 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 " ], "text": "" }

Sumatriptan is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. You have a higher risk for heart disease if you:

{ "type": "p", "children": [], "text": "Sumatriptan is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. You have a higher risk for heart disease if you:" }

{ "type": "ul", "children": [ "have high blood pressure", "have high cholesterol levels", "smoke", "are overweight", "have diabetes", "have a family history of heart disease" ], "text": "" }

What is Sumatriptan? Sumatriptan injection is a prescription medicine used to treat acute migraine headaches with or without aura and acute cluster headaches in adults who have been diagnosed with migraine or cluster headaches. Sumatriptan is not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines. Sumatriptan is not used to prevent or decrease the number of migraine or cluster headaches you have. It is not known if sumatriptan is safe and effective in children under 18 years of age. Do not take sumatriptan if you have:

{ "type": "p", "children": [], "text": "\nWhat is Sumatriptan?\n\n Sumatriptan injection is a prescription medicine used to treat acute migraine headaches with or without aura and acute cluster headaches in adults who have been diagnosed with migraine or cluster headaches.\n Sumatriptan is not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines.\n Sumatriptan is not used to prevent or decrease the number of migraine or cluster headaches you have.\n It is not known if sumatriptan is safe and effective in children under 18 years of age.\n\n Do not take sumatriptan if you have:\n" }

{ "type": "ul", "children": [ "heart problems or a history of heart problems. ", "narrowing of blood vessels to your legs, arms, stomach, or kidneys (peripheral vascular disease).", "uncontrolled high blood pressure.", "severe liver problems.", "hemiplegic migraines or basilar migraines. If you are not sure if you have these types of migraines, ask your healthcare provider.", "had a stroke, transient ischemic attacks (TIAs), or problems with your blood circulation.", "taken any of the following medicines in the last 24 hours: o almotriptan (AXERT)                                                           o eletriptan (RELPAX) o frovatriptan (FROVA)                                                           o naratriptan (AMERGE) o rizatriptan (MAXALT, MAXALT-MLT)                             o sumatriptan and naproxen (TREXIMET) o ergotamines (CAFERGOT, ERGOMAR, MIGERGOT)      o dihydroergotamine (D.H.E. 45, MIGRANAL)" ], "text": "" }

Ask your healthcare provider if you are not sure if your medicine is listed above.

{ "type": "p", "children": [], "text": "Ask your healthcare provider if you are not sure if your medicine is listed above." }

{ "type": "ul", "children": [ " an allergy to sumatriptan or any of the ingredients in sumatriptan injection. See the end of this leaflet for a complete list of ingredients in sumatriptan injection." ], "text": "" }

Before taking sumatriptan, tell your healthcare provider about all of your medical conditions, including if you:

{ "type": "p", "children": [], "text": "\nBefore taking sumatriptan, tell your healthcare provider about all of your medical conditions, including if you:\n" }

{ "type": "ul", "children": [ "have high blood pressure", "have high cholesterol", "have diabetes", "smoke", "are overweight", "have heart problems or family history of heart problems or stroke", "have kidney problems", "have liver problems", "have had epilepsy or seizures", "are not using effective birth control", "are pregnant or plan to become pregnant. It is not known if sumatriptan can harm your unborn baby.", "are breastfeeding or plan to breastfeed. Sumatriptan passes into your breast milk. It is not known if this can harm your baby. Talk with your healthcare provider about the best way to feed your baby if you take sumatriptan. " ], "text": "" }

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Sumatriptan and certain other medicines can affect each other, causing serious side effects. Especially tell your healthcare provider if you take antidepressant medicines called:

{ "type": "p", "children": [], "text": "\nTell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.\n Sumatriptan and certain other medicines can affect each other, causing serious side effects.\n\n Especially tell your healthcare provider if you take antidepressant medicines called: " }

{ "type": "ul", "children": [ "selective serotonin reuptake inhibitors (SSRIs)", "serotonin norepinephrine reuptake inhibitors (SNRIs)", "tricyclic antidepressants (TCAs)", "monoamine oxidase inhibitors (MAOIs) " ], "text": "" }

Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure. Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine. How should I take sumatriptan?

{ "type": "p", "children": [], "text": "Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure.\n Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.\n\n How should I take sumatriptan?\n" }

{ "type": "ul", "children": [ "Certain people should take their first dose of sumatriptan in their healthcare provider’s office or in another medical setting. Ask your healthcare provider if you should take your first dose in a medical setting.", "Use sumatriptan exactly as your healthcare provider tells you to use it.", "Your healthcare provider may change your dose. Do not change your dose without first talking with your healthcare provider.", "For adults, the usual dose is a single injection given just below the skin.", "You should give an injection as soon as the symptoms of your headache start, but it may be given at any time during a migraine or cluster headache attack.", "If you did not get any relief after the first injection, do not give a second injection without first talking with your healthcare provider.", "If your headache comes back or you only get some relief after your first injection, you can take a second injection 1 hour after the first injection, but not sooner.", "Do not take more than 12 mg in a 24-hour period. ", "If you use too much sumatriptan, call your healthcare provider or go to the nearest hospital emergency room right away.", "You should write down when you have headaches and when you take sumatriptan so you can talk with your healthcare provider about how sumatriptan is working for you." ], "text": "" }

What should I avoid while taking sumatriptan? Sumatriptan can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery, or do anything where you need to be alert. What are the possible side effects of sumatriptan? Sumatriptan may cause serious side effects. See “What is the most important information I should know about sumatriptan?” These serious side effects include:

{ "type": "p", "children": [], "text": "\nWhat should I avoid while taking sumatriptan?\n\n Sumatriptan can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery, or do anything where you need to be alert.\n\n What are the possible side effects of sumatriptan?\n\n Sumatriptan may cause serious side effects. See “What is the most important information I should know about sumatriptan?”\n These serious side effects include:" }

{ "type": "ul", "children": [ "changes in color or sensation in your fingers and toes (Raynaud’s syndrome)", "stomach and intestinal problems (gastrointestinal and colonic ischemic events). Symptoms of gastrointestinal and colonic ischemic events include: o sudden or severe stomach pain         o nausea or vomiting o stomach pain after meals                  o constipation or diarrhea o weight loss                                        o bloody diarrhea o fever", "problems with blood circulation to your legs and feet (peripheral vascular ischemia). Symptoms of peripheral vascular ischemia include: o cramping and pain in your legs or hips o feeling of heaviness or tightness in your leg muscles o burning or aching pain in your feet or toes while resting o numbness, tingling, or weakness in your legs o cold feeling or color changes in 1 or both legs or feet", "medication overuse headaches. Some people who use too many sumatriptan injections may have worse headaches (medication overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with sumatriptan.", "serotonin syndrome. Serotonin syndrome is a rare but serious problem that can happen in people using sumatriptan, especially if sumatriptan is used with anti-depressant medicines called SSRIs or SNRIs. Call your healthcare provider right away if you have any of the following symptoms of serotonin syndrome: o mental changes such as seeing things that are not there (hallucinations), agitation, or coma o fast heartbeat o changes in blood pressure o high body temperature o tight muscles o trouble walking", "hives (itchy bumps); swelling of your tongue, mouth or throat. ", "seizures. Seizures have happened in people taking sumatriptan who have never had seizures before. Talk with your healthcare provider about your chance of having seizures while you take sumatriptan. " ], "text": "" }

The most common side effects of sumatriptan injection include:

{ "type": "p", "children": [], "text": "The most common side effects of sumatriptan injection include: " }

{ "type": "ul", "children": [ "pain or redness at your 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 " ], "text": "" }

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

{ "type": "p", "children": [], "text": "Tell your healthcare provider if you have any side effect that bothers you or that does not go away. " }

These are not all the possible side effects of sumatriptan. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store Sumatriptan Injection?

{ "type": "p", "children": [], "text": "\n These are not all the possible side effects of sumatriptan. Call your doctor for medical advice about side effects.\n You may report side effects to FDA at 1-800-FDA-1088.\n\nHow should I store Sumatriptan Injection?\n" }

{ "type": "ul", "children": [ "Store sumatriptan injection between 36°F to 86°F (2°C to 30°C).", "Store your medicine away from light.", "Keep your medicine in the packaging provided with it. " ], "text": "" }

Keep sumatriptan and all medicines out of the reach of children. General information about the safe and effective use of sumatriptan Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use sumatriptan for a condition for which it was not prescribed. Do not give sumatriptan to other people, even if they have the same symptoms you have. It may harm them. This Patient Information leaflet summarizes the most important information about sumatriptan. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about sumatriptan that is written for healthcare professionals. For more information, call 1-866-850-2876. What are the ingredients in Sumatriptan Injection? Active ingredient: sumatriptan succinate Inactive ingredients: sodium chloride, water for injection All brands listed are the trademarks of their respective owners and are not trademarks of Eugia Pharma Specialities Limited. This Patient Information has been approved by the U.S. Food and Drug Administration. Distributed by: Eugia US LLC 279 Princeton-Hightstown Rd. E. Windsor, NJ 08520 Manufactured by: Eugia Pharma Specialities Limited Hyderabad - 500032 India Revised: May 2025

{ "type": "p", "children": [], "text": "\nKeep sumatriptan and all medicines out of the reach of children.\n\n General information about the safe and effective use of sumatriptan\n\n Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use sumatriptan for a condition for which it was not prescribed. Do not give sumatriptan to other people, even if they have the same symptoms you have. It may harm them.\n This Patient Information leaflet summarizes the most important information about sumatriptan. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about sumatriptan that is written for healthcare professionals.\n For more information, call 1-866-850-2876.\n\n What are the ingredients in Sumatriptan Injection?\n\n Active ingredient: sumatriptan succinate\n Inactive ingredients: sodium chloride, water for injection\n All brands listed are the trademarks of their respective owners and are not trademarks of Eugia Pharma Specialities Limited.\n This Patient Information has been approved by the U.S. Food and Drug Administration.\n Distributed by:\nEugia US LLC\n279 Princeton-Hightstown Rd. E. Windsor, NJ 08520\n Manufactured by:\nEugia Pharma Specialities Limited\nHyderabad - 500032 India\nRevised: May 2025" }

Rx Only      NDC 55150-173-01 Sumatriptan Injection USP 6 mg per 0.5 mL For subcutaneous injection only.

{ "type": "p", "children": [], "text": "\nRx Only      NDC 55150-173-01\nSumatriptan Injection USP 6 mg per 0.5 mL For subcutaneous injection only.\n" }

NDC 55150-173-01            5 x 0.5 mL Single-Dose Vials Rx only Sumatriptan Injection USP   6 mg per 0.5 mL For subcutaneous injection only.                                                              PHARMACIST: Single-dose vial.                                  Please dispense with patient information                           Discard unused portion.                      leaflet provided separately. eugia                            

{ "type": "p", "children": [], "text": "\nNDC 55150-173-01            5 x 0.5 mL Single-Dose Vials Rx only Sumatriptan Injection USP   \n6 mg per 0.5 mL For subcutaneous injection only.\n\n                                                             PHARMACIST: \n Single-dose vial.                                  Please dispense with patient information                           Discard unused portion.                      leaflet provided separately.\neugia\n                           " }

Limitations of Use:

The recommended dose of TOSYMRA is 10 mg given as a single spray in one nostril.

{ "type": "p", "children": [], "text": "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 a 24-hour period is 30 mg, with doses of TOSYMRA separated by at least 1 hour. TOSYMRA may also be given at least 1 hour following a dose of another sumatriptan product.

{ "type": "p", "children": [], "text": "The maximum cumulative dose that may be given in a 24-hour period is 30 mg, with doses of TOSYMRA separated by at least 1 hour. TOSYMRA may also be given at least 1 hour following a dose of another sumatriptan product." }

Single-dose nasal spray device delivering 10 mg of sumatriptan.

{ "type": "p", "children": [], "text": "Single-dose nasal spray device delivering 10 mg of sumatriptan." }

TOSYMRA is contraindicated in patients with:

{ "type": "p", "children": [], "text": "TOSYMRA is contraindicated in patients with:" }

{ "type": "ul", "children": [ "Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetal's angina [see Warnings and Precautions (5.1)].", "Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.2)].", "History of stroke or transient ischemic attack (TIA) or history of hemiplegic or basilar migraine because these patients are at a higher risk of stroke [see Warnings and Precautions (5.4)].", "Peripheral vascular disease [see Warnings and Precautions (5.5)].", "Ischemic bowel disease [see Warnings and Precautions (5.5)].", "Uncontrolled hypertension [see Warnings and Precautions (5.8)].", "Recent use (i.e., within 24 hours) of ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide), or another 5-hydroxytryptamine1 (5-HT1) agonist [see Drug Interactions (7.1, 7.3)].", "Concurrent administration of a monoamine oxidase (MAO)-A inhibitor or recent (within 2 weeks) use of an MAO-A inhibitor [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)].", "Hypersensitivity to sumatriptan (angioedema and anaphylaxis seen) [see Warnings and Precautions (5.9)].", "Severe hepatic impairment [see Clinical Pharmacology (12.3)]." ], "text": "" }

The use of TOSYMRA 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-HT1 agonists, including TOSYMRA, may cause coronary artery vasospasm (Prinzmetal's angina), even in patients without a history of CAD.

Perform a cardiovascular evaluation in triptan-naive patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving TOSYMRA. If there is evidence of CAD or coronary artery vasospasm, TOSYMRA is contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of TOSYMRA in a medically supervised setting and performing an electrocardiogram (ECG) immediately following administration of TOSYMRA. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of TOSYMRA.

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 TOSYMRA if these disturbances occur.

TOSYMRA is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

Sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw commonly occur after treatment with sumatriptan injection and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of TOSYMRA is contraindicated in patients shown to have CAD and those with Prinzmetal's variant angina.

Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). Discontinue 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. TOSYMRA is contraindicated in patients with a history of stroke or TIA.

TOSYMRA 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 non-coronary vasospasm reaction following the use of any 5-HT1 agonist, rule out a vasospastic reaction before receiving additional TOSYMRA.

Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1 agonists have not been clearly established.

Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or combination 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.

Serotonin syndrome may occur with TOSYMRA, 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 aberrations (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 TOSYMRA if serotonin syndrome is suspected.

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-HT1 agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with TOSYMRA. TOSYMRA is contraindicated in patients with uncontrolled hypertension.

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. TOSYMRA is contraindicated in patients with a history of hypersensitivity reaction to sumatriptan.

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. TOSYMRA should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.

Local irritative symptoms were reported in approximately 46% of patients treated with TOSYMRA in an open-label trial which allowed repeated use of TOSYMRA over the course of 6 months. Of these, the most common local irritative symptoms were application site reaction (36%), dysgeusia (21%), and throat irritation (5%). Approximately 0.5% of the cases were reported as severe.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse Reactions in Placebo-Controlled Trials with Sumatriptan Injection

Table 1 lists adverse reactions that occurred in 2 placebo-controlled clinical trials in patients with migraine (Studies 2 and 3) following either a single 6 mg dose of sumatriptan injection or placebo. Only reactions that occurred at a frequency of 2% or more in groups treated with sumatriptan injection 6 mg and that occurred at a frequency greater than the placebo group are included in Table 1.

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 1: Adverse Reactions in Pooled Placebo-Controlled Trials in Patients with Migraine (Studies 2 and 3)</span> </caption> <col align="left" valign="top" width="45%"/> <col align="center" valign="top" width="28%"/> <col align="center" valign="top" width="27%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule" valign="bottom">Adverse Reaction</th><th align="center" class="Rrule">Sumatriptan Injection<br/>6 mg Subcutaneous<br/>(n = 547)<br/>%</th><th align="center" class="Rrule" valign="bottom">Placebo<br/>(n = 370)<br/>%</th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Lrule Rrule">Atypical sensations</td><td align="center" class="Rrule">42</td><td align="center" class="Rrule">9</td> </tr> <tr> <td align="left" class="Lrule Rrule">  Tingling</td><td align="center" class="Rrule">14</td><td align="center" class="Rrule">3</td> </tr> <tr> <td align="left" class="Lrule Rrule">  Warm/hot sensation</td><td align="center" class="Rrule">11</td><td align="center" class="Rrule">4</td> </tr> <tr> <td align="left" class="Lrule Rrule">  Burning sensation</td><td align="center" class="Rrule">7</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr> <td align="left" class="Lrule Rrule">  Feeling of heaviness</td><td align="center" class="Rrule">7</td><td align="center" class="Rrule">1</td> </tr> <tr> <td align="left" class="Lrule Rrule">  Pressure sensation</td><td align="center" class="Rrule">7</td><td align="center" class="Rrule">2</td> </tr> <tr> <td align="left" class="Lrule Rrule">  Feeling of tightness</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr> <td align="left" class="Lrule Rrule">  Numbness</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">2</td> </tr> <tr> <td align="left" class="Lrule Rrule">  Feeling strange</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Tight feeling in head</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr> <td align="left" class="Lrule Rrule">Cardiovascular</td><td align="center" class="Rrule"></td><td align="center" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule Rrule">  Flushing</td><td align="center" class="Rrule">7</td><td align="center" class="Rrule">2</td> </tr> <tr> <td align="left" class="Lrule Rrule">  Chest discomfort</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">1</td> </tr> <tr> <td align="left" class="Lrule Rrule">  Tightness in chest</td><td align="center" class="Rrule">3</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Pressure in chest</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr> <td align="left" class="Lrule Rrule">Ear, nose, and throat</td><td align="center" class="Rrule"></td><td align="center" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule Rrule">  Throat discomfort</td><td align="center" class="Rrule">3</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Discomfort: nasal cavity/sinuses</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr> <td align="left" class="Lrule Rrule">Miscellaneous</td><td align="center" class="Rrule"></td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Jaw discomfort</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">0</td> </tr> <tr> <td align="left" class="Lrule Rrule">Musculoskeletal</td><td align="center" class="Rrule"></td><td align="center" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule Rrule">  Weakness</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr> <td align="left" class="Lrule Rrule">  Neck pain/stiffness</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Myalgia</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr> <td align="left" class="Lrule Rrule">Neurological</td><td align="center" class="Rrule"></td><td align="center" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule Rrule">  Dizziness/vertigo</td><td align="center" class="Rrule">12</td><td align="center" class="Rrule">4</td> </tr> <tr> <td align="left" class="Lrule Rrule">  Drowsiness/sedation</td><td align="center" class="Rrule">3</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Headache</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">&lt;1</td> </tr> <tr> <td align="left" class="Lrule Rrule">Skin</td><td align="center" class="Rrule"></td><td align="center" class="Rrule"></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">  Sweating</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">1</td> </tr> </tbody> </table></div>

The incidence of adverse reactions in controlled clinical trials was not affected by gender or age of the patients. There were insufficient data to assess the impact of race on the incidence of adverse reactions.

Adverse Reactions in Studies with TOSYMRA

In an open-label study that was designed to evaluate the local tolerability of TOSYMRA, repeated use of TOSYMRA was allowed over the course of 6 months. In this study, local irritative symptoms were reported in approximately 46% of patients treated with TOSYMRA, the most common of which were application site reactions (e.g., burning sensations in the nose), dysgeusia, and throat irritation [see Warnings and Precautions (5.11)].

The following adverse reactions have been identified during post-approval use of sumatriptan tablets, sumatriptan nasal spray, and sumatriptan injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular:

Hypotension, palpitations.

Neurological:

Dystonia, tremor.

Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and TOSYMRA within 24 hours of each other is contraindicated.

MAO-A inhibitors increase systemic exposure by 2-fold. Therefore, the use of TOSYMRA in patients receiving MAO-A inhibitors is contraindicated [see Clinical Pharmacology (12.3)].

Because their vasospastic effects may be additive, coadministration of TOSYMRA and other 5-HT1 agonists (e.g., triptans) within 24 hours of each other is contraindicated.

Cases of serotonin syndrome have been reported during co-administration of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7)].

Risk Summary

Data from a prospective pregnancy exposure registry and epidemiological studies of pregnant women have not detected an increased frequency of birth defects or a consistent pattern of birth defects among women exposed to sumatriptan compared with the general population (see Data). In developmental toxicity studies in rats and rabbits, oral administration of sumatriptan to pregnant animals was associated with embryo lethality, fetal abnormalities, and pup mortality. When administered by the intravenous route to pregnant rabbits, sumatriptan was embryo lethal (see Data).

In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of major birth defects among deliveries to women with migraine ranged from 2.2% to 2.9% and the reported rate of miscarriage was 17%, which were similar to rates reported in women without migraine.

Clinical Considerations

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.

Data

Human Data

The Sumatriptan/Naratriptan/Treximet (sumatriptan and naproxen sodium) Pregnancy Registry, a population-based international prospective study, collected data for sumatriptan from January 1996 to September 2012. The Registry documented outcomes of 626 infants and fetuses exposed to sumatriptan during pregnancy (528 with earliest exposure during the first trimester, 78 during the second trimester, 16 during the third trimester, and 4 unknown). The occurrence of major birth defects (excluding fetal deaths and induced abortions without reported defects and all spontaneous pregnancy losses) during first-trimester exposure to sumatriptan was 4.2% (20/478 [95% CI: 2.6% to 6.5%]) and during any trimester of exposure was 4.2% (24/576 [95% CI: 2.7% to 6.2%]). The sample size in this study had 80% power to detect at least a 1.73- to 1.91-fold increase in the rate of major malformations. The number of exposed pregnancy outcomes accumulated during the registry was insufficient to support definitive conclusions about overall malformation risk or for making comparisons of the frequencies of specific birth defects. Of the 20 infants with reported birth defects after exposure to sumatriptan in the first trimester, 4 infants had ventricular septal defects, including one infant who was exposed to both sumatriptan and naratriptan, and 3 infants had pyloric stenosis. No other birth defect was reported for more than 2 infants in this group.

In a study using data from the Swedish Medical Birth Register, live births to women who reported using triptans or ergots during pregnancy were compared with those of women who did not. Of the 2,257 births with first-trimester exposure to sumatriptan, 107 infants were born with malformations (relative risk 0.99 [95% CI: 0.91 to 1.21]). A study using linked data from the Medical Birth Registry of Norway to the Norwegian Prescription Database compared pregnancy outcomes in women who redeemed prescriptions for triptans during pregnancy, as well as a migraine disease comparison group who redeemed prescriptions for sumatriptan before pregnancy only, compared with a population control group. Of the 415 women who redeemed prescriptions for sumatriptan during the first trimester, 15 had infants with major congenital malformations (OR 1.16 [95% CI: 0.69 to 1.94]) while for the 364 women who redeemed prescriptions for sumatriptan before, but not during, pregnancy, 20 had infants with major congenital malformations (OR 1.83 [95% CI: 1.17 to 2.88]), each compared with the population comparison group. Additional smaller observational studies evaluating use of sumatriptan during pregnancy have not suggested an increased risk of teratogenicity.

Animal Data

Oral administration of sumatriptan to pregnant rats during the period of organogenesis resulted in an increased incidence of fetal blood vessel (cervicothoracic and umbilical) abnormalities. The highest no-effect dose for embryofetal developmental toxicity in rats was 60 mg/kg/day. Oral administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in increased incidences of embryo lethality and fetal cervicothoracic vascular and skeletal abnormalities. Intravenous administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in an increased incidence of embryo lethality. The highest oral and intravenous no-effect doses for developmental toxicity in rabbits were 15 and 0.75 mg/kg/day, respectively.

Oral administration of sumatriptan to rats prior to and throughout gestation resulted in embryofetal toxicity (decreased body weight, decreased ossification, increased incidence of skeletal abnormalities). The highest no-effect dose was 50 mg/kg/day. In offspring of pregnant rats treated orally with sumatriptan during organogenesis, there was a decrease in pup survival. The highest no-effect dose for this effect was 60 mg/kg/day. Oral treatment of pregnant rats with sumatriptan during the latter part of gestation and throughout lactation resulted in a decrease in pup survival. The highest no-effect dose for this finding was 100 mg/kg/day.

Risk Summary

Sumatriptan is excreted in human milk following subcutaneous administration (see Data). There are no data on the effects of sumatriptan on the breastfed infant or the effects of sumatriptan on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TOSYMRA and any potential adverse effects on the breastfed infant from sumatriptan or from the underlying maternal condition.

Clinical Considerations

Infant exposure to sumatriptan can be minimized by avoiding breastfeeding for 12 hours after treatment with TOSYMRA.

Data

Following subcutaneous administration of a 6 mg dose of sumatriptan injection in 5 lactating volunteers, sumatriptan was present in milk.

Safety and effectiveness of TOSYMRA in pediatric patients have not been established. TOSYMRA is not recommended for use in patients younger than 18 years of age.

Two controlled clinical trials evaluated sumatriptan nasal spray (5 mg to 20 mg) in 1,248 pediatric migraineurs 12 to 17 years of age who treated a single attack. The trials did not establish the efficacy of sumatriptan nasal spray compared with placebo in the treatment of migraine in pediatric patients. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults.

Five controlled clinical trials (2 single-attack trials, 3 multiple-attack trials) evaluating oral sumatriptan (25 mg to 100 mg) in pediatric subjects 12 to 17 years of age enrolled a total of 701 pediatric migraineurs. These trials did not establish the efficacy of oral sumatriptan compared with placebo in the treatment of migraine in pediatric patients. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults. The frequency of all adverse reactions in these patients appeared to be both dose- and age-dependent, with younger patients reporting reactions more commonly than older pediatric patients.

Post-marketing experience documents that serious adverse reactions have occurred in the pediatric population after use of subcutaneous, oral, and/or intranasal sumatriptan. These reports include reactions similar in nature to those reported rarely in adults, including stroke, visual loss, and death. A myocardial infarction has been reported in a 14-year-old male following the use of oral sumatriptan; clinical signs occurred within 1 day of drug administration. Clinical data to determine the frequency of serious adverse reactions in pediatric patients who might receive subcutaneous, oral, or intranasal sumatriptan are not presently available.

Clinical trials of sumatriptan did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving TOSYMRA [see Warnings and Precautions (5.1)].

Coronary vasospasm was observed after intravenous administration of sumatriptan injection [see Contraindications (4)]. Overdoses would be expected from animal data (dogs at 0.1 g/kg, rats at 2 g/kg) to possibly cause convulsions, tremor, inactivity, erythema of the extremities, reduced respiratory rate, cyanosis, ataxia, mydriasis, injection site reactions (desquamation, hair loss, and scab formation), and paralysis.

{ "type": "p", "children": [], "text": "Coronary vasospasm was observed after intravenous administration of sumatriptan injection [see Contraindications (4)]. Overdoses would be expected from animal data (dogs at 0.1 g/kg, rats at 2 g/kg) to possibly cause convulsions, tremor, inactivity, erythema of the extremities, reduced respiratory rate, cyanosis, ataxia, mydriasis, injection site reactions (desquamation, hair loss, and scab formation), and paralysis." }

The elimination half-life of sumatriptan is about 2 hours [see Clinical Pharmacology (12.3)], and therefore monitoring of patients after overdose with TOSYMRA should continue for at least 10 hours or while symptoms or signs persist.

{ "type": "p", "children": [], "text": "The elimination half-life of sumatriptan is about 2 hours [see Clinical Pharmacology (12.3)], and therefore monitoring of patients after overdose with TOSYMRA should continue for at least 10 hours or while symptoms or signs persist." }

It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan.

{ "type": "p", "children": [], "text": "It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan." }

TOSYMRA contains sumatriptan, a selective 5-HT1B/1D receptor agonist. Sumatriptan is chemically designated as 1-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-N-methylmethanesulfonamide, and it has the following structure:

{ "type": "p", "children": [], "text": "TOSYMRA contains sumatriptan, a selective 5-HT1B/1D receptor agonist. Sumatriptan is chemically designated as 1-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-N-methylmethanesulfonamide, and it has the following structure:" }

The empirical formula is C14H21N3O2S, representing a molecular weight of 295.40. Sumatriptan is a white to pale yellow powder that is very slightly soluble in water.

{ "type": "p", "children": [], "text": "The empirical formula is C14H21N3O2S, representing a molecular weight of 295.40. Sumatriptan is a white to pale yellow powder that is very slightly soluble in water." }

TOSYMRA nasal spray is a clear, pale yellow to yellow colored liquid. Each 100 uL of TOSYMRA contains 10 mg of sumatriptan in single-dose aqueous buffered solution containing citric acid monohydrate, n-Dodecyl beta-D-maltoside, potassium phosphate monobasic, sodium chloride, and sodium phosphate dibasic anhydrous in water for injection.

{ "type": "p", "children": [], "text": "TOSYMRA nasal spray is a clear, pale yellow to yellow colored liquid. Each 100 uL of TOSYMRA contains 10 mg of sumatriptan in single-dose aqueous buffered solution containing citric acid monohydrate, n-Dodecyl beta-D-maltoside, potassium phosphate monobasic, sodium chloride, and sodium phosphate dibasic anhydrous in water for injection." }

The pH range of solution is approximately 5.0 to 6.0 and the osmolality is between 270 to 330 mOsmol.

{ "type": "p", "children": [], "text": "The pH range of solution is approximately 5.0 to 6.0 and the osmolality is between 270 to 330 mOsmol." }

Sumatriptan binds with high affinity to human cloned 5-HT1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine headache through agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

Blood Pressure

Significant elevation in blood pressure, including hypertensive crisis, has been reported in patients with and without a history of hypertension [see Warnings and Precautions (5.8)].

Peripheral (Small) Arteries

In healthy volunteers (N = 18), a trial evaluating the effects of sumatriptan on peripheral (small vessel) arterial reactivity failed to detect a clinically significant increase in peripheral resistance.

Heart Rate

Transient increases in blood pressure observed in some subjects in clinical trials carried out during sumatriptan's development as a treatment for migraine were not accompanied by any clinically significant changes in heart rate.

Following nasal administration of 10 mg TOSYMRA in 73 healthy subjects, the relative bioavailability of TOSYMRA was approximately 87% [90% confidence interval (CI) 82 to 94] of that obtained following 4 mg subcutaneous injection of sumatriptan. The relative bioavailability of TOSYMRA was 58% [90% CI 55 to 62] following 6 mg subcutaneous injection of sumatriptan.

Absorption

Peak plasma concentration of sumatriptan was observed in a median time of 10 minutes (range 5 to 23 minutes). After single nasal administration of the 10 mg dose, the mean (CV%) Cmax and AUC were 51.8 ng/mL (58%) and 60.70 ng•hr/mL (42%), respectively.

Distribution

Sumatriptan protein binding, determined by equilibrium dialysis over the concentration range of 10 to 1,000 ng/mL, is low, approximately 14% to 21%. The effect of sumatriptan on the protein binding of other drugs has not been evaluated.

Following a 6-mg subcutaneous injection into the deltoid area of the arm in 9 males (mean age: 33 years, mean weight: 77 kg) the volume of distribution central compartment of sumatriptan was 50 ± 8 liters and the distribution half-life was 15 ± 2 minutes.

Elimination

The elimination half-life of sumatriptan following administration of TOSYMRA is 2.44 ± 1.00 hours.

Metabolism

In vitro studies with human microsomes suggest that sumatriptan is metabolized by MAO, predominantly the A isoenzyme. Most of a radiolabeled dose of sumatriptan excreted in the urine is the major metabolite indole acetic acid (IAA) or the IAA glucuronide, both of which are inactive.

Excretion

After a single 6 mg subcutaneous dose, 22% ± 4% was excreted in the urine as unchanged sumatriptan and 38% ± 7% as the IAA metabolite.

Following a 6 mg subcutaneous injection into the deltoid area of the arm, the systemic clearance of sumatriptan was 1,194 ± 149 mL/min and the terminal half-life was 115 ± 19 minutes.

Specific Populations

Age

The pharmacokinetics of sumatriptan in the elderly (mean age: 72 years, 2 males and 4 females) and in subjects with migraine (mean age: 38 years, 25 males and 155 females) were similar to that in healthy male subjects (mean age: 30 years).

Patients with Hepatic Impairment

The effect of hepatic disease on the pharmacokinetics of TOSYMRA has not been evaluated. The effect of mild to moderate hepatic disease on the pharmacokinetics of subcutaneously administered sumatriptan has been evaluated. There were no significant differences in the pharmacokinetics of subcutaneously administered sumatriptan in moderately hepatically impaired subjects compared with healthy controls. The pharmacokinetics of subcutaneously administered sumatriptan in patients with severe hepatic impairment has not been studied. The use of TOSYMRA in this population is contraindicated [see Contraindications (4)].

Racial Groups

The systemic clearance and Cmax of subcutaneous sumatriptan were similar in black (n=34) and Caucasian (n=38) healthy male subjects. TOSYMRA has not been evaluated for race differences.

Drug Interaction Studies

Monoamine Oxidase-A Inhibitors

In a trial of 14 healthy females, pretreatment with an MAO-A inhibitor decreased the clearance of subcutaneous sumatriptan, resulting in a 2-fold increase in the area under the sumatriptan plasma concentration-time curve (AUC), corresponding to a 40% increase in elimination half-life.

Carcinogenesis

In carcinogenicity studies in mouse and rat, sumatriptan was administered orally for 78 weeks and 104 weeks, respectively, at doses up to 160 mg/kg/day (the highest dose in rat was reduced from 360 mg/kg/day during Week 21). There was no evidence in either species of an increase in tumors related to sumatriptan administration.

Mutagenesis

Sumatriptan was negative in in vitro (bacterial reverse mutation [Ames], gene cell mutation in Chinese hamster V79/HGPRT, chromosomal aberration in human lymphocytes) and in vivo (rat micronucleus) assays.

Impairment of Fertility

When sumatriptan (0, 5, 50, 500 mg/kg/day) was administered orally to male and female rats prior to and throughout the mating period, there was a treatment-related decrease in fertility secondary to a decrease in mating in animals treated with doses greater than 5 mg/kg/day. It is not clear whether this finding was due to an effect on males or females or both.

When sumatriptan was administered by subcutaneous injection to male and female rats prior to and throughout the mating period, there was no evidence of impaired fertility at doses up to 60 mg/kg/day.

Corneal Opacities

Dogs receiving oral sumatriptan developed corneal opacities and defects in the corneal epithelium. Corneal opacities were seen at the lowest dose tested, 2 mg/kg/day, and were present after 1 month of treatment. Defects in the corneal epithelium were noted in a 60-week study. Earlier examinations for these toxicities were not conducted and no-effect doses were not established.

The efficacy of TOSYMRA is based on the relative bioavailability of TOSYMRA nasal spray compared to sumatriptan subcutaneous injection (4 mg) in healthy adults [see Clinical Pharmacology (12.3)].

{ "type": "p", "children": [], "text": "The efficacy of TOSYMRA is based on the relative bioavailability of TOSYMRA nasal spray compared to sumatriptan subcutaneous injection (4 mg) in healthy adults [see Clinical Pharmacology (12.3)]." }

In controlled clinical trials enrolling more than 1,000 patients during migraine attacks who were experiencing moderate or severe pain and 1 or more of the symptoms enumerated in Table 3, onset of relief began as early as 10 minutes following a 6 mg sumatriptan injection. Lower doses of sumatriptan injection may also prove effective, although the proportion of patients obtaining adequate relief was decreased and the latency to that relief is greater with lower doses.

{ "type": "p", "children": [], "text": "In controlled clinical trials enrolling more than 1,000 patients during migraine attacks who were experiencing moderate or severe pain and 1 or more of the symptoms enumerated in Table 3, onset of relief began as early as 10 minutes following a 6 mg sumatriptan injection. Lower doses of sumatriptan injection may also prove effective, although the proportion of patients obtaining adequate relief was decreased and the latency to that relief is greater with lower doses." }

In Study 1, 6 different doses of sumatriptan injection (n = 30 each group) were compared with placebo (n = 62) in a single-attack, parallel-group design; the dose-response relationship was found to be as shown in Table 2.

{ "type": "p", "children": [], "text": "In Study 1, 6 different doses of sumatriptan injection (n = 30 each group) were compared with placebo (n = 62) in a single-attack, parallel-group design; the dose-response relationship was found to be as shown in Table 2." }

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 2: Proportion of Patients with Migraine Relief and Incidence of Adverse Reactions by Time and by Sumatriptan Dose in Study 1</span> </caption> <col align="left" valign="top" width="20%"/> <col align="center" valign="top" width="16%"/> <col align="center" valign="top" width="16%"/> <col align="center" valign="top" width="16%"/> <col align="center" valign="top" width="16%"/> <col align="center" valign="top" width="16%"/> <thead> <tr class="Botrule First"> <th align="center" class="Lrule Rrule" rowspan="2" valign="middle">Dose of sumatriptan Injection</th><th align="center" class="Rrule" colspan="4">Percent Patients with Relief<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></th><th align="center" class="Rrule" rowspan="2">Adverse Reactions Incidence<br/>(%)</th> </tr> <tr class="Last"> <th align="center" class="Rrule">at 10 Minutes</th><th align="center" class="Rrule">at 30 Minutes</th><th align="center" class="Rrule">at 1 Hour</th><th align="center" class="Rrule">at 2 Hours</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Relief is defined as the reduction of moderate or severe pain to no or mild pain after dosing without use of rescue medication.</dd> <dt> <a href="#footnote-reference-2" name="footnote-2">†</a> </dt> <dd>Efficacy of Tosymra nasal spray was demonstrated based on bioavailability to 4 mg sumatriptan SC injection.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td align="left" class="Lrule Rrule">Placebo</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">15</td><td align="center" class="Rrule">24</td><td align="center" class="Rrule">21</td><td align="center" class="Rrule">55</td> </tr> <tr> <td align="left" class="Lrule Rrule">1 mg</td><td align="center" class="Rrule">10</td><td align="center" class="Rrule">40</td><td align="center" class="Rrule">43</td><td align="center" class="Rrule">40</td><td align="center" class="Rrule">63</td> </tr> <tr> <td align="left" class="Lrule Rrule">2 mg</td><td align="center" class="Rrule">7</td><td align="center" class="Rrule">23</td><td align="center" class="Rrule">57</td><td align="center" class="Rrule">43</td><td align="center" class="Rrule">63</td> </tr> <tr> <td align="left" class="Lrule Rrule">3 mg</td><td align="center" class="Rrule">17</td><td align="center" class="Rrule">47</td><td align="center" class="Rrule">57</td><td align="center" class="Rrule">60</td><td align="center" class="Rrule">77</td> </tr> <tr> <td align="left" class="Lrule Rrule"><span class="Bold">4 mg</span><a class="Sup" href="#footnote-2" name="footnote-reference-2">†</a></td><td align="center" class="Rrule"><span class="Bold">13</span></td><td align="center" class="Rrule"><span class="Bold">37</span></td><td align="center" class="Rrule"><span class="Bold">50</span></td><td align="center" class="Rrule"><span class="Bold">57</span></td><td align="center" class="Rrule"><span class="Bold">80</span></td> </tr> <tr> <td align="left" class="Lrule Rrule">6 mg</td><td align="center" class="Rrule">10</td><td align="center" class="Rrule">63</td><td align="center" class="Rrule">73</td><td align="center" class="Rrule">70</td><td align="center" class="Rrule">83</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">8 mg</td><td align="center" class="Rrule">23</td><td align="center" class="Rrule">57</td><td align="center" class="Rrule">80</td><td align="center" class="Rrule">83</td><td align="center" class="Rrule">93</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"90%\">\n<caption>\n<span>Table 2:\tProportion of Patients with Migraine Relief and Incidence of Adverse Reactions by Time and by Sumatriptan Dose in Study 1</span>\n</caption>\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<col align=\"center\" valign=\"top\" width=\"16%\"/>\n<col align=\"center\" valign=\"top\" width=\"16%\"/>\n<col align=\"center\" valign=\"top\" width=\"16%\"/>\n<col align=\"center\" valign=\"top\" width=\"16%\"/>\n<col align=\"center\" valign=\"top\" width=\"16%\"/>\n<thead>\n<tr class=\"Botrule First\">\n<th align=\"center\" class=\"Lrule Rrule\" rowspan=\"2\" valign=\"middle\">Dose of sumatriptan Injection</th><th align=\"center\" class=\"Rrule\" colspan=\"4\">Percent Patients with Relief<a class=\"Sup\" href=\"#footnote-1\" name=\"footnote-reference-1\">*</a></th><th align=\"center\" class=\"Rrule\" rowspan=\"2\">Adverse Reactions Incidence<br/>(%)</th>\n</tr>\n<tr class=\"Last\">\n<th align=\"center\" class=\"Rrule\">at 10 Minutes</th><th align=\"center\" class=\"Rrule\">at 30 Minutes</th><th align=\"center\" class=\"Rrule\">at 1 Hour</th><th align=\"center\" class=\"Rrule\">at 2 Hours</th>\n</tr>\n</thead>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"6\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-1\" name=\"footnote-1\">*</a>\n</dt>\n<dd>Relief is defined as the reduction of moderate or severe pain to no or mild pain after dosing without use of rescue medication.</dd>\n<dt>\n<a href=\"#footnote-reference-2\" name=\"footnote-2\">†</a>\n</dt>\n<dd>Efficacy of Tosymra nasal spray was demonstrated based on bioavailability to 4 mg sumatriptan SC injection.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\" class=\"Lrule Rrule\">Placebo</td><td align=\"center\" class=\"Rrule\">5</td><td align=\"center\" class=\"Rrule\">15</td><td align=\"center\" class=\"Rrule\">24</td><td align=\"center\" class=\"Rrule\">21</td><td align=\"center\" class=\"Rrule\">55</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">1 mg</td><td align=\"center\" class=\"Rrule\">10</td><td align=\"center\" class=\"Rrule\">40</td><td align=\"center\" class=\"Rrule\">43</td><td align=\"center\" class=\"Rrule\">40</td><td align=\"center\" class=\"Rrule\">63</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">2 mg</td><td align=\"center\" class=\"Rrule\">7</td><td align=\"center\" class=\"Rrule\">23</td><td align=\"center\" class=\"Rrule\">57</td><td align=\"center\" class=\"Rrule\">43</td><td align=\"center\" class=\"Rrule\">63</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">3 mg</td><td align=\"center\" class=\"Rrule\">17</td><td align=\"center\" class=\"Rrule\">47</td><td align=\"center\" class=\"Rrule\">57</td><td align=\"center\" class=\"Rrule\">60</td><td align=\"center\" class=\"Rrule\">77</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">4 mg</span><a class=\"Sup\" href=\"#footnote-2\" name=\"footnote-reference-2\">†</a></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">13</span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">37</span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">50</span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">57</span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">80</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">6 mg</td><td align=\"center\" class=\"Rrule\">10</td><td align=\"center\" class=\"Rrule\">63</td><td align=\"center\" class=\"Rrule\">73</td><td align=\"center\" class=\"Rrule\">70</td><td align=\"center\" class=\"Rrule\">83</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\">8 mg</td><td align=\"center\" class=\"Rrule\">23</td><td align=\"center\" class=\"Rrule\">57</td><td align=\"center\" class=\"Rrule\">80</td><td align=\"center\" class=\"Rrule\">83</td><td align=\"center\" class=\"Rrule\">93</td>\n</tr>\n</tbody>\n</table></div>" }

In 2 randomized, placebo-controlled clinical trials of sumatriptan injection 6 mg in 1,104 patients with moderate or severe migraine pain (Studies 2 and 3), the onset of relief was less than 10 minutes. Headache relief, as defined by a reduction in pain from severe or moderately severe to mild or no headache, was achieved in 70% of the patients within 1 hour of a single 6 mg subcutaneous dose of sumatriptan injection. Approximately 82% and 65% of patients treated with sumatriptan 6 mg had headache relief and were pain free within 2 hours, respectively.

{ "type": "p", "children": [], "text": "In 2 randomized, placebo-controlled clinical trials of sumatriptan injection 6 mg in 1,104 patients with moderate or severe migraine pain (Studies 2 and 3), the onset of relief was less than 10 minutes. Headache relief, as defined by a reduction in pain from severe or moderately severe to mild or no headache, was achieved in 70% of the patients within 1 hour of a single 6 mg subcutaneous dose of sumatriptan injection. Approximately 82% and 65% of patients treated with sumatriptan 6 mg had headache relief and were pain free within 2 hours, respectively." }

Table 3 shows the 1- and 2-hour efficacy results for sumatriptan injection 6 mg in Studies 2 and 3.

{ "type": "p", "children": [], "text": "Table 3 shows the 1- and 2-hour efficacy results for sumatriptan injection 6 mg in Studies 2 and 3." }

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 3: Proportion of Patients with Pain Relief and Relief of Migraine Symptoms after 1 and 2 Hours of Treatment in Studies 2 and 3</span> </caption> <col align="left" valign="top" width="35%"/> <col align="center" valign="top" width="16%"/> <col align="center" valign="top" width="16%"/> <col align="center" valign="top" width="16%"/> <col align="center" valign="top" width="17%"/> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-3" name="footnote-3">*</a> </dt> <dd>P&lt;0.05 versus placebo.</dd> <dt> <a href="#footnote-reference-4" name="footnote-4">†</a> </dt> <dd>A successful outcome in terms of clinical disability was defined prospectively as ability to work mildly impaired or ability to work and function normally.</dd> <dt> <a href="#footnote-reference-5" name="footnote-5">‡</a> </dt> <dd>Includes patients that may have received an additional placebo injection 1 hour after the initial injection.</dd> <dt> <a href="#footnote-reference-6" name="footnote-6">§</a> </dt> <dd>Includes patients that may have received an additional 6 mg of sumatriptan injection 1 hour after the initial injection.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" rowspan="2" valign="bottom"><span class="Bold">1-Hour Data</span></td><td align="center" class="Rrule" colspan="2"><span class="Bold">Study 2</span></td><td align="center" class="Rrule" colspan="2"><span class="Bold">Study 3</span></td> </tr> <tr class="Botrule"> <td align="center" class="Rrule" valign="bottom"><span class="Bold">Placebo<br/>(n = 190)</span></td><td align="center" class="Rrule"><span class="Bold">Sumatriptan Injection<br/>6 mg<br/>(n = 384)</span></td><td align="center" class="Rrule" valign="bottom"><span class="Bold">Placebo<br/>(n = 180)</span></td><td align="center" class="Rrule"><span class="Bold">Sumatriptan Injection<br/>6 mg<br/>(n = 350)</span></td> </tr> <tr> <td align="left" class="Lrule Rrule">Patients with pain relief (Grade 0/1)</td><td align="center" class="Rrule">18%</td><td align="center" class="Rrule">70%<a class="Sup" href="#footnote-3" name="footnote-reference-3">*</a></td><td align="center" class="Rrule">26%</td><td align="center" class="Rrule">70%<a class="Sup" href="#footnote-3">*</a></td> </tr> <tr> <td align="left" class="Lrule Rrule">Patients with no pain</td><td align="center" class="Rrule">5%</td><td align="center" class="Rrule">48%<a class="Sup" href="#footnote-3">*</a></td><td align="center" class="Rrule">13%</td><td align="center" class="Rrule">49%<a class="Sup" href="#footnote-3">*</a></td> </tr> <tr> <td align="left" class="Lrule Rrule">Patients without nausea</td><td align="center" class="Rrule">48%</td><td align="center" class="Rrule">73%<a class="Sup" href="#footnote-3">*</a></td><td align="center" class="Rrule">50%</td><td align="center" class="Rrule">73%<a class="Sup" href="#footnote-3">*</a></td> </tr> <tr> <td align="left" class="Lrule Rrule">Patients without photophobia</td><td align="center" class="Rrule">23%</td><td align="center" class="Rrule">56%<a class="Sup" href="#footnote-3">*</a></td><td align="center" class="Rrule">25%</td><td align="center" class="Rrule">58%<a class="Sup" href="#footnote-3">*</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Patients with little or no clinical disability<a class="Sup" href="#footnote-4" name="footnote-reference-4">†</a></td><td align="center" class="Rrule">34%</td><td align="center" class="Rrule">76%<a class="Sup" href="#footnote-3">*</a></td><td align="center" class="Rrule">34%</td><td align="center" class="Rrule">76%<a class="Sup" href="#footnote-3">*</a></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" rowspan="2" valign="bottom"><span class="Bold">2-Hour Data</span></td><td align="center" class="Rrule" colspan="2"><span class="Bold">Study 2</span></td><td align="center" class="Rrule" colspan="2"><span class="Bold">Study 3</span></td> </tr> <tr class="Botrule"> <td align="center" class="Rrule" valign="bottom"><span class="Bold">Placebo</span><a class="Sup" href="#footnote-5" name="footnote-reference-5">‡</a></td><td align="center" class="Rrule"><span class="Bold">Sumatriptan Injection<br/>6 mg</span><a class="Sup" href="#footnote-6" name="footnote-reference-6">§</a></td><td align="center" class="Rrule" valign="bottom"><span class="Bold">Placebo</span><a class="Sup" href="#footnote-5">‡</a></td><td align="center" class="Rrule"><span class="Bold">Sumatriptan Injection<br/>6 mg</span><a class="Sup" href="#footnote-6">§</a></td> </tr> <tr> <td align="left" class="Lrule Rrule">Patients with pain relief (Grade 0/1)</td><td align="center" class="Rrule">31%</td><td align="center" class="Rrule">81%<a class="Sup" href="#footnote-3">*</a></td><td align="center" class="Rrule">39%</td><td align="center" class="Rrule">82%<a class="Sup" href="#footnote-3">*</a></td> </tr> <tr> <td align="left" class="Lrule Rrule">Patients with no pain</td><td align="center" class="Rrule">11%</td><td align="center" class="Rrule">63%<a class="Sup" href="#footnote-3">*</a></td><td align="center" class="Rrule">19%</td><td align="center" class="Rrule">65%<a class="Sup" href="#footnote-3">*</a></td> </tr> <tr> <td align="left" class="Lrule Rrule">Patients without nausea</td><td align="center" class="Rrule">56%</td><td align="center" class="Rrule">82%<a class="Sup" href="#footnote-3">*</a></td><td align="center" class="Rrule">63%</td><td align="center" class="Rrule">81%<a class="Sup" href="#footnote-3">*</a></td> </tr> <tr> <td align="left" class="Lrule Rrule">Patients without photophobia</td><td align="center" class="Rrule">31%</td><td align="center" class="Rrule">72%<a class="Sup" href="#footnote-3">*</a></td><td align="center" class="Rrule">35%</td><td align="center" class="Rrule">71%<a class="Sup" href="#footnote-3">*</a></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Patients with little or no clinical disability<a class="Sup" href="#footnote-4">†</a></td><td align="center" class="Rrule">42%</td><td align="center" class="Rrule">85%<a class="Sup" href="#footnote-3">*</a></td><td align="center" class="Rrule">49%</td><td align="center" class="Rrule">84%<a class="Sup" href="#footnote-3">*</a></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"90%\">\n<caption>\n<span>Table 3:\tProportion of Patients with Pain Relief and Relief of Migraine Symptoms after 1 and 2 Hours of Treatment in Studies 2 and 3</span>\n</caption>\n<col align=\"left\" valign=\"top\" width=\"35%\"/>\n<col align=\"center\" valign=\"top\" width=\"16%\"/>\n<col align=\"center\" valign=\"top\" width=\"16%\"/>\n<col align=\"center\" valign=\"top\" width=\"16%\"/>\n<col align=\"center\" valign=\"top\" width=\"17%\"/>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"5\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-3\" name=\"footnote-3\">*</a>\n</dt>\n<dd>P&lt;0.05 versus placebo.</dd>\n<dt>\n<a href=\"#footnote-reference-4\" name=\"footnote-4\">†</a>\n</dt>\n<dd>A successful outcome in terms of clinical disability was defined prospectively as ability to work mildly impaired or ability to work and function normally.</dd>\n<dt>\n<a href=\"#footnote-reference-5\" name=\"footnote-5\">‡</a>\n</dt>\n<dd>Includes patients that may have received an additional placebo injection 1 hour after the initial injection.</dd>\n<dt>\n<a href=\"#footnote-reference-6\" name=\"footnote-6\">§</a>\n</dt>\n<dd>Includes patients that may have received an additional 6 mg of sumatriptan injection 1 hour after the initial injection.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" rowspan=\"2\" valign=\"bottom\"><span class=\"Bold\">1-Hour Data</span></td><td align=\"center\" class=\"Rrule\" colspan=\"2\"><span class=\"Bold\">Study 2</span></td><td align=\"center\" class=\"Rrule\" colspan=\"2\"><span class=\"Bold\">Study 3</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Rrule\" valign=\"bottom\"><span class=\"Bold\">Placebo<br/>(n = 190)</span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Sumatriptan Injection<br/>6 mg<br/>(n = 384)</span></td><td align=\"center\" class=\"Rrule\" valign=\"bottom\"><span class=\"Bold\">Placebo<br/>(n = 180)</span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Sumatriptan Injection<br/>6 mg<br/>(n = 350)</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">Patients with pain relief (Grade 0/1)</td><td align=\"center\" class=\"Rrule\">18%</td><td align=\"center\" class=\"Rrule\">70%<a class=\"Sup\" href=\"#footnote-3\" name=\"footnote-reference-3\">*</a></td><td align=\"center\" class=\"Rrule\">26%</td><td align=\"center\" class=\"Rrule\">70%<a class=\"Sup\" href=\"#footnote-3\">*</a></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">Patients with no pain</td><td align=\"center\" class=\"Rrule\">5%</td><td align=\"center\" class=\"Rrule\">48%<a class=\"Sup\" href=\"#footnote-3\">*</a></td><td align=\"center\" class=\"Rrule\">13%</td><td align=\"center\" class=\"Rrule\">49%<a class=\"Sup\" href=\"#footnote-3\">*</a></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">Patients without nausea</td><td align=\"center\" class=\"Rrule\">48%</td><td align=\"center\" class=\"Rrule\">73%<a class=\"Sup\" href=\"#footnote-3\">*</a></td><td align=\"center\" class=\"Rrule\">50%</td><td align=\"center\" class=\"Rrule\">73%<a class=\"Sup\" href=\"#footnote-3\">*</a></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">Patients without photophobia</td><td align=\"center\" class=\"Rrule\">23%</td><td align=\"center\" class=\"Rrule\">56%<a class=\"Sup\" href=\"#footnote-3\">*</a></td><td align=\"center\" class=\"Rrule\">25%</td><td align=\"center\" class=\"Rrule\">58%<a class=\"Sup\" href=\"#footnote-3\">*</a></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Patients with little or no clinical disability<a class=\"Sup\" href=\"#footnote-4\" name=\"footnote-reference-4\">†</a></td><td align=\"center\" class=\"Rrule\">34%</td><td align=\"center\" class=\"Rrule\">76%<a class=\"Sup\" href=\"#footnote-3\">*</a></td><td align=\"center\" class=\"Rrule\">34%</td><td align=\"center\" class=\"Rrule\">76%<a class=\"Sup\" href=\"#footnote-3\">*</a></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" rowspan=\"2\" valign=\"bottom\"><span class=\"Bold\">2-Hour Data</span></td><td align=\"center\" class=\"Rrule\" colspan=\"2\"><span class=\"Bold\">Study 2</span></td><td align=\"center\" class=\"Rrule\" colspan=\"2\"><span class=\"Bold\">Study 3</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Rrule\" valign=\"bottom\"><span class=\"Bold\">Placebo</span><a class=\"Sup\" href=\"#footnote-5\" name=\"footnote-reference-5\">‡</a></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Sumatriptan Injection<br/>6 mg</span><a class=\"Sup\" href=\"#footnote-6\" name=\"footnote-reference-6\">§</a></td><td align=\"center\" class=\"Rrule\" valign=\"bottom\"><span class=\"Bold\">Placebo</span><a class=\"Sup\" href=\"#footnote-5\">‡</a></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Sumatriptan Injection<br/>6 mg</span><a class=\"Sup\" href=\"#footnote-6\">§</a></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">Patients with pain relief (Grade 0/1)</td><td align=\"center\" class=\"Rrule\">31%</td><td align=\"center\" class=\"Rrule\">81%<a class=\"Sup\" href=\"#footnote-3\">*</a></td><td align=\"center\" class=\"Rrule\">39%</td><td align=\"center\" class=\"Rrule\">82%<a class=\"Sup\" href=\"#footnote-3\">*</a></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">Patients with no pain</td><td align=\"center\" class=\"Rrule\">11%</td><td align=\"center\" class=\"Rrule\">63%<a class=\"Sup\" href=\"#footnote-3\">*</a></td><td align=\"center\" class=\"Rrule\">19%</td><td align=\"center\" class=\"Rrule\">65%<a class=\"Sup\" href=\"#footnote-3\">*</a></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">Patients without nausea</td><td align=\"center\" class=\"Rrule\">56%</td><td align=\"center\" class=\"Rrule\">82%<a class=\"Sup\" href=\"#footnote-3\">*</a></td><td align=\"center\" class=\"Rrule\">63%</td><td align=\"center\" class=\"Rrule\">81%<a class=\"Sup\" href=\"#footnote-3\">*</a></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">Patients without photophobia</td><td align=\"center\" class=\"Rrule\">31%</td><td align=\"center\" class=\"Rrule\">72%<a class=\"Sup\" href=\"#footnote-3\">*</a></td><td align=\"center\" class=\"Rrule\">35%</td><td align=\"center\" class=\"Rrule\">71%<a class=\"Sup\" href=\"#footnote-3\">*</a></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\">Patients with little or no clinical disability<a class=\"Sup\" href=\"#footnote-4\">†</a></td><td align=\"center\" class=\"Rrule\">42%</td><td align=\"center\" class=\"Rrule\">85%<a class=\"Sup\" href=\"#footnote-3\">*</a></td><td align=\"center\" class=\"Rrule\">49%</td><td align=\"center\" class=\"Rrule\">84%<a class=\"Sup\" href=\"#footnote-3\">*</a></td>\n</tr>\n</tbody>\n</table></div>" }

Sumatriptan injection also relieved photophobia, phonophobia (sound sensitivity), nausea, and vomiting associated with migraine attacks.

{ "type": "p", "children": [], "text": "Sumatriptan injection also relieved photophobia, phonophobia (sound sensitivity), nausea, and vomiting associated with migraine attacks." }

The efficacy of sumatriptan injection was unaffected by whether or not the migraine was associated with aura, duration of attack, gender or age of the patient, or concomitant use of common migraine prophylactic drugs (e.g., beta-blockers).

{ "type": "p", "children": [], "text": "The efficacy of sumatriptan injection was unaffected by whether or not the migraine was associated with aura, duration of attack, gender or age of the patient, or concomitant use of common migraine prophylactic drugs (e.g., beta-blockers)." }

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F).

Do not store in the refrigerator or freezer. Do not test before use.

Risk of Myocardial Ischemia and/or Infarction, Prinzmetal's Angina, Other Vasospasm-Related Events, Arrhythmias, and Cerebrovascular Events

Inform patients that TOSYMRA may cause serious cardiovascular side effects such as myocardial infarction or stroke. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, irregular heartbeat, significant rise in blood pressure, weakness, and slurring of speech and should ask for medical advice when observing any indicative sign or symptoms are observed. Apprise patients of the importance of this follow-up [see Warnings and Precautions (5.1, 5.2, 5.4, 5.5, 5.8)].

Hypersensitivity Reactions

Inform patients that anaphylactic reactions 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 [see Contraindications (4) and Warnings and Precautions (5.9)].

Concomitant Use with Other Triptans or Ergot Medications

Inform patients that use of TOSYMRA within 24 hours of another triptan or an ergot-type medication (including dihydroergotamine or methylsergide) is contraindicated [see Contraindications (4), Drug Interactions (7.1, 7.3)].

Serotonin Syndrome

Caution patients about the risk of serotonin syndrome with the use of TOSYMRA or other triptans, particularly during combined use with SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7), Drug Interactions (7.4)].

Medication Overuse Headache

Inform patients that use of acute migraine drugs for 10 or more days per month may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6)].

Pregnancy

Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant [see Use in Specific Populations (8.1)].

Lactation

Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.2)].

Ability to Perform Complex Tasks

Treatment with TOSYMRA may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks during migraine attacks and after administration of TOSYMRA.

Local Irritation

Inform patients that they may experience local irritation of their nose, mouth, and throat; and changes in taste [see Warnings and Precautions (5.11)].

How to Use TOSYMRA

Provide patients instruction on the proper use of TOSYMRA. Caution patients to avoid spraying the contents of the device in their eyes.

Manufactured for TONIX MEDICINES, INC..Chatham, NJ 07928

{ "type": "p", "children": [], "text": "Manufactured for\nTONIX MEDICINES, INC..Chatham, NJ 07928" }

TOSYMRA is a registered trademark of Tonix Medicines, Inc.

{ "type": "p", "children": [], "text": "TOSYMRA is a registered trademark of Tonix Medicines, Inc." }

This product may be covered by one or more U.S. patent(s).

{ "type": "p", "children": [], "text": "This product may be covered by one or more U.S. patent(s)." }

Revised: 10/2023

{ "type": "p", "children": [], "text": "Revised: 10/2023" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule" colspan="4">Patient Information<br/>TOSYMRA<span class="Sup">®</span> (toe-SIM-ruh)<br/>(sumatriptan)<br/>Nasal Spray</th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="3">This Patient Information has been approved by the U.S. Food and Drug Administration.</td><td align="right">Revised: 10/2023</td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold"><a name="important"></a>What is the most important information I should know about TOSYMRA?<br/>TOSYMRA can cause serious side effects, including:<br/>Heart attack and other heart problems. Heart problems may lead to death.<br/>Stop taking TOSYMRA and get emergency medical help right away if you have any of the following symptoms of a heart attack:</span> <ul class="Disc"> <li>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</li> <li>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</li> <li>pain or discomfort in your arms, back, neck, jaw, or stomach</li> <li>shortness of breath with or without chest discomfort</li> <li>breaking out in a cold sweat</li> <li>nausea or vomiting</li> <li>feeling lightheaded</li> </ul>TOSYMRA is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. You have a higher risk for heart disease if you:<ul class="Disc"> <li>have high blood pressure</li> <li>have high cholesterol levels</li> <li>smoke</li> <li>are overweight</li> <li>have diabetes</li> <li>have a family history of heart disease</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">What is TOSYMRA?</span> <br/>TOSYMRA is a prescription medicine used to treat acute migraine headaches with or without aura in adults.<br/>TOSYMRA is not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines.<br/>TOSYMRA is not used to prevent or decrease the number of migraines you have. TOSYMRA is not used to treat cluster headaches.<br/>It is not known if TOSYMRA is safe and effective in children under 18 years of age.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Do not take TOSYMRA if you have:</span> <ul class="Disc"> <li>heart problems or a history of heart problems</li> <li>narrowing of blood vessels to your legs, arms, stomach, or kidney (peripheral vascular disease)</li> <li>uncontrolled high blood pressure</li> <li>severe liver problems</li> <li>hemiplegic migraines or basilar migraines. If you are not sure if you have these types of migraines, ask your healthcare provider.</li> <li>had a stroke, transient ischemic attacks (TIAs), or problems with your blood circulation</li> <li>taken any of the following medicines in the last 24 hours:<ul class="Circle"> <li>almotriptan</li> <li>eletriptan</li> <li>frovatriptan</li> <li>naratriptan</li> <li>rizatriptan</li> <li>ergotamines</li> <li>dihydroergotamine</li> </ul>Ask your healthcare provider if you are not sure if your medicine is listed above.</li> </ul> <ul> <li>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 healthcare provider or pharmacist for a list of these medicines if you are not sure.</li> <li>an allergy to sumatriptan or any of the ingredients in TOSYMRA. See the end of this Patient Information leaflet for a complete list of ingredients in TOSYMRA.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Before taking TOSYMRA, tell your healthcare provider about all of your medical conditions, including if you:</span> <ul class="Disc"> <li>have high blood pressure.</li> <li>have high cholesterol.</li> <li>have diabetes.</li> <li>smoke.</li> <li>are overweight.</li> <li>have heart problems or family history of heart problems or stroke.</li> <li>have kidney problems.</li> <li>have liver problems.</li> <li>have had epilepsy or seizures.</li> <li>are not using effective birth control.</li> <li>are pregnant or plan to become pregnant. It is not known if TOSYMRA can harm your unborn baby.</li> <li>are breastfeeding or plan to breastfeed. TOSYMRA passes into your breast milk. It is not known if this can harm your baby. Talk with your healthcare provider about the best way to feed your baby if you take TOSYMRA.</li> </ul> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements.<br/>TOSYMRA and certain other medicines can affect each other, causing serious side effects.<br/> <span class="Bold">Especially tell your healthcare provider if</span> you take anti-depressant medicines called:<ul class="Disc"> <li>selective serotonin reuptake inhibitors (SSRIs)</li> <li>serotonin norepinephrine reuptake inhibitors (SNRIs)</li> <li>tricyclic antidepressants (TCAs)</li> <li>monoamine oxidase inhibitors (MAOIs)</li> </ul>Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure.<br/>Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">How should I take TOSYMRA?</span> <ul class="Disc"> <li>See the <a href="#IFU">Instructions for Use</a> for complete information on how to use TOSYMRA nasal spray.</li> <li>Certain people should take their first dose of TOSYMRA in their healthcare provider's office or in another medical setting. Ask your healthcare provider if you should take your first dose in a medical setting.</li> <li>Use TOSYMRA exactly as your healthcare provider tells you to use it.</li> <li>You should take TOSYMRA as soon as the symptoms of your headache start, but it may be taken at any time during a migraine.</li> <li>If your headache comes back after the first nasal spray or you only get some relief from your headache, you can use a second nasal spray 1 hour after the first nasal spray.</li> <li>Do not use more than 30 mg of TOSYMRA Nasal Spray in a 24-hour period.</li> <li>If you use too much TOSYMRA, call your healthcare provider or go to the nearest hospital emergency room right away.</li> <li>You should write down when you have headaches and when you take TOSYMRA, so you can talk with your healthcare provider about how TOSYMRA is working for you.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">What should I avoid while taking TOSYMRA?</span> <br/>TOSYMRA can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery, or do anything where you need to be alert.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">What are the possible side effects of TOSYMRA?<br/>TOSYMRA may cause serious side effects.</span> See "<a href="#important">What is the most important information I should know about TOSYMRA?</a>"<br/>These serious side effects include:<ul class="Disc"> <li>changes in color or sensation in your fingers and toes (Raynaud's syndrome)</li> <li>stomach and intestinal problems (gastrointestinal and colonic ischemic events). Symptoms of gastrointestinal and colonic ischemic events include:<ul class="Circle"> <li>sudden or severe stomach pain</li> <li>stomach pain after meals</li> <li>weight loss</li> <li>nausea or vomiting</li> <li>constipation or diarrhea</li> <li>bloody diarrhea</li> <li>fever</li> </ul> </li> <li>problems with blood circulation to your legs and feet (peripheral vascular ischemia). Symptoms of peripheral vascular ischemia include:<ul class="Circle"> <li>cramping and pain in your legs or hips</li> <li>feeling of heaviness or tightness in your leg muscles</li> <li>burning or aching pain in your feet or toes while resting</li> <li>numbness, tingling, or weakness in your legs</li> <li>cold feeling or color changes in 1 or both legs or feet</li> </ul> </li> <li>medication overuse headaches. Some people who use too much migraine medicine, such as TOSYMRA, for 10 or more days each month may have worse headaches (medication overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with TOSYMRA.</li> <li>serotonin syndrome. Serotonin syndrome is a rare but serious problem that can happen in people using TOSYMRA, especially if TOSYMRA is used with anti-depressant medicines called SSRIs or SNRIs. Call your healthcare provider right away if you have any of the following symptoms of serotonin syndrome:<ul class="Circle"> <li>mental changes such as seeing things that are not there (hallucinations), agitation, or coma</li> <li>fast heartbeat</li> <li>changes in blood pressure</li> <li>high body temperature</li> <li>tight muscles</li> <li>trouble walking</li> </ul> </li> <li>increased blood pressure including a sudden severe increase (hypertensive crisis) even if you have no history of high blood pressure.</li> <li>hives (itchy bumps); swelling of your tongue, mouth, or throat.</li> <li>seizures. Seizures have happened in people taking TOSYMRA who have never had seizures before. Talk with your healthcare provider about your chance of having seizures while you take TOSYMRA.</li> </ul>The most common side effects of TOSYMRA include:</td> </tr> <tr> <td align="left" class="Lrule"> <ul class="Disc"> <li>tingling</li> <li>feeling of heaviness</li> <li>numbness</li> </ul> </td><td align="left"> <ul class="Disc"> <li>dizziness</li> <li>feeling of pressure</li> <li>application site (nasal) reactions</li> </ul> </td><td align="left"> <ul class="Disc"> <li>feeling warm or hot</li> <li>flushing</li> <li>abnormal taste</li> </ul> </td><td align="left" class="Rrule"> <ul class="Disc"> <li>burning feeling</li> <li>feeling of tightness</li> <li>throat irritation</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4">Tell your healthcare provider if you have any side effect that bothers you or that does not go away.<br/>These are not all the possible side effects of TOSYMRA. For more information, ask your healthcare provider or pharmacist.<br/>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">How should I store TOSYMRA?</span> <ul class="Disc"> <li>Store between 68° to 77°F (20° to 25°C)</li> <li>Do not store in the refrigerator or freeze.</li> <li>Do not test before use.</li> </ul> <span class="Bold">Keep TOSYMRA and all medicines out of the reach of children.</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">General information about the safe and effective use of TOSYMRA.</span> <br/>Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use TOSYMRA for a condition for which it was not prescribed. Do not give TOSYMRA to other people, even if they have the same symptoms you have. It may harm them.<br/>You can ask your healthcare provider or pharmacist for information about TOSYMRA that is written for healthcare professionals.<br/>For more information, go to www.TOSYMRA.com or call 1-888-869-7633 (1-888-TNXPMED).</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">What are the ingredients in TOSYMRA?</span> <br/>Active ingredient: sumatriptan<br/>Inactive ingredients: citric acid monohydrate, n-Dodecyl beta-D-maltoside, potassium phosphate monobasic, sodium chloride, and sodium phosphate dibasic anhydrous in water for injection.<br/>Manufactured for<br/> <span class="Bold">TONIX MEDICINES, INC.</span> <br/>Chatham, NJ 07928<br/>TOSYMRA is a registered trademark of Tonix Medicines, Inc.<br/>This product may be covered by one or more U.S. patent(s). </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"center\" class=\"Lrule Rrule\" colspan=\"4\">Patient Information<br/>TOSYMRA<span class=\"Sup\">®</span> (toe-SIM-ruh)<br/>(sumatriptan)<br/>Nasal Spray</th>\n</tr>\n</thead>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"3\">This Patient Information has been approved by the U.S. Food and Drug Administration.</td><td align=\"right\">Revised: 10/2023</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\"><a name=\"important\"></a>What is the most important information I should know about TOSYMRA?<br/>TOSYMRA can cause serious side effects, including:<br/>Heart attack and other heart problems. Heart problems may lead to death.<br/>Stop taking TOSYMRA and get emergency medical help right away if you have any of the following symptoms of a heart attack:</span>\n<ul class=\"Disc\">\n<li>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</li>\n<li>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</li>\n<li>pain or discomfort in your arms, back, neck, jaw, or stomach</li>\n<li>shortness of breath with or without chest discomfort</li>\n<li>breaking out in a cold sweat</li>\n<li>nausea or vomiting</li>\n<li>feeling lightheaded</li>\n</ul>TOSYMRA is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. You have a higher risk for heart disease if you:<ul class=\"Disc\">\n<li>have high blood pressure</li>\n<li>have high cholesterol levels</li>\n<li>smoke</li>\n<li>are overweight</li>\n<li>have diabetes</li>\n<li>have a family history of heart disease</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">What is TOSYMRA?</span>\n<br/>TOSYMRA is a prescription medicine used to treat acute migraine headaches with or without aura in adults.<br/>TOSYMRA is not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines.<br/>TOSYMRA is not used to prevent or decrease the number of migraines you have. TOSYMRA is not used to treat cluster headaches.<br/>It is not known if TOSYMRA is safe and effective in children under 18 years of age.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Do not take TOSYMRA if you have:</span>\n<ul class=\"Disc\">\n<li>heart problems or a history of heart problems</li>\n<li>narrowing of blood vessels to your legs, arms, stomach, or kidney (peripheral vascular disease)</li>\n<li>uncontrolled high blood pressure</li>\n<li>severe liver problems</li>\n<li>hemiplegic migraines or basilar migraines. If you are not sure if you have these types of migraines, ask your healthcare provider.</li>\n<li>had a stroke, transient ischemic attacks (TIAs), or problems with your blood circulation</li>\n<li>taken any of the following medicines in the last 24 hours:<ul class=\"Circle\">\n<li>almotriptan</li>\n<li>eletriptan</li>\n<li>frovatriptan</li>\n<li>naratriptan</li>\n<li>rizatriptan</li>\n<li>ergotamines</li>\n<li>dihydroergotamine</li>\n</ul>Ask your healthcare provider if you are not sure if your medicine is listed above.</li>\n</ul>\n<ul>\n<li>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 healthcare provider or pharmacist for a list of these medicines if you are not sure.</li>\n<li>an allergy to sumatriptan or any of the ingredients in TOSYMRA. See the end of this Patient Information leaflet for a complete list of ingredients in TOSYMRA.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Before taking TOSYMRA, tell your healthcare provider about all of your medical conditions, including if you:</span>\n<ul class=\"Disc\">\n<li>have high blood pressure.</li>\n<li>have high cholesterol.</li>\n<li>have diabetes.</li>\n<li>smoke.</li>\n<li>are overweight.</li>\n<li>have heart problems or family history of heart problems or stroke.</li>\n<li>have kidney problems.</li>\n<li>have liver problems.</li>\n<li>have had epilepsy or seizures.</li>\n<li>are not using effective birth control.</li>\n<li>are pregnant or plan to become pregnant. It is not known if TOSYMRA can harm your unborn baby.</li>\n<li>are breastfeeding or plan to breastfeed. TOSYMRA passes into your breast milk. It is not known if this can harm your baby. Talk with your healthcare provider about the best way to feed your baby if you take TOSYMRA.</li>\n</ul>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements.<br/>TOSYMRA and certain other medicines can affect each other, causing serious side effects.<br/>\n<span class=\"Bold\">Especially tell your healthcare provider if</span> you take anti-depressant medicines called:<ul class=\"Disc\">\n<li>selective serotonin reuptake inhibitors (SSRIs)</li>\n<li>serotonin norepinephrine reuptake inhibitors (SNRIs)</li>\n<li>tricyclic antidepressants (TCAs)</li>\n<li>monoamine oxidase inhibitors (MAOIs)</li>\n</ul>Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure.<br/>Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">How should I take TOSYMRA?</span>\n<ul class=\"Disc\">\n<li>See the <a href=\"#IFU\">Instructions for Use</a> for complete information on how to use TOSYMRA nasal spray.</li>\n<li>Certain people should take their first dose of TOSYMRA in their healthcare provider's office or in another medical setting. Ask your healthcare provider if you should take your first dose in a medical setting.</li>\n<li>Use TOSYMRA exactly as your healthcare provider tells you to use it.</li>\n<li>You should take TOSYMRA as soon as the symptoms of your headache start, but it may be taken at any time during a migraine.</li>\n<li>If your headache comes back after the first nasal spray or you only get some relief from your headache, you can use a second nasal spray 1 hour after the first nasal spray.</li>\n<li>Do not use more than 30 mg of TOSYMRA Nasal Spray in a 24-hour period.</li>\n<li>If you use too much TOSYMRA, call your healthcare provider or go to the nearest hospital emergency room right away.</li>\n<li>You should write down when you have headaches and when you take TOSYMRA, so you can talk with your healthcare provider about how TOSYMRA is working for you.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">What should I avoid while taking TOSYMRA?</span>\n<br/>TOSYMRA can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery, or do anything where you need to be alert.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">What are the possible side effects of TOSYMRA?<br/>TOSYMRA may cause serious side effects.</span> See \"<a href=\"#important\">What is the most important information I should know about TOSYMRA?</a>\"<br/>These serious side effects include:<ul class=\"Disc\">\n<li>changes in color or sensation in your fingers and toes (Raynaud's syndrome)</li>\n<li>stomach and intestinal problems (gastrointestinal and colonic ischemic events). Symptoms of gastrointestinal and colonic ischemic events include:<ul class=\"Circle\">\n<li>sudden or severe stomach pain</li>\n<li>stomach pain after meals</li>\n<li>weight loss</li>\n<li>nausea or vomiting</li>\n<li>constipation or diarrhea</li>\n<li>bloody diarrhea</li>\n<li>fever</li>\n</ul>\n</li>\n<li>problems with blood circulation to your legs and feet (peripheral vascular ischemia). Symptoms of peripheral vascular ischemia include:<ul class=\"Circle\">\n<li>cramping and pain in your legs or hips</li>\n<li>feeling of heaviness or tightness in your leg muscles</li>\n<li>burning or aching pain in your feet or toes while resting</li>\n<li>numbness, tingling, or weakness in your legs</li>\n<li>cold feeling or color changes in 1 or both legs or feet</li>\n</ul>\n</li>\n<li>medication overuse headaches. Some people who use too much migraine medicine, such as TOSYMRA, for 10 or more days each month may have worse headaches (medication overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with TOSYMRA.</li>\n<li>serotonin syndrome. Serotonin syndrome is a rare but serious problem that can happen in people using TOSYMRA, especially if TOSYMRA is used with anti-depressant medicines called SSRIs or SNRIs. Call your healthcare provider right away if you have any of the following symptoms of serotonin syndrome:<ul class=\"Circle\">\n<li>mental changes such as seeing things that are not there (hallucinations), agitation, or coma</li>\n<li>fast heartbeat</li>\n<li>changes in blood pressure</li>\n<li>high body temperature</li>\n<li>tight muscles</li>\n<li>trouble walking</li>\n</ul>\n</li>\n<li>increased blood pressure including a sudden severe increase (hypertensive crisis) even if you have no history of high blood pressure.</li>\n<li>hives (itchy bumps); swelling of your tongue, mouth, or throat.</li>\n<li>seizures. Seizures have happened in people taking TOSYMRA who have never had seizures before. Talk with your healthcare provider about your chance of having seizures while you take TOSYMRA.</li>\n</ul>The most common side effects of TOSYMRA include:</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\">\n<ul class=\"Disc\">\n<li>tingling</li>\n<li>feeling of heaviness</li>\n<li>numbness</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>dizziness</li>\n<li>feeling of pressure</li>\n<li>application site (nasal) reactions</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>feeling warm or hot</li>\n<li>flushing</li>\n<li>abnormal taste</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Disc\">\n<li>burning feeling</li>\n<li>feeling of tightness</li>\n<li>throat irritation</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">Tell your healthcare provider if you have any side effect that bothers you or that does not go away.<br/>These are not all the possible side effects of TOSYMRA. For more information, ask your healthcare provider or pharmacist.<br/>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">How should I store TOSYMRA?</span>\n<ul class=\"Disc\">\n<li>Store between 68° to 77°F (20° to 25°C)</li>\n<li>Do not store in the refrigerator or freeze.</li>\n<li>Do not test before use.</li>\n</ul>\n<span class=\"Bold\">Keep TOSYMRA and all medicines out of the reach of children.</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">General information about the safe and effective use of TOSYMRA.</span>\n<br/>Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use TOSYMRA for a condition for which it was not prescribed. Do not give TOSYMRA to other people, even if they have the same symptoms you have. It may harm them.<br/>You can ask your healthcare provider or pharmacist for information about TOSYMRA that is written for healthcare professionals.<br/>For more information, go to www.TOSYMRA.com or call 1-888-869-7633 (1-888-TNXPMED).</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">What are the ingredients in TOSYMRA?</span>\n<br/>Active ingredient: sumatriptan<br/>Inactive ingredients: citric acid monohydrate, n-Dodecyl beta-D-maltoside, potassium phosphate monobasic, sodium chloride, and sodium phosphate dibasic anhydrous in water for injection.<br/>Manufactured for<br/>\n<span class=\"Bold\">TONIX MEDICINES, INC.</span>\n<br/>Chatham, NJ 07928<br/>TOSYMRA is a registered trademark of Tonix Medicines, Inc.<br/>This product may be covered by one or more U.S. patent(s). </td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <col align="center" valign="top" width="50%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule" colspan="3">Instructions for Use<br/>TOSYMRA<span class="Sup">®</span> (toe-SIM-ruh)<br/>(sumatriptan)<br/>Nasal Spray</th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="2">This Instructions for Use has been approved by the U.S. Food and Drug Administration.</td><td align="right">Revised: 10/2023</td> </tr> </tfoot> <tbody> <tr class="First"> <td align="center" class="Lrule"><span class="Bold">About TOSYMRA</span></td><td align="center"><span class="Bold">Important Information</span></td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule"><span class="Bold">Read this Instructions for Use before you start using TOSYMRA and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about TOSYMRA, ask your healthcare provider or pharmacist.</span> <ul class="Disc"> <li> <span class="Bold">Only 1 device is needed to deliver a full dose (See <a href="#figureA">Figure A</a>).</span> </li> <li> <span class="Bold">The device gives a single spray that should be delivered into 1 nostril.</span> </li> <li> <span class="Bold">Never use more than 1 device or dose into more than 1 nostril.</span> </li> </ul> </td><td align="left"> <ul class="Disc"> <li> <span class="Bold">Keep TOSYMRA and all medicines out of reach of children.</span> </li> <li> <span class="Bold">Do not</span> remove the device from its packaging until ready to use.</li> <li> <span class="Bold">Do not</span> test the spray or press the plunger before giving a dose into the nostril.</li> <li> <span class="Bold">Do not</span> use after the expiration date has passed.</li> </ul> <span class="Bold">        Storage Information</span> <ul class="Disc"> <li>The device should be stored at room temperature between 68° to 77°F (20° to 25°C).</li> <li> <span class="Bold">Do not</span> store in the refrigerator or freezer.</li> <li>Always keep the device in the sealed blister package until time of use.</li> </ul> </td><td align="center" class="Rrule"><a name="figureA"></a><img alt="Figure A" src="/dailymed/image.cfm?name=tosymra-02.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Instructions for Use</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 1 – Gently Blow Your Nose</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2" valign="top">While sitting upright, gently blow your nose to clear your nostrils <span class="Bold">(See <a href="#figureB">Figure B</a>)</span>.</td><td align="center" class="Rrule"><a name="figureB"></a><img alt="Figure B" src="/dailymed/image.cfm?name=tosymra-03.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 2 – Remove 1 Device from Carton</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2" valign="top">Remove only 1 device from the carton <span class="Bold">(See <a href="#figureC">Figure C</a>)</span>.<br/> <span class="Bold">Do not use more than 1 device to get your dose.</span></td><td align="center" class="Rrule"><a name="figureC"></a><img alt="Figure C" src="/dailymed/image.cfm?name=tosymra-04.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 3 – Check the Expiration Date on Back of Blister Package</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2" valign="top">Check the expiration date on the back of the blister package <span class="Bold">(See <a href="#figureD">Figure D</a>)</span>.<br/> <span class="Bold">Do not use if the expiration date has passed. Throw away the expired device in the household trash if the expiration date has passed.</span></td><td align="center" class="Rrule"><a name="figureD"></a><img alt="Figure D" src="/dailymed/image.cfm?name=tosymra-05.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 4 – Remove Device from Blister Package</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2" valign="top">Peel off the paper backing completely from the blister package.<br/>Flip the blister package onto your hand to remove the device from its packaging <span class="Bold">(See <a href="#figureE">Figure E</a>)</span>.</td><td align="center" class="Rrule"><a name="figureE"></a><img alt="Figure E" src="/dailymed/image.cfm?name=tosymra-06.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3" valign="top"><span class="Bold">Step 5 <span class="Italics">–</span> Check the Expiration Date on the Device</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2" valign="top">Check the expiration date on the device <span class="Bold">(See <a href="#figureF">Figure F</a>)</span>.<br/> <span class="Bold">Do not use the device if the expiration date has passed. Throw away the expired device in the household trash if the expiration date has passed.</span></td><td align="center" class="Rrule"><a name="figureF"></a><img alt="Figure F" src="/dailymed/image.cfm?name=tosymra-07.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 6 – Close 1 Nostril</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2" valign="top">Gently press 1 nostril with your finger to keep it closed <span class="Bold">(See <a href="#figureG">Figure G</a>)</span>.</td><td align="center" class="Rrule"><a name="figureG"></a><img alt="Figure G" src="/dailymed/image.cfm?name=tosymra-08.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 7 – Place Spray Nozzle in Open Nostril</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2" valign="top">Hold the device upright between your thumb and first 2 fingers <span class="Bold">(See <a href="#figureH-I">Figure H</a>)</span>.<br/>Insert half of the spray nozzle into the open nostril and angle outward <span class="Bold">(See <a href="#figureH-I">Figure I</a>)</span>.</td><td align="center" class="Rrule"><a name="figureH-I"></a><img alt="Figure H-I" src="/dailymed/image.cfm?name=tosymra-09.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 8 – Tilt Head Back Slightly</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2" valign="top">While keeping the device in your nose, tilt your head back slightly <span class="Bold">(See <a href="#figureJ">Figure J</a>)</span>.<br/>This will allow the medicine to go into your nasal passage without dripping out.</td><td align="center" class="Rrule"><a name="figureJ"></a><img alt="Figure J" src="/dailymed/image.cfm?name=tosymra-10.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 9 – Deliver the Dose</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2" valign="top">As you slowly breathe through your nose, firmly press the plunger all the way up to release the dose <span class="Bold">(See <a href="#figureK">Figure K</a>)</span>.<br/> <span class="Bold">Note:</span> The plunger is stiff so make sure to press firmly.</td><td align="center" class="Rrule"><a name="figureK"></a><img alt="Figure K" src="/dailymed/image.cfm?name=tosymra-11.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 10 – Remove Device and Breathe Gently for 10 to 20 Seconds</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2" valign="top">Remove the device from your nostril. While keeping your head upright, gently breathe in through your nose and breathe out through your mouth. Repeat this for 10 to 20 seconds <span class="Bold">(See <a href="#figureL">Figure L</a>)</span>.<br/>It is normal for you to feel liquid in your nose or at the back of your throat.<br/> <span class="Bold">Do not look down because the medicine may drip from your nose.</span> <br/> <span class="Bold">Do not breathe in deeply.</span></td><td align="center" class="Rrule"><a name="figureL"></a><img alt="Figure L" src="/dailymed/image.cfm?name=tosymra-12.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Step 11 – Dispose of the Used Device</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2" valign="top">Throw away the used device and its packaging into your household trash <span class="Bold">(See <a href="#figureM">Figure M</a>)</span>.<br/> <span class="Bold">You have received your full dose, if you have:</span> <dl> <dt>🗸</dt> <dd>Used 1 device</dd> <dt>🗸</dt> <dd>Given 1 spray into 1 nostril</dd> </dl> </td><td align="center" class="Rrule"><a name="figureM"></a><img alt="Figure M" src="/dailymed/image.cfm?name=tosymra-13.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5"/></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="3">Manufactured for<br/> <span class="Bold">TONIX MEDICINES, INC.</span> <br/>Chatham, NJ 07928<br/>TOSYMRA is a registered trademark of Tonix Medicines, Inc.<br/>This product may be covered by one or more U.S. patent(s).</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"50%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"center\" class=\"Lrule Rrule\" colspan=\"3\">Instructions for Use<br/>TOSYMRA<span class=\"Sup\">®</span> (toe-SIM-ruh)<br/>(sumatriptan)<br/>Nasal Spray</th>\n</tr>\n</thead>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"2\">This Instructions for Use has been approved by the U.S. Food and Drug Administration.</td><td align=\"right\">Revised: 10/2023</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td align=\"center\" class=\"Lrule\"><span class=\"Bold\">About TOSYMRA</span></td><td align=\"center\"><span class=\"Bold\">Important Information</span></td><td align=\"center\" class=\"Rrule\"></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule\"><span class=\"Bold\">Read this Instructions for Use before you start using TOSYMRA and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about TOSYMRA, ask your healthcare provider or pharmacist.</span>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Only 1 device is needed to deliver a full dose (See <a href=\"#figureA\">Figure A</a>).</span>\n</li>\n<li>\n<span class=\"Bold\">The device gives a single spray that should be delivered into 1 nostril.</span>\n</li>\n<li>\n<span class=\"Bold\">Never use more than 1 device or dose into more than 1 nostril.</span>\n</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Keep TOSYMRA and all medicines out of reach of children.</span>\n</li>\n<li>\n<span class=\"Bold\">Do not</span> remove the device from its packaging until ready to use.</li>\n<li>\n<span class=\"Bold\">Do not</span> test the spray or press the plunger before giving a dose into the nostril.</li>\n<li>\n<span class=\"Bold\">Do not</span> use after the expiration date has passed.</li>\n</ul>\n<span class=\"Bold\">        Storage Information</span>\n<ul class=\"Disc\">\n<li>The device should be stored at room temperature between 68° to 77°F (20° to 25°C).</li>\n<li>\n<span class=\"Bold\">Do not</span> store in the refrigerator or freezer.</li>\n<li>Always keep the device in the sealed blister package until time of use.</li>\n</ul>\n</td><td align=\"center\" class=\"Rrule\"><a name=\"figureA\"></a><img alt=\"Figure A\" src=\"/dailymed/image.cfm?name=tosymra-02.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Instructions for Use</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 1 – Gently Blow Your Nose</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">While sitting upright, gently blow your nose to clear your nostrils <span class=\"Bold\">(See <a href=\"#figureB\">Figure B</a>)</span>.</td><td align=\"center\" class=\"Rrule\"><a name=\"figureB\"></a><img alt=\"Figure B\" src=\"/dailymed/image.cfm?name=tosymra-03.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 2 – Remove 1 Device from Carton</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">Remove only 1 device from the carton <span class=\"Bold\">(See <a href=\"#figureC\">Figure C</a>)</span>.<br/>\n<span class=\"Bold\">Do not use more than 1 device to get your dose.</span></td><td align=\"center\" class=\"Rrule\"><a name=\"figureC\"></a><img alt=\"Figure C\" src=\"/dailymed/image.cfm?name=tosymra-04.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 3 – Check the Expiration Date on Back of Blister Package</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">Check the expiration date on the back of the blister package <span class=\"Bold\">(See <a href=\"#figureD\">Figure D</a>)</span>.<br/>\n<span class=\"Bold\">Do not use if the expiration date has passed. Throw away the expired device in the household trash if the expiration date has passed.</span></td><td align=\"center\" class=\"Rrule\"><a name=\"figureD\"></a><img alt=\"Figure D\" src=\"/dailymed/image.cfm?name=tosymra-05.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 4 – Remove Device from Blister Package</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">Peel off the paper backing completely from the blister package.<br/>Flip the blister package onto your hand to remove the device from its packaging <span class=\"Bold\">(See <a href=\"#figureE\">Figure E</a>)</span>.</td><td align=\"center\" class=\"Rrule\"><a name=\"figureE\"></a><img alt=\"Figure E\" src=\"/dailymed/image.cfm?name=tosymra-06.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\"><span class=\"Bold\">Step 5 <span class=\"Italics\">–</span> Check the Expiration Date on the Device</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">Check the expiration date on the device <span class=\"Bold\">(See <a href=\"#figureF\">Figure F</a>)</span>.<br/>\n<span class=\"Bold\">Do not use the device if the expiration date has passed. Throw away the expired device in the household trash if the expiration date has passed.</span></td><td align=\"center\" class=\"Rrule\"><a name=\"figureF\"></a><img alt=\"Figure F\" src=\"/dailymed/image.cfm?name=tosymra-07.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 6 – Close 1 Nostril</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">Gently press 1 nostril with your finger to keep it closed <span class=\"Bold\">(See <a href=\"#figureG\">Figure G</a>)</span>.</td><td align=\"center\" class=\"Rrule\"><a name=\"figureG\"></a><img alt=\"Figure G\" src=\"/dailymed/image.cfm?name=tosymra-08.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 7 – Place Spray Nozzle in Open Nostril</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">Hold the device upright between your thumb and first 2 fingers <span class=\"Bold\">(See <a href=\"#figureH-I\">Figure H</a>)</span>.<br/>Insert half of the spray nozzle into the open nostril and angle outward <span class=\"Bold\">(See <a href=\"#figureH-I\">Figure I</a>)</span>.</td><td align=\"center\" class=\"Rrule\"><a name=\"figureH-I\"></a><img alt=\"Figure H-I\" src=\"/dailymed/image.cfm?name=tosymra-09.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 8 – Tilt Head Back Slightly</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">While keeping the device in your nose, tilt your head back slightly <span class=\"Bold\">(See <a href=\"#figureJ\">Figure J</a>)</span>.<br/>This will allow the medicine to go into your nasal passage without dripping out.</td><td align=\"center\" class=\"Rrule\"><a name=\"figureJ\"></a><img alt=\"Figure J\" src=\"/dailymed/image.cfm?name=tosymra-10.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 9 – Deliver the Dose</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">As you slowly breathe through your nose, firmly press the plunger all the way up to release the dose <span class=\"Bold\">(See <a href=\"#figureK\">Figure K</a>)</span>.<br/>\n<span class=\"Bold\">Note:</span> The plunger is stiff so make sure to press firmly.</td><td align=\"center\" class=\"Rrule\"><a name=\"figureK\"></a><img alt=\"Figure K\" src=\"/dailymed/image.cfm?name=tosymra-11.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 10 – Remove Device and Breathe Gently for 10 to 20 Seconds</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">Remove the device from your nostril. While keeping your head upright, gently breathe in through your nose and breathe out through your mouth. Repeat this for 10 to 20 seconds <span class=\"Bold\">(See <a href=\"#figureL\">Figure L</a>)</span>.<br/>It is normal for you to feel liquid in your nose or at the back of your throat.<br/>\n<span class=\"Bold\">Do not look down because the medicine may drip from your nose.</span>\n<br/>\n<span class=\"Bold\">Do not breathe in deeply.</span></td><td align=\"center\" class=\"Rrule\"><a name=\"figureL\"></a><img alt=\"Figure L\" src=\"/dailymed/image.cfm?name=tosymra-12.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Step 11 – Dispose of the Used Device</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">Throw away the used device and its packaging into your household trash <span class=\"Bold\">(See <a href=\"#figureM\">Figure M</a>)</span>.<br/>\n<span class=\"Bold\">You have received your full dose, if you have:</span>\n<dl>\n<dt>🗸</dt>\n<dd>Used 1 device</dd>\n<dt>🗸</dt>\n<dd>Given 1 spray into 1 nostril</dd>\n</dl>\n</td><td align=\"center\" class=\"Rrule\"><a name=\"figureM\"></a><img alt=\"Figure M\" src=\"/dailymed/image.cfm?name=tosymra-13.jpg&amp;setid=d9f682f0-d50a-4fe6-ab1b-e5a7ec27b3a5\"/></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\">Manufactured for<br/>\n<span class=\"Bold\">TONIX MEDICINES, INC.</span>\n<br/>Chatham, NJ 07928<br/>TOSYMRA is a registered trademark of Tonix Medicines, Inc.<br/>This product may be covered by one or more U.S. patent(s).</td>\n</tr>\n</tbody>\n</table></div>" }

TONIXMEDICINES

{ "type": "p", "children": [], "text": "TONIXMEDICINES" }

NDC 70792-812-61Rx only

{ "type": "p", "children": [], "text": "NDC 70792-812-61Rx only" }

tosymra® (sumatriptan nasal spray) 10 mg

{ "type": "p", "children": [], "text": "tosymra®\n(sumatriptan nasal spray) 10 mg" }

This box contains six (6) unit-dose nasal spray devices.Each unit-dose contains 10 mg of sumatriptan in 0.1 mL.

{ "type": "p", "children": [], "text": "This box contains six (6) unit-dose nasal spray devices.Each unit-dose contains 10 mg of sumatriptan in 0.1 mL." }

For Intranasal Use Only

{ "type": "p", "children": [], "text": "For Intranasal Use Only" }

1 spray per unit.Do not test before use.

{ "type": "p", "children": [], "text": "1 spray per unit.Do not test before use." }