Sumatriptan Nasal Spray

Dosage Form: nasal spray

Sumatriptan Nasal Spray

Sumatriptan Nasal Spray Description

Sumatriptan Nasal Spray contains sumatriptan, a selective 5-hydroxytryptamine1 receptor subtype agonist. Sumatriptan is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide, and it has the following structure:

The empirical formula is C14H21N3O2S, representing a molecular weight of 295.4. Sumatriptan is a white to off-white powder that is readily soluble in water and in saline. Each Sumatriptan Nasal Spray contains 5 or 20 mg of sumatriptan in a 100-μL unit dose aqueous buffered solution containing monobasic potassium phosphate NF, anhydrous dibasic sodium phosphate USP, sulfuric acid NF, sodium hydroxide NF, and purified water USP. The pH of the solution is approximately 5.5. The osmolality of the solution is 372 or 742 mOsmol for the 5- and 20-mg Sumatriptan Nasal Spray, respectively.

Sumatriptan Nasal Spray - Clinical Pharmacology

Mechanism of Action

Sumatriptan is an agonist for a vascular 5‑hydroxytryptamine1 receptor subtype (probably a member of the 5‑HT1D family) having only a weak affinity for 5‑HT1A, 5‑HT5A, and 5‑HT7 receptors and no significant affinity (as measured using standard radioligand binding assays) or pharmacological activity at 5‑HT2, 5‑HT3, or 5‑HT4 receptor subtypes or at alpha1-, alpha2-, or beta‑adrenergic; dopamine1; dopamine2; muscarinic; or benzodiazepine receptors.

The vascular 5‑HT1 receptor subtype that sumatriptan activates is present on cranial arteries in both dog and primate, on the human basilar artery, and in the vasculature of human dura mater and mediates vasoconstriction. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that sumatriptan also activates 5‑HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels. Such an action may contribute to the antimigrainous effect of sumatriptan in humans.

In the anesthetized dog, sumatriptan selectively reduces the carotid arterial blood flow with little or no effect on arterial blood pressure or total peripheral resistance. In the cat, sumatriptan selectively constricts the carotid arteriovenous anastomoses while having little effect on blood flow or resistance in cerebral or extracerebral tissues.

Pharmacokinetics

In a study of 20 female volunteers, the mean maximum concentration following a 5- and 20‑mg intranasal dose was 5 and 16 ng/mL, respectively. The mean Cmax following a 6‑mg subcutaneous injection is 71 ng/mL (range: 49 to 110 ng/mL). The mean Cmax is 18 ng/mL (range: 7 to 47 ng/mL) following oral dosing with 25 mg and 51 ng/mL (range: 28 to 100 ng/mL) following oral dosing with 100 mg of sumatriptan. In a study of 24 male volunteers, the bioavailability relative to subcutaneous injection was low, approximately 17%, primarily due to presystemic metabolism and partly due to incomplete absorption.

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, but would be expected to be minor, given the low rate of protein binding. The mean volume of distribution after subcutaneous dosing is 2.7 L/kg and the total plasma clearance is approximately 1,200 mL/min.

The elimination half‑life of sumatriptan administered as a nasal spray is approximately 2 hours, similar to the half‑life seen after subcutaneous injection. Only 3% of the dose is excreted in the urine as unchanged sumatriptan; 42% of the dose is excreted as the major metabolite, the indole acetic acid analogue of sumatriptan.

Clinical and pharmacokinetic data indicate that administration of two 5‑mg doses, 1 dose in each nostril, is equivalent to administration of a single 10‑mg dose in 1 nostril.

Special Populations

Renal Impairment: The effect of renal impairment on the pharmacokinetics of sumatriptan has not been examined, but little clinical effect would be expected as sumatriptan is largely metabolized to an inactive substance.

Hepatic Impairment: The effect of hepatic disease on the pharmacokinetics of subcutaneously and orally administered sumatriptan has been evaluated, but the intranasal dosage form has not been studied in hepatic impairment. There were no statistically significant differences in the pharmacokinetics of subcutaneously administered sumatriptan in hepatically impaired patients compared with healthy controls. However, the liver plays an important role in the presystemic clearance of orally administered sumatriptan. In 1 small study involving oral sumatriptan in hepatically impaired patients (N = 8) matched for sex, age, and weight with healthy subjects, the hepatically impaired patients had an approximately 70% increase in AUC and Cmax and a Tmax 40 minutes earlier compared with the healthy subjects. The bioavailability of nasally absorbed sumatriptan following intranasal administration, which would not undergo first‑pass metabolism, should not be altered in hepatically impaired patients. The bioavailability of the swallowed portion of the intranasal sumatriptan dose has not been determined, but would be increased in these patients. The swallowed intranasal dose is small, however, compared with the usual oral dose, so that its impact should be minimal.

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 (see PRECAUTIONS: Geriatric Use).

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

Drug Interactions

Monoamine Oxidase Inhibitors: Treatment with monoamine oxidase inhibitors (MAOIs) generally leads to an increase of sumatriptan plasma levels (see CONTRAINDICATIONS and PRECAUTIONS).

MAOI interaction studies have not been performed with intranasal sumatriptan. Due to gut and hepatic metabolic first‑pass effects, the increase of systemic exposure after coadministration of an MAO‑A inhibitor with oral sumatriptan is greater than after coadministration of the MAOI with subcutaneous sumatriptan. The effects of an MAOI 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 study of 14 healthy females, pretreatment with an MAO‑A inhibitor decreased the clearance of subcutaneous sumatriptan. Under the conditions of this experiment, the result was a 2‑fold increase in the area under the sumatriptan plasma concentration x time curve (AUC), corresponding to a 40% increase in elimination half‑life. This interaction was not evident with an MAO‑B inhibitor.

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 study indicated that 3 drops of xylometazoline (0.1% w/v), a decongestant, administered 15 minutes prior to a 20‑mg nasal dose of sumatriptan did not alter the pharmacokinetics of sumatriptan.

Clinical Trials

The efficacy of Sumatriptan Nasal Spray in the acute treatment of migraine headaches was demonstrated in 8, randomized, double-blind, placebo-controlled studies, of which 5 used the recommended dosing regimen and used the marketed formulation. Patients enrolled in these 5 studies were predominately female (86%) and Caucasian (95%), with a mean age of 41 (range of 18 to 65). 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 2 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 Nasal Spray or other medication was allowed 2 to 24 hours after the initial treatment for recurrent headache. The frequency and time to use of these additional treatments were also determined. In all studies, doses of 10 and 20 mg were compared with placebo in the treatment of 1 to 3 migraine attacks. Patients received doses as a single spray into 1 nostril. In 2 studies, a 5-mg dose was also evaluated.

In all 5 trials utilizing the market formulation and recommended dosage regimen, the percentage of patients achieving headache response 2 hours after treatment was significantly greater among patients receiving Sumatriptan Nasal Spray at all doses (with one exception) compared with those who received placebo. In 4 of the 5 studies, there was a statistically significant greater percentage of patients with headache response at 2 hours in the 20-mg group when compared with the lower dose groups (5 and 10 mg). There were no statistically significant differences between the 5- and 10-mg dose groups in any study. The results from the 5 controlled clinical trials are summarized in Table 1. Note that, in general, comparisons of results obtained in studies conducted under different conditions by different investigators with different samples of patients are ordinarily unreliable for purposes of quantitative comparison.

Table 1. Percentage of Patients With Headache Response (No or Mild Pain) 2 Hours Following Treatment

Placebo

Sumatriptan Nasal Spray

5 mg

Sumatriptan Nasal Spray

10 mg

Sumatriptan Nasal Spray

20 mg

Study 1

25%

49%a

46%a

64%abc

(n = 63)

(n = 121)

(n = 112)

(n = 118)

Study 2

25%

Not applicable

44%a

55%ab

(n = 138)

(n = 273)

(n = 277)

Study 3

35%

Not applicable

54%a

63%a

(n = 100)

(n = 106)

(n = 202)

Study 4

29%

Not applicable

43%

62%ab

(n = 112)

(n = 106)

(n = 215)

Study 5d

36%

45%a

53%a

60%ac

(n = 198)

(n = 296)

(n = 291)

(n = 286)

aP<0.05 in comparison with placebo.

bP<0.05 in comparison with 10 mg.

cP<0.05 in comparison with 5 mg.

dData are for attack 1 only of multiattack study for comparison.

The estimated probability of achieving an initial headache response over the 2 hours following treatment is depicted in Figure 1.

Figure 1. Estimated Probability of Achieving Initial Headache Response Within 120 Minutesa

aThe figure shows the probability over time of obtaining headache response (no or mild pain) following treatment with intranasal sumatriptan. The averages displayed are based on pooled data from the 5 clinical controlled trials providing evidence of efficacy. Kaplan-Meier plot with patients not achieving response within 120 minutes censored to 120 minutes.

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 Sumatriptan Nasal Spray compared with placebo.

Two to 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 or Other Medication for Migraine Over the 24 Hours Following the Initial Dose of Study Treatmenta

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 20 mg do not provide a greater effect than 20 mg. There was no evidence to suggest that treatment with sumatriptan was associated with an increase in the severity of recurrent headaches. The efficacy of Sumatriptan Nasal Spray was unaffected by presence of aura; duration of headache prior to treatment; gender, age, or weight of the patient; 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.

Indications and Usage for Sumatriptan Nasal Spray

Sumatriptan Nasal Spray is indicated for the acute treatment of migraine attacks with or without aura in adults.

Sumatriptan Nasal Spray is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine (see CONTRAINDICATIONS). Safety and effectiveness of Sumatriptan Nasal Spray have not been established for cluster headache, which is present in an older, predominantly male population.

Contraindications

Sumatriptan Nasal Spray should not be given to patients with history, symptoms, or signs of ischemic cardiac, cerebrovascular, or peripheral vascular syndromes. In addition, patients with other significant underlying cardiovascular diseases should not receive Sumatriptan Nasal Spray. Ischemic cardiac syndromes include, but are not limited to, angina pectoris of any type (e.g., stable angina of effort, vasospastic forms of angina such as the Prinzmetal variant), all forms of myocardial infarction, and silent myocardial ischemia. Cerebrovascular syndromes include, but are not limited to, strokes of any type as well as transient ischemic attacks. Peripheral vascular disease includes, but is not limited to, ischemic bowel disease (see WARNINGS).

Because Sumatriptan Nasal Spray may increase blood pressure, it should not be given to patients with uncontrolled hypertension.

Concurrent administration of MAO-A inhibitors or use within 2 weeks of discontinuation of MAO-A inhibitor therapy is contraindicated (see CLINICAL PHARMACOLOGY: Drug Interactions and PRECAUTIONS: Drug Interactions).

Sumatriptan Nasal Spray and any ergotamine-containing or ergot-type medication (like dihydroergotamine or methysergide) should not be used within 24 hours of each other, nor should Sumatriptan Nasal Spray and another 5-HT1 agonist.

Sumatriptan Nasal Spray should not be administered to patients with hemiplegic or basilar migraine.

Sumatriptan Nasal Spray is contraindicated in patients with hypersensitivity to sumatriptan or any of its components.

Sumatriptan Nasal Spray is contraindicated in patients with severe hepatic impairment.

Warnings

Sumatriptan Nasal Spray should only be used where a clear diagnosis of migraine headache has been established.

Risk of Myocardial Ischemia and/or Infarction and Other Adverse Cardiac Events

Sumatriptan should not be given to patients with documented ischemic or vasospastic coronary artery disease (CAD) (see CONTRAINDICATIONS). It is strongly recommended that sumatriptan not be given to patients in whom unrecognized CAD is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, male over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best. If, during the cardiovascular evaluation, the patient’s medical history or electrocardiographic investigations reveal findings indicative of, or consistent with, coronary artery vasospasm or myocardial ischemia, sumatriptan should not be administered (see CONTRAINDICATIONS).

For patients with risk factors predictive of CAD, who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of Sumatriptan Nasal Spray take place in the setting of a physician’s office or similar medically staffed and equipped facility unless the patient has previously received sumatriptan. Because cardiac ischemia can occur in the absence of clinical symptoms, consideration should be given to obtaining an electrocardiogram (ECG) during the interval immediately following the first dose in these patients with risk factors.

It is recommended that patients who are intermittent long-term users of sumatriptan and who have or acquire risk factors predictive of CAD, as described above, undergo periodic interval cardiovascular evaluation as they continue to use sumatriptan.

The systematic approach described above is intended to reduce the likelihood that patients with unrecognized cardiovascular disease will be inadvertently exposed to sumatriptan.

Drug-Associated Cardiac Events and Fatalities

Serious adverse cardiac events, including acute myocardial infarction, life-threatening disturbances of cardiac rhythm, and death have been reported within a few hours following the administration of sumatriptan injection or tablets. Considering the extent of use of sumatriptan in patients with migraine, the incidence of these events is extremely low.

The fact that sumatriptan can cause coronary vasospasm, that some of these events have occurred in patients with no prior cardiac disease history and with documented absence of CAD, and the close proximity of the events to sumatriptan use support the conclusion that some of these cases were caused by the drug. In many cases, however, where there has been known underlying coronary artery disease, the relationship is uncertain.

Premarketing Experience With Sumatriptan: Among approximately 4,000 patients with migraine who participated in premarketing controlled and uncontrolled clinical trials of Sumatriptan Nasal Spray, 1 patient experienced an asymptomatic subendocardial infarction possibly subsequent to a coronary vasospastic event.

Of 6,348 patients with migraine who participated in premarketing controlled and uncontrolled clinical trials of oral sumatriptan, 2 experienced clinical adverse events shortly after receiving oral sumatriptan that may have reflected coronary vasospasm. Neither of these adverse events was associated with a serious clinical outcome.

Among the more than 1,900 patients with migraine who participated in premarketing controlled clinical trials of subcutaneous sumatriptan, there were 8 patients who sustained clinical events during or shortly after receiving sumatriptan that may have reflected coronary artery vasospasm. Six of these 8 patients had ECG changes consistent with transient ischemia, but without accompanying clinical symptoms or signs. Of these 8 patients, 4 had either findings suggestive of CAD or risk factors predictive of CAD prior to study enrollment.

Postmarketing Experience With Sumatriptan: Serious cardiovascular events, some resulting in death, have been reported in association with the use of sumatriptan injection or tablets. The uncontrolled nature of postmarketing surveillance, however, makes it impossible to determine definitively the proportion of the reported cases that were actually caused by sumatriptan or to reliably assess causation in individual cases. On clinical grounds, the longer the latency between the administration of sumatriptan and the onset of the clinical event, the less likely the association is to be causative. Accordingly, interest has focused on events beginning within 1 hour of the administration of sumatriptan.

Cardiac events that have been observed to have onset within 1 hour of sumatriptan administration include: coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia and ventricular fibrillation, cardiac arrest, and death.

Some of these events occurred in patients who had no findings of CAD and appear to represent consequences of coronary artery vasospasm. However, among domestic reports of serious cardiac events within 1 hour of sumatriptan administration, almost all of the patients had risk factors predictive of CAD and the presence of significant underlying CAD was established in most cases (see CONTRAINDICATIONS).

Drug-Associated Cerebrovascular Events and Fatalities

Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with oral or subcutaneous sumatriptan, and some have resulted in fatalities. The relationship of sumatriptan to these events is uncertain. In a number of cases, it appears possible that the cerebrovascular events were primary, sumatriptan having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, care should be taken to exclude other potentially serious neurological conditions. It should also be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g., cerebrovascular accident, transient ischemic attack).

Other Vasospasm-Related Events

Sumatriptan may cause vasospastic reactions other than coronary artery vasospasm. Both peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea have been reported. Very rare reports of transient and permanent blindness and significant partial vision loss have been reported with the use of sumatriptan. Visual disorders may also be part of a migraine attack.

Serotonin Syndrome

Serotonin syndrome may occur with triptans, including sumatriptan, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). 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 can occur within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Treatment with sumatriptan should be discontinued if serotonin syndrome is suspected.

Increase in Blood Pressure

Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasions in patients with and without a history of hypertension. Sumatriptan is contraindicated in patients with uncontrolled hypertension (see CONTRAINDICATIONS). Sumatriptan should be administered with caution to patients with controlled hypertension as transient increases in blood pressure and peripheral vascular resistance have been observed in a small proportion of patients.

Local Irritation

Of the 3,378 patients using the nasal spray (5-, 10-, or 20-mg doses) on 1 or 2 occasions in controlled clinical studies, approximately 5% noted irritation in the nose and throat. Irritative symptoms such as burning, numbness, paresthesia, discharge, and pain or soreness were noted to be severe in about 1% of patients treated. The symptoms were transient and in approximately 60% of the cases, the symptoms resolved in less than 2 hours. Limited examinations of the nose and throat did not reveal any clinically noticeable injury in these patients.

The consequences of extended and repeated use of Sumatriptan Nasal Spray on the nasal and/or respiratory mucosa have not been systematically evaluated in patients. No increase in the incidence of local irritation was observed in patients using Sumatriptan Nasal Spray repeatedly for up to 1 year.

In inhalation studies in rats dosed daily for up to 1 month at exposures as low as one half the maximum daily human exposure (based on dose per surface area of nasal cavity), epithelial hyperplasia (with and without keratinization) and squamous metaplasia were observed in the larynx at all doses tested. These changes were partially reversible after a 2-week drug-free period. When dogs were dosed daily with various formulations by intranasal instillation for up to 13 weeks at exposures of 2 to 4 times the maximum daily human exposure (based on dose per surface area of nasal cavity), respiratory and nasal mucosa exhibited evidence of epithelial hyperplasia, focal squamous metaplasia, granulomata, bronchitis, and fibrosing alveolitis. A no-effect dose was not established. The changes observed in both species are not considered to be signs of either preneoplastic or neoplastic transformation.

Local effects on nasal and respiratory tissues after chronic intranasal dosing in animals have not been studied.

Concomitant Drug Use

In patients taking MAO-A inhibitors, sumatriptan plasma levels attained after treatment with recommended doses are 2-fold (following subcutaneous administration) to 7-fold (following oral administration) higher than those obtained under other conditions. Accordingly, the coadministration of sumatriptan and an MAO-A inhibitor is contraindicated (see CLINICAL PHARMACOLOGY and CONTRAINDICATIONS).

Hypersensitivity

Hypersensitivity (anaphylaxis/anaphylactoid) reactions have occurred on rare occasions in patients receiving sumatriptan. Such reactions can be life threatening or fatal. In general, hypersensitivity reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens (see CONTRAINDICATIONS).

Precautions

General

Chest discomfort and jaw or neck tightness have been reported infrequently following the administration of Sumatriptan Nasal Spray and have also been reported following use of sumatriptan tablets. Chest, jaw, or neck tightness is relatively common after administration of sumatriptan injection. Only rarely have these symptoms been associated with ischemic ECG changes. However, because sumatriptan may cause coronary artery vasospasm, patients who experience signs or symptoms suggestive of angina following sumatriptan should be evaluated for the presence of CAD or a predisposition to Prinzmetal variant angina before receiving additional doses of sumatriptan, and should be monitored electrocardiographically if dosing is resumed and similar symptoms recur. Similarly, patients who experience other symptoms or signs suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud syndrome following sumatriptan should be evaluated for atherosclerosis or predisposition to vasospasm (see WARNINGS).

Sumatriptan should also be administered with caution to patients with diseases that may alter the absorption, metabolism, or excretion of drugs, such as impaired hepatic or renal function.

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

Care should be taken to exclude other potentially serious neurologic conditions before treating headache in patients not previously diagnosed with migraine headache or who experience a headache that is atypical for them. There have been rare reports where patients received sumatriptan for severe headaches that were subsequently shown to have been secondary to an evolving neurologic lesion (see WARNINGS).

For a given attack, if a patient does not respond to the first dose of sumatriptan, the diagnosis of migraine headache should be reconsidered before administration of a second dose.

Overuse

Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or a combination of 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. Migraine patients should be informed about the risks of medication overuse and encouraged to record headache frequency and drug use.

Information for Patients

See PATIENT INFORMATION at the end of this labeling for the text of the separate leaflet provided for patients.

Patients should be cautioned about the risk of serotonin syndrome with the use of sumatriptan or other triptans, especially during combined use with SSRIs or SNRIs.

Laboratory Tests

No specific laboratory tests are recommended for monitoring patients prior to and/or after treatment with sumatriptan.

Drug Interactions

Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome: Cases of life-threatening serotonin syndrome have been reported during combined use of SSRIs or SNRIs and triptans (see WARNINGS).

Ergot-Containing Drugs: Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because there is a theoretical basis that these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and sumatriptan within 24 hours of each other should be avoided (see CONTRAINDICATIONS).

Monoamine Oxidase-A Inhibitors: MAO-A inhibitors reduce sumatriptan clearance, significantly increasing systemic exposure. Therefore, the use of Sumatriptan Nasal Spray in patients receiving MAO-A inhibitors is contraindicated (see CLINICAL PHARMACOLOGY and CONTRAINDICATIONS).

Drug/Laboratory Test Interactions

Sumatriptan is not known to interfere with commonly employed clinical laboratory tests.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis: In carcinogenicity studies, rats and mice were given sumatriptan by oral gavage (rats: 104 weeks) or drinking water (mice: 78 weeks). Average exposures achieved in mice receiving the highest dose (target dose of 160 mg/kg/day) were approximately 184 times the exposure attained in humans after the maximum recommended single intranasal dose of 20 mg. The highest dose administered to rats (160 mg/kg/day, reduced from 360 mg/kg/day during week 21) was approximately 78 times the maximum recommended single intranasal dose of 20 mg on a mg/m2 basis. There was no evidence of an increase in tumors in either species related to sumatriptan administration. Local effects on nasal and respiratory tissue after chronic intranasal dosing in animals have not been evaluated (see WARNINGS).

Mutagenesis: Sumatriptan was not mutagenic in the presence or absence of metabolic activation when tested in 2 gene mutation assays (the Ames test and the in vitro mammalian Chinese hamster V79/HGPRT assay). In 2 cytogenetics assays (the in vitro human lymphocyte assay and the in vivo rat micronucleus assay) sumatriptan was not associated with clastogenic activity.

Impairment of Fertility: In a study in which male and female rats were dosed daily with oral sumatriptan 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 50 and 500 mg/kg/day. The highest no-effect dose for this finding was 5 mg/kg/day, or approximately twice the maximum recommended single human intranasal dose of 20 mg on a mg/m2 basis. It is not clear whether the problem is associated with treatment of the males or females or both combined. In a similar study by the subcutaneous route there was no evidence of impaired fertility at 60 mg/kg/day, the maximum dose tested, which is equivalent to approximately 29 times the maximum recommended single human intranasal dose of 20 mg on a mg/m2 basis. Fertility studies, in which sumatriptan was administered by the intranasal route, were not conducted.

Pregnancy

Pregnancy Category C. In reproductive toxicity studies in rats and rabbits, oral treatment with sumatriptan was associated with embryolethality, fetal abnormalities, and pup mortality. When administered by the intravenous route to rabbits, sumatriptan has been shown to be embryolethal. Reproductive toxicity studies for sumatriptan by the intranasal route have not been conducted.

There are no adequate and well-controlled studies in pregnant women. Therefore, Sumatriptan Nasal Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In assessing this information, the following findings should be considered.

Embryolethality: When given orally or intravenously to pregnant rabbits daily throughout the period of organogenesis, sumatriptan caused embryolethality at doses at or close to those producing maternal toxicity. In the oral studies this dose was 100 mg/kg/day, and in the intravenous studies this dose was 2.0 mg/kg/day. The mechanism of the embryolethality is not known. The highest no-effect dose for embryolethality by the oral route was 50 mg/kg/day, which is approximately 48 times the maximum single recommended human intranasal dose of 20 mg on a mg/m2 basis. By the intravenous route, the highest no-effect dose was 0.75 mg/kg/day, or approximately 0.7 times the maximum single recommended human intranasal dose of 20 mg on a mg/m2 basis.

The intravenous administration of sumatriptan to pregnant rats throughout organogenesis at 12.5 mg/kg/day, the maximum dose tested, did not cause embryolethality. This dose is approximately 6 times the maximum single recommended human intranasal dose of 20 mg on a mg/m2 basis. Additionally, in a study in rats given subcutaneous sumatriptan daily, prior to and throughout pregnancy, at 60 mg/kg/day, the maximum dose tested, there was no evidence of increased embryo/fetal lethality. This dose is equivalent to approximately 29 times the maximum recommended single human intranasal dose of 20 mg on a mg/m2 basis.

Teratogenicity: Oral treatment of pregnant rats with sumatriptan during the period of organogenesis resulted in an increased incidence of blood vessel abnormalities (cervicothoracic and umbilical) at doses of approximately 250 mg/kg/day or higher. The highest no-effect dose was approximately 60 mg/kg/day, which is approximately 29 times the maximum single recommended human intranasal dose of 20 mg on a mg/m2 basis. Oral treatment of pregnant rabbits with sumatriptan during the period of organogenesis resulted in an increased incidence of cervicothoracic vascular and skeletal abnormalities. The highest no-effect dose for these effects was 15 mg/kg/day, or approximately 14 times the maximum single recommended human intranasal dose of 20 mg on a mg/m2 basis.

A study in which rats were dosed daily with oral sumatriptan prior to and throughout gestation demonstrated embryo/fetal toxicity (decreased body weight, decreased ossification, increased incidence of rib variations) and an increased incidence of a syndrome of malformations (short tail/short body and vertebral disorganization) at 500 mg/kg/day. The highest no-effect dose was 50 mg/kg/day, or approximately 24 times the maximum single recommended human intranasal dose of 20 mg on a mg/m2 basis. In a study in rats dosed daily with subcutaneous sumatriptan prior to and throughout pregnancy, at a dose of 60 mg/kg/day, the maximum dose tested, there was no evidence of teratogenicity. This dose is equivalent to approximately 29 times the maximum recommended single human intranasal dose of 20 mg on a mg/m2 basis.

Pup Deaths: Oral treatment of pregnant rats with sumatriptan during the period of organogenesis resulted in a decrease in pup survival between birth and postnatal day 4 at doses of approximately 250 mg/kg/day or higher. The highest no-effect dose for this effect was approximately 60 mg/kg/day, or 29 times the maximum single recommended human intranasal dose of 20 mg on a mg/m2 basis.

Oral treatment of pregnant rats with sumatriptan from gestational day 17 through postnatal day 21 demonstrated a decrease in pup survival measured at postnatal days 2, 4, and 20 at the dose of 1,000 mg/kg/day. The highest no-effect dose for this finding was 100 mg/kg/day, approximately 49 times the maximum single recommended human intranasal dose of 20 mg on a mg/m2 basis. In a similar study in rats by the subcutaneous route there was no increase in pup death at 81 mg/kg/day, the highest dose tested, which is equivalent to 40 times the maximum single recommended human intranasal dose of 20 mg on a mg/m2 basis.

Nursing Mothers

Sumatriptan is excreted in human breast milk following subcutaneous administration. Infant exposure to sumatriptan can be minimized by avoiding breastfeeding for 12 hours after treatment with Sumatriptan Nasal Spray.

Pediatric Use

Safety and effectiveness of sumatriptan in pediatric patients under 18 years of age have not been established; therefore, Sumatriptan Nasal Spray is not recommended for use in patients under 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 studies did not establish the efficacy of Sumatriptan Nasal Spray compared with placebo in the treatment of migraine in adolescents. Adverse events 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 with placebo in the treatment of migraine in adolescents. Adverse events observed in these clinical trials were similar in nature to those reported in clinical trials in adults. The frequency of all adverse events in these patients appeared to be both dose- and age-dependent, with younger patients reporting events more commonly than older adolescents.

Postmarketing experience documents that serious adverse events have occurred in the pediatric population after use of subcutaneous, oral, and/or intranasal sumatriptan. These reports include events 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. Since clinical data to determine the frequency of serious adverse events in pediatric patients who might receive injectable, oral, or intranasal sumatriptan are not presently available, the use of sumatriptan in patients aged younger than 18 years is not recommended.

Geriatric Use

The use of sumatriptan in elderly patients is not recommended because elderly patients are more likely to have decreased hepatic function, they are at higher risk for CAD, and blood pressure increases may be more pronounced in the elderly (see WARNINGS).

Adverse Reactions

Serious cardiac events, including some that have been fatal, have occurred following the use of sumatriptan injection or tablets. These events are extremely rare and most have been reported in patients with risk factors predictive of CAD. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation (see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS).

Significant hypertensive episodes, including hypertensive crises, have been reported on rare occasions in patients with or without a history of hypertension (see WARNINGS).

Incidence in Controlled Clinical Trials

Among 3,653 patients treated with Sumatriptan Nasal Spray in active- and placebo-controlled clinical trials, less than 0.4% of patients withdrew for reasons related to adverse events. Table 2 lists adverse events that occurred in worldwide placebo-controlled clinical trials in 3,419 migraineurs. The events cited reflect experience gained under closely monitored conditions of clinical trials in a highly selected patient population. In actual clinical practice or in other clinical trials, these frequency estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients treated may differ.

Only events that occurred at a frequency of 1% or more in the Sumatriptan Nasal Spray 20-mg treatment group and were more frequent in that group than in the placebo group are included in Table 2.

Table 2. Treatment-Emergent Adverse Events Reported by at Least 1% of Patients in Controlled Migraine Trials

Adverse Event Type

Percent of Patients Reporting

Placebo (n = 704)

Sumatriptan 5 mg (n = 496)

Sumatriptan 10 mg (n = 1,007)

Sumatriptan 20 mg (n = 1,212)

Atypical sensations

Burning sensation

0.1%

0.4%

0.6%

1.4%

Ear, nose, and throat

Disorder/discomfort of nasal cavity/sinuses

2.4%

2.8%

2.5%

3.8%

Throat discomfort

0.9%

0.8%

1.8%

2.4%

Gastrointestinal

Nausea and/or vomiting

11.3%

12.2%

11.0%

13.5%

Neurological

Bad/unusual taste

1.7%

13.5%

19.3%

24.5%

Dizziness/vertigo

0.9%

1.0%

1.7%

1.4%

Phonophobia also occurred in more than 1% of patients but was more frequent on placebo.

Sumatriptan Nasal Spray is generally well tolerated. Across all doses, most adverse reactions were mild and transient and did not lead to long-lasting effects. The incidence of adverse events in controlled clinical trials was not affected by gender, weight, or age of the patients; use of prophylactic medications; or presence of aura. There were insufficient data to assess the impact of race on the incidence of adverse events.

Other Events Observed in Association With the Administration of Sumatriptan Nasal Spray

In the paragraphs that follow, the frequencies of less commonly reported adverse clinical events are presented. Because the reports include events observed in open and uncontrolled studies, the role of Sumatriptan Nasal Spray in their causation cannot be reliably determined. Furthermore, variability associated with adverse event reporting, the terminology used to describe adverse events, etc., limit the value of the quantitative frequency estimates provided.

Event frequencies are calculated as the number of patients who used Sumatriptan Nasal Spray (5, 10, or 20 mg in controlled and uncontrolled trials) and reported an event divided by the total number of patients (N = 3,711) exposed to Sumatriptan Nasal Spray. All reported events are included except those already listed in the previous table, those too general to be informative, and those not reasonably associated with the use of the drug. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: infrequent adverse events are those occurring in 1/100 to 1/1,000 patients and rare adverse events are those occurring in fewer than 1/1,000 patients.

Atypical Sensations: Infrequent were tingling, warm/hot sensation, numbness, pressure sensation, feeling strange, feeling of heaviness, feeling of tightness, paresthesia, cold sensation, and tight feeling in head. Rare were dysesthesia and prickling sensation.

Cardiovascular: Infrequent were flushing and hypertension (see WARNINGS), palpitations, tachycardia, changes in ECG, and arrhythmia (see WARNINGS and PRECAUTIONS). Rare were abdominal aortic aneurysm, hypotension, bradycardia, pallor, and phlebitis.

Chest Symptoms: Infrequent were chest tightness, chest discomfort, and chest pressure/heaviness (see PRECAUTIONS: General).

Ear, Nose, and Throat: Infrequent were disturbance of hearing and ear infection. Rare were otalgia and Meniere disease.

Endocrine and Metabolic: Infrequent was thirst. Rare were galactorrhea, hypothyroidism, and weight loss.

Eye: Infrequent were irritation of eyes and visual disturbance.

Gastrointestinal: Infrequent were abdominal discomfort, diarrhea, dysphagia, and gastroesophageal reflux. Rare were constipation, flatulence/eructation, hematemesis, intestinal obstruction, melena, gastroenteritis, colitis, hemorrhage of gastrointestinal tract, and pancreatitis.

Mouth and Teeth: Infrequent was disorder of mouth and tongue (e.g., burning of tongue, numbness of tongue, dry mouth).

Musculoskeletal: Infrequent were neck pain/stiffness, backache, weakness, joint symptoms, arthritis, and myalgia. Rare were muscle cramps, tetany, intervertebral disc disorder, and muscle stiffness.

Neurological: Infrequent were drowsiness/sedation, anxiety, sleep disturbances, tremors, syncope, shivers, chills, depression, agitation, sensation of lightness, and mental confusion. Rare were difficulty concentrating, hunger, lacrimation, memory disturbances, monoplegia/diplegia, apathy, disturbance of smell, disturbance of emotions, dysarthria, facial pain, intoxication, stress, decreased appetite, difficulty coordinating, euphoria, and neoplasm of pituitary.

Respiratory: Infrequent were dyspnea and lower respiratory tract infection. Rare was asthma.

Skin: Infrequent were rash/skin eruption, pruritus, and erythema. Rare were herpes, swelling of face, sweating, and peeling of skin.

Urogenital: Infrequent were dysuria, disorder of breasts, and dysmenorrhea. Rare were endometriosis and increased urination.

Miscellaneous: Infrequent were cough, edema, and fever. Rare were hypersensitivity, swelling of extremities, voice disturbances, difficulty in walking, and lymphadenopathy.

Other Events Observed in the Clinical Development of Sumatriptan

The following adverse events occurred in clinical trials with sumatriptan injection and sumatriptan tablets. Because the reports include events observed in open and uncontrolled studies, the role of sumatriptan in their causation cannot be reliably determined. All reported events are included except those already listed, those too general to be informative, and those not reasonably associated with the use of the drug.

Breasts: Breast swelling; cysts, lumps, and masses of breasts; nipple discharge; primary malignant breast neoplasm; and tenderness.

Cardiovascular: Abnormal pulse, angina, atherosclerosis, cerebral ischemia, cerebrovascular lesion, heart block, peripheral cyanosis, pulsating sensations, Raynaud syndrome, thrombosis, transient myocardial ischemia, various transient ECG changes (nonspecific ST or T wave changes, prolongation of PR or QTc intervals, sinus arrhythmia, nonsustained ventricular premature beats, isolated junctional ectopic beats, atrial ectopic beats, delayed activation of the right ventricle), and vasodilation.

Ear, Nose, and Throat: Allergic rhinitis; ear, nose, and throat hemorrhage; external otitis; feeling of fullness in the ear(s); hearing disturbances; hearing loss; nasal inflammation; sensitivity to noise; sinusitis; tinnitus; and upper respiratory inflammation.

Endocrine and Metabolic: Dehydration; endocrine cysts, lumps, and masses; elevated thyrotropin stimulating hormone (TSH) levels; fluid disturbances; hyperglycemia; hypoglycemia; polydipsia; and weight gain.

Eye: Accommodation disorders, blindness and low vision, conjunctivitis, disorders of sclera, external ocular muscle disorders, eye edema and swelling, eye itching, eye hemorrhage, eye pain, keratitis, mydriasis, and vision alterations.

Gastrointestinal: Abdominal distention, dental pain, disturbances of liver function tests, dyspeptic symptoms, feelings of gastrointestinal pressure, gallstones, gastric symptoms, gastritis, gastrointestinal pain, hypersalivation, hyposalivation, oral itching and irritation, peptic ulcer, retching, salivary gland swelling, and swallowing disorders.

Hematological Disorders: Anemia.

Injection Site Reaction

Miscellaneous: Contusions, fluid retention, hematoma, hypersensitivity to various agents, jaw discomfort, miscellaneous laboratory abnormalities, overdose, “serotonin agonist effect,” and speech disturbance.

Musculoskeletal: Acquired musculoskeletal deformity, arthralgia and articular rheumatitis, muscle atrophy, muscle tiredness, musculoskeletal inflammation, need to flex calf muscles, rigidity, tightness, and various joint disturbances (pain, stiffness, swelling, ache).

Neurological: Aggressiveness, bradylogia, cluster headache, convulsions, detachment, disturbances of taste, drug abuse, dystonia, facial paralysis, globus hystericus, hallucinations, headache, heat sensitivity, hyperesthesia, hysteria, increased alertness, malaise/fatigue, migraine, motor dysfunction, myoclonia, neuralgia, neurotic disorders, paralysis, personality change, phobia, photophobia, psychomotor disorders, radiculopathy, raised intracranial pressure, relaxation, stinging sensations, transient hemiplegia, simultaneous hot and cold sensations, suicide, tickling sensations, twitching, and yawning.

Pain and Other Pressure Sensations: Chest pain, neck tightness/pressure, throat/jaw pain/tightness/pressure, and pain (location specified).

Respiratory: Breathing disorders, bronchitis, diseases of the lower respiratory tract, hiccoughs, and influenza.

Skin: Dry/scaly skin, eczema, seborrheic dermatitis, skin nodules, skin tenderness, tightness of skin, and wrinkling of skin.

Urogenital: Abortion, abnormal menstrual cycle, bladder inflammation, hematuria, inflammation of fallopian tubes, intermenstrual bleeding, menstruation symptoms, micturition disorders, renal calculus, urethritis, urinary frequency, and urinary infections.

Postmarketing Experience (Reports for Subcutaneous or Oral Sumatriptan)

The following section enumerates potentially important adverse events that have occurred in clinical practice and that have been reported spontaneously to various surveillance systems. The events enumerated represent reports arising from both domestic and nondomestic use of oral or subcutaneous dosage forms of sumatriptan. The events enumerated include all except those already listed in the ADVERSE REACTIONS section above or those too general to be informative. Because the reports cite events reported spontaneously from worldwide postmarketing experience, frequency of events and the role of sumatriptan in their causation cannot be reliably determined. It is assumed, however, that systemic reactions following sumatriptan use are likely to be similar regardless of route of administration.

Blood: Hemolytic anemia, pancytopenia, thrombocytopenia.

Cardiovascular: Atrial fibrillation, cardiomyopathy, colonic ischemia (see WARNINGS), Prinzmetal variant angina, pulmonary embolism, shock, thrombophlebitis.

Ear, Nose, and Throat: Deafness.

Eye: Ischemic optic neuropathy, retinal artery occlusion, retinal vein thrombosis, loss of vision.

Gastrointestinal: Ischemic colitis with rectal bleeding (see WARNINGS), xerostomia.

Hepatic: Elevated liver function tests.

Neurological: Central nervous system vasculitis, cerebrovascular accident, dysphasia, serotonin syndrome, subarachnoid hemorrhage.

Non-Site Specific: Angioneurotic edema, cyanosis, death (see WARNINGS), temporal arteritis.

Psychiatry: Panic disorder.

Respiratory: Bronchospasm in patients with and without a history of asthma.

Skin: Exacerbation of sunburn, hypersensitivity reactions (allergic vasculitis, erythema, pruritus, rash, shortness of breath, urticaria; in addition, severe anaphylaxis/anaphylactoid reactions have been reported [see WARNINGS]), photosensitivity.

Urogenital: Acute renal failure.

Drug Abuse and Dependence

One clinical study with sumatriptan injection enrolling 12 patients with a history of substance abuse failed to induce subjective behavior and/or physiologic response ordinarily associated with drugs that have an established potential for abuse.

Overdosage

In clinical trials, the highest single doses of Sumatriptan Nasal Spray administered without significant adverse effects were 40 mg to 12 volunteers and 40 mg to 85 migraine patients, 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 events.

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 about 2 hours (see CLINICAL PHARMACOLOGY), and therefore monitoring of patients after overdose with Sumatriptan Nasal Spray 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.

Sumatriptan Nasal Spray Dosage and Administration

In controlled clinical trials, single doses of 5, 10, or 20 mg of Sumatriptan Nasal Spray administered into 1 nostril were effective for the acute treatment of migraine in adults. A greater proportion of patients had headache response following a 20-mg dose than following a 5- or 10-mg dose (see CLINICAL TRIALS). Individuals may vary in response to doses of Sumatriptan Nasal Spray. The choice of dose should therefore be made on an individual basis, weighing the possible benefit of the 20-mg dose with the potential for a greater risk of adverse events. A 10-mg dose may be achieved by the administration of a single 5-mg dose in each nostril. There is evidence that doses above 20 mg do not provide a greater effect than 20 mg.

If the headache returns, the dose may be repeated once after 2 hours, not to exceed a total daily dose of 40 mg. The safety of treating an average of more than 4 headaches in a 30-day period has not been established.

How is Sumatriptan Nasal Spray Supplied

Sumatriptan Nasal Spray 5 mg (NDC 0781-6524-86) and 20 mg (NDC 0781-6523-86) are each supplied in boxes of 6 nasal spray devices. Each unit dose spray supplies 5 and 20 mg, respectively, of sumatriptan.

Store between 36° and 86°F (2° and 30°C). Protect from light.

Animal Toxicology

Corneal Opacities

Dogs receiving oral sumatriptan developed corneal opacities and defects in the corneal epithelium. Corneal opacities were seen at the lowest dosage 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 exposure at the lowest dose tested was approximately 5 times the human exposure after a 100-mg oral dose or 3 times the human exposure after a 6-mg subcutaneous dose or 22 times the human exposure after a single 20-mg intranasal dose. There is evidence of alterations in corneal appearance on the first day of intranasal dosing to dogs. Changes were noted at the lowest dose tested, which was approximately 2 times the maximum single human intranasal dose of 20 mg on a mg/m2 basis.

Manufactured by

GlaxoSmithKline Manufacturing S.p.A.

for Sandoz Inc.

Princeton, NJ 08540

March 2012

SNS-SZ:3PI

PATIENT INFORMATION

The following wording is contained in a separate leaflet provided for patients.

Patient Information

Sumatriptan Nasal Spray

Read this Patient Information before you start using Sumatriptan Nasal Spray 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 Sumatriptan Nasal Spray?

Sumatriptan Nasal Spray can cause serious side effects, including:

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

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

discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back
chest pain or chest discomfort that feels like heavy pressure, squeezing, or fullness
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

Sumatriptan Nasal Spray 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:

have high blood pressure
have high cholesterol levels
smoke
are overweight
have diabetes
have a family history of heart disease
are a female who has gone through menopause
are a male over age 40

Serotonin syndrome. Serotonin syndrome is a serious and life-threatening problem that can happen in people using Sumatriptan Nasal Spray, especially if Sumatriptan Nasal Spray is used with anti-depressant medicines called selective serotonin reuptake inhibitors (SSRIs) or selective norepinephrine reuptake inhibitors (SNRIs).

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

Call your healthcare provider right away if you have any of the following symptoms of serotonin syndrome:

mental changes such as seeing things that are not there (hallucinations), agitation, or coma
fast heartbeat
changes in blood pressure
high body temperature
tight muscles
trouble walking
nausea, vomiting, or diarrhea

What is Sumatriptan Nasal Spray?

Sumatriptan Nasal Spray is a prescription medicine used to treat acute migraine headaches with or without aura in adults.
Sumatriptan Nasal Spray is not used to prevent or decrease the number of migraine headaches you have.
Sumatriptan Nasal Spray 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).
It is not known if Sumatriptan Nasal Spray is safe and effective to treat cluster headaches.
It is not known if Sumatriptan Nasal Spray is safe and effective in children under 18 years of age.

Who should not use Sumatriptan Nasal Spray?

Do not use Sumatriptan Nasal Spray if you have:

heart problems or a 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:
almotriptan (AXERT®)
eletriptan (RELPAX®)
frovatriptan (FROVA®)
naratriptan (AMERGE®)
rizatriptan (MAXALT®, MAXALT-MLT®)
sumatriptan (IMITREX®)
sumatriptan and naproxen (TREXIMET®)
ergotamines (CAFERGOT®, ERGOMAR®, MIGERGOT®)
dihydroergotamine (D.H.E. 45®, MIGRANAL®)

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

an allergy to sumatriptan or any of the ingredients in Sumatriptan Nasal Spray. See the end of this leaflet for a complete list of ingredients in Sumatriptan Nasal Spray.

What should I tell my healthcare provider before taking Sumatriptan Nasal Spray?

Before you use Sumatriptan Nasal Spray, tell your healthcare provider about all of your medical conditions, including if you:

have high blood pressure
have high cholesterol
have diabetes
smoke
are overweight
are a female who has gone through menopause
have heart disease or a family history of heart disease 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 Nasal Spray will harm your unborn baby.
become pregnant while taking Sumatriptan Nasal Spray
are breastfeeding or plan to breastfeed. Sumatriptan Nasal Spray passes into your breast milk and may harm your baby. Talk with your healthcare provider about the best way to feed your baby if you use Sumatriptan Nasal Spray.

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

Sumatriptan Nasal Spray and other medicines may affect each other, causing side effects.

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

selective serotonin reuptake inhibitors (SSRIs)
serotonin norepinephrine reuptake inhibitors (SNRIs)
monoamine oxidase inhibitors (MAOIs)

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 use Sumatriptan Nasal Spray?

Before using Sumatriptan Nasal Spray, read the Instructions for Use at the end of the Patient Information leaflet.

Certain people should take their first dose of Sumatriptan Nasal Spray 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 Nasal Spray 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.
If you do not get any relief after your first nasal spray, do not use a second nasal spray without first talking with your healthcare provider.
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 2 hours after the first nasal spray.
Do not take more than a total of 40 mg of Sumatriptan Nasal Spray in a 24‑hour period.
It is not known how using Sumatriptan Nasal Spray for a long time affects the nose and throat.
Some people who use too much Sumatriptan Nasal Spray may have worse headaches (medication overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with Sumatriptan Nasal Spray.
If you use too much Sumatriptan Nasal Spray, 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 Nasal Spray so you can talk with your healthcare provider about how Sumatriptan Nasal Spray is working for you.

What should I avoid while taking Sumatriptan Nasal Spray?

Sumatriptan Nasal Spray 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 Nasal Spray?

Sumatriptan Nasal Spray may cause serious side effects. See “What is the most important information I should know about Sumatriptan Nasal Spray?”

These serious side effects include:

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:
sudden or severe stomach pain
stomach pain after meals
weight loss
nausea or vomiting
constipation or diarrhea
bloody diarrhea
fever
problems with blood circulation to your legs and feet (peripheral vascular ischemia). Symptoms of peripheral vascular ischemia include:
cramping and pain in your legs or hips
feeling of heaviness or tightness in your leg muscles
burning or aching pain in your feet or toes while resting
numbness, tingling, or weakness in your legs
cold feeling or color changes in 1 or both legs or feet
shortness of breath or wheezing
hives (itchy bumps); swelling of your tongue, mouth, or throat

The most common side effects of Sumatriptan Nasal Spray include:

dizziness
warm, hot, burning feeling to your face (flushing)
discomfort of your neck, throat, or nose
unusual or bad taste in your mouth
feeling weak, drowsy, or tired
sensitivity to loud noises

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 Nasal Spray. 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.

How should I store Sumatriptan Nasal Spray?

Store between 36°F to 86°F (2°C to 30°C).
Store your medicine away from light.

Keep Sumatriptan Nasal Spray and all medicines out of the reach of children.

General information about the safe and effective use of Sumatriptan Nasal Spray.

Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use Sumatriptan Nasal Spray for a condition for which it was not prescribed. Do not give Sumatriptan Nasal Spray 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 Nasal Spray. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Sumatriptan Nasal Spray that is written for healthcare professionals.

For more information, go to www.gsk.com or call 1-888-825-5249.

What are the ingredients in Sumatriptan Nasal Spray?

Active ingredient: sumatriptan

Inactive ingredients: monobasic potassium phosphate NF, anhydrous dibasic sodium phosphate USP, sulfuric acid NF, sodium hydroxide NF, and purified water USP.

March 2012

SZS-SZ:3PPI

Instructions for Use

Sumatriptan Nasal Spray

For use in the nose only. Do not spray in your eyes.

Figure A

Step 1. Remove the Sumatriptan Nasal Spray unit from the plastic pack (see Figure A).

Do not remove the unit until you are ready to use. The unit contains only 1 spray. Do not test before use.

Figure B

Step 2. While sitting down, gently blow your nose to clear your nasal passages (see Figure B).

Figure C

Step 3. Keeping your head in an upright position, gently close 1 nostril with your index finger and breathe out gently through your mouth (see Figure C).

Figure D

Step 4. With your other hand, hold the container with your thumb supporting the container at the bottom, and your index and middle fingers on either side of the nozzle (see Figure D).

Insert the nozzle into your open nostril about ½ inch. Do not press the blue plunger yet.

Figure E

Step 5. Keep your head upright and close your mouth. While gently taking a breath in through your nose, press the blue plunger firmly to release the dose of Sumatriptan Nasal Spray (see Figure E).

Figure F

Step 6. Keep your head level and remove the nozzle from your nostril. While holding your head level, gently breathe in through your nose and out through your mouth for 10 to 20 seconds (see Figure F).

Do not breathe in deeply.

AMERGE, IMITREX, and TREXIMET are registered trademarks of GlaxoSmithKline. The other brands listed are trademarks of their respective owners and are not trademarks of GlaxoSmithKline. The makers of these brands are not affiliated with and do not endorse GlaxoSmithKline or its products.

This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration.

Manufactured by

GlaxoSmithKline Manufacturing S.p.A.

for Sandoz Inc.

Princeton, NJ 08540

March 2012

SNS-SZ:3PIL

Principal Display Panel

NDC 0781-6523-06

Sumatriptan Nasal Spray

20 mg

Each unit dose spray contains 20 mg of sumatriptan.

1 Spray per unit. Do not test before use.

See package insert for full prescribing information.

Store between 36° and 86°F (2° and 30°C).

Protect from light.

Rx only

Manufactured by

GlaxoSmithKline Manufacturing S.p.A.

for Sandoz Inc.

Princeton, NJ 08540

10000000105723 Rev. 4/12

Principal Display Panel

NDC 0781-6524-06

Sumatriptan Nasal Spray

5 mg

Each unit dose spray contains 5 mg of sumatriptan.

1 Spray per unit. Do not test before use.

See package insert for full prescribing information.

Store between 36° and 86°F (2° and 30°C).

Protect from light.

Rx only

Manufactured by

GlaxoSmithKline Manufacturing S.p.A.

for Sandoz Inc.

Princeton, NJ 08540

10000000105510 Rev. 4/12

SUMATRIPTAN 
sumatriptan spray
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0781-6524
Route of Administration NASAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SUMATRIPTAN (SUMATRIPTAN) SUMATRIPTAN 5 mg  in 100 uL
Inactive Ingredients
Ingredient Name Strength
POTASSIUM PHOSPHATE, MONOBASIC  
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS  
SULFURIC ACID  
SODIUM HYDROXIDE  
WATER  
Packaging
# Item Code Package Description
1 NDC:0781-6524-86 6 CONTAINER in 1 BOX
1 NDC:0781-6524-06 100 uL in 1 CONTAINER
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA020626 09/11/2008
SUMATRIPTAN 
sumatriptan spray
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0781-6523
Route of Administration NASAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SUMATRIPTAN (SUMATRIPTAN) SUMATRIPTAN 20 mg  in 100 uL
Inactive Ingredients
Ingredient Name Strength
POTASSIUM PHOSPHATE, MONOBASIC  
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS  
SULFURIC ACID  
SODIUM HYDROXIDE  
WATER  
Packaging
# Item Code Package Description
1 NDC:0781-6523-86 6 CONTAINER in 1 BOX
1 NDC:0781-6523-06 100 uL in 1 CONTAINER
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA020626 09/11/2008
Labeler - Sandoz Inc (110342024)
Revised: 05/2012
 
Sandoz Inc
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