HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use IMITREX safely and effectively. See full prescribing information for IMITREX.
IMITREX (sumatriptan) Nasal Spray
Initial U.S. Approval: 1992
INDICATIONS AND USAGE
IMITREX is a serotonin (5-HT1B/1D) receptor agonist (triptan) indicated for acute treatment of migraine with or without aura in adults. (1)
Limitations of Use:
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
Nasal spray: 5 mg and 20 mg (3, 16)
WARNINGS AND PRECAUTIONS
Most common adverse reactions (≥1% and >placebo) were burning sensation, disorder/discomfort of nasal cavity/sinuses, throat discomfort, nausea and/or vomiting, bad/unusual taste, and dizziness/vertigo. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
Pregnancy: Based on animal data, may cause fetal harm. (8.1)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
3 DOSAGE FORMS AND STRENGTHS
5 WARNINGS AND PRECAUTIONS
5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal’s Angina
5.3 Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure
5.4 Cerebrovascular Events
5.5 Other Vasospasm Reactions
5.6 Medication Overuse Headache
5.7 Serotonin Syndrome
5.8 Increase in Blood Pressure
5.9 Local Irritation
5.10 Anaphylactic/Anaphylactoid Reactions
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 Ergot-Containing Drugs
7.2 Monoamine Oxidase-A Inhibitors
7.3 Other 5-HT1 Agonists
7.4 Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome
8 USE IN SPECIFIC POPULATIONS
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
IMITREX® Nasal Spray is indicated for the acute treatment of migraine with or without aura in adults.
Limitations of Use:
The recommended adult dose of IMITREX Nasal Spray for the acute treatment of migraine is 5 mg, 10 mg, or 20 mg. The 20-mg dose may provide a greater effect than the 5-mg and 10-mg doses, but may have a greater risk of adverse reactions [see Clinical Studies (14)].
The 5-mg and 20-mg doses are given as a single spray in 1 nostril. The 10-mg dose may be achieved by the administration of a single 5-mg dose in each nostril.
If the migraine has not resolved by 2 hours after taking IMITREX Nasal Spray, or returns after a transient improvement, 1 additional dose may be administered at least 2 hours after the first dose. The maximum daily dose is 40 mg in a 24-hour period.
The safety of treating an average of more than 4 headaches in a 30‑day period has not been established.
Unit dose nasal spray devices containing 5 mg or 20 mg sumatriptan.
IMITREX Nasal Spray is contraindicated in patients with:
The use of IMITREX Nasal Spray 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 IMITREX Nasal Spray. Some of these reactions occurred in patients without known CAD. IMITREX Nasal Spray 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 IMITREX Nasal Spray. If there is evidence of CAD or coronary artery vasospasm, IMITREX Nasal Spray is contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of IMITREX Nasal Spray in a medically supervised setting and performing an electrocardiogram (ECG) immediately following administration of IMITREX Nasal Spray. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of IMITREX Nasal Spray.
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 IMITREX Nasal Spray if these disturbances occur. IMITREX Nasal Spray 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 may occur after treatment with IMITREX Nasal Spray and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of IMITREX Nasal Spray 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 IMITREX Nasal Spray 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. IMITREX Nasal Spray is contraindicated in patients with a history of stroke or TIA.
IMITREX Nasal Spray 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 using additional IMITREX Nasal Spray.
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 IMITREX Nasal Spray, 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 IMITREX Nasal Spray 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 IMITREX. IMITREX Nasal Spray is contraindicated in patients with uncontrolled hypertension.
Local irritative symptoms such as burning, numbness, paresthesia, discharge, and pain or soreness were reported in approximately 5% of patients in controlled clinical trials and were noted to be severe in about 1%. The symptoms were transient and generally 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 Imitrex Nasal Spray on the nasal and/or respiratory mucosa have not been systematically evaluated in patients.
Anaphylactic/anaphylactoid reactions have occurred in patients receiving IMITREX. 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. IMITREX Nasal Spray is contraindicated in patients with a history of hypersensitivity reaction to IMITREX.
Seizures have been reported following administration of IMITREX. 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. IMITREX Nasal Spray should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.
The following adverse reactions are discussed in more detail in other sections of the prescribing information:
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 worldwide placebo-controlled clinical trials in 3,419 patients with migraine. Only treatment-emergent adverse reactions that occurred at a frequency of 1% or more in the group treated with IMITREX Nasal Spray 20 mg and that occurred at a frequency greater than the placebo group are included in Table 1.
Percent of Patients Reporting
(n = 496)
(n = 1,007)
(n = 1,212)
(n = 704)
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Ear, nose, and throat
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The incidence of adverse reactions 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 reactions.
The following adverse reactions have been identified during postapproval use of IMITREX Tablets, IMITREX Nasal Spray, and IMITREX 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 IMITREX 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 IMITREX Nasal Spray within 24 hours of each other is contraindicated.
MAO-A inhibitors increase systemic exposure by up to 7-fold. Therefore, the use of IMITREX Nasal Spray in patients receiving MAO-A inhibitors is contraindicated [see Clinical Pharmacology (12.3)].
Because their vasospastic effects may be additive, co-administration of IMITREX Nasal Spray 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)].
Pregnancy Category C: There are no adequate and well-controlled trials in pregnant women. 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. Developmental toxicity studies of sumatriptan by the intranasal route have not been conducted. IMITREX Nasal Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
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.
Sumatriptan is excreted in human milk following subcutaneous administration. Infant exposure to sumatriptan can be minimized by avoiding breastfeeding for 12 hours after treatment with IMITREX Nasal Spray.
Safety and effectiveness in pediatric patients have not been established. IMITREX Nasal Spray is not recommended for use in patients younger than 18 years of age.
Two controlled clinical trials evaluated IMITREX 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 IMITREX 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 IMITREX (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 IMITREX 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 IMITREX. 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 IMITREX; 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 IMITREX are not presently available.
Clinical trials of IMITREX Nasal Spray 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 IMITREX Nasal Spray [see Warnings and Precautions (5.1)].
In clinical trials, the highest single doses of IMITREX 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.
The elimination half‑life of sumatriptan is approximately 2 hours [see Clinical Pharmacology (12.3)], and therefore monitoring of patients after overdose with IMITREX 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.
IMITREX Nasal Spray contains sumatriptan, a selective 5-HT1B/1D receptor agonist. Sumatriptan is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-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 IMITREX 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 IMITREX Nasal Spray, respectively.
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 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 and Bioavailability: In a trial 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 trial 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.
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.
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 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: 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. The total plasma clearance is approximately 1,200 mL/min.
Special 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). Intranasal sumatriptan has not been evaluated for age differences.
Renal Impairment: The effect of renal impairment on the pharmacokinetics of sumatriptan has not been examined.
Hepatic Impairment: The effect of mild to moderate hepatic disease on the pharmacokinetics of the intranasal formulation of sumatriptan has not been evaluated. Sumatriptan bioavailability following intranasal administration is 17%, similar to that after oral administration (15%). 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. The use of IMITREX Nasal Spray in patients with severe hepatic impairment is contraindicated [see Contraindications (4)].
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.
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 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.
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 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 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 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. 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.
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 Imitrex Nasal Spray in the acute treatment of migraine headaches was demonstrated in 8, randomized, double-blind, placebo-controlled trials, of which 5 used the recommended dosing regimen and used the marketed formulation. Patients enrolled in these 5 trials were predominately female (86%) and Caucasian (95%), with a mean age of 41 years (range of 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 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 IMITREX 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 trials, 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 trials, 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 Imitrex Nasal Spray at all doses (with one exception) compared with those who received placebo. In 4 of the 5 trials, 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 trial. The results from the 5 controlled clinical trials are summarized in Table 2. Note that, in general, comparisons of results obtained in trials conducted under different conditions by different investigators with different samples of patients are ordinarily unreliable for purposes of quantitative comparison
IMITREX Nasal Spray
(n = 121)
(n = 112)
(n = 118)
(n = 63)
(n = 273)
(n = 277)
(n = 138)
(n = 106)
(n = 202)
(n = 100)
(n = 106)
(n = 215)
(n = 112)
(n = 296)
(n = 291)
(n = 286)
(n = 198)
a P<0.05 in comparison with placebo.
b P<0.05 in comparison with 10 mg.
c P<0.05 in comparison with 5 mg.
dData are for attack 1 only of multi-attack trial 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 IMITREX 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 IMITREX Nasal Spray 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 were insufficient data to assess the impact of race on efficacy.
IMITREX Nasal Spray 5 mg (NDC 0173-0524-00) and 20 mg (NDC 0173-0523-00) are each supplied in boxes of 6 nasal spray devices. Each unit dose spray supplies 5 mg and 20 mg, respectively, of sumatriptan.
Store between 2°C and 30°C (36°F and 86°F). Protect from light.
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 IMITREX Nasal Spray 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 IMITREX Nasal Spray. 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 (5.10)].
Concomitant Use With Other Triptans or Ergot Medications: Inform patients that use of IMITREX Nasal Spray 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 IMITREX Nasal Spray 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: Inform patients that IMITREX Nasal Spray should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus [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 (8.3)].
Ability to Perform Complex Tasks: Treatment with IMITREX Nasal Spray may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks after administration of IMITREX Nasal Spray.
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 IMITREX Nasal Spray: Provide patients instruction on the proper use of IMITREX Nasal Spray. Caution patients to avoid spraying the contents of the device in their eyes.
Imitrex is a registered trademark of the GlaxoSmithKline group of companies.
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Read this Patient Information before you start using IMITREX 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 IMITREX?
IMITREX can cause serious side effects, including:
Heart attack and other heart problems. Heart problems may lead to death.
Stop taking IMITREX and get emergency medical help right away if you have any of the following symptoms of a heart attack:
IMITREX 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:
What is IMITREX?
IMITREX is a prescription medicine used to treat acute migraine headaches with or without aura in adults.
IMITREX 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.
IMITREX is not used to prevent or decrease the number of migraine headaches you have.
It is not known if IMITREX is safe and effective to treat cluster headaches.
It is not known if IMITREX is safe and effective in children under 18 years of age.
Who should not use IMITREX?
Do not use IMITREX if you have:
What should I tell my healthcare provider before using IMITREX?
Before you use IMITREX, tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.
IMITREX and certain other medicines can affect each other, causing serious side effects.
Especially tell your healthcare provider if you take anti-depressant medicines called:
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 IMITREX?
What should I avoid while using IMITREX?
IMITREX 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 IMITREX?
IMITREX may cause serious side effects. See “What is the most important information I should know about IMITREX?”
These serious side effects include:
The most common side effects of IMITREX Nasal Spray include:
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 IMITREX. 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 IMITREX Nasal Spray?
Keep IMITREX and all medicines out of the reach of children.
General information about the safe and effective use of IMITREX.
Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use IMITREX for a condition for which it was not prescribed. Do not give IMITREX 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 IMITREX. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about IMITREX 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 IMITREX 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.
This Patient Information has been approved by the U.S. Food and Drug Administration.
IMITREX, AMERGE, and TREXIMET are registered trademarks of the GlaxoSmithKline group of companies. 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.
Research Triangle Park, NC 27709
©2013, GlaxoSmithKline group of companies. All rights reserved.
Instructions for Use
For use in the nose only. Do not spray in your eyes.
Step 1. Remove the IMITREX 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.
Step 2. While sitting down, gently blow your nose to clear your nasal passages (see Figure B).
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).
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.
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 IMITREX Nasal Spray (see Figure E).
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.
IIMITREX, AMERGE, and TREXIMET are registered trademarks of the GlaxoSmithKline group of companies. The other brands listed are trademarks of their respective owners and are not trademarks of the GlaxoSmithKline group of companies. The makers of these brands are not affiliated with and do not endorse the GlaxoSmithKline group of companies or its products.
This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration.
Research Triangle Park, NC 27709
©2013, GlaxoSmithKline group of companies. All rights reserved.