ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following serious adverse reactions are described below and elsewhere in the labeling:Myocardial ischemia, myocardial infarction, and Prinzmetals angina [see Warnings and Precautions (5.1)] Arrhythmias [see Warnings and Precautions (5.2)] Chest, throat, neck, and/or jaw pain/tightness/pressure [see Warnings and Precautions (5.3)] Cerebrovascular events [see Warnings and Precautions (5.4)] Other vasospasm reactions [see Warnings and Precautions (5.5)] Medication overuse headache [see Warnings and Precautions (5.6)] Serotonin syndrome [see Warnings and Precautions (5.7)] Increase in blood pressure [see Warnings and Precautions (5.8)] Hypersensitivity reactions [see Contraindications (4), Warnings and Precautions (5.9)] Seizures [see Warnings and Precautions (5.10)] Myocardial ischemia, myocardial infarction, and Prinzmetals angina [see Warnings and Precautions (5.1)] Arrhythmias [see Warnings and Precautions (5.2)] Chest, throat, neck, and/or jaw pain/tightness/pressure [see Warnings and Precautions (5.3)] Cerebrovascular events [see Warnings and Precautions (5.4)] Other vasospasm reactions [see Warnings and Precautions (5.5)] Medication overuse headache [see Warnings and Precautions (5.6)] Serotonin syndrome [see Warnings and Precautions (5.7)] Increase in blood pressure [see Warnings and Precautions (5.8)] Hypersensitivity reactions [see Contraindications (4), Warnings and Precautions (5.9)] Seizures [see Warnings and Precautions (5.10)] Most common adverse reactions (>=5% and placebo) were injection site reactions, tingling, dizziness/vertigo, warm/hot sensation, burning sensation, feeling of heaviness, pressure sensation, flushing, feeling of tightness, and numbness. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-877-233-2001 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Migraine Headache: Table lists adverse reactions that occurred in U.S. placebo-controlled clinical trials in migraine patients (Studies and 3) following either single mg dose of sumatriptan injection or placebo. Only reactions that occurred at frequency of 2% or more in groups treated with sumatriptan injection mg and that occurred at frequency greater than the placebo group are included in Table 1.Table 1. Adverse Reactions in Pooled Placebo-Controlled Trials in Patients with Migraine (Studies and 3) Sumatriptan Injection mg Subcutaneous(n 547)% Placbo(n 370)% Atypical sensations429 Tingling143 Warm/hot sensation114 Burning sensation7<1 Feeling of heaviness71 Pressure sensation72 Feeling of tightness5<1 Numbness52 Feeling strange2<1 Tight feeling in head2<1Cardiovascular Flushing72 Chest discomfort51 Tightness in chest3<1 Pressure in chest2<1Ear, nose, and throat Throat discomfort3<1 Discomfort: nasal cavity/sinuses2<1Injection site reactionIncludes injection site pain, stinging/burning, swelling, erythema, bruising, bleeding. 5924Miscellaneous Jaw discomfort20Musculoskeletal Weakness5<1 Neck pain/stiffness5<1 Myalgia2<1Neurological Dizziness/vertigo124 Drowsiness/sedation32 Headache2<1Skin Sweating21The incidence of adverse reactions in controlled clinical trials was not affected by gender or age of the patients. There were insufficient data to assess the impact of race on the incidence of adverse reactions. Cluster Headache: In the controlled clinical trials assessing the efficacy of sumatriptan injection as treatment for cluster headache (Studies and 5), no new significant adverse reactions were detected that had not already been identified in trials of sumatriptan in patients with migraine. Overall, the frequency of adverse reactions reported in the trials of cluster headache was generally lower than in the migraine trials. Exceptions include reports of paresthesia (5% sumatriptan, 0% placebo), nausea and vomiting (4% sumatriptan, 0% placebo), and bronchospasm (1% sumatriptan, 0% placebo).. 6.2 Postmarketing Experience. The following adverse reactions have been identified during postapproval use of sumatriptan tablets, sumatriptan nasal spray, and sumatriptan injection. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.Cardiovascular: Hypotension, palpitations.Neurological: Dystonia, tremor.

ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION.

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

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Carcinogenesis: In carcinogenicity studies in mouse and rat in which sumatriptan was administered orally for 78 weeks and 104 weeks, respectively, at doses up to 160 mg/kg/day (the highest dose in rat was reduced from 360 mg/kg/day during Week 21). The highest dose to mice and rats was approximately 130 and 260 times the single MRHD of mg administered subcutaneously on mg/m2 basis. There was no evidence in either species of an increase in tumors related to sumatriptan administration. Mutagenesis: Sumatriptan was negative in in vitro (bacterial reverse mutation [Ames], gene cell mutation in Chinese hamster V79/HGPRT, chromosomal aberration in human lymphocytes) and in vivo (rat micronucleus) assays. Impairment of Fertility: When sumatriptan 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 or approximately 100 times the single human dose of mg on mg/m2 basis. When sumatriptan (5, 50, 500 mg/kg/day) was administered orally to male and female rats prior to and throughout the mating period, there was treatment-related decrease in fertility secondary to decrease in mating in animals treated with doses greater than mg/kg/day. It is not clear whether this finding was due to an effect on males or females or both.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Sumatriptan binds with high affinity to human cloned 5-HT1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine and cluster headaches through agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.. 12.2 Pharmacodynamics. Blood Pressure: Significant elevation in blood pressure, including hypertensive crisis, has been reported in patients with and without history of hypertension [see Warnings and Precautions (5.8)].Peripheral (Small) Arteries: In healthy volunteers (N 18), trial evaluating the effects of sumatriptan on peripheral (small vessel) arterial reactivity failed to detect clinically significant increase in peripheral resistance.Heart Rate: Transient increases in blood pressure observed in some patients in clinical trials carried out during sumatriptans development as treatment for migraine were not accompanied by any clinically significant changes in heart rate.. 12.3 Pharmacokinetics. Absorption and Bioavailability: The bioavailability of sumatriptan via subcutaneous site injection to 18 healthy male subjects was 97% +- 16% of that obtained following intravenous injection. After single mg subcutaneous manual injection into the deltoid area of the arm in 18 healthy males (age: 24 +- years, weight: 70 kg), the maximum serum concentration (Cmax) of sumatriptan was (mean +- standard deviation) 74 +- 15 ng/mL and the time to peak concentration (Tmax) was 12 minutes after injection (range: to 20 minutes). In this trial, the same dose injected subcutaneously in the thigh gave Cmax of 61 +- 15 ng/mL by manual injection versus 52 +- 15 ng/mL by autoinjector techniques. The Tmax or amount absorbed was not significantly altered by either the site or technique of injection. Distribution: Protein binding, determined by equilibrium dialysis over the concentration range of 10 to 1,000 ng/mL, is low, approximately 14% to 21%. The effect of sumatriptan on the protein binding of other drugs has not been evaluated. Following 6 mg subcutaneous injection into the deltoid area of the arm in males (mean age: 33 years, mean weight: 77 kg) the volume of distribution central compartment of sumatriptan was 50 +- liters and the distribution half-life was 15 +- minutes. Metabolism: In vitro studies with human microsomes suggest that sumatriptan is metabolized by MAO, predominantly the isoenzyme. Most of radiolabeled dose of sumatriptan excreted in the urine is the major metabolite indole acetic acid (IAA) or the IAA glucuronide, both of which are inactive. Elimination: After single mg subcutaneous dose, 22% +- 4% was excreted in the urine as unchanged sumatriptan and 38% +- 7% as the IAA metabolite. Following 6 mg subcutaneous injection into the deltoid area of the arm, the systemic clearance of sumatriptan was 1,194 +- 149 mL/min and the terminal half-life was 115 +- 19 minutes. Special Populations: Age: The pharmacokinetics of sumatriptan in the elderly (mean age: 72 years, males and 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). Hepatic Impairment: The effect of mild to moderate hepatic disease on the pharmacokinetics of subcutaneously administered sumatriptan has been evaluated. There were no significant differences in the pharmacokinetics of subcutaneously administered sumatriptan in moderately hepatically impaired subjects compared with healthy controls. The pharmacokinetics of subcutaneously administered sumatriptan in patients with severe hepatic impairment has not been studied. The use of sumatriptan injection in this population is contraindicated [see Contraindications (4)]. Race: The systemic clearance and Cmax of subcutaneous sumatriptan were similar in black (n 34) and Caucasian (n 38) healthy male subjects. Drug Interaction Studies: Monoamine Oxidase-A Inhibitors: In trial of 14 healthy females, pretreatment with an MAO-A inhibitor decreased the clearance of subcutaneous sumatriptan, resulting in 2-fold increase in the area under the sumatriptan plasma concentration-time curve (AUC), corresponding to 40% increase in elimination half-life.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. 14.1 Migraine. In controlled clinical trials enrolling more than 1,000 patients during migraine attacks who were experiencing moderate or severe pain and or more of the symptoms enumerated in Table 3, onset of relief began as early as 10 minutes following 6 mg sumatriptan injection. Lower doses of sumatriptan injection may also prove effective, although the proportion of patients obtaining adequate relief was decreased and the latency to that relief is greater with lower doses.In Study 1, different doses of sumatriptan injection (n 30 each group) were compared with placebo (n 62), in single-attack, parallel-group design, the dose response relationship was found to be as shown in Table 2.Table 2. Proportion of Patients with Migraine Relief and Incidence of Adverse Reactions by Time and by Sumatriptan Dose in Study 1Dose of Sumatriptan Injection Percent Patients With ReliefRelief is defined as the reduction of moderate or severe pain to no or mild pain after dosing without use of rescue medication. Adverse Reactions Incidence (%)at 10 Minutes at 30 Minutesat Hourat HoursPlacebo5152421551 mg10404340632 mg7235743633 mg17475760774 mg13375057806 mg10637370838 mg2357808393In randomized, placebo-controlled clinical trials of sumatriptan injection mg in 1,104 patients with moderate or severe migraine pain (Studies and 3), the onset of relief was less than 10 minutes. Headache relief, as defined by reduction in pain from severe or moderately severe to mild or no headache, was achieved in 70% of the patients within hour of single mg subcutaneous dose of sumatriptan injection. Approximately 82% and 65% of patients treated with sumatriptan mg had headache relief and were pain free within hours, respectively. Table shows the 1- and 2-hour efficacy results for sumatriptan injection mg in Studies and 3. Table 3. Proportion of Patients with Pain Relief and Relief of Migraine Symptoms After and Hours of Treatment in Studies and 31-Hour DataStudy 2Study 3Placebo(n 190)Sumatriptan6 mg (n 384)Placebo(n 180)Sumatriptan6 mg (n 350)Patients with pain relief (grade 0/1)18%70%P<0.05 versus placebo. 26%70% Patients with no pain5%48% 13%49% Patients without nausea48%73% 50%73% Patients without photophobia23%56% 25%58% Patients with little or no clinical disabilityA successful outcome in terms of clinical disability was defined prospectively as ability to work mildly impaired or ability to work and function normally. 34%76% 34%76% 2-Hour DataStudy 2Study 3PlaceboIncludes patients that may have received an additional placebo injection hour after the initial injection. Sumatriptan Succinate6 mgIncludes patients that may have received an additional mg of sumatriptan injection hour after the initial injection. Placebo Sumatriptan Succinate6 mg Patients with pain relief (grade 0/1)31%81% 39%82% Patients with no pain11%63% 19%65% Patients without nausea56%82% 63%81% Patients without photophobia31%72% 35%71% Patients with little or no clinical disability 42%85% 49%84% Sumatriptan injection also relieved photophobia, phonophobia (sound sensitivity), nausea, and vomiting associated with migraine attacks. The efficacy of sumatriptan injection was unaffected by whether or not the migraine was associated with aura, duration of attack, gender or age of the patient, or concomitant use of common migraine prophylactic drugs (e.g., beta-blockers).. 14.2 Cluster Headache. The efficacy of sumatriptan injection in the acute treatment of cluster headache was demonstrated in randomized, double-blind, placebo-controlled, 2-period crossover trials (Studies and 5). Patients 21 to 65 years of age were enrolled and were instructed to treat moderate to very severe headache within 10 minutes of onset. Headache relief was defined as reduction in headache severity to mild or no pain. In both trials, the proportion of individuals gaining relief at 10 or 15 minutes was significantly greater among patients receiving mg of sumatriptan injection compared with those who received placebo (see Table 4).Table 4. Proportion of Patients with Cluster Headache Relief by Time in Studies and Study 4Study 5Placebo(n 39)Sumatriptan6 mg(n 39)Placebo(n 88)Sumatriptan6 mg(n 92)Patients with pain relief (no/mild) Minutes post-injection8%21%7%23%P<0.05. 10 Minutes post-injection10%49% 25%49% 15 Minutes post-injection26%74% 35%75% (n Number of headaches treated.) An estimate of the cumulative probability of patient with cluster headache obtaining relief after being treated with either sumatriptan injection or placebo is presented in Figure 1. Figure 1. Time to Relief of Cluster Headache from Time of Injectiona The figure uses Kaplan-Meier (product limit) Survivorship Plot. Patients taking rescue medication were censored at 15 minutes.The plot was constructed with data from patients who either experienced relief or did not require (request) rescue medication within period of hours following treatment. As consequence, the data in the plot are derived from only subset of the 258 headaches treated (rescue medication was required in 52 of the 127 placebo-treated headaches and 18 of the 131 headaches treated with sumatriptan injection). Other data suggest that treatment with sumatriptan injection is not associated with an increase in early recurrence of headache and has little effect on the incidence of later-occurring headaches (i.e., those occurring after 2, but before 18 or 24 hours).. Figure 1. Time to Relief of Cluster Headache from Time of Injection.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. Sumatriptan injection is contraindicated in patients with:Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetals angina [see Warnings and Precautions (5.1)]. Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.2)]. History of stroke or transient ischemic attack (TIA) or history of hemiplegic or basilar migraine because these patients are at higher risk of stroke [see Warnings and Precautions (5.4)]. Peripheral vascular disease [see Warnings and Precautions (5.5)]. Ischemic bowel disease [see Warnings and Precautions (5.5)]. Uncontrolled hypertension [see Warnings and Precautions (5.8)]. Recent use (i.e., within 24 hours) of ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide), or another 5-hydroxytryptamine1 (5-HT1) agonist [see Drug Interactions (7.1, 7.3)]. Concurrent administration of monoamine oxidase (MAO)-A inhibitor or recent (within weeks) use of an MAO-A inhibitor [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)]. Hypersensitivity to sumatriptan (angioedema and anaphylaxis seen) [see Warnings and Precautions (5.9)]. Severe hepatic impairment [see Clinical Pharmacology (12.3)].. Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetals angina [see Warnings and Precautions (5.1)]. Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.2)]. History of stroke or transient ischemic attack (TIA) or history of hemiplegic or basilar migraine because these patients are at higher risk of stroke [see Warnings and Precautions (5.4)]. Peripheral vascular disease [see Warnings and Precautions (5.5)]. Ischemic bowel disease [see Warnings and Precautions (5.5)]. Uncontrolled hypertension [see Warnings and Precautions (5.8)]. Recent use (i.e., within 24 hours) of ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide), or another 5-hydroxytryptamine1 (5-HT1) agonist [see Drug Interactions (7.1, 7.3)]. Concurrent administration of monoamine oxidase (MAO)-A inhibitor or recent (within weeks) use of an MAO-A inhibitor [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)]. Hypersensitivity to sumatriptan (angioedema and anaphylaxis seen) [see Warnings and Precautions (5.9)]. Severe hepatic impairment [see Clinical Pharmacology (12.3)].. History of coronary artery disease or coronary artery vasospasm (4) Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders (4) History of stroke, transient ischemic attack, or hemiplegic or basilar migraine (4) Peripheral vascular disease (4) Ischemic bowel disease (4) Uncontrolled hypertension (4) Recent (within 24 hours) use of another 5-HT1 agonist (e.g., another triptan) or of an ergotamine-containing medication (4) Concurrent or recent (past weeks) use of monoamine oxidase-A inhibitor (4) Hypersensitivity to sumatriptan (angioedema and anaphylaxis seen) (4) Severe hepatic impairment (4). History of coronary artery disease or coronary artery vasospasm (4) Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders (4) History of stroke, transient ischemic attack, or hemiplegic or basilar migraine (4) Peripheral vascular disease (4) Ischemic bowel disease (4) Uncontrolled hypertension (4) Recent (within 24 hours) use of another 5-HT1 agonist (e.g., another triptan) or of an ergotamine-containing medication (4) Concurrent or recent (past weeks) use of monoamine oxidase-A inhibitor (4) Hypersensitivity to sumatriptan (angioedema and anaphylaxis seen) (4) Severe hepatic impairment (4).

DESCRIPTION SECTION.

11 DESCRIPTION. Sumatriptan Injection, USP contains sumatriptan succinate, selective 5-HT1B/1D receptor agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1), and it has the following structure:The empirical formula is C14H21N3O2SoC4H6O4, representing molecular weight of 413.5. Sumatriptan succinate is white to off-white powder that is readily soluble in water and in saline.Sumatriptan Injection, USP is clear, colorless to pale yellow, sterile, nonpyrogenic solution for subcutaneous injection. Each 0.5 mL of sumatriptan injection 12 mg/mL solution contains mg of sumatriptan as the succinate salt and 3.5 mg of sodium chloride, USP in Water for Injection, USP. The pH range is approximately 4.2 to 5.3. The osmolality is 291 mOsmol.. chemical structure.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. For subcutaneous use only. (2.1)Acute treatment of migraine: Single dose of mg to mg. (2.1)Acute treatment of cluster headache: Single dose of mg. (2.1)Maximum dose in 24-hour period: 12 mg, Separate doses by at least hour. (2.1)Patients receiving doses other than or mg: Use the mg single-dose vial. (2.3). For subcutaneous use only. (2.1). Acute treatment of migraine: Single dose of mg to mg. (2.1). Acute treatment of cluster headache: Single dose of mg. (2.1). Maximum dose in 24-hour period: 12 mg, Separate doses by at least hour. (2.1). Patients receiving doses other than or mg: Use the mg single-dose vial. (2.3). 2.1 Dosing Information. The maximum single recommended adult dose of sumatriptan injection for the acute treatment of migraine or cluster headache is mg injected subcutaneously. For the treatment of migraine, if side effects are dose limiting, lower doses (1 to mg) may be used [see Clinical Studies (14.1)]. For the treatment of cluster headache, the efficacy of lower doses has not been established. The maximum cumulative dose that may be given in 24 hours is 12 mg, two mg injections separated by at least hour. second mg dose should only be considered if some response to first injection was observed.. 2.3 Administration of Doses of Sumatriptan other than or mg. In patients receiving doses other than or mg, use the mg single-dose vial. Visually inspect the vial for particulate matter and discoloration before administration. Do not use if particulates and discolorations are noted.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Injection: mg single-dose vial. Injection: mg single-dose vial. Injection: mg single-dose vial (3). Injection: mg single-dose vial (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. 7.1 Ergot-Containing Drugs. Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and sumatriptan injection within 24 hours of each other is contraindicated.. 7.2 Monoamine Oxidase-A Inhibitors. MAO-A inhibitors increase systemic exposure by 2-fold. Therefore, the use of sumatriptan injection in patients receiving MAO-A inhibitors is contraindicated [see Clinical Pharmacology (12.3)].. 7.3 Other 5-HT1 Agonists. Because their vasospastic effects may be additive, coadministration of sumatriptan injection and other 5-HT1 agonists (e.g., triptans) within 24 hours of each other is contraindicated.. 7.4 Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome. Cases of serotonin syndrome have been reported during coadministration of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7)].

GERIATRIC USE SECTION.

8.5 Geriatric Use. Clinical trials of sumatriptan injection did not include sufficient numbers of patients 65 years of age 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. cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving sumatriptan injection [see Warnings and Precautions (5.1)].

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. Sumatriptan Injection, USP contains sumatriptan (base) as the succinate salt and is supplied as clear, colorless to pale yellow, sterile, nonpyrogenic solution as follows: Single-Dose Vial: Sumatriptan Injection, USP single-dose vial (6 mg/0.5 mL) in cartons containing vials (NDC 0143-9638-05). Sumatriptan Injection, USP single-dose vial (6 mg/0.5 mL) in cartons containing 25 vials (NDC 0143-9638-25). Store between and 30C (36 and 86F). Protect from light.

PHARMACODYNAMICS SECTION.

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

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Sumatriptan Injection, USP is indicated in adults for (1) the acute treatment of migraine, with or without aura, and (2) the acute treatment of cluster headache.Limitations of Use:Use only if clear diagnosis of migraine or cluster headache has been established. If patient has no response to the first migraine or cluster headache attack treated with Sumatriptan Injection, USP, reconsider the diagnosis before Sumatriptan Injection, USP is administered to treat any subsequent attacks. Sumatriptan Injection, USP is not indicated for the prevention of migraine or cluster headache attacks.. Use only if clear diagnosis of migraine or cluster headache has been established. If patient has no response to the first migraine or cluster headache attack treated with Sumatriptan Injection, USP, reconsider the diagnosis before Sumatriptan Injection, USP is administered to treat any subsequent attacks. Sumatriptan Injection, USP is not indicated for the prevention of migraine or cluster headache attacks.. Sumatriptan succinate is serotonin (5-HT1B/1D) receptor agonist (triptan) indicated for:Acute treatment of migraine with or without aura in adults (1) Acute treatment of cluster headache in adults (1)Limitations of Use:Use only if clear diagnosis of migraine or cluster headache has been established. (1) Not indicated for the prophylactic therapy of migraine or cluster headache attacks. (1). Acute treatment of migraine with or without aura in adults (1) Acute treatment of cluster headache in adults (1). Use only if clear diagnosis of migraine or cluster headache has been established. (1) Not indicated for the prophylactic therapy of migraine or cluster headache attacks. (1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise the patient to read the FDA-approved patient labeling (Patient Information). Risk of Myocardial Ischemia and/or Infarction, Prinzmetals Angina, Other Vasospasm-Related Events, Arrhythmias, and Cerebrovascular Events Inform patients that sumatriptan injection may cause serious cardiovascular side effects such as myocardial infarction or stroke. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, irregular heartbeat, significant rise in blood pressure, weakness, and slurring of speech and should ask for medical advice if any indicative sign or symptoms are observed. Apprise patients of the importance of this follow-up [see Warnings and Precautions (5.1, 5.2, 5.4, 5.5, 5.8)]. Anaphylactic/Anaphylactoid Reactions Inform patients that anaphylactic/anaphylactoid reactions have occurred in patients receiving sumatriptan injection. Such reactions can be life threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with history of sensitivity to multiple allergens [see Contraindications (4), Warnings and Precautions (5.9)]. Concomitant Use with Other Triptans or Ergot MedicationsInform patients that use of sumatriptan injection within 24 hours of another triptan or an ergot-type medication (including dihydroergotamine or methysergide) is contraindicated [see Contraindications (4), Drug Interactions (7.1, 7.3)].Serotonin SyndromeCaution patients about the risk of serotonin syndrome with the use of sumatriptan injection or other triptans, particularly during combined use with SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7), Drug Interactions (7.4)].Medication Overuse Headache 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 headache diary) [see Warnings and Precautions (5.6)]. Pregnancy Inform patients that sumatriptan injection 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 sumatriptan injection may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks after administration of sumatriptan injection. How to Use Sumatriptan Injection Provide patients instruction on the proper use of sumatriptan injection if they are able to self-administer sumatriptan injection in medically unsupervised situations. Inform patients that the injection is intended to be given subcutaneously and intramuscular or intravascular delivery should be avoided. Instruct patients to use injection sites with an adequate skin and subcutaneous thickness to accommodate the length of the needle.Manufactured by: HIKMA FARMACEUTICA (PORTUGAL), S.A.Estrada do Rio da Mo, 8, 8A 8B Fervenca 2705-906 Terrugem SNT, PORTUGALDistributed by: WEST-WARD PHARMACEUTICALSEATONTOWN, NJ 07724 USARevised: October 2015PIN311-WES/3.

MECHANISM OF ACTION SECTION.

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

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Carcinogenesis: In carcinogenicity studies in mouse and rat in which sumatriptan was administered orally for 78 weeks and 104 weeks, respectively, at doses up to 160 mg/kg/day (the highest dose in rat was reduced from 360 mg/kg/day during Week 21). The highest dose to mice and rats was approximately 130 and 260 times the single MRHD of mg administered subcutaneously on mg/m2 basis. There was no evidence in either species of an increase in tumors related to sumatriptan administration. Mutagenesis: Sumatriptan was negative in in vitro (bacterial reverse mutation [Ames], gene cell mutation in Chinese hamster V79/HGPRT, chromosomal aberration in human lymphocytes) and in vivo (rat micronucleus) assays. Impairment of Fertility: When sumatriptan 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 or approximately 100 times the single human dose of mg on mg/m2 basis. When sumatriptan (5, 50, 500 mg/kg/day) was administered orally to male and female rats prior to and throughout the mating period, there was treatment-related decrease in fertility secondary to decrease in mating in animals treated with doses greater than mg/kg/day. It is not clear whether this finding was due to an effect on males or females or both.. 13.2 Animal Toxicology and/or Pharmacology. Corneal Opacities: Dogs receiving oral sumatriptan developed corneal opacities and defects in the corneal epithelium. Corneal opacities were seen at the lowest dose tested, mg/kg/day, and were present after month of treatment. Defects in the corneal epithelium were noted in 60-week study. Earlier examinations for these toxicities were not conducted and no-effect doses were not established; however, the relative plasma exposure at the lowest dose tested was approximately times the human exposure after 6 mg subcutaneous dose.

NURSING MOTHERS SECTION.

8.3 Nursing Mothers. 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 sumatriptan injection.

OVERDOSAGE SECTION.

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

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL. PRINCIPAL DISPLAY PANELNDC 0143-9638-01 SUMATRIPTAN INJECTION, USP6 mg/0.5 mLFOR SUBCUTANEOUSINJECTION ONLYRx ONLY0.5 mL Single Dose VialStore between 2o and 30oC (36o to 86oF). Protect from light. NDC 0143-9638-01 SUMATRIPTAN INJECTION, USP mg (base)/0.5 mL FOR SUBCUTANEOUS INJECTION ONLY Rx ONLY 0.5 mL Single Dose Vial Store between 2o and 30oC (36o to 86oF). Protect from light.

PEDIATRIC USE SECTION.

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

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. Absorption and Bioavailability: The bioavailability of sumatriptan via subcutaneous site injection to 18 healthy male subjects was 97% +- 16% of that obtained following intravenous injection. After single mg subcutaneous manual injection into the deltoid area of the arm in 18 healthy males (age: 24 +- years, weight: 70 kg), the maximum serum concentration (Cmax) of sumatriptan was (mean +- standard deviation) 74 +- 15 ng/mL and the time to peak concentration (Tmax) was 12 minutes after injection (range: to 20 minutes). In this trial, the same dose injected subcutaneously in the thigh gave Cmax of 61 +- 15 ng/mL by manual injection versus 52 +- 15 ng/mL by autoinjector techniques. The Tmax or amount absorbed was not significantly altered by either the site or technique of injection. Distribution: Protein binding, determined by equilibrium dialysis over the concentration range of 10 to 1,000 ng/mL, is low, approximately 14% to 21%. The effect of sumatriptan on the protein binding of other drugs has not been evaluated. Following 6 mg subcutaneous injection into the deltoid area of the arm in males (mean age: 33 years, mean weight: 77 kg) the volume of distribution central compartment of sumatriptan was 50 +- liters and the distribution half-life was 15 +- minutes. Metabolism: In vitro studies with human microsomes suggest that sumatriptan is metabolized by MAO, predominantly the isoenzyme. Most of radiolabeled dose of sumatriptan excreted in the urine is the major metabolite indole acetic acid (IAA) or the IAA glucuronide, both of which are inactive. Elimination: After single mg subcutaneous dose, 22% +- 4% was excreted in the urine as unchanged sumatriptan and 38% +- 7% as the IAA metabolite. Following 6 mg subcutaneous injection into the deltoid area of the arm, the systemic clearance of sumatriptan was 1,194 +- 149 mL/min and the terminal half-life was 115 +- 19 minutes. Special Populations: Age: The pharmacokinetics of sumatriptan in the elderly (mean age: 72 years, males and 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). Hepatic Impairment: The effect of mild to moderate hepatic disease on the pharmacokinetics of subcutaneously administered sumatriptan has been evaluated. There were no significant differences in the pharmacokinetics of subcutaneously administered sumatriptan in moderately hepatically impaired subjects compared with healthy controls. The pharmacokinetics of subcutaneously administered sumatriptan in patients with severe hepatic impairment has not been studied. The use of sumatriptan injection in this population is contraindicated [see Contraindications (4)]. Race: The systemic clearance and Cmax of subcutaneous sumatriptan were similar in black (n 34) and Caucasian (n 38) healthy male subjects. Drug Interaction Studies: Monoamine Oxidase-A Inhibitors: In trial of 14 healthy females, pretreatment with an MAO-A inhibitor decreased the clearance of subcutaneous sumatriptan, resulting in 2-fold increase in the area under the sumatriptan plasma concentration-time curve (AUC), corresponding to 40% increase in elimination half-life.

PREGNANCY SECTION.

8.1 Pregnancy. Pregnancy Category C: There are no adequate and well-controlled trials of sumatriptan injection 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. Sumatriptan injection 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 rates was 60 mg/kg/day, or approximately 100 times the single maximum recommended human dose (MRHD) of mg administered subcutaneously on mg/m2 basis. 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, or approximately 50 and times, respectively, the single MRHD of mg administered subcutaneously on mg/m2 basis.Oral administration of sumatriptan to rats prior to and throughout gestation resulted in embryofetal toxicity (decreased body weight, decreased ossification, increased incidence of skeletal abnormalities). The highest no-effect dose was 50 mg/kg/day, or approximately 80 times the single MRHD of mg administered subcutaneously on mg/m2 basis. In offspring of pregnant rats treated orally with sumatriptan during organogenesis, there was decrease in pup survival. The highest no-effect dose for this effect was 60 mg/kg/day, or approximately 100 times the single MRHD of mg administered subcutaneously on mg/m2 basis. Oral treatment of pregnant rats with sumatriptan during the latter part of gestation and throughout lactation resulted in decrease in pup survival. The highest no-effect dose for this finding was 100 mg/kg/day, or approximately 160 times the single MRHD of mg administered subcutaneously on mg/m2 basis.

SPL PATIENT PACKAGE INSERT SECTION.

Patient InformationSumatriptan Injection, USPRead this Patient Information before you start taking sumatriptan and each time you get 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 should know about sumatriptan Sumatriptan can cause serious side effects, including: Heart attack and other heart problems. Heart problems may lead to death. Stop taking sumatriptan and get emergency medical help right away if you have any of the following symptoms of heart attack:discomfort in the center of your chest that lasts for more than few minutes, or that goes away and comes back severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw pain or discomfort in your arms, back, neck, jaw, or stomach shortness of breath with or without chest discomfort breaking out in cold sweat nausea or vomiting feeling lightheaded Sumatriptan is not for people with risk factors for heart disease unless heart exam is done and shows no problem. You have higher risk for heart disease if you: have high blood pressure have high cholesterol levels smoke are overweight have diabetes have family history of heart disease What is sumatriptan Sumatriptan is prescription medicine used to treat acute migraine headaches with or without aura and acute cluster headaches in adults who have been diagnosed with migraine or cluster headaches. Sumatriptan is not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines. Sumatriptan is not used to prevent or decrease the number of migraine or cluster headaches you have. It is not known if sumatriptan is safe and effective in children under 18 years of age. Who should not take sumatriptan Do not take sumatriptan if you have: heart problems or history of heart problems narrowing of blood vessels to your legs, arms, stomach, or kidneys (peripheral vascular disease) uncontrolled high blood pressuresevere liver problemshemiplegic migraines or basilar migraines. If you are not sure if you have these types of migraines, ask your healthcare provider. had stroke, transient ischemic attacks (TIAs), or problems with your blood circulation taken any of the following medicines in the last 24 hours: almotriptan (AXERT(R)) eletriptan (RELPAX(R)) frovatriptan (FROVA(R)) naratriptan (AMERGE(R)) rizatriptan (MAXALT(R), MAXALT-MLT(R)) sumatriptan and naproxen (TREXIMET(R)) ergotamines (CAFERGOT(R), ERGOMAR(R), MIGERGOT(R)) dihydroergotamine (D.H.E. 45(R), MIGRANAL(R)) Ask your healthcare provider if you are not sure if your medicine is listed above. an allergy to sumatriptan or any of the ingredients in sumatriptan injection. See the end of this leaflet for complete list of ingredients in sumatriptan injection. What should tell my healthcare provider before taking sumatriptan Before you take sumatriptan, 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 have heart problems or family history of heart problems or strokehave kidney problemshave liver problems have had epilepsy or seizures are not using effective birth control become pregnant while taking sumatriptan are breastfeeding or plan to breastfeed. Sumatriptan 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 take sumatriptan. Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.Sumatriptan and certain other medicines can affect each other, causing serious side effects. Especially tell your healthcare provider if you take antidepressant medicines called: selective serotonin reuptake inhibitors (SSRIs) serotonin norepinephrine reuptake inhibitors (SNRIs) tricyclic antidepressants (TCAs) monoamine oxidase inhibitors (MAOIs) Ask your healthcare provider or pharmacist for list of these medicines if you are not sure.Know the medicines you take. Keep list of them to show your healthcare provider or pharmacist when you get new medicine. How should take sumatriptan Certain people should take their first dose of sumatriptan in their healthcare providers office or in another medical setting. Ask your healthcare provider if you should take your first dose in medical setting. Use sumatriptan exactly as your healthcare provider tells you to use it. Your healthcare provider may change your dose. Do not change your dose without first talking with your healthcare provider. For adults, the usual dose is single injection given just below the skin. You should give an injection as soon as the symptoms of your headache start, but it may be given at any time during migraine or cluster headache attack. If you did not get any relief after the first injection, do not give second injection without first talking with your healthcare provider.If your headache comes back or you only get some relief after your first injection, you can take second injection hour after the first injection, but not sooner.Do not take more than 12 mg in 24-hour period. If you use too much sumatriptan, call your healthcare provider or go to the nearest hospital emergency room right away. You should write down when you have headaches and when you take sumatriptan so you can talk with your healthcare provider about how sumatriptan is working for you. What should avoid while taking sumatriptan Sumatriptan can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive car, use machinery, or do anything where you need to be alert. What are the possible side effects of sumatriptan Sumatriptan may cause serious side effects. See What is the most important information should know about sumatriptan These serious side effects include: changes in color or sensation in your fingers and toes (Raynauds 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 or both legs or feet hives (itchy bumps); swelling of your tongue, mouth, or throatmedication overuse headaches. Some people who use too many sumatriptan injections may have worse headaches (medication overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with sumatriptan. serotonin syndrome. Serotonin syndrome is rare but serious problem that can happen in people using sumatriptan, especially if sumatriptan is used with antidepressant medicines called SSRIs or SNRIs. 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 walkingseizures. Seizures have happened in people taking sumatriptan who have never had seizures before. Talk with your healthcare provider about your chance of having seizures while you take sumatriptan. The most common side effects of sumatriptan injection include: pain or redness at your injection site tingling or numbness in your fingers or toes dizziness warm, hot, burning feeling to your face (flushing) discomfort or stiffness in your neck feeling weak, drowsy, or tired 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. 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 store sumatriptan injection Store sumatriptan injection between 36F to 86F (2C to 30C). Store your medicine away from light. Keep your medicine in the packaging or carrying case provided with it. Keep sumatriptan and all medicines out of the reach of children. General information about the safe and effective use of sumatriptan Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use sumatriptan for condition for which it was not prescribed. Do not give sumatriptan to other people, even if they have the same symptoms you have. It may harm them.This Patient Information leaflet summarizes the most important information about sumatriptan. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about sumatriptan that is written for healthcare professionals. To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-877-233-2001 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. What are the ingredients in sumatriptan injection Active ingredient: sumatriptan succinateInactive ingredients: sodium chloride, water for injectionThis Patient Information has been approved by the U.S. Food and Drug Administration. The brands listed are trademarks of their respective owners. The makers of these brands are not affiliated with and do not endorse this product.Manufactured by: HIKMA FARMACEUTICA (PORTUGAL), S.A.Estrada do Rio da Mo, 8, 8A 8B Fervenca 2705-906 Terrugem SNT, PORTUGALDistributed by: WEST-WARD PHARMACEUTICALS CORP.Eatontown, NJ 07724 USAOctober 2015. discomfort in the center of your chest that lasts for more than few minutes, or that goes away and comes back severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw pain or discomfort in your arms, back, neck, jaw, or stomach shortness of breath with or without chest discomfort breaking out in cold sweat nausea or vomiting feeling lightheaded have high blood pressure have high cholesterol levels smoke are overweight have diabetes have family history of heart disease heart problems or history of heart problems narrowing of blood vessels to your legs, arms, stomach, or kidneys (peripheral vascular disease) uncontrolled high blood pressure. severe liver problems. hemiplegic migraines or basilar migraines. If you are not sure if you have these types of migraines, ask your healthcare provider. had stroke, transient ischemic attacks (TIAs), or problems with your blood circulation taken any of the following medicines in the last 24 hours: almotriptan (AXERT(R)) eletriptan (RELPAX(R)) frovatriptan (FROVA(R)) naratriptan (AMERGE(R)) rizatriptan (MAXALT(R), MAXALT-MLT(R)) sumatriptan and naproxen (TREXIMET(R)) ergotamines (CAFERGOT(R), ERGOMAR(R), MIGERGOT(R)) dihydroergotamine (D.H.E. 45(R), MIGRANAL(R)) almotriptan (AXERT(R)) eletriptan (RELPAX(R)) frovatriptan (FROVA(R)) naratriptan (AMERGE(R)) rizatriptan (MAXALT(R), MAXALT-MLT(R)) sumatriptan and naproxen (TREXIMET(R)) ergotamines (CAFERGOT(R), ERGOMAR(R), MIGERGOT(R)) dihydroergotamine (D.H.E. 45(R), MIGRANAL(R)) an allergy to sumatriptan or any of the ingredients in sumatriptan injection. See the end of this leaflet for complete list of ingredients in sumatriptan injection. have high blood pressure have high cholesterol have diabetes smoke are overweight have heart problems or family history of heart problems or stroke. have kidney problems. have liver problems have had epilepsy or seizures are not using effective birth control become pregnant while taking sumatriptan are breastfeeding or plan to breastfeed. Sumatriptan 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 take sumatriptan. selective serotonin reuptake inhibitors (SSRIs) serotonin norepinephrine reuptake inhibitors (SNRIs) tricyclic antidepressants (TCAs) monoamine oxidase inhibitors (MAOIs) Certain people should take their first dose of sumatriptan in their healthcare providers office or in another medical setting. Ask your healthcare provider if you should take your first dose in medical setting. Use sumatriptan exactly as your healthcare provider tells you to use it. Your healthcare provider may change your dose. Do not change your dose without first talking with your healthcare provider. For adults, the usual dose is single injection given just below the skin. You should give an injection as soon as the symptoms of your headache start, but it may be given at any time during migraine or cluster headache attack. If you did not get any relief after the first injection, do not give second injection without first talking with your healthcare provider.. If your headache comes back or you only get some relief after your first injection, you can take second injection hour after the first injection, but not sooner.. Do not take more than 12 mg in 24-hour period. If you use too much sumatriptan, call your healthcare provider or go to the nearest hospital emergency room right away. You should write down when you have headaches and when you take sumatriptan so you can talk with your healthcare provider about how sumatriptan is working for you. changes in color or sensation in your fingers and toes (Raynauds 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 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 or both legs or feet 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 or both legs or feet hives (itchy bumps); swelling of your tongue, mouth, or throat. medication overuse headaches. Some people who use too many sumatriptan injections may have worse headaches (medication overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with sumatriptan. serotonin syndrome. Serotonin syndrome is rare but serious problem that can happen in people using sumatriptan, especially if sumatriptan is used with antidepressant medicines called SSRIs or SNRIs. 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. seizures. Seizures have happened in people taking sumatriptan who have never had seizures before. Talk with your healthcare provider about your chance of having seizures while you take sumatriptan. pain or redness at your injection site tingling or numbness in your fingers or toes dizziness warm, hot, burning feeling to your face (flushing) discomfort or stiffness in your neck feeling weak, drowsy, or tired Store sumatriptan injection between 36F to 86F (2C to 30C). Store your medicine away from light. Keep your medicine in the packaging or carrying case provided with it.

SPL UNCLASSIFIED SECTION.

2.1 Dosing Information. The maximum single recommended adult dose of sumatriptan injection for the acute treatment of migraine or cluster headache is mg injected subcutaneously. For the treatment of migraine, if side effects are dose limiting, lower doses (1 to mg) may be used [see Clinical Studies (14.1)]. For the treatment of cluster headache, the efficacy of lower doses has not been established. The maximum cumulative dose that may be given in 24 hours is 12 mg, two mg injections separated by at least hour. second mg dose should only be considered if some response to first injection was observed.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. Pregnancy: Based on animal data, may cause fetal harm (8.1). Pregnancy: Based on animal data, may cause fetal harm (8.1). 8.1 Pregnancy. Pregnancy Category C: There are no adequate and well-controlled trials of sumatriptan injection 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. Sumatriptan injection 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 rates was 60 mg/kg/day, or approximately 100 times the single maximum recommended human dose (MRHD) of mg administered subcutaneously on mg/m2 basis. 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, or approximately 50 and times, respectively, the single MRHD of mg administered subcutaneously on mg/m2 basis.Oral administration of sumatriptan to rats prior to and throughout gestation resulted in embryofetal toxicity (decreased body weight, decreased ossification, increased incidence of skeletal abnormalities). The highest no-effect dose was 50 mg/kg/day, or approximately 80 times the single MRHD of mg administered subcutaneously on mg/m2 basis. In offspring of pregnant rats treated orally with sumatriptan during organogenesis, there was decrease in pup survival. The highest no-effect dose for this effect was 60 mg/kg/day, or approximately 100 times the single MRHD of mg administered subcutaneously on mg/m2 basis. Oral treatment of pregnant rats with sumatriptan during the latter part of gestation and throughout lactation resulted in decrease in pup survival. The highest no-effect dose for this finding was 100 mg/kg/day, or approximately 160 times the single MRHD of mg administered subcutaneously on mg/m2 basis.. 8.3 Nursing Mothers. 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 sumatriptan injection.. 8.4 Pediatric Use. Safety and effectiveness in pediatric patients have not been established. Sumatriptan injection is not recommended for use in patients younger than 18 years of age. Two controlled clinical trials evaluated sumatriptan nasal spray (5 to 20 mg) in 1,248 pediatric migraineurs 12 to 17 years of age who treated single attack. The trials did not establish the efficacy of sumatriptan nasal spray compared with placebo in the treatment of migraine in pediatric patients. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults. Five controlled clinical trials (2 single-attack trials, multiple-attack trials) evaluating oral sumatriptan (25 to 100 mg) in pediatric patients 12 to 17 years of age enrolled total of 701 pediatric migraineurs. These trials did not establish the efficacy of oral sumatriptan compared with placebo in the treatment of migraine in pediatric patients. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults. The frequency of all adverse reactions in these patients appeared to be both dose- and age-dependent, with younger patients reporting reactions more commonly than older pediatric patients. Postmarketing experience documents that serious adverse reactions have occurred in the pediatric population after use of subcutaneous, oral, and/or intranasal sumatriptan. These reports include reactions similar in nature to those reported rarely in adults, including stroke, visual loss, and death. myocardial infarction has been reported in 14-year-old male following the use of oral sumatriptan; clinical signs occurred within day of drug administration. Clinical data to determine the frequency of serious adverse reactions in pediatric patients who might receive subcutaneous, oral, or intranasal sumatriptan are not presently available.. 8.5 Geriatric Use. Clinical trials of sumatriptan injection did not include sufficient numbers of patients 65 years of age 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. cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving sumatriptan injection [see Warnings and Precautions (5.1)].

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Myocardial ischemia/infarction and Prinzmetals angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors. (5.1)Arrhythmias: Discontinue sumatriptan if occurs. (5.2)Chest/throat/neck/jaw pain, tightness, pressure, or heaviness: Generally not associated with myocardial ischemia; evaluate for coronary artery disease in patients at high risk. (5.3)Cerebral hemorrhage, subarachnoid hemorrhage, and stroke: Discontinue sumatriptan if occurs. (5.4)Gastrointestinal ischemic reactions and peripheral vasospastic reactions: Discontinue sumatriptan if occurs. (5.5)Medication overuse headache: Detoxification may be necessary. (5.6)Serotonin syndrome: Discontinue sumatriptan if occurs. (5.7)Seizures: Use with caution in patients with epilepsy or lowered seizure threshold. (5.10). Myocardial ischemia/infarction and Prinzmetals angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors. (5.1). Arrhythmias: Discontinue sumatriptan if occurs. (5.2). Chest/throat/neck/jaw pain, tightness, pressure, or heaviness: Generally not associated with myocardial ischemia; evaluate for coronary artery disease in patients at high risk. (5.3). Cerebral hemorrhage, subarachnoid hemorrhage, and stroke: Discontinue sumatriptan if occurs. (5.4). Gastrointestinal ischemic reactions and peripheral vasospastic reactions: Discontinue sumatriptan if occurs. (5.5). Medication overuse headache: Detoxification may be necessary. (5.6). Serotonin syndrome: Discontinue sumatriptan if occurs. (5.7). Seizures: Use with caution in patients with epilepsy or lowered seizure threshold. (5.10). 5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetals Angina. The use of sumatriptan injection is contraindicated in patients with ischemic or vasospastic CAD. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within few hours following administration of sumatriptan injection. Some of these reactions occurred in patients without known CAD. Sumatriptan injection may cause coronary artery vasospasm (Prinzmetals angina), even in patients without history of CAD. Perform cardiovascular evaluation in triptan-naive patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving sumatriptan injection. If there is evidence of CAD or coronary artery vasospasm, sumatriptan injection is contraindicated. For patients with multiple cardiovascular risk factors who have negative cardiovascular evaluation, consider administering the first dose of sumatriptan injection in medically supervised setting and performing an electrocardiogram (ECG) immediately following administration of sumatriptan injection. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of sumatriptan injection.. 5.2 Arrhythmias. Life-threatening disturbances of cardiac rhythm, including ventricular tachycardia and ventricular fibrillation leading to death, have been reported within few hours following the administration of 5-HT1 agonists. Discontinue sumatriptan injection if these disturbances occur. Sumatriptan injection is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.. 5.3 Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure. Sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw commonly occur after treatment with sumatriptan injection and are usually non-cardiac in origin. However, perform cardiac evaluation if these patients are at high cardiac risk. The use of sumatriptan injection is contraindicated in patients with CAD and those with Prinzmetals variant angina.. 5.4 Cerebrovascular Events. Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities. In 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 consequence of migraine when they were not. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). Discontinue sumatriptan injection if cerebrovascular event occurs. Before treating headaches in patients not previously diagnosed with migraine or cluster headache or in patients who present with atypical symptoms, exclude other potentially serious neurological conditions. Sumatriptan injection is contraindicated in patients with history of stroke or TIA.. 5.5 Other Vasospasm Reactions. Sumatriptan injection may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynauds syndrome. In patients who experience symptoms or signs suggestive of non-coronary vasospasm reaction following the use of any 5-HT1 agonist, rule out vasospastic reaction before receiving additional sumatriptan injections.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 migraine attack, causal relationship between these events and the use of 5-HT1 agonists have not been clearly established. 5.6 Medication Overuse Headache. 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 marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes transient worsening of headache) may be necessary.. 5.7 Serotonin Syndrome. Serotonin syndrome may occur with sumatriptan injection, particularly during coadministration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions (7.4)]. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually occurs within minutes to hours of receiving new or greater dose of serotonergic medication. Discontinue sumatriptan injection if serotonin syndrome is suspected.. 5.8 Increase in Blood Pressure. Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported on rare occasions in patients treated with 5-HT1 agonists, including patients without history of hypertension. Monitor blood pressure in patients treated with sumatriptan. Sumatriptan injection is contraindicated in patients with uncontrolled hypertension.. 5.9 Anaphylactic/Anaphylactoid Reactions. Anaphylactic/anaphylactoid reactions have occurred in patients receiving sumatriptan. Such reactions can be life threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with history of sensitivity to multiple allergens. Sumatriptan injection is contraindicated in patients with history of hypersensitivity reaction to sumatriptan.. 5.10 Seizures. Seizures have been reported following administration of sumatriptan. Some have occurred in patients with either history of seizures or concurrent conditions predisposing to seizures. There are also reports in patients where no such predisposing factors are apparent. Sumatriptan injection should be used with caution in patients with history of epilepsy or conditions associated with lowered seizure threshold.