Sumavel Dosepro
FDA Label NDC 43376-106

Sumavel DosePro 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 a clear diagnosis of migraine or cluster headache has been established.
  
• If a patient has no response to the first migraine attack treated with Sumavel DosePro, reconsider the diagnosis of migraine before Sumavel DosePro is administered to treat any subsequent attacks.
  
• Sumavel DosePro is not indicated for the prevention of migraine attacks.

The maximum single recommended dose of Sumavel DosePro for the acute treatment of migraine or cluster headache is 6 mg given subcutaneously. For the treatment of migraine, if side effects are dose limiting, a lower dose (4 mg) may be used [see Clinical Studies (14.1)]. For the treatment of cluster headache, the efficacy of a lower dose has not been established.

The maximum cumulative injected dose that may be given in 24 hours is 12 mg, with doses of Sumavel DosePro separated by at least 1 hour. Sumavel DosePro may be given at least 1 hour following a dose of another sumatriptan product. A second dose should only be considered if some response to a first dose was observed.

Sumavel DosePro is available for use as 4 mg or 6 mg needle-free delivery systems. It is intended to be given subcutaneously only. Sumavel DosePro is designed for patient self-administration to sites on the abdomen or the thigh with an adequate subcutaneous thickness to accommodate penetration of sumatriptan injection into the subcutaneous space. Administration should not be made within 2 inches of the naval. Sumavel DosePro is not to be administered to other areas of the body, including the arm.  

Instruct patients on the proper use of Sumavel DosePro and direct them to use proper injection sites. Patients should be instructed not to use Sumavel DosePro if the tip of the device is tilted or broken off upon removal from packaging [see Patient counseling Information (17)].

Sumavel DosePro is for single use only. Discard after use.

Sumavel DosePro is a prefilled, single-dose, needle-free subcutaneous delivery system delivering 0.5 mL of sterile solution containing 4 mg or 6 mg sumatriptan (as the succinate salt).

Sumavel DosePro 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 Prinzmetal’s angina [see Warnings and Precautions (5.1)]
  
• Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.2)] 
  
• History of stroke or transient ischemic attack (TIA) because these patients are at a higher risk of stroke [see Warnings and Precautions (5.4)]
  
• History of hemiplegic or basilar migraine
  
• 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 (i.e., within 24 hours) use of ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide), or another 5-hydroxytryptamine1 (5-HT₁) agonist [see Drug Interactions (7.1, 7.3)]
  
• Concurrent administration of a monamine oxidase (MAO)-A inhibitor or recent (within 2 weeks) use of an MAO-A inhibitor [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)]
  
• Hypersensitivity to Sumavel DosePro (angioedema and anaphylaxis seen) [see Warnings and Precautions (5.9) and Adverse Reactions (6)]

Sumavel DosePro 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 Sumavel DosePro. Some of these reactions occurred in patients without known CAD. Sumavel DosePro 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 Sumavel DosePro. If there is evidence of CAD or coronary artery vasospasm, Sumavel DosePro is contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of Sumavel DosePro in a medically supervised setting and performing an electrocardiogram (ECG) immediately following Sumavel DosePro. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of Sumavel DosePro.

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

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

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

Sumavel DosePro, may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud’s syndrome. In patients who experience symptoms or signs suggestive of non-coronary vasospasm reaction following the use of any 5-HT₁ agonist, rule out a vasospastic reaction before receiving additional doses of Sumavel DosePro.

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 Sumavel DosePro, 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 Sumavel DosePro 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 Sumavel DosePro. Sumavel DosePro is contraindicated in patients with uncontrolled hypertension.

There have been reports of anaphylaxis, anaphylactoid, and hypersensitivity reactions including angioedema in patients receiving Sumavel DosePro. 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. Sumavel DosePro is contraindicated in patients with a history of hypersensitivity reaction to Sumavel DosePro.

Seizures have been reported following administration of Sumavel DosePro. 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. Sumavel DosePro 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 labeling:

• Myocardial ischemia, myocardial infarction, and Prinzmetal’s angina [see Warnings and Precautions (5.1)]
  
• Arrhythmias [see Warnings and Precautions (5.2)]
  
• Chest, throat, neck, and/or jaw pain/tightness/pressure [see Warnings and Precautions (5.3)]
  
• Cerebrovascular events [see Warnings and Precautions (5.4)]
  
• Other vasospasm reactions [see Warnings and Precautions (5.5)]
  
• Medication overuse headache [see Warnings and Precautions (5.6)]
  
• Serotonin syndrome [see Warnings and Precautions (5.7)]
  
• Increase in blood pressure [see Warnings and Precautions (5.8)]
  
• Hypersensitivity reactions [see Contraindications (4) and Warnings and Precautions (5.9)]
  
• Seizures [see Warnings and Precautions (5.10)]

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

Migraine Headache: Table 1 lists adverse reactions that occurred in 2 US placebo-controlled clinical trials in migraine subjects [see Clinical Studies (14.1)] following either a single 6 mg dose of sumatriptan injection or placebo. Only reactions that occurred at a frequency of 2% or more in groups treated with sumatriptan injection 6 mg and that occurred at a frequency greater than the placebo group are included in Table 1.

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

Cluster Headache: In the controlled clinical trials assessing the efficacy of sumatriptan injection as a treatment for cluster headache [see Clinical Studies (14.2)], no new significant adverse reactions were detected that had not already been identified in trials of sumatriptan in subjects 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).

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 Sumavel DosePro within 24 hours of each other is contraindicated.

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

Because their vasospastic effects may be additive, co-administration of Sumavel DosePro 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, or SNRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7)].

Pregnancy Category C: There are no adequate and well-controlled trials of sumatriptan injection in pregnant women. Sumavel DosePro should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

When sumatriptan was administered intravenously to pregnant rabbits daily throughout the period of organogenesis, embryolethality was observed at doses at or close to those producing maternal toxicity. These doses were less than the maximum recommended human dose (MRHD) of 12 mg/day on a mg/m² basis. Oral administration of sumatriptan to rabbits during organogenesis was associated with increased incidences of fetal vascular and skeletal abnormalities. The highest no-effect dose for these effects was 15 mg/kg/day. The intravenous administration of sumatriptan to pregnant rats throughout organogenesis at doses that are approximately 10 times the MRHD on a mg/m² basis, did not produce evidence of embryolethality. The subcutaneous administration to pregnant rats prior to and throughout pregnancy did not produce evidence of embryolethality or teratogenicity.

It is not known whether sumatriptan is excreted in human breast milk following subcutaneous administration. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Sumavel DosePro, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Safety and effectiveness of sumatriptan injection in pediatric patients under 18 years of age have not been established; therefore, sumatriptan injection is not recommended for use in patients under 18 years of age.

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

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

Postmarketing experience documents that serious adverse reactions have occurred in the pediatric population after use of subcutaneous, oral, and/or intranasal sumatriptan. These reports include reactions similar in nature to those reported rarely in adults, including stroke, visual loss, and death. A myocardial infarction has been reported in a 14-year-old male following the use of oral sumatriptan; clinical signs occurred within 1 day of drug administration. Since 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, the use of sumatriptan in patients under 18 years of age is not recommended.

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

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

The effect of severe hepatic impairment on Sumavel DosePro metabolism has not been evaluated. Sumavel DosePro is not recommended for use in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].

The elimination half-life of sumatriptan is about 2 hours [see Clinical Pharmacology (12.3)], and therefore monitoring of patients after overdose with subcutaneous sumatriptan 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.

Sumavel DosePro contains sumatriptan succinate, a selective 5-HT_1B/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 Chemical Structure For Sumatriptan Succinate. (Sumavel Dosepro 1)

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

Sumatriptan solution is a clear, colorless to pale yellow, sterile, nonpyrogenic solution for subcutaneous delivery. Each 0.5 mL of Sumavel DosePro 8 mg/mL solution contains 4 mg of sumatriptan (base) as the succinate salt and 3.8 mg of sodium chloride, USP in Water for Injection, USP. Each 0.5 mL of Sumavel DosePro 12 mg/mL solution contains 6 mg of sumatriptan (base) as the succinate salt and 3.5 mg of sodium chloride, USP, in water for injection, USP. The pH range of both solutions is approximately 4.2 to 5.3. The osmolality of both solutions is 291 mOsmol.

Sumavel DosePro is a pre-filled, single-use, disposable, needle-free subcutaneous delivery system delivering sterile sumatriptan injection. Sumavel DosePro consists of the following components: a gray plastic handle and snap-off tip, a lavender (4 mg) or green (6 mg) lever, and a glass medication chamber that is pre-filled with 4 mg or 6 mg per 0.5 mL sumatriptan injection. Utilizing pressure from a compressed nitrogen gas source in the handle, Sumavel DosePro delivers the medication by pushing it through a small, precise hole in the glass medication chamber. The resulting stream of medication is propelled through the skin and is delivered subcutaneously without a needle, following a biphasic pressure profile.

Sumatriptan is the active component of Sumavel DosePro. Sumatriptan binds with high affinity to human cloned 5-HT_1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine headache by binding to 5-HT_1B/1D receptors located on intracranial blood vessels and sensory nerves of the trigeminal system.

Current theories proposed to explain the etiology of migraine headache suggest that symptoms are due to local cranial vasodilatation and/or to the release of sensory neuropeptides (including substance P and calcitonin gene-related peptide) through nerve endings in the trigeminal system. The therapeutic activity of sumatriptan for the treatment of migraine and cluster headaches is thought to be due to the agonist effects at the 5-HT_1B/1D receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

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

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

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

Absorption and Bioavailability: Sumavel DosePro is bioequivalent to sumatriptan needle-based injection via autoinjector at the thigh and abdomen administration sites. A sub-optimal dose may be delivered when administered to the arm and therefore, the arm is not recommended as a site of administration. 

Pharmacokinetic parameters following a 6 mg subcutaneous dose of Sumavel DosePro into the thigh were determined in 32 subjects (males and females). The maximum serum concentration (C_max) (mean ± standard deviation) was 71.9 ± 14.4 ng/mL; the time to peak concentration (T_max) was 12 minutes after dosing (range, 4 to 20 minutes); and the terminal half-life was 103 ± 22 minutes.

Pharmacokinetic parameters following a 6 mg subcutaneous dose of Sumavel DosePro into the abdomen were determined in 35 subjects (males and females). The maximum serum concentration (C_max) (mean ± standard deviation) was 78.6 ± 17.3 ng/mL; the time to peak concentration (T_max) was 12 minutes after dosing (range, 6 to 20 minutes); and the terminal half-life was 102 ± 12 minutes.

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

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

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

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).

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 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 Sumavel DosePro in this population is not recommended [see Use in Specific Populations (8.6)].

Race: The systemic clearance and C_max of sumatriptan were similar in Black (n = 34) and Caucasian (n = 38) healthy male subjects.

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

Carcinogenesis: In carcinogenicity studies, rats and mice were given sumatriptan by oral gavage. Mice were dosed for 78 weeks and rats were dosed for 104 weeks. Average exposures achieved in mice receiving the highest dose were approximately 110 times the exposure attained in humans after the maximum recommended single dose of 6 mg. The highest dose to rats was approximately 260 times the maximum single dose of 6 mg on a mg/m² basis. There was no evidence of an increase in tumors in either species related to sumatriptan administration.

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

Impairment of Fertility: A fertility study (Segment I) by the subcutaneous route, during which male and female rats were dosed daily with sumatriptan prior to and throughout the mating period, has shown no evidence of impaired fertility at doses equivalent to approximately 100 times the maximum recommended single human dose of 6 mg on a mg/m² basis. However, following oral administration, a treatment-related decrease in fertility, secondary to a decrease in mating, was seen for rats treated with 50 and 500 mg/kg/day. The no-effect dose for this finding was approximately 8 times the maximum recommended single human dose of 6 mg on a mg/m² basis. It is not clear whether the problem is associated with the treatment of males or females or both.

Corneal Opacities: Dogs receiving oral sumatriptan developed corneal opacities and defects in the corneal epithelium. Corneal opacities were seen at the lowest dosage tested, 2 mg/kg/day, and were present after 1 month of treatment. Defects in the corneal epithelium were noted in a 60-week study. Earlier examinations for these toxicities were not conducted and no-effect doses were not established; however, the relative exposure at the lowest dose tested was approximately 5 times the human exposure after a 100 mg oral dose or 3 times the human exposure after a 6 mg subcutaneous dose.

Melanin Binding: In rats with a single subcutaneous dose (0.5 mg/kg) of radiolabeled sumatriptan, the elimination half-life of radioactivity from the eye was 15 days, suggesting that sumatriptan and its metabolites bind to the melanin of the eye. The clinical significance of this binding is unknown.

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

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

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

Subcutaneous sumatriptan 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 subject, or concomitant use of common migraine prophylactic drugs (e.g., beta-blockers).

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

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

Figure 1. Time To Relief Of Cluster Headache From Time Of Injection (Sumavel Dosepro 2)

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

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

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

Each Sumavel DosePro needle-free delivery system contains sumatriptan (base) in 0.5 mL, in a sterile, nonpyrogenic solution and is supplied as follows:

• Sumavel DosePro, 4 mg in a package of six prefilled, single-dose units (NDC 43376-104-06).
  
• Sumavel DosePro, 6 mg in a package of six prefilled, single-dose units (NDC 43376-106-06).

Store at 20 ^oC to 25 ^oC (68 ^oF to 77 ^oF), with excursions permitted between 15 ^oC to 30 ^oC (59 ^oF to 86 ^oF). Do not freeze. Protect from light.

See FDA-approved patient labeling.

Risk of Myocardial Ischemia and/or Infarction, Prinzmetal’s Angina, Other Vasospasm-Related Events, Arrhythmias and Cerebrovascular Events
Inform patients that Sumavel DosePro may cause serious cardiovascular side effects such as myocardial infarction or stroke. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, irregular heartbeat, significant rise in blood pressure, weakness, and slurring of speech and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised 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 Sumavel DosePro. Such reactions can be life threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens [see Warnings and Precautions (5.9)].

Serotonin Syndrome
Patients should be cautioned about the risk of serotonin syndrome with the use of Sumavel DosePro 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 Sumavel DosePro 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
Since migraines or treatment with Sumavel DosePro may cause somnolence and dizziness, instruct patients to evaluate their ability to perform complex tasks during migraine attacks and after administration of Sumavel DosePro.

How to Use Sumavel DosePro
Importance of Training
Patients who are to self-administer Sumavel DosePro in medically unsupervised situations should receive instruction on the proper use of Sumavel DosePro from the physician or healthcare professional prior to administering for the first time.
Patients should be made aware that a loud burst of air will be heard and a sensation felt at the time the dose is delivered via Sumavel DosePro. Patients should be advised not to use a device if the tip of the device is tilted or broken off upon removal from packaging.

Choosing Administration Sites
Sumavel DosePro delivers the medication to the subcutaneous space in a manner similar to a subcutaneous injection. Since delivery is to be given subcutaneously, patients should be instructed to use administration sites on the abdomen or the thigh with adequate subcutaneous thickness to accommodate penetration of the drug into the subcutaneous space. Administration should not be made within 2 inches of the navel. Instruct patients not to administer Sumavel DosePro to the arms or other areas of the body. Inform patients that Sumavel DosePro is for subcutaneous use only and is not designed for intramuscular or intravenous use.