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What is Sumavel DosePro and how is it used?
Sumavel DosePro is a prescription medicine used to treat acute migraine headaches with or without aura and acute cluster headaches in adults who have been diagnosed with migraine or cluster headaches.
Sumavel DosePro 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.
Sumavel DosePro is not used to prevent or decrease the number of migraine or cluster headaches you have.
It is not known if Sumavel DosePro is safe and effective in children under 18 years of age.
What are the possible side effects of Sumavel DosePro?
See “What is the most important information I should know about Sumavel DosePro?”
The most common side effects of Sumavel DosePro include:
These are not all the possible side effects of Sumavel DosePro. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Sumavel DosePro contains sumatriptan succinate, a selective 5-HT1B/1D receptor agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1), and it has the following structure:
 |
The 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.
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.
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]. 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. Instruct patients to not use Sumavel DosePro if the tip of the device is tilted or broken off upon removal from packaging [see PATIENT INFORMATION and Instructions for Use].
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).
Each Sumavel DosePro needle-free delivery system contains sumatriptan (base) in 0.5 mL, in a sterile, nonpyrogenic solution and is supplied as follows:
Store at 20 °C to 25 °C (68 °F to 77 °F), with excursions permitted between 15 °C to 30 °C (59 °F to 86 °F). Do not freeze. Protect from light.
Manufactured by: Patheon UK, Limited, Swindon, United Kingdom. Revised: Jan 2020
The following adverse reactions are discussed in more detail in other sections of the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Table 1 lists adverse reactions that occurred in 2 US placebo-controlled clinical trials in patients with migraine [see Clinical Studies] following either a single 6 mg dose of sumatriptan injection or placebo. Only reactions that occurred at a frequency of 2% or more in groups treated with sumatriptan injection 6 mg and that occurred at a frequency greater than the placebo group are included in Table 1.
Table 1. Adverse Reactions Reported by at Least 2% of Patients and at a Greater Frequency Than Placebo in 2 Placebo-Controlled Migraine Clinical Trialsa
| Adverse Reaction | Sumatriptan Injection 6 mg Subcutaneous (n = 547) % | Placebo (n = 370) % |
| Atypical sensations | 42 | 9 |
| Tingling | 14 | 3 |
| Warm/hot sensation | 11 | 4 |
| Burning sensation | 7 | <1 |
| Feeling of heaviness | 7 | 1 |
| Pressure sensation | 7 | 2 |
| Feeling of tightness | 5 | <1 |
| Numbness | 5 | 2 |
| Feeling strange | 2 | <1 |
| Tight feeling in head | 2 | <1 |
| Cardiovascular | ||
| Flushing | 7 | 2 |
| Chest discomfort | 5 | 1 |
| Tightness in chest | 3 | <1 |
| Discomfort: nasal cavity/sinuses | 2 | <1 |
| Injection site reactionb | 59 | 24 |
| Miscellaneous | ||
| Jaw discomfort | 2 | 0 |
| Musculoskeletal | ||
| Weakness | 5 | <1 |
| Neck pain/stiffness | 5 | <1 |
| Myalgia | 2 | <1 |
| Neurological | ||
| Dizziness/vertigo | 12 | 4 |
| Drowsiness/sedation | 3 | 2 |
| Headache | 2 | <1 |
| Skin | ||
| Sweating | 2 | 1 |
| a The sum of percentages cited is greater than 100% because subjects may have experienced more than 1 type of adverse reaction. Only reactions that occurred at a frequency of 2% or more in groups treated with sumatriptan injection and occurred at a frequency greater than that of the placebo group are included. b Includes injection site pain, stinging/burning, swelling, erythema, bruising, bleeding. | ||
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.
In the controlled clinical trials assessing the efficacy of sumatriptan injection as a treatment for cluster headache [see Clinical Studies], 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).
The following adverse reactions have been identified during postapproval use of sumatriptan tablets, sumatriptan nasal spray, or sumatriptan injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypotension, palpitations.
Dystonia, tremor.
Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and 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].
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, SNRIs, TCAs, and MAO inhibitors [see WARNINGS AND PRECAUTIONS].
Included as part of the "PRECAUTIONS" Section
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 with CAD and those with Prinzmetal’s variant angina.
Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). Discontinue Sumavel DosePro if a cerebrovascular event occurs.
Before treating headaches in patients not previously diagnosed with migraine or cluster headache or in patients who present with atypical symptoms, exclude other potentially serious neurological conditions. 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]. 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.
Hypersensitivity reactions, including anaphylaxis and angioedema, 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. 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.
Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION and Instructions for Use).
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 if any indicative sign or symptoms are observed. Apprise patients of the importance of this follow-up [see WARNINGS AND PRECAUTIONS] .
Inform patients that anaphylactic 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].
Inform patients that the use of SUMAVEL within 24 hours of another triptan or an ergot-type medication (including dihydroergotamine or methysergide) is contraindicated [see CONTRAINDICATIONS, DRUG INTERACTIONS].
Caution patients 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 and DRUG INTERACTIONS].
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 ].
Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant [see Use In Specific Populations].
Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use In Specific Populations].
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.
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.
Advise patients that they will hear a click and feel a burst of air. Inform the patients that they will feel the dose being delivered. Instruct patients not to use a device if the tip of the device is tilted or broken off upon removal from packaging [see INSTRUCTIONS FOR USE].
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.
In carcinogenicity studies in mouse and rat, sumatriptan was administered orally for 78 and 104 weeks, respectively, at doses up to 160 mg/kg/day (the high dose in rat was reduced from 360 mg/kg/day during Week 21). The highest dose to mice and rats was approximately 130 and 260 times the single MRHD of 6 mg administered subcutaneously on a mg/m2 basis. There was no evidence in either species of an increase in tumors related to sumatriptan administration.
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.
When sumatriptan (5, 50, 500 mg/kg/day) was administered orally to male and female rats prior to and throughout the mating period, there was a treatment-related decrease in fertility secondary to a decrease in mating in animals treated with doses greater than 5 mg/kg/day. It is not clear whether this finding was due to an effect on males or females or both.
When sumatriptan was administered by subcutaneous injection to male and female rats prior to and throughout the mating period, there was no evidence of impaired fertility at doses up to 60 mg/kg/day.
Data from a prospective pregnancy exposure registry and epidemiological studies of pregnant women have not detected an increased frequency of birth defects or a consistent pattern of birth defects among women exposed to sumatriptan compared with the general population (see Data).
In developmental toxicity studies in rats and rabbits, oral administration of sumatriptan to pregnant animals was associated with embryolethality, fetal abnormalities, and pup mortality. When administered by the intravenous route to pregnant rabbits, sumatriptan was embryolethal (see Data).
In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of major birth defects among deliveries to women with migraine ranged from 2.2 to 2.9% and the reported rate of miscarriage was 17%, which were similar to rates reported in women without migraine.
Disease-Associated Maternal and/or Embryo/Fetal Risk
Several studies have suggested that women with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy.
Human Data
The Sumatriptan/Naratriptan/Treximet (sumatriptan and naproxen sodium) Pregnancy Registry, a population-based international prospective study, collected data for sumatriptan from January 1996 to September 2012. The Registry documented outcomes of 626 infants and fetuses exposed to sumatriptan during pregnancy (528 with earliest exposure during the first trimester, 78 during the second trimester, 16 during the third trimester, and 4 unknown). The occurrence of major birth defects (excluding fetal deaths and induced abortions without reported defects and all spontaneous pregnancy losses) during first-trimester exposure to sumatriptan was 4.2% (20/478 [95% CI: 2.6% to 6.5%]) and during any trimester of exposure was 4.2% (24/576 [95% CI: 2.7% to 6.2%]). The sample size in this study had 80% power to detect at least a 1.73-to 1.91-fold increase in the rate of major malformations. The number of exposed pregnancy outcomes accumulated during the registry was insufficient to support definitive conclusions about overall malformation risk or to support comparisons of the frequencies of specific birth defects. Of the 20 infants with reported birth defects after exposure to sumatriptan in the first trimester, 4 infants had ventricular septal defects, including one infant who was exposed to both sumatriptan and naratriptan, and 3 infants had pyloric stenosis. No other birth defect was reported for more than 2 infants in this group.
In a study using data from the Swedish Medical Birth Register, live births to women who reported using triptans or ergots during pregnancy were compared with those of women who did not. Of the 2,257 births with first-trimester exposure to sumatriptan, 107 infants were born with malformations (relative risk 0.99 [95% CI: 0.91 to 1.21]). A study using linked data from the Medical Birth Registry of Norway to the Norwegian Prescription Database compared pregnancy outcomes in women who redeemed prescriptions for triptans during pregnancy, as well as a migraine disease comparison group who redeemed prescriptions for sumatriptan before pregnancy only, compared with a population control group. Of the 415 women who redeemed prescriptions for sumatriptan during the first trimester, 15 had infants with major congenital malformations (OR 1.16 [95% CI: 0.69 to 1.94]) while for the 364 women who redeemed prescriptions for sumatriptan before, but not during, pregnancy, 20 had infants with major congenital malformations (OR 1.83 [95% CI: 1.17 to 2.88]), each compared with the population comparison group. Additional smaller observational studies evaluating use of sumatriptan during pregnancy have not suggested an increased risk of teratogenicity.
Animal Data
Oral administration of sumatriptan to pregnant rats during the period of organogenesis resulted in an increased incidence of fetal blood vessel (cervicothoracic and umbilical) abnormalities. The highest no-effect dose for embryofetal developmental toxicity in rats was 60 mg/kg/day. Oral administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in increased incidences of embryolethality and fetal cervicothoracic vascular and skeletal abnormalities. Intravenous administration of sumatriptan to pregnant rabbits during the period of organogenesis resulted in an increased incidence of embryolethality. The highest oral and intravenous no-effect doses for developmental toxicity in rabbits were 15 and 0.75 mg/kg/day, respectively.
Oral administration of sumatriptan to rats prior to and throughout gestation resulted in embryofetal toxicity (decreased body weight, decreased ossification, increased incidence of skeletal abnormalities). The highest no-effect dose was 50 mg/kg/day. In offspring of pregnant rats treated orally with sumatriptan during organogenesis, there was a decrease in pup survival. The highest no-effect dose for this effect was 60 mg/kg/day. Oral treatment of pregnant rats with sumatriptan during the latter part of gestation and throughout lactation resulted in a decrease in pup survival. The highest no-effect dose for this finding was 100 mg/kg/day.
Sumatriptan is excreted in human milk following subcutaneous administration (see Data). There are no data on the effects of sumatriptan on the breastfed infant or the effects of sumatriptan on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Sumavel DosePro and any potential adverse effects on the breastfed infant from sumatriptan or from the underlying maternal condition.
Infant exposure to sumatriptan can be minimized by avoiding breastfeeding for 12 hours after treatment with Sumavel DosePro.
Following subcutaneous administration of a 6-mg dose of sumatriptan succinate injection in 5 lactating volunteers, sumatriptan was present in milk.
Safety and effectiveness in pediatric patients have not been established. SUMAVEL 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 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. Clinical data to determine the frequency of serious adverse reactions in pediatric patients who might receive subcutaneous, oral, or intranasal sumatriptan are not presently available.
Clinical trials of sumatriptan injection did not include sufficient numbers of 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].
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].
The elimination half-life of sumatriptan is about 2 hours [see CLINICAL PHARMACOLOGY], 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 is contraindicated in patients with:
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.
Significant elevation in blood pressure, including hypertensive crisis, has been reported in patients with and without a history of hypertension [see WARNINGS AND PRECAUTIONS].
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.
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.
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 (Cmax) (mean ± standard deviation) was 71.9 ± 14.4 ng/mL; the time to peak concentration (Tmax) 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 (Cmax) (mean ± standard deviation) was 78.6 ± 17.3 ng/mL; the time to peak concentration (Tmax) was 12 minutes after dosing (range, 6 to 20 minutes); and the terminal half-life was 102 ± 12 minutes.
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.
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.
After a single 6 mg subcutaneous dose, 22% ± 4% was excreted in the urine as unchanged sumatriptan and 38% ± 7% as the IAA metabolite.
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).
The effect of renal impairment on the pharmacokinetics of sumatriptan has not been examined.
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].
The systemic clearance and Cmax of sumatriptan were similar in Black (n = 34) and Caucasian (n = 38) healthy male subjects.
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.
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 plasma exposure at the lowest dose tested was approximately 3 times the human exposure after a 6 mg subcutaneous dose.
In controlled clinical trials enrolling more than 1,000 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.
Table 2. Proportion of Patients with Migraine Relief and Incidence of Adverse Reactions by Time and by Sumatriptan Dose
| Dose of Sumatriptan Injection | Percent Patients with Reliefa | Adverse Reactions Incidence (%) | |||
| at 10 Minutes | at 30 Minutes | at 1 Hour | at 2 Hours | ||
| Placebo | 5 | 15 | 24 | 21 | 55 |
| 1 mg | 10 | 40 | 43 | 40 | 63 |
| 2 mg | 7 | 23 | 57 | 43 | 63 |
| 3 mg | 17 | 47 | 57 | 60 | 77 |
| 4 mg | 13 | 37 | 50 | 57 | 80 |
| 6 mg | 10 | 63 | 73 | 70 | 83 |
| 8 mg | 23 | 57 | 80 | 83 | 93 |
| a Relief is defined as the reduction of moderate or severe pain to no pain or mild pain after dosing without use of rescue medication. | |||||
In 2 randomized, placebo-controlled clinical trials of sumatriptan injection 6 mg in 1,104 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.
Table 3. Proportion of Patients with Pain Relief and Relief of Migraine Symptoms After 1 and 2 Hours of Treatment
| 1-Hour Data | Study 1 | Study 2 | ||
| Placebo (n = 190) | Sumatriptan Injection 6 mg (n = 384) | Placebo (n = 180) | Sumatriptan Injection 6mg (n = 350) | |
| Subjects with pain relief (grade 0/1) | 18% | 70%a | 26% | 70%a |
| Subjects with no pain | 5% | 48%a | 13% | 49%a |
| Subjects without nausea | 48% | 73%a | 50% | 73%a |
| Subjects without photophobia | 23% | 56%a | 25% | 58%a |
| Subjects with little or no clinical disabilityb | 34% | 76%a | 34% | 76%a |
| 2-Hour Datac | ||||
| Subjects with pain relief (grade 0/1) | 31% | 81%a | 39% | 82%a |
| Subjects with no pain | 11% | 63%a | 19% | 65%a |
| Subjects without nausea | 56% | 82%a | 63% | 81%a |
| Subjects without photophobia | 31% | 72%a | 35% | 71%a |
| Subjects with little or no clinical disabilityb | 42% | 85%a | 49% | 84%a |
| a P<0.05 versus placebo. b A successful outcome in terms of clinical disability was defined prospectively as ability to work mildly impaired or ability to work and function normally. c Includes patients who may have received an additional injection of the assigned treatment (placebo or sumatriptan 6 mg) 1 hour after the initial injection | ||||
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).
Table 4. Proportion of Subjects with Cluster Headache Relief by Time
| Study 1 | Study 2 | |||
| Placebo (n = 39) | Sumatriptan Injection 6 mg (n = 39) | Placebo (n = 88) | Sumatriptan Injection 6 mg (n = 92) | |
| Subjects with pain relief (no/mild) | ||||
| 5 Minutes post-injection | 8% | 21% | 7% | 23%a |
| 10 Minutes post-injection | 10% | 49%a | 25% | 49%a |
| 15 Minutes post-injection | 26% | 74%a | 35% | 75%a |
| a P<0.05. (n = Number of headaches treated.) | ||||
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 Injectiona
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| 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).
Sumavel® DosePro®
(SUE-muh-vell DOSE-pro)
(sumatriptan injection) for subcutaneous use
Needle-free Delivery System
What is the most important information I should know about Sumavel DosePro?
Sumavel DosePro can cause serious side effects, including:
Sumavel DosePro is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. You have a higher risk for heart disease if you:
What is Sumavel DosePro?
Sumavel DosePro is a prescription medicine used to treat acute migraine headaches with or without aura and acute cluster headaches in adults who have been diagnosed with migraine or cluster headaches.
Sumavel DosePro 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.
Sumavel DosePro is not used to prevent or decrease the number of migraine or cluster headaches you have.
It is not known if Sumavel DosePro is safe and effective in children under 18 years of age.
Do not take Sumavel DosePro:
Ask your healthcare provider if you are not sure if your medicine is listed above.
Before taking Sumavel DosePro, tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Using Sumavel DosePro with certain other medicines can affect each other, causing serious side effects.
Especially tell your healthcare provider if you take anti-depressant medicines called:
Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure.
Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.
How should I take Sumavel DosePro?
What should I avoid while taking Sumavel DosePro?
Sumavel DosePro can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery, or do anything where you need to be alert.
What are the possible side effects of Sumavel DosePro?
See “What is the most important information I should know about Sumavel DosePro?”
The most common side effects of Sumavel DosePro include:
These are not all the possible side effects of Sumavel DosePro. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Sumavel DosePro?
Keep Sumavel DosePro and all medicines out of the reach of children.
General information about the safe and effective use of Sumavel DosePro.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Sumavel DosePro for a condition for which it was not prescribed. Do not give Sumavel DosePro to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Sumavel DosePro that is written for health professionals.
What are the ingredients in Sumavel DosePro?
Active ingredient: sumatriptan succinate
Inactive ingredients: sodium chloride, water for injection
This Patient Information has been approved by the U.S. Food and Drug Administration.
Instructions for Use
Sumavel® DosePro®
(SUE-muh-vell DOSE-pro)
(sumatriptan injection), for subcutaneous use
Needle-free Delivery System
Read these Instructions for Use which come with Sumavel DosePro before you start using it and each time you get a refill.
Follow these instructions each time you use Sumavel DosePro. Before you use Sumavel DosePro for the first time, make sure your doctor shows you the right way to use it.
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A. Check your device:
The snap-off tip should sit firmly on the end of the clear medication chamber. Do not use Sumavel DosePro if the snap-off tip is tilted or broken off.
The medicine inside Sumavel DosePro should be clear and colorless or pale yellow. Do not use Sumavel DosePro if the medicine looks dark-colored or cloudy.
The expiration date is printed on both the Sumavel DosePro label and carton. Do not use Sumavel DosePro if the medicine is expired.
B. Choose a delivery site:
Select a delivery site such as your stomach area (abdomen) or your thigh.
Do not deliver Sumavel DosePro in the arm.
Your skin should be clean, dry, and free of clothing.
Do not deliver through your clothes.
Do not deliver into scars or moles, or within 2 inches of your belly button (navel). Do not deliver into the same spot. Change delivery sites with each use.
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Shaded areas show all possible areas of delivery.
1. Snap: In this step, you will learn how to correctly remove the snap-off tip.
Do not begin these steps until you are ready to take your dose.
Firmly hold the handle of Sumavel DosePro in one hand. With the other hand, use your fingers to grip the top and bottom of the snap-off tip where the finger grips are located.
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To break off the snap-off tip, firmly snap it off in a downward motion. You may need to use some force. You do not need to twist or pull the snap-off tip; doing so will not work.
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2. Flip: In this step, you will learn how to prepare Sumavel DosePro for delivery of the medicine. Firmly press the lavender (4 mg) or green (6 mg) lever all the way down (away from the clear plastic end), until it clicks and locks into the handle. You may feel some resistance - this is normal.
Once you have flipped the lever, do not touch the end of the clear medication chamber. Keep the medication chamber pointed away from your face or eyes.
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3. Pinch and Press: In this step, you will learn how to deliver the medicine.
Deliver the dose exactly as shown to you by your healthcare provider.
Pinch about 2 inches of the skin of your stomach (abdomen) or thigh to create a firm section of skin.
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Place Sumavel DosePro straight out from the delivery site with the end of the clear medication chamber against your skin.
Do not hold Sumavel DosePro at an angle to your skin.
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During the next step, you will hear a click and feel a burst of air. Do not be alarmed. This means that the medicine has been delivered.
Steadily press Sumavel DosePro straight down against your skin until you hear a click and feel a burst of air. You will feel the dose being delivered. There is no button to push. After you hear the click and feel the burst of air, the medicine has been delivered and you can remove Sumavel DosePro from your skin.
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Let go of your pinched skin after the medicine has been delivered.
After removing Sumavel DosePro from your skin, a small droplet of blood may be present. You can gently press a cotton ball or gauze over the injection site. Do not rub the injection site. You may cover the injection site with a small adhesive bandage, if needed.
This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.
