Sumavel DosePro - Product Information
|Manufacture:||Endo Pharmaceuticals Inc.|
|Condition:||Cluster Headaches, Migraine, Migraine Headache (Migraine)|
|Form:||Liquid solution, Subcutaneous (SC)|
|Ingredients:||sumatriptan succinate, sodium chloride, water for injection|
Indications and Usage
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.
Dosage and Administration
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. 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.
Administration Using Sumavel DosePro
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].
Sumavel DosePro is for single use only. Discard after use.
Dosage Forms and Strengths
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]
- Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions]
- History of stroke or transient ischemic attack (TIA) because these patients are at a higher risk of stroke [see Warnings and Precautions]
- History of hemiplegic or basilar migraine
- Peripheral vascular disease [see Warnings and Precautions]
- Ischemic bowel disease [see Warnings and Precautions]
- Uncontrolled hypertension [see Warnings and Precautions]
- 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]
- Concurrent administration of a monamine oxidase (MAO)-A inhibitor or recent (within 2 weeks) use of an MAO-A inhibitor [see Drug Interactions ]
- Hypersensitivity to Sumavel DosePro (angioedema and anaphylaxis seen) [see Warnings and Precautions and Adverse Reactions]
Warnings and Precautions
Myocardial Ischemia, Myocardial Infarction, and Prinzmetal’s Angina
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.
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 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.
Other Vasospasm Reactions
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.
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 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.
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 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]
- Arrhythmias [see Warnings and Precautions)]
- Chest, throat, neck, and/or jaw pain/tightness/pressure [see Warnings and Precautions]
- Cerebrovascular events [see Warnings and Precautions]
- Other vasospasm reactions [see Warnings and Precautions]
- Medication overuse headache [see Warnings and Precautions)]
- Serotonin syndrome [see Warnings and Precautions]
- Increase in blood pressure [see Warnings and Precautions]
- Hypersensitivity reactions [see Contraindications and Warnings and Precautions]
- Seizures [see Warnings and Precautions]
Clinical Trials Experience
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 migraine subjects 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.
|Adverse Reaction||Percent of Subjects Reporting|
6 mg Subcutaneous
(n = 547)
(n = 370)
Feeling of heaviness
Feeling of tightness
Tight feeling in head
Tightness in chest
Discomfort: nasal cavity/sinuses
|Injection site reactionb||59||24|
aThe 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.
bIncludes 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, 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.
Monoamine Oxidase-A Inhibitors
MAO-A inhibitors increase systemic exposure by 2-fold. Therefore, the use of Sumavel DosePro in patients receiving MAO-A inhibitors is contraindicated.
Other 5-HT1 Agonists
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.
Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome
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].
Use in Specific Populations
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].
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.
The elimination half-life of sumatriptan is about 2 hours, 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.
How Supplied/Storage and Handling
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 63481-229-06).
- Sumavel DosePro, 6 mg in a package of six prefilled, single-dose units (NDC 63481-367-06).
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.
Patient Counseling Information
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].
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].
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 and Drug Interactions].
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].
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].
Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations].
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 they will hear a click and feel a burst of air and a sensation will be felt at the time the dose is delivered. 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.
Endo Pharmaceuticals Inc.
Malvern, PA 19355
Patheon UK, Limited
Swindon, United Kingdom