sumatriptan succinate
Dosage Form: subcutaneous injection
FULL PRESCRIBING INFORMATION
Indications and Usage for Sumavel Dosepro
Acute Treatment of Migraine Attacks and Cluster Headache
Sumavel Dosepro (sumatriptan injection) is indicated for the acute treatment of migraine attacks, with or without aura, and the acute treatment of cluster headache episodes.
Important Limitations
Sumavel Dosepro should only be used where a clear diagnosis of migraine or cluster headache has been established. Care should be taken to exclude other potentially serious neurologic conditions before treating headache in patients not previously diagnosed with migraine or cluster headache or who experience a headache that is atypical for them.
For a given attack, if a patient does not respond to the first dose of Sumavel Dosepro, the diagnosis of migraine or cluster headache should be reconsidered before administration of a second dose.
Sumavel Dosepro is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. [see Contraindications (4.7)]
Sumavel Dosepro Dosage and Administration
Sumavel Dosepro is for subcutaneous use only and is designed for patient self-administration to the abdomen or thigh. Sumavel Dosepro is not to be administered to other areas of the body, including the arm. Sumavel Dosepro is not to be administered intramuscularly or intravenously.
Administer one Sumavel Dosepro to the abdomen or thigh to deliver subcutaneously 6 mg of sumatriptan (as the succinate salt) per 0.5 mL dose. One Sumavel Dosepro is the maximum single recommended adult dose. The maximum recommended dose that may be given in 24 hours is two doses of Sumavel Dosepro (or one dose of Sumavel Dosepro and one dose of another sumatriptan product), separated by at least 1 hour. Controlled clinical trials with sumatriptan injection have failed to show that clear benefit is associated with the administration of a second 6 mg dose in patients who have failed to respond to a first dose.
Patients should be instructed to use administration 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 navel. 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 (17.5)]
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 6 mg sumatriptan (as the succinate salt).
Contraindications
Intravenous Administration
Sumavel Dosepro is not designed to administer sumatriptan injection intravenously. Do not administer intravenously since sumatriptan may cause coronary vasospasm.
Ischemic or Vasospastic Coronary Artery Disease
Do not use Sumavel Dosepro in patients with ischemic heart disease (e.g. angina pectoris, history of myocardial infarction, or documented silent ischemia), or in patients who have symptoms or findings consistent with ischemic heart disease, coronary artery vasospasm, including Prinzmetal's variant angina or other significant underlying cardiovascular disease. [see Warnings and Precautions (5.1)]
Cerebrovascular Syndromes
Do not use Sumavel Dosepro in patients with cerebrovascular syndromes including (but not limited to) strokes of any type as well as transient ischemic attacks. [see Warnings and Precautions (5.3)]
Peripheral Vascular Disease
Do not use Sumavel Dosepro in patients with peripheral vascular disease including (but is not limited to) ischemic bowel disease. [see Warnings and Precautions (5.4)]
Uncontrolled Hypertension
Because Sumavel Dosepro may increase blood pressure, do not use in patients with uncontrolled hypertension. [see Warnings and Precautions (5.6)]
Do not use within 24 hours of treatment with Ergotamine-Containing or Ergot-Type Medications or Other 5-HT1 Agonists (e.g. triptans)
Do not use Sumavel Dosepro and any ergotamine-containing or ergot-type medication (such as dihydroergotamine or methysergide) within 24 hours of each other; do not use Sumavel Dosepro and another 5-HT1 agonist (e.g. triptan) within 24 hours of each other (with the exception of a single dose of another sumatriptan product, provided the doses are separated by at least 1 hour) [see Drug Interactions (7.3)].
Hemiplegic or Basilar Migraine
Do not use Sumavel Dosepro in patients with hemiplegic or basilar migraine.
Hypersensitivity
Sumavel Dosepro is contraindicated in patients with known hypersensitivity to sumatriptan.
Warnings and Precautions
Risk of Myocardial Ischemia and Infarction and Other Adverse Cardiac Events
Cardiac Events and Fatalities with 5-HT1 Agonists
Serious adverse cardiac events, including acute myocardial infarction, life-threatening disturbances of cardiac rhythm, and death have been reported within a few hours following the administration of sumatriptan. Considering the extent of use of sumatriptan in patients with migraine, the incidence of these events is extremely low.
Sumatriptan can cause coronary vasospasm. Some of these events have occurred in patients with no prior cardiac disease history and with documented absence of CAD with close proximity of the events to sumatriptan use. Because Sumavel Dosepro may cause coronary artery vasospasm, patients who experience signs or symptoms suggestive of angina following Sumavel Dosepro administration should be evaluated for the presence of CAD or a predisposition to Prinzmetal variant angina before receiving additional doses of sumatriptan and should be monitored electrocardiographically if dosing is resumed and similar symptoms recur.
Premarketing Experience with Sumatriptan
Among the more than 1,900 patients with migraine who participated in reported premarketing controlled clinical trials of subcutaneous sumatriptan, there were 8 patients who sustained clinical events during or shortly after receiving sumatriptan that may have reflected coronary artery vasospasm. Six of these 8 patients had ECG changes consistent with transient ischemia, without accompanying clinical symptoms or signs. Of these 8 patients, 4 had either findings suggestive of CAD or risk factors predictive of CAD prior to study enrollment.
Of 6,348 patients with migraine who participated in premarketing controlled and uncontrolled clinical trials of oral sumatriptan, 2 experienced clinical adverse events shortly after receiving oral sumatriptan that may have reflected coronary vasospasm. Neither of these adverse events was associated with a serious clinical outcome.
Among approximately 4,000 patients with migraine who participated in premarketing controlled and uncontrolled clinical trials of sumatriptan nasal spray, 1 patient experienced an asymptomatic subendocardial infarction possibly subsequent to a coronary vasospastic event.
Post-marketing Experience with Sumatriptan
Serious cardiovascular events, some resulting in death, have been reported in association with the use of subcutaneous sumatriptan injection. The uncontrolled nature of post-marketing surveillance, however, makes it impossible to determine definitively the proportion of the reported cases that were actually caused by sumatriptan or to reliably assess causation in individual cases. On clinical grounds, the longer the latency between the administration of sumatriptan and the onset of the clinical event, the less likely the association is to be causative. Interest has focused on events beginning within 1 hour of the administration of sumatriptan.
Cardiac events that have been observed to have onset within 1 hour of sumatriptan administration include coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia and ventricular fibrillation, cardiac arrest, and death.
Some of these events occurred in patients who had no findings of CAD and appear to represent consequences of coronary artery vasospasm. However, among reports of serious cardiac events within 1 hour of sumatriptan administration, the majority had risk factors predictive of CAD, and the presence of significant underlying CAD was established in most cases. [see Contraindications (4.2)]
Patients with documented coronary artery disease
Because of the potential of this class of compound (5-HT1 agonists) to cause coronary vasospasm, Sumavel Dosepro should not be given to patients with documented ischemic or vasospastic coronary artery disease. [see Contraindications (4.2)]
Patients with risk factors for CAD
It is strongly recommended that Sumavel Dosepro not be given to patients in whom unrecognized CAD is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoking, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best. If, during the cardiovascular evaluation, the patient's medical history or electrocardiographic investigations reveal findings indicative of or consistent with coronary artery vasospasm or myocardial ischemia, Sumavel Dosepro should not be administered. [see Contraindications (4.2)]
For patients with risk factors predictive of CAD who have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of Sumavel Dosepro take place in the setting of a physician's office or similar medically staffed and equipped facility. Because cardiac ischemia can occur in the absence of clinical symptoms, consideration should be given to obtaining, on the first occasion of use, an electrocardiogram (ECG) during the interval immediately following use of Sumavel Dosepro in these patients with risk factors.
It is recommended that patients who are intermittent long-term users of Sumavel Dosepro and who have or acquire risk factors predictive of CAD, as described above, undergo cardiovascular evaluation periodically as they continue to use sumatriptan. In considering this recommendation for periodic cardiovascular evaluation, it is noted that patients with cluster headache are predominantly male and over 40 years of age, which are risk factors for CAD.
Sensations of Pain, Tightness, Pressure in the Chest and/or Throat, Neck and Jaw
Sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw are relatively common after treatment with sumatriptan. Only rarely have these symptoms been associated with ischemic ECG changes.
However, because sumatriptan may cause coronary vasospasm, patients who experience signs or symptoms suggestive of angina following dosing should be evaluated for the presence of CAD or a predisposition to Prinzmetal's variant angina before receiving additional doses of medication, and should be monitored electrocardiographically if dosing is resumed and similar symptoms occur. Patients shown to have CAD and those with Prinzmetal's variant angina should not receive 5-HT1 agonists. [see Contraindications (4.2) and Warnings and Precautions (5.1)]
Similarly, patients who experience other symptoms or signs suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud syndrome, following sumatriptan should be evaluated for atherosclerosis or predisposition to vasospasm. [see Contraindications (4.4) and Warnings and Precautions (5.4)]
Cerebrovascular Events and Fatalities
Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with subcutaneous sumatriptan, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, sumatriptan having been administered in the incorrect belief the symptoms experienced were a consequence of migraine when they were not. As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, care should be taken to exclude other potentially serious neurological conditions. It should also be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, transient ischemic attack) [see Contraindications (4.3)].
Other Vasospasm-Related Events, Including Peripheral Vascular Ischemia and Colonic Ischemia
5-HT1 agonists, including Sumavel Dosepro, may cause vasospastic reactions other than coronary artery vasospasm. Both peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea have been reported.
Very rare reports of transient and permanent blindness and significant partial vision loss have been reported with the use of sumatriptan. Visual disorders may also be part of a migraine attack.
Patients who experience other symptoms or signs suggestive of decreased arterial flow following the use of any 5-HT1 agonist, such as ischemic bowel syndrome or Raynaud's syndrome, are candidates for further evaluation [see Contraindications (4.4)].
Serotonin Syndrome
The development of a potentially life-threatening serotonin syndrome may occur with triptans, including Sumavel Dosepro, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). If concomitant treatment with sumatriptan and an SSRI (e.g., fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram) or SNRI (e.g., venlafaxine, duloxetine) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. 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). [see Drug Interactions (7.4)].
Increase in Blood Pressure
Sumavel Dosepro is contraindicated in patients with uncontrolled hypertension. Sumatriptan should be administered with caution to patients with controlled hypertension, as transient increases in blood pressure and peripheral vascular resistance have been observed in a small proportion of patients. Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasions in patients with and without a history of hypertension. [see Contraindications (4.5)]
Concomitant MAO-A Inhibitors
The co-administration of Sumavel Dosepro and an MAO-A inhibitor is not generally recommended. In patients taking MAO-A inhibitors, sumatriptan plasma levels are nearly doubled. If such therapy is clinically warranted, however, do not use Sumavel Dosepro to administer sumatriptan, as Sumavel Dosepro only exists as a 6 mg fixed-dose needle-free delivery system and dose adjustments are not possible. [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]
Hypersensitivity
Hypersensitivity (anaphylaxis/anaphylactoid) reactions have occurred on rare occasions in patients receiving sumatriptan. Such reactions can be life threatening or fatal. [see Contraindications (4.8)].
Seizures
There have been rare reports of seizure following administration of sumatriptan. Sumatriptan should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.
Corneal Opacities
Sumatriptan causes corneal opacities and defects in the corneal epithelium in dogs; this raises the possibility that these changes may occur in humans. While patients were not systematically evaluated for these changes in clinical trials, and no specific recommendations for monitoring are being offered, prescribers should be aware of the possibility of these changes. [see Nonclinical Toxicology (13.2)]
Adverse Reactions
This section provides a summary of adverse reactions reported in subjects in clinical studies conducted with Sumavel Dosepro and sumatriptan injection.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug, and may not reflect the rates observed in practice.
Serious cardiac reactions, including myocardial infarction, have occurred following the use of sumatriptan. These reactions are extremely rare and most have been reported in patients with risk factors predictive of CAD. Reactions reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation [see Contraindications (4.2) and Warnings and Precautions (5.1)].
Significant hypertensive episodes, including hypertensive crises, have been reported on rare occasions in patients with or without a history of hypertension [see Warnings and Precautions (5.6)].
The following other adverse reactions are discussed in more detail in other sections of labeling:
Sensations of Chest Pain and Tightness [see Warnings and Precautions (5.2)]
Cerebrovascular Events and Fatalities [see Warnings and Precautions (5.3)]
Other Vasospasm related Events including Peripheral Vascular Ischemia and Colonic Ischemia [see Warnings and Precautions (5.4)]
Serotonin Syndrome [see Warnings and Precautions (5.5)]
Among patients in clinical trials of subcutaneous sumatriptan succinate injection (n = 6,218), up to 3.5% of patients withdrew for reasons related to adverse reactions.
Controlled Clinical Trials in Patients with Migraine Headache
Table 1 lists adverse reactions that occurred in 2 large placebo-controlled clinical trials in migraine patients following either a single 6 mg sumatriptan injection or placebo. Only adverse reactions that occurred at a frequency of 2% or more in groups treated with sumatriptan injection 6 mg and occurred at a frequency greater than in the placebo group are included in Table 1.
| * The sum of the percentages cited is greater than 100% because patients could have experienced more than 1 type of adverse event. Only events that occurred at a frequency of 2% or more in groups treated with sumatriptan injection and that occurred at a frequency greater than that in the placebo group are included. | ||
| Adverse Reactions | Percent of Patients Reporting | |
| Sumatriptan Injection, 6 mg SC (n = 547) | Placebo Injection, SC (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 reaction | 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 |
The incidence of adverse reactions in controlled clinical trials was not affected by gender or age of the patients. There were insufficient data to assess the impact of race on the incidence of adverse events.
Controlled Clinical Trials in Patients with Cluster Headache
In the controlled clinical trials assessing sumatriptan injection as a treatment for cluster headache, no new significant adverse reactions associated with the use of sumatriptan were detected that had not already been identified in association with the drug's use in migraine.
Overall, the frequency of adverse events reported in studies of cluster headache was generally lower. Exceptions include reports of paresthesia (5% sumatriptan, 0% placebo), nausea and vomiting (4% sumatriptan, 0% placebo), and bronchospasm (1% sumatriptan, 0% placebo).
Other Adverse Reactions Observed in Association with the Administration of Sumatriptan Injection
The frequencies of less commonly reported adverse clinical reactions are presented. Because the reports include events observed in open and uncontrolled studies, the role of sumatriptan injection in their causation cannot be reliably determined. Furthermore, variability associated with adverse reactions reporting, the terminology used to describe adverse reactions limits the value of the quantitative frequency estimates provided.
Adverse reactions frequencies are calculated as the number of patients reporting an event divided by the total number of patients (N = 6,218) exposed to subcutaneous sumatriptan. All reported adverse reactions are included except those already listed in the previous table, those too general to be informative, and those not reasonably associated with the use of the drug. Adverse reactions are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse reactions are defined as those occurring in at least 1/100 patients, infrequent adverse reactions are those occurring in 1/100 to 1/1,000 patients, and rare adverse reactions are those occurring in fewer than 1/1,000 patients.
Cardiovascular: Infrequent were hypertension, hypotension, bradycardia, tachycardia, palpitations, pulsating sensations, various transient ECG changes (nonspecific ST or T-wave changes, prolongation of PR or QTc intervals, sinus arrhythmia, non-sustained ventricular premature beats, isolated junctional ectopic beats, atrial ectopic beats, delayed activation of the right ventricle), and syncope. Rare were pallor, arrhythmia, abnormal pulse, vasodilation, and Raynaud syndrome.
Endocrine and Metabolic: Infrequent was thirst. Rare were polydipsia and dehydration.
Eye: Frequent were vision alterations. Infrequent was irritation of the eye.
Gastrointestinal: Frequent were abdominal discomfort and dysphagia. Infrequent were gastroesophageal reflux and diarrhea. Rare were peptic ulcer, retching, flatulence/eructation, and gallstones.
Musculoskeletal: Frequent were muscle cramps. Infrequent were various joint disturbances (pain, stiffness, swelling, ache). Rare were muscle stiffness, need to flex calf muscles, backache, muscle tiredness, and swelling of the extremities.
Neurological: Frequent was anxiety. Infrequent were mental confusion, euphoria, agitation, relaxation, chills, sensation of lightness, tremor, shivering, disturbances of taste, prickling sensations, paresthesia, stinging sensations, facial pain, photophobia, and lacrimation. Rare were transient hemiplegia, hysteria, globus hystericus, intoxication, depression, myoclonia, monoplegia/diplegia, sleep disturbance, difficulties in concentration, disturbances of smell, hyperesthesia, dysesthesia, simultaneous hot and cold sensations, tickling sensations, dysarthria, yawning, reduced appetite, hunger, and dystonia.
Respiratory: Infrequent was dyspnea. Rare were influenza, diseases of the lower respiratory tract, and hiccoughs.
Skin: Infrequent were erythema, pruritus, and skin rashes and eruptions. Rare was skin tenderness.
Urogenital: Rare were dysuria, frequency, dysmenorrhea, and renal calculus.
Miscellaneous: Infrequent were miscellaneous laboratory abnormalities, including minor disturbances in liver function tests, "serotonin agonist effect," and hypersensitivity to various agents. Rare was fever.
Other Adverse Reactions Observed in the Clinical Development of Sumatriptan
The following adverse reactions occurred in clinical trials with sumatriptan tablets and sumatriptan nasal spray. Because the reports include events observed in open and uncontrolled studies, the role of sumatriptan in their causation cannot be reliably determined. All reported events are included except those already listed, those too general to be informative, and those not reasonably associated with the use of the drug.
Breasts: Breast swelling, cysts, disorder of breasts, lumps, masses of breasts, nipple discharge, primary malignant breast neoplasm, and tenderness.
Cardiovascular: Abdominal aortic aneurysm, angina, atherosclerosis, cerebral ischemia, cerebrovascular lesion, heart block, peripheral cyanosis, phlebitis, thrombosis, and transient myocardial ischemia.
Ear, Nose, and Throat: Allergic rhinitis; disorder of nasal cavity/sinuses; ear, nose, and throat hemorrhage; ear infection; external otitis; feeling of fullness in the ear(s); hearing disturbances; hearing loss; Meniere disease; nasal inflammation; otalgia; sensitivity to noise; sinusitis; tinnitus; and upper respiratory inflammation.
Endocrine and Metabolic: Elevated thyrotropin stimulating hormone (TSH) levels; endocrine cysts, lumps, and masses; fluid disturbances; galactorrhea; hyperglycemia; hypoglycemia; hypothyroidism; weight gain; and weight loss.
Eye: Accommodation disorders, blindness and low vision, conjunctivitis, disorders of sclera, external ocular muscle disorders, eye edema and swelling, eye hemorrhage, eye itching, eye pain, keratitis, mydriasis, and visual disturbances.
Gastrointestinal: Abdominal distention, colitis, constipation, dental pain, dyspeptic symptoms, feelings of gastrointestinal pressure, gastric symptoms, gastritis, gastroenteritis, gastrointestinal bleeding, gastrointestinal pain, hematemesis, hypersalivation, hyposalivation, intestinal obstruction, melena, nausea and/or vomiting, oral itching and irritation, pancreatitis, salivary gland swelling, and swallowing disorders.
Hematological Disorders: Anemia.
Mouth and Teeth: Disorder of mouth and tongue (e.g., burning of tongue, numbness of tongue, dry mouth).
Musculoskeletal: Acquired musculoskeletal deformity, arthralgia and articular rheumatitis, arthritis, intervertebral disc disorder, muscle atrophy, muscle tightness and rigidity, musculoskeletal inflammation, and tetany.
Neurological: Apathy, aggressiveness, bad/unusual taste, bradylogia, cluster headache, convulsions, depressive disorders, detachment, disturbance of emotions, drug abuse, facial paralysis, hallucinations, heat sensitivity, incoordination, increased alertness, memory disturbance, migraine, motor dysfunction, neoplasm of pituitary, neuralgia, neurotic disorders, paralysis, personality change, phobia, phonophobia, psychomotor disorders, radiculopathy, raised intracranial pressure, rigidity, stress, syncope, suicide, and twitching.
Respiratory: Asthma, breathing disorders, bronchitis, cough, and lower respiratory tract infection.
Skin: Dry/scaly skin, eczema, herpes, seborrheic dermatitis, skin nodules, tightness of skin, and wrinkling of skin.
Urogenital: Abnormal menstrual cycle, abortion, bladder inflammation, endometriosis, hematuria, increased urination, inflammation of fallopian tubes, intermenstrual bleeding, menstruation symptoms, micturition disorders, urethritis, and urinary infections.
Miscellaneous: Contusions, difficulty in walking, edema, hematoma, hypersensitivity, fever, fluid retention, lymphadenopathy, overdose, speech disturbance, swelling of extremities, swelling of face, and voice disturbances.
Pain and Other Pressure Sensations: Chest pain and/or heaviness, neck/throat/jaw pain/tightness/pressure, and pain (location specified).
Clinical Studies Using Sumavel Dosepro
Four clinical trials compared the safety and tolerability of Sumavel Dosepro (n = 243 administrations) and sumatriptan injection (n = 217 injections) in 120 adult healthy subjects. Local site reactions were prospectively recorded in these trials. There was a higher incidence of bleeding, swelling, erythema, and bruising initially with Sumavel Dosepro than with sumatriptan needle based injection (see Table 2). Bleeding was considered minor in all cases, and did not require medical intervention. Most injection site reactions resolved spontaneously, with no apparent difference between Sumavel Dosepro and sumatriptan needle injection for bleeding and bruising at 8-hrs post dose, and for swelling and erythema at 24-hrs post dose. No injection site reactions were reported as adverse reactions, and no subject discontinued the studies due to an injection site reaction or adverse reaction in these trials.
| Sumavel DosePro (n = 243 injections) | Sumatriptan Injection (n = 217 injections) | |
| Bleeding | ||
| Immediately after | 42% | 22% |
| 1 hour post-injection | 7% | 0% |
| 8 hours post-injection | 0% | 0% |
| 24 hours post-injection | 0% | 0% |
| Swelling | ||
| Immediately after | 86% | 1% |
| 1 hour post-injection | 72% | 15% |
| 8 hours post-injection | 6% | 0% |
| 24 hours post-injection | 1% | 1% |
| Erythema | ||
| Immediately after | 18% | 4% |
| 1 hour post-injection | 53% | 25% |
| 8 hours post-injection | 20% | 4% |
| 24 hours post-injection | 9% | 3% |
| Bruising | ||
| Immediately after | 11% | 1% |
| 1 hour post-injection | 3% | 3% |
| 8 hours post-injection | 3% | 5% |
| 24 hours post-injection | 5% | 6% |
Administration site pain was reported as an adverse event in 2% of administrations in patients after delivery of Sumavel Dosepro, compared to 1% after administration of sumatriptan needle injection.
Post-marketing Experience
Reports for Subcutaneous or Oral Sumatriptan
The following adverse reactions have been identified during post-approval use of sumatriptan. 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. However, systemic reactions following sumatriptan use are likely to be similar regardless of route of administration.
Blood: Hemolytic anemia, pancytopenia, thrombocytopenia.
Cardiovascular: Atrial fibrillation, cardiomyopathy, colonic ischemia [see Warnings and Precautions (5.5)], Prinzmetal variant angina, pulmonary embolism, shock, thrombophlebitis.
Ear, Nose, and Throat: Deafness.
Eye: Ischemic optic neuropathy, retinal artery occlusion, retinal vein thrombosis, loss of vision.
Gastrointestinal: Ischemic colitis with rectal bleeding [see Warnings and Precautions (5.5)], xerostomia.
Hepatic: Elevated liver function tests.
Neurological: Central nervous system vasculitis, cerebrovascular accident, dysphasia, serotonin syndrome, subarachnoid hemorrhage.
Non-Site Specific: Angioneurotic edema, cyanosis, death [see Warnings and Precautions (5.3)], temporal arteritis.
Psychiatry: Panic disorder.
Respiratory: Bronchospasm in patients with and without a history of asthma.
Skin: Exacerbation of sunburn, hypersensitivity reactions (allergic vasculitis, erythema, pruritus, rash, shortness of breath, urticaria; in addition, severe anaphylaxis/anaphylactoid reactions have been reported [see Warnings and Precautions (5.8)]), photosensitivity. Following subcutaneous administration of sumatriptan, pain, redness, stinging, induration, swelling, contusion, subcutaneous bleeding, and, on rare occasions, lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) has been reported.
Urogenital: Acute renal failure.
Drug Interactions
Monoamine Oxidase Inhibitors
MAO-A inhibitors reduce sumatriptan clearance, significantly increasing systemic exposure. Therefore, the use of sumatriptan in patients receiving MAO-A inhibitors is not ordinarily recommended. If the clinical situation warrants the combined use of sumatriptan and an MAOI, the dose of sumatriptan employed should be reduced. [see Warnings and Precautions (5.7) and Clinical Pharmacology (12.3)]
5-HT1B/1D Agonists (e.g. triptans)
Concomitant use of other 5-HT1B/1D agonists (e.g. triptans) within 24 hours of sumatriptan treatment is not recommended. [see Contraindications (4.6) and Clinical Pharmacology (12.3)].
Ergot-Containing Drugs
Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Since these effects may be additive, use of ergotamine containing or ergot-type medications (like dihydroergotamine or methysergide) and sumatriptan within 24 hours of each other should be avoided [see Contraindications (4.6)].
Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome
Cases of life-threatening serotonin syndrome have been reported during combined use of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) and triptans. If concomitant treatment with sumatriptan injection is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases [see Warnings and Precautions (5.5)].
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category C.
Sumatriptan produced evidence of developmental toxicity (embryolethality and increased incidences of fetal abnormalities) in rabbits. Embryolethality was observed at a dose less than the maximum recommended human dose (MRHD) of 12 mg/day on a body surface area (mg/m2) basis. There are no adequate and well-controlled studies of Sumavel Dosepro 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 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 of sumatriptan to pregnant rats prior to and throughout pregnancy did not produce evidence of embryolethality or teratogenicity.
Nursing Mothers
Sumatriptan is excreted in human milk following subcutaneous administration. Therefore, caution should be exercised when considering the administration of Sumavel Dosepro to a nursing woman.
Pediatric Use
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 evaluating sumatriptan nasal spray (5 to 20 mg) in pediatric patients aged 12 to 17 years enrolled a total of 1,248 adolescent migraineurs who treated a single attack. The studies did not establish the efficacy of sumatriptan nasal spray compared to placebo in the treatment of migraine in adolescents. Adverse events observed in these clinical trials were similar in nature to those reported in clinical trials in adults.
Five controlled clinical trials (2 single-attack studies, 3 multiple-attack studies) evaluating oral sumatriptan (25 to 100 mg) in pediatric patients aged 12 to 17 years enrolled a total of 701 adolescent migraineurs. These studies did not establish the efficacy of oral sumatriptan compared to placebo in the treatment of migraine in adolescents. Adverse events observed in these clinical trials were similar in nature to those reported in clinical trials in adults. The frequency of all adverse events in these patients appeared to be both dose- and age-dependent, with younger patients reporting events more commonly than older adolescents.
Post-marketing experience documents that serious adverse events have occurred in the pediatric population after use of subcutaneous, oral, and/or intranasal sumatriptan. These reports include events 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.
Geriatric Use
The use of Sumavel Dosepro in elderly patients is not recommended because they are more likely to have decreased hepatic function, they are at higher risk for CAD, and blood pressure increases may be more pronounced in the elderly [see Warnings and Precautions (5.1, 5.6)].
Overdosage
Patients (N = 269) have received single injections of 8 to 12 mg sumatriptan without significant adverse effects. Volunteers (N = 47) have received single subcutaneous doses of up to 16 mg without serious adverse events.
No gross overdoses in clinical practice have been reported. The half-life of elimination of sumatriptan is about 2 hours [see Clinical Pharmacology (12.3)], and therefore monitoring of patients after overdose with subcutaneous sumatriptan should continue while symptoms or signs persist, and for at least 10 hours. It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan.
Sumavel Dosepro Description
Sumatriptan, the active component of Sumavel Dosepro, is a selective 5-hydroxy-tryptamine receptor subtype 1 (5-HT1) agonist. Sumatriptan delivered as the succinate salt 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 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 the solution is approximately 4.2 to 5.3. The osmolality of the solution 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 green lever, and a glass medication chamber that is pre-filled with 6 mg per 0.5 mL sumatriptan injection. Utilizing pressure from a compressed nitrogen gas source in the handle, Sumavel D
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