SUMATRIPTAN SUCCINATE- sumatriptan succinate injection
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use SUMATRIPTAN INJECTION safely and effectively.
See full prescribing information for SUMATRIPTAN INJECTION.
SUMATRIPTAN injection, for subcutaneous use
Initial U.S. Approval: 1992
INDICATIONS AND USAGE
Sumatriptan injection is a serotonin (5-HT 1B/1D) receptor agonist (triptan) indicated for:
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
Injection: 6 mg single-dose prefilled syringe assembled in an autoinjector (3)
WARNINGS AND PRECAUTIONS
Most common adverse reactions (≥5% and > placebo) were injection site reactions, tingling, dizziness/vertigo, warm/hot sensation, burning sensation, feeling of heaviness, pressure sensation, flushing, feeling of tightness, and numbness (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Dr.Reddy's Laboratories Inc., at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
FULL PRESCRIBING INFORMATION: CONTENTS*
7.4 Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome
Sumatriptan injection 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:
The maximum single recommended adult dose of sumatriptan injection for the acute treatment of migraine or cluster headache is 6 mg injected subcutaneously. For the treatment of migraine, if side effects are dose limiting, lower doses (1 mg to 5 mg) may be used [see Clinical Studies ( 14.1)]. For the treatment of cluster headache, the efficacy of lower doses has not been established.
The maximum cumulative dose that may be given in 24 hours is 12 mg, two 6 mg injections separated by at least 1 hour. A second 6 mg dose should only be considered if some response to a first injection was observed.
An autoinjector device (sumatriptan autoinjector) is available for use with 6 mg prefilled syringe to facilitate self-administration in patients using the 6 mg dose. With this device, the needle penetrates approximately 1/4 inch (5 to 6 mm). The injection is intended to be given subcutaneously, and intramuscular or intravascular delivery must be avoided. Instruct patients on the proper use of the sumatriptan autoinjector and direct them to use injection sites with an adequate skin and subcutaneous thickness to accommodate the length of the needle.
In patients receiving doses other than 6 mg, use the 6 mg single-dose vial; do not use the Sumatriptan Autoinjector Pen. Visually inspect the vial for particulate matter and discoloration before administration. Do not use if particulates and discolorations are noted.
Sumatriptan injection is contraindicated in patients with:
The use of sumatriptan injection is contraindicated in patients with ischemic or vasospastic CAD. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of sumatriptan injection. Some of these reactions occurred in patients without known CAD. Sumatriptan injection 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 sumatriptan injection. If there is evidence of CAD or coronary artery vasospasm, sumatriptan injection is contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of sumatriptan injection in a medically supervised setting and performing an electrocardiogram (ECG) immediately following administration of sumatriptan injection. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of sumatriptan injection.
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-HT 1 agonists. Discontinue sumatriptan injection if these disturbances occur. Sumatriptan injection is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.
Sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw commonly occur after treatment with sumatriptan injection and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of sumatriptan injection 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-HT 1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT 1 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 sumatriptan injection 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. Sumatriptan injection is contraindicated in patients with a history of stroke or TIA.
Sumatriptan injection may cause non-coronary vasospastic reactions, such as peripheral vascularischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain andbloody diarrhea), splenic infarction, and Raynaud’s syndrome. In patients who experiencesymptoms or signs suggestive of non-coronary vasospasm reaction following the use of any 5-HT1 agonist, rule out a vasospastic reaction before receiving additional sumatriptan injections.1 agonist, rule out a vasospastic reaction before receiving additional injections of sumatriptan.
Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT 1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT 1 agonists has 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 sumatriptan injection, particularly during coadministration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions ( 7.4)]. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g. hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Discontinue sumatriptan injection 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-HT 1 agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with sumatriptan injection. Sumatriptan injection is contraindicated in patients with uncontrolled hypertension.
Hypersensitivity reactions, including angioedema and anaphylaxis have occurred in patients receiving sumatriptan injection. Such reactions can be life-threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens. Sumatriptan injection is contraindicated in patients with a history of hypersensitivity reaction to sumatriptan injection.
Seizures have been reported following administration of sumatriptan injection. 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. Sumatriptan injection should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.
The following serious adverse reactions are described below and elsewhere in 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 U.S. placebo-controlled clinical trials in patients with migraines (Studies 2 and 3) 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 in Pooled Placebo-Controlled Trials in Patients with Migraine (Studies 2 and 3)
|||Percent of Patients Reporting|
|Adverse Event Type||Sumatriptan Injection 6 mg
(n = 547)
(n = 370)
|Feeling of heaviness||7||1|
|Feeling of tightness||5||<1|
|Tight feeling in head||2||<1|
|Tightness in chest||3||<1|
|Pressure in chest||2||<1|
|Ear, nose, and throat|||||
|Discomfort: nasal cavity/sinuses||2||<1|
|Injection site reaction a||59||24|
a 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 patients. 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 (Studies 4 and 5), no new significant adverse reactions were detected that had not already been identified in trials of sumatriptan injection 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 injection, 0% placebo), nausea and vomiting (4% sumatriptan injection, 0% placebo), and bronchospasm (1% sumatriptan injection, 0% placebo).
The following adverse reactions have been identified during postapproval use of sumatriptan tablets, sumatriptan nasal spray, and sumatriptan injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and sumatriptan injection within 24 hours of each other is contraindicated.
MAO-A inhibitors increase systemic exposure by 2-fold. Therefore, the use of sumatriptan injection in patients receiving MAO-A inhibitors is contraindicated [see Clinical Pharmacology ( 12.3)].
Because their vasospastic effects may be additive, co-administration of sumatriptan injection and other 5-HT 1 agonists (e.g., triptans) within 24 hours of each other is contraindicated.
Cases of serotonin syndrome have been reported during coadministration of triptans and SSRIs, or SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7)].
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 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 for making 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 sumatriptan injection 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 sumatriptan injection.
Following subcutaneous administration of a 6 mg dose of sumatriptan injection in 5 lactating volunteers, sumatriptan was present in milk.
Safety and effectiveness in pediatric patients have not been established. Sumatriptan injection is not recommended for use in patients younger than 18 years of age.
Two controlled clinical trials evaluated sumatriptan nasal spray (5 to 20 mg) in 1,248 pediatric migraineurs 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 pediatric patients. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults.
Five controlled clinical trials (2 single-attack trials, 3 multiple-attack trials) evaluating oral sumatriptan (25 to 100 mg) in pediatric patients aged 12 to 17 years enrolled a total of 701 pediatric migraineurs. These trials did not establish the efficacy of oral sumatriptan compared with placebo in the treatment of migraine in pediatric patients. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults. The frequency of all adverse reactions in these patients appeared to be both dose- and age-dependent, with younger patients reporting reactions more commonly than older pediatric patients.
Postmarketing experience documents that serious adverse reactions have occurred in the pediatric population after use of subcutaneous, oral, and/or intranasal sumatriptan. These reports include reactions similar in nature to those reported rarely in adults, including stroke, visual loss, and death. 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 patients aged 65 years and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
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 sumatriptan injection [see Warnings and Precautions ( 5.1)].
Coronary vasospasm was observed after intravenous administration of sumatriptan injection [see Contraindications ( 4)]. Overdoses would be expected from animal data (dogs at 0.1 g/kg, rats at 2 g/kg) to possibly cause convulsions, tremor, inactivity, erythema of the extremities, reduced respiratory rate, cyanosis, ataxia, mydriasis, injection site reactions (desquamation, hair loss, and scab formation), and paralysis.
The elimination half-life of sumatriptan is about 2 hours [see Clinical Pharmacology (12.3)]; therefore, monitoring of patients after overdose with sumatriptan injection should continue for at least 10 hours or while symptoms or signs persist.
It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of sumatriptan.
Sumatriptan injection USP contains sumatriptan succinate, a selective 5-HT 1B/1D receptor agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1), and it has the following structure:
The molecular formula is C 14H 21N 3O 2S•C 4H 6O 4, representing a molecular weight of 413.5. Sumatriptan succinate USP is a white or almost white powder and is freely soluble in water, sparingly soluble in methanol, practically insoluble in methylene chloride.
Sumatriptan injection USP is a clear, colorless to pale yellow, free from visible particulate matter, sterile, nonpyrogenic solution for subcutaneous injection. Each 0.5 mL of sumatriptan injection 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 solutions is approximately 4.2 to 5.3. The osmolality of the injection is between 275 and 315 mOsm/kg.
Sumatriptan binds with high affinity to human cloned 5-HT 1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine and cluster headaches through agonist effects at the 5-HT 1B/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 ( 5.8)].
Peripheral (Small) Arteries
In healthy volunteers (N = 18), a trial evaluating the effects of sumatriptan on peripheral (small vessel) arterial reactivity failed to detect a clinically 359 significant increase in peripheral resistance.
Transient increases in blood pressure observed in some patients 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.
The bioavailability of sumatriptan via subcutaneous site injection to 18 healthy male subjects was 97% ± 16% of that obtained following intravenous injection.
After a single 6 mg subcutaneous manual injection into the deltoid area of the arm in 18 healthy males (age: 24 ± 6 years, weight: 70 kg), the maximum serum concentration (C max) of sumatriptan was (mean ± standard deviation) 74 ± 15 ng/mL and the time to peak concentration (T max) was 12 minutes after injection (range: 5 to 20 minutes). In this trial, the same dose injected subcutaneously in the thigh gave a C max of 61 ± 15 ng/mL by manual injection versus 52 ±15 ng/mL by autoinjector techniques. The T max or amount absorbed was not significantly altered by either the site or technique of 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.
Following a 6 mg subcutaneous injection into the deltoid area of the arm in 9 males (mean age: 33 years, mean weight: 77 kg) the volume of distribution central compartment of sumatriptan was 50 ± 8 liters and the distribution half-life was 15± 2 minutes.
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.
Following a 6 mg subcutaneous injection into the deltoid area of the arm, the systemic clearance of sumatriptan was 1,194 ± 149 mL/min and the terminal half-life was 115 ± 19 minutes.
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).
Patients with Hepatic Impairment: The effect of mild to moderate hepatic disease on the pharmacokinetics of subcutaneously administered sumatriptan has been evaluated. There were no significant differences in the pharmacokinetics of subcutaneously administered sumatriptan in moderately hepatically impaired subjects compared with healthy controls. The pharmacokinetics of subcutaneously administered sumatriptan in patients with severe hepatic impairment has not been studied. The use of sumatriptan injection in this population is contraindicated [see Contraindications (4)].
Racial Groups: The systemic clearance and C max of subcutaneous sumatriptan were similar in black (n = 34) and Caucasian (n = 38) healthy male subjects.
Drug Interaction Studies
Monoamine Oxidase-A Inhibitors
In a trial of 14 healthy females, pretreatment with an MAO-A inhibitor decreased the clearance of subcutaneous 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.
In carcinogenicity studies in mouse and rat, sumatriptan was administered orally for 78 weeks 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/m 2 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.
Impairment of Fertility
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.
Dogs receiving oral sumatriptan developed corneal opacities and defects in the corneal epithelium. Corneal opacities were seen at the lowest dose-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 patients 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 patients obtaining adequate relief was decreased and the latency to that relief is greater with lower doses.
In Study 1, 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 in Study 1
|Dose of Sumatriptan
|at 10 Minutes||at 30 Minutes||at 1 Hour||at 2 Hours||Adverse Reactions
a Relief is defined as the reduction of moderate or severe pain to no 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 patients with moderate or severe migraine pain (Studies 2 and 3), 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 patients within 1 hour of a single 6 mg subcutaneous dose of sumatriptan injection. Approximately 82% and 65% of patients treated with sumatriptan injection 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 in Studies 2 and 3.
Table 3. Proportion of Patients with Pain Relief and Relief of Migraine Symptoms after 1 and 2 Hours of Treatment in Studies 2 and 3
|1-Hour Data||Study 2||Study 3|
(n = 190)
|Sumatriptan Injection 6 mg
(n = 384)
(n = 180)
|Sumatriptan Injection 6 mg
(n = 350)
|Patients with pain relief (Grade 0/1)||18%||70% a||26%||70% a|
|Patients with no pain||5%||48% a||13%||49% a|
|Patients without nausea||48%||73% a||50%||73% a|
|Patients without photophobia||23%||56% a||25%||58% a|
|Patients with little or no clinical disability b||34%||76% a||34%||76% a|
|2-Hour Data||Study 2||Study 3|
|Placebo c||Sumatriptan Injection
6 mg d
|Placebo c||Sumatriptan Injection
6 mg d
|Patients with pain relief (Grade 0/1)||31%||81% a||39%||82% a|
|Patients with no pain||11%||63% a||19%||65% a|
|Patients without nausea||56%||82% a||63%||81% a|
|Patients without photophobia||31%||72% a||35%||71% a|
|Patients with little or no clinical disability b||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 that may have received an additional placebo injection 1 hour after the initial injection.
d Includes patients that may have received an additional 6 mg of sumatriptan injection 1 hour after the initial injection.
Sumatriptan injection also relieved photophobia, phonophobia (sound sensitivity), nausea, and vomiting associated with migraine attacks. Similar efficacy was seen when patients self-administered sumatriptan injection using the sumatriptan autoinjector.
The efficacy of sumatriptan injection was unaffected by whether or not the migraine was associated with aura, duration of attack, gender or age of the patient, or concomitant use of common migraine prophylactic drugs (e.g., beta-blockers).
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 (Studies 4 and 5). Patients 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 patients receiving 6 mg of sumatriptan injection compared with those who received placebo (see Table 4).
Table 4. Proportion of Patients with Cluster Headache Relief by Time in Studies 4 and 5
|Study 4||Study 5|
(n = 39)
(n = 39)
(n = 88)
(n = 92)
|Patients 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|
n = Number of headaches treated
An estimate of the cumulative probability of a patient with a cluster headache obtaining relief after being treated with either sumatriptan injection or placebo is presented in Figure 1.
Figure 1. Time to Relief of Cluster Headache from Time of Injection a
a The figure uses Kaplan-Meier (product limit) Survivorship Plot. Patients taking rescue medication were censored at 15 minutes.
The plot was constructed with data from patients who either experienced relief or did not require (request) rescue medication within 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).
Sumatriptan injection USP contains sumatriptan (base) as the succinate salt and is supplied as a clear, colorless to pale yellow, sterile, nonpyrogenic solution as follows:
PACKAGING: 2 in 1 CARTON, 0.5 mL in 1 SYRINGE TYPE 2
Store at 25°C (77°F); excursions permitted 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from light.
Repackaged and Distributed By:
Remedy Repack, Inc.
625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
Risk of Myocardial Ischemia and/or Infarction, Prinzmetal’s Angina, Other Vasospasm-Related Events, Arrhythmias, and Cerebrovascular Events
Inform patients that sumatriptan injection may cause serious cardiovascular side effects such as myocardial infarction or stroke. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, irregular heartbeat, significant rise in blood pressure, weakness, and slurring of speech and should ask for medical advice if any indicative sign or symptoms are observed. Apprise patients of the importance of this follow-up [see Warnings and Precautions ( 5.1, 5.2, 5.4, 5.5, 5.8)].
Inform patients that anaphylactic/anaphylactoid reactions have occurred in patients receiving sumatriptan injection. Such reactions can be life-threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens [see Contraindications (4), Warnings and Precautions (5.9)].
Concomitant Use with Other Triptans or Ergot Medications
Inform patients that use of sumatriptan injection within 24 hours of another triptan or an ergot-type medication (including dihydroergotamine or methysergide) is contraindicated [see Contraindications (4), Drug Interactions ( 7.1, 7.3)].
Caution patients about the risk of serotonin syndrome with the use of sumatriptan injection or other triptans, particularly during combined use with SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7), Drug Interactions (7.4)].
Medication Overuse Headache
Inform patients that use of acute migraine drugs for 10 or more days per month may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6)].
Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant [see Use in Specific Populations ( 8.1) ].
Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.2)].
Ability to Perform Complex Tasks
Treatment with sumatriptan injection may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks after administration of sumatriptan injection.
How to Use Sumatriptan Injection
Instruct patients to read the Instructions for Use before starting therapy. Provide patients instruction on the proper use of sumatriptan injection if they are able to self-administer sumatriptan injection in medicaly unsupervised situations. Instruct patients on storage and disposal of the pen [see How Supplied/Storage and Handling ( 16)].
Inform patients that the needle in the sumatriptan autoinjector penetrates approximately 1/4 of an inch (5 to 6 mm). Inform patients that the injection is intended to be given subcutaneously and intramuscular or intravascular delivery should be avoided. Instruct patients to use injection sites with an adequate skin and subcutaneous thickness to accommodate the length of the needle.
Repackaged By / Distributed By: RemedyRepack Inc.
625 Kolter Drive, Indiana, PA 15701
Sumatriptan Injection USP
(soo'' ma trip' tan)
What is the most important information I should know about sumatriptan injection?
Sumatriptan can cause serious side effects, including:
Heart attack and other heart problems. Heart problems may lead to death.
Stop taking sumatriptan and get emergency medical help right away if you have any of thefollowing symptoms of a heart attack:
Sumatriptan 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 sumatriptan?
Sumatriptan injection 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.
Sumatriptan is not used to treat other types of headaches such as hemiplegic (that make you unable to move on one side of your body) or basilar (rare form of migraine with aura) migraines. Sumatriptan is not used to prevent or decrease the number of migraine or cluster headaches you have.
It is not known if sumatriptan is safe and effective in children under 18 years of age.
Do not take sumatriptan injection if you have:
Ask your healthcare provider if you are not sure if your medicine is listed above.
Before you take sumatriptan, 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.
Sumatriptan and certain other medicines can affect each other, causing serious side effects.
Especially tell your healthcare provider if you take antidepressant 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 sumatriptan injection?
What should I avoid while taking sumatriptan injection?
Sumatriptan 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 sumatriptan injection?
Sumatriptan may cause serious side effects. See “What is the most important information I should know about sumatriptan injection?”
These serious side effects include:
Call your healthcare provider right away if you have any of the following symptoms of serotonin syndrome:
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of sumatriptan injection. 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 sumatriptan injection?
Keep sumatriptan injection and all medicines out of the reach of children.
General information about the safe and effective use of sumatriptan injection
Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use sumatriptan injection for a condition for which it was not prescribed. Do not give sumatriptan injection to other people, even if they have the same symptoms you have. It may harm them.
This Patient Information leaflet summarizes the most important information about sumatriptan injection. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about sumatriptan injection that is written for healthcare professionals.
For more information, call 1-888-375-3784.
What are the ingredients in sumatriptan injection?
Active ingredient: sumatriptan succinate USP
Inactive ingredients: sodium chloride, water for injection.
The other brands listed are trademarks of their respective owners and are not trademarks of Dr. Reddy’s Laboratories Limited. The makers of these brands are not affiliated with and do not endorse Dr. Reddy’s Laboratories Limited or its products.
INSTRUCTIONS FOR USE OF DISPOSABLE SUMATRIPTAN AUTOINJECTOR SYSTEM
Read this Patient Instructions for Use before you start to use Sumatriptan Autoinjector System. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about sumatriptan injection when you start taking it and at regular checkups.
Instructions for Use of Autoinjector Pen
Important things that you need to know
This device is called an Autoinjector pen. Here we use the shorter name ‘pen’.
1.Read all of the instructions carefully before using this pen.
2. Follow these step-by-step instructions every time you use the pen.
3. Only use each pen once - do not try to use more than once.
If you have any further questions, ask your doctor or pharmacist.
A. ABOUT THE AUTOINJECTOR PEN
B. GETTING READY
Getting ready for the injection
1.Wash your hands.
2.Choose an area with an adequate fatty tissue layer.
3.Clean the skin area to be injected with alcohol or a new sterile swab
Getting the pen ready
4. Take the pen out of the package.
5. Look in the medicine window on the pen.
If the plunger rod can be seen through the medicine window, the device is spent and cannot be used again.
6. Pull the cap off the pen
7. Look inside the cap, check that the gray needle cover is inside.
Do not use the pen if the gray needle cover is not inside the cap.
8. Do not try to put the cap back
You are now ready to inject the medicine, go to step 9.
C. INJECTING THE MEDICINE
9. Without pressing the blue button, push the pen firmly against your skin.
Keep the pen pressed against your skin for the next steps
10. Do not attempt to re-engage the safety lock at any time.
11. Firmly press down the blue button on the top of the pen until it will not go further.
12. Do not take the pen off your skin
If you take the pen off before the second click, not all the medicine will be injected.
13. Carefully take the pen off your skin.
D.WHAT TO DO AFTER THE INJECTION
14. Replace the cap right away
If you notice a spot of blood at the injection site, dab away with a cotton ball or tissue paper. Do not rub the injection site. If needed, you may cover the injection site with a bandage.
15. Discard the whole sumatriptan injection autoinjector after use.
Do not try to reuse the autoinjector pen
This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.
To reorder additional Patient information sheets contact Dr. Reddy’s Customer Service at 1-866-733-3952.
Repackaged and Distributed By:
Remedy Repack, Inc.
625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762
DRUG: Sumatriptan Succinate
GENERIC: Sumatriptan Succinate
PACKAGING: 0.5 mL in 1 SYRINGE
OUTER PACKAGING: 2 in 1 CARTON
sumatriptan succinate injection
|Labeler - REMEDYREPACK INC. (829572556)|