Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 24 November 2019

Indication(s)

1 INDICATIONS AND USAGE ZEMBRACE SymTouch is indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use: Use only if a clear diagnosis of migraine has been established. If a patient has no response to the first migraine attack treated with ZEMBRACE SymTouch, reconsider the diagnosis before ZEMBRACE SymTouch is administered to treat any subsequent attacks. ZEMBRACE SymTouch injection is not indicated for the prevention of migraine attacks. ZEMBRACE SymTouch is a serotonin (5-HT1B/1D) receptor agonist (triptan) indicated for: Acute treatment of migraine with or without aura in adults (1) Limitations of Use: Use only if a clear diagnosis of migraine has been established. (1) Not indicated for the prophylactic therapy of migraine. (1)

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Advisory information

contraindications
4 CONTRAINDICATIONS ZEMBRACE SymTouch injection is contraindicated in patients with: Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetal’s angina [see Warnings and Precautions (5.1)]. Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.2)]. History of stroke or transient ischemic attack (TIA) or history of hemiplegic or basilar migraine because these patients are at a higher risk of stroke [see Warnings and Precautions (5.4)]. Peripheral vascular disease [see Warnings and Precautions (5.5)]. Ischemic bowel disease [see Warnings and Precautions (5.5)]. Uncontrolled hypertension [see Warnings and Precautions (5.8)]. Recent (i.e., within 24 hours) use of ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide), or another 5-hydroxytryptamine1 (5-HT1) agonist [see Drug Interactions (7.1, 7.3)]. Concurrent administration of an MAO-A inhibitor or recent (within 2 weeks) use of an MAO-A inhibitor [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)]. Known hypersensitivity to sumatriptan (angioedema and anaphylaxis seen) [see Warnings and Precautions (5.9)]. Severe hepatic impairment [see Clinical Pharmacology (12.3)]. History of coronary artery disease or coronary vasospasm (4) Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders (4) History of stroke, transient ischemic attack, or hemiplegic or basilar migraine (4) Peripheral vascular disease (4) Ischemic bowel disease (4) Uncontrolled hypertension (4) Recent (within 24 hours) use of another 5-HT1 agonist (e.g., another triptan) or of an ergotamine-containing medication (4) Concurrent or recent (past 2 weeks) use of monoamine oxidase-A inhibitor (4) Hypersensitivity to sumatriptan (angioedema and anaphylaxis seen) (4) Severe hepatic impairment (4)
Adverse reactions
6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Myocardial ischemia, myocardial infarction, and Prinzmetal’s angina [see Warnings and Precautions (5.1)] Arrhythmias [see Warnings and Precautions (5.2)] Chest, throat, neck, and/or jaw pain/tightness/pressure [see Warnings and Precautions (5.3)] Cerebrovascular events [see Warnings and Precautions (5.4)] Other vasospasm reactions [see Warnings and Precautions (5.5)] Medication overuse headache [see Warnings and Precautions (5.6)] Serotonin syndrome [see Warnings and Precautions (5.7)] Increase in blood pressure [see Warnings and Precautions (5.8)] Hypersensitivity reactions [see Contraindications (4), Warnings and Precautions (5.9)] Seizures [see Warnings and Precautions (5.10)] 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/paresthesia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Promius Pharma, LLC. at 1-888-966-8766 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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. Adverse Reactions in Placebo-Controlled Trials with Sumatriptan Injection Migraine Headache: Table 1 lists adverse reactions that occurred in 2 US placebo-controlled clinical trials in migraine subjects (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) a Includes injection site pain, stinging/burning, swelling, erythema, bruising, bleeding. Adverse Reaction Percent of Subjects Reporting Sumatriptan Injection 6 mg Subcutaneous (n = 547) Placebo (n = 370) Atypical sensations Tingling Warm/hot sensation Burning sensation Feeling of heaviness Pressure sensation Feeling of tightness Numbness Feeling strange Tight feeling in head 42 14 11 7 7 7 5 5 2 2 9 3 4 <1 1 2 <1 2 <1 <1 Cardiovascular Flushing Chest discomfort Tightness in chest Pressure in chest 7 5 3 2 2 1 <1 <1 Ear, nose, and throat Throat discomfort Discomfort: nasal cavity/sinuses 3 2 <1 <1 Injection site reactiona 59 24 Miscellaneous Jaw discomfort 2 0 Musculoskeletal Weakness Neck pain/stiffness Myalgia 5 5 2 <1 <1 <1 Neurological Dizziness/vertigo Drowsiness/sedation Headache 12 3 2 4 2 <1 Skin Sweating 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 reactions. Adverse Reactions in a Study with ZEMBRACE SymTouch The most common adverse reactions in a placebo-controlled trial with ZEMBRACE SymTouch were injection site reactions (including injection site bruising, erythema, hemorrhage, induration, irritation, pain, paresthesia, pruritis, swelling, and urticaria), occurring in 30% of ZEMBRACE SymTouch-treated patients compared to 13% of placebo-treated patients. Adverse reactions with ZEMRACE SymTouch are expected to be similar to those observed with sumatriptan injection. 6.2 Postmarketing Experience 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. Cardiovascular Hypotension, palpitations Neurological Dystonia, tremor

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION For subcutaneous use only. (2.1) Acute treatment of migraine: 3 mg Single dose. (2.1) Maximum dose in a 24-hour period: 12 mg. Separate doses by at least 1 hour. (2.1) 2.1 Dosing Information The recommended dose of ZEMBRACE SymTouch is 3 mg injected subcutaneously. The maximum cumulative injected dose that may be given in 24 hours is 12 mg, with doses of ZEMBRACE SymTouch separated by at least 1 hour. ZEMBRACE SymTouch may also be given at least 1 hour following a dose of another sumatriptan product. 2.2 Administration Using ZEMBRACE SymTouch ZEMBRACE SymTouch is available as a prefilled, ready-to-use, single dose, disposable auto-injector containing 3 mg sumatriptan. With ZEMBRACE SymTouch, the needle penetrates approximately ¼ inch (6 mm). The injection is intended to be given subcutaneously. Do not administer by any other route. Instruct patients on the proper use of ZEMBRACE SymTouch and direct them to use injection sites with an adequate skin and subcutaneous thickness to accommodate the length of the needle.
Use in special populations
8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm. (8.1) 8.1 Pregnancy Risk Summary 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. Clinical Considerations 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. Data 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. 8.2 Lactation Risk Summary 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 ZEMBRACE SymTouch and any potential adverse effects on the breastfed infant from sumatriptan or from the underlying maternal condition. Clinical Considerations Infant exposure to sumatriptan can be minimized by avoiding breastfeeding for 12 hours after treatment with ZEMBRACE SymTouch. Data Following subcutaneous administration of a 6 mg dose of sumatriptan injection in 5 lactating volunteers, sumatriptan was present in milk. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. ZEMBRACE SymTouch 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 12 to 17 years of age 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 subjects 12 to 17 years of age 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. 8.5 Geriatric Use Clinical trials of sumatriptan injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger patients. 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 ZEMBRACE SymTouch injection [see Warnings and Precautions (5.1)].

Interactions

7 DRUG INTERACTIONS 7.1 Ergot-Containing Drugs 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 ZEMBRACE SymTouch within 24 hours of each other is contraindicated. 7.2 Monoamine Oxidase-A Inhibitors MAO-A inhibitors increase systemic exposure by 2-fold. Therefore, the use of ZEMBRACE SymTouch injection in patients receiving MAO-A inhibitors is contraindicated [see Clinical Pharmacology (12.3)]. 7.3 Other 5-HT1 Agonists Because their vasospastic effects may be additive, coadministration of ZEMBRACE SymTouch injection and other 5-HT1 agonists (e.g., triptans) within 24 hours of each other is contraindicated. 7.4 Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome Cases of serotonin syndrome have been reported during coadministration of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7)].

More information

Category Value
Authorisation number NDA208223
Agency product number J8BDZ68989
Orphan designation No
Product NDC 67857-809
Date Last Revised 10-06-2019
Type HUMAN PRESCRIPTION DRUG
RXCUI 1738576
Storage and handling 16.2 Storage and Handling Store between 20°C and 25°C (68°F and 77°F) Excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from light.
Marketing authorisation holder Promius Pharma, LLC