Zembrace SymTouch

Do not use sumatriptan within 24 hours before or after using another migraine headache medicine, including:

• sumatriptan tablets or nasal spray, almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, zolmitriptan; or
• ergot medicine such as dihydroergotamine, ergotamine, ergonovine, or methylergonovine.

Sumatriptan may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with sumatriptan, especially:

• an antibiotic--clarithromycin, erythromycin, telithromycin;
• an antidepressant--amitriptyline, citalopram, clomipramine, desipramine, doxepin, escitalopram, fluoxetine (Prozac), fluvoxamine, imipramine, nefazodone, nortriptyline, paroxetine, sertraline (Zoloft), trazodone, or vilazodone;
• antifungal medication--itraconazole, ketoconazole, posaconazole, voriconazole;
• heart medication--nicardipine, quinidine; or
• antiviral medicine to treat hepatitis C or HIV/AIDS--boceprevir, atazanavir, cobicistat (Stribild, Tybost), delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, telaprevir.

This list is not complete. Other drugs may interact with sumatriptan, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

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]
• Arrhythmias [see WARNINGS AND PRECAUTIONS]
• Chest, throat, neck, and/or jaw pain/tightness/pressure [see WARNINGS AND PRECAUTIONS]
• Cerebrovascular events [see WARNINGS AND PRECAUTIONS]
• Other vasospasm reactions [see WARNINGS AND PRECAUTIONS]
• Medication overuse headache [see WARNINGS AND PRECAUTIONS]
• Serotonin syndrome [see WARNINGS AND PRECAUTIONS]
• Increase in blood pressure [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity reactions [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS]
• Seizures [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Table 1 lists adverse reactions that occurred in 2 US placebo-controlled clinical trials in migraine subjects (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)

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.

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.

Hypotension, palpitations

Dystonia, tremor

Read the entire FDA prescribing information for Zembrace SymTouch (Sumatriptan Succinate Subcutaneous Injection, USP)

Zembrace SymTouch can cause serious side effects, including:

Heart attack and other heart problems. Heart problems may lead to death. Stop taking Zembrace SymTouch and get emergency medical help right away if you have any of the following symptoms of a heart attack:

• discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back
• chest pain or chest discomfort that feels like heavy pressure, squeezing, or fullness
• pain or discomfort in your arms, back, neck, jaw, or stomach
• shortness of breath with or without chest discomfort
• breaking out in a cold sweat
• nausea or vomiting
• feeling lightheaded

Zembrace SymTouch 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:

• have high blood pressure
• have high cholesterol levels
• smoke
• are overweight
• have diabetes
• have a family history of heart disease
• are a female who has gone through menopause
• are a male over age 40

Serotonin syndrome. Serotonin syndrome is a serious and life-threatening problem that can happen in people taking Zembrace SymTouch, especially if Zembrace SymTouch is used with anti-depressant medicines called selective serotonin reuptake inhibitors (SSRIs) or selective norepinephrine reuptake inhibitors (SNRIs). Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure.

Call your healthcare provider right away if you have any of the following symptoms of serotonin syndrome:

• mental changes such as seeing things that are not there (hallucinations), agitation, or coma
• fast heartbeat
• changes in blood pressure
• high body temperature
• tight muscles
• trouble walking
• nausea, vomiting, or diarrhea

Medication overuse headaches. Some people who take/use too much Zembrace SymTouch may have worse headaches (medication overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with Zembrace SymTouch.

Seizures. Seizures have happened in people taking Zembrace SymTouch who have never had seizures before. Talk with your healthcare provider about your chance of having seizures while you take Zembrace SymTouch.

Do not take Zembrace SymTouch if you have:

• heart problems or a history of heart problems
• narrowing of blood vessels to your legs, arms, stomach, or kidney (peripheral vascular disease)
• uncontrolled high blood pressure
• severe liver problems
• hemiplegic migraines or basilar migraines. If you are not sure if you have these types of migraines, ask your healthcare provider.
• had a stroke, transient ischemic attacks (TIAs), or problems with your blood circulation
• taken any of the following medicines in the last 24 hours:
  • almotriptan (Axert)
  • eletriptan (Relpax)
  • frovatriptan (Frova)
  • naratriptan (Amerge)
  • rizatriptan (Maxalt, Maxalt-MLT)
  • sumatriptan and naproxen (Treximet)
  • ergotamines (Cafergot, Ergomar, Migergot)
  • dihydroergotamine (D.H.E. 45, Migranal)
• an allergy to Zembrace SymTouch or any of the ingredients in Zembrace SymTouch. 

Zembrace SymTouch 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.

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. Zembrace SymTouch may pass into your breast milk and may harm your baby. Talk with your healthcare provider about the best way to feed your baby if you take Zembrace SymTouch.

• Store between 68° and 77°F (20° and 25°C).
• Store your medicine away from light. 
• Keep your medicine in the packaging or carrying case provided with it. 
• Keep Zembrace SymTouch and all medicines out of the reach of children.

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.

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)].

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.

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)].

Zembrace Symtouch injection contains sumatriptan succinate, a selective 5-HT1B/1D receptor agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino) ethyl]-N- methyl-indole-5-methanesulfonamide succinate (1:1), and it has the following structure:

The empirical formula is C14H21N3O2S•C4H6O4, representing a molecular weight of 413.5. Sumatriptan succinate is a white to off-white powder that is readily soluble in water and in saline.

Zembrace Symtouch is a clear, colorless to pale yellow, sterile, nonpyrogenic solution for subcutaneous injection. Each 0.5 mL of Zembrace Symtouch contains 4.2 mg of sumatriptan succinate equivalent to 3-mg of sumatriptan (base) and 4.15 mg of sodium chloride, USP in Water for Injection, USP.

The pH range of solution is approximately 4.2 to 5.3 and the osmolality of injection is approximately 291 mOsmol (275 to 315 mOsmol).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

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 highest dose in rat was reduced from 360 mg/kg/day during Week 21). There was no evidence in either species of an increase in tumors related to sumatriptan administration.

Mutagenesis

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 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. 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.

Animal Toxicology and/or Pharmacology

Corneal Opacities: 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.

How Supplied

• Zembrace Symtouch 3 mg/0.5 mL Injection contains sumatriptan as the succinate salt and is supplied as a clear, colorless to pale yellow, sterile, nonpyrogenic solution in a prefilled, ready-to-use, single dose, disposable auto-injector unit (NDC # 67857-809-37).
• Each carton contains 4 units (NDC # 67857-809-38) and a Patient Information and Instructions for Use leaflet.

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.