Zecuity Patch

ZECUITY 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 ZECUITY reconsider the diagnosis of migraine before ZECUITY is administered to treat any subsequent attacks. • ZECUITY is not intended for the prevention of migraine attacks.

ZECUITY is for transdermal use only and is designed for patient self-administration to the upper arm or thigh (see Figure 1). ZECUITY should not be applied to other areas of the body. ZECUITY should not be cut.

The maximum recommended single dose is one ZECUITY iontophoretic transdermal system (TDS). No more than two ZECUITY TDS should be used in any 24 hour period, and the second ZECUITY TDS should be applied no sooner than 2 hours after activation of the first ZECUITY TDS. There is no evidence of benefit for the use of a second ZECUITY TDS to treat headache recurrence or incomplete headache relief during a migraine attack.

ZECUITY should be applied to dry intact, non-irritated skin on the upper arm or thigh on a site that is relatively hair free and is without scars, tattoos, abrasions, or other skin conditions (i.e., generalized skin irritation or disease including eczema, psoriasis, melanoma, contact dermatitis). ZECUITY should not be applied to a previous application site until the site remains erythema free for at least 3 days.

Figure 1: Applied Transdermal System

ZECUITY delivers 6.5 mg of sumatriptan over 4 hours. Once applied, the activation button must be pushed, and the red light emitting diode (LED) will turn on. ZECUITY TDS must be applied and activated within 15 minutes of initiation of assembly. When dosing is completed, the system stops operating and the activation light turns off, signaling that the system can be removed. Once dosing is completed, the system cannot be reactivated. If the light turns off before 4 hours, dosing has stopped and ZECUITY can be removed. If headache relief is incomplete, a second ZECUITY TDS can be applied to a different site. [see Patient Counseling Information (17)].

The ZECUITY TDS should remain in place for 4 hours or until the red LED light goes off. The iontophoretic device can be secured with medical tape if needed.

The safety of using more than 4 ZECUITY in one month has not been established.

ZECUITY is for single use only. After use, the TDS should be folded so the adhesive side sticks to itself and safely discarded away from children and pets. ZECUITY contains lithium-manganese dioxide batteries; it should be disposed in accordance with state and local regulations.

Pregnancy

Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. ZECUITY 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. 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 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

It is not known whether sumatriptan is excreted in human milk following transdermal administration. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ZECUITY, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Two controlled clinical trials evaluated sumatriptan nasal spray (5 to 20 mg) in 1,248 adolescent migraineurs aged 12 to 17 years who treated a single attack. The trials did not establish the efficacy of sumatriptan nasal spray compared with placebo in the treatment of migraine in adolescents. Adverse reactions observed in these clinical trials were similar in nature to those reported in clinical trials in adults.

Five controlled clinical trials (2 single-attack 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. Since clinical data to determine the frequency of serious adverse reactions in pediatric patients who might receive subcutaneous, oral, or intranasal sumatriptan are not presently available, the use of ZECUITY in patients under 18 years of age is not recommended.

Geriatric Use

Clinical trials of ZECUITY did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to using ZECUITY [see Warnings and Precautions (5.3)].

ZECUITY (sumatriptan iontophoretic transdermal system) is a disposable, single use system designed to deliver sumatriptan through the skin using iontophoresis. Iontophoresis is a non-invasive method of delivering a drug through the skin using a low electrical current. The ZECUITY electronics, powered by two coin cell lithium batteries, control the amount of current applied and the rate and amount of sumatriptan delivered.

Sumatriptan succinate, the active component of ZECUITY, is a selective 5-hydroxy-tryptamine receptor subtype 1 (5-HT1) agonist (triptan). Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1), and 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 freely soluble in water. Each ZECUITY iontophoretic transdermal system contains 86 mg sumatriptan (base) as the succinate salt in an aqueous formulation. ZECUITY, upon activation, delivers 6.5 mg of sumatriptan through the skin over 4 hours [see Dosage and Administration (2)].

ZECUITY iontophoretic transdermal system is composed of an iontophoretic device and a drug reservoir card. The reservoir card contains 2 non-woven pads and 2 different gel formulations; one a sumatriptan succinate formulation and the other a sodium salt formulation. The sumatriptan succinate formulation and pad contains the following inactive ingredients: purified water, basic butylated methacrylate copolymer (polyamine), lauric acid, adipic acid, methylparaben and a non-woven viscose pad. The salt formulation and pad contains: purified water, hydroxypropylcellulose, sodium chloride, methylparaben and a non-woven viscose pad. ZECUITY is a non-sterile product.

The iontophoretic device consists of medical grade adhesive fabric and foam and a plastic dome that contains an activation button, batteries, and electronics (see Figure 2).

  Figure 2: Iontophoretic Device

Top View	Bottom View

The sumatriptan and salt pads are housed in individual reservoirs. Each reservoir is sealed by a foil strip that is removed prior to transfer of the pads to the iontophoretic device (see Figure 3). The iontophoretic device and foil reservoirs are co-packaged in a single unit pouch [see Patient Counseling Information (17)].

  Figure 3: Reservoir Card

For ZECUITY to function, the pads must completely cover the electrodes [see Patient Counseling Information (17)].

ZECUITY contains 86 mg sumatriptan that delivers 6.5 mg of sumatriptan over 4 hours.

After use, fold used system so the adhesive side sticks to itself and safely discard away from children and pets. ZECUITY contains lithium-manganese dioxide batteries; dispose in accordance with state and local regulations.

Store at room temperature, between 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C to 30°C (59°F to 86°F). Do not store in the refrigerator or freezer.

ZECUITY is packaged individually in a sealed pouch. ZECUITY is supplied in cartons of 4 systems, NDC 51759-101-04.

  ZECUITY® (zeh-CUE-eh-tee)

(sumatriptan iontophoretic transdermal system)

for topical use

Read this Patient Information before you start using ZECUITY and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about ZECUITY?

ZECUITY can cause serious side effects, including:

Heart attack and other heart problems. Heart problems may lead to death.

Stop using ZECUITY 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 an uncomfortable heavy pressure, squeezing, fullness, or pain • 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

ZECUITY 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

What is ZECUITY?

ZECUITY is a prescription medicine used for the acute treatment of migraine headaches with or without aura in adults. ZECUITY comes in an iontophoretic transdermal system (TDS) that uses a mild electrical current to deliver the medicine sumatriptan through your skin.

ZECUITY is used for people who have been told by a healthcare provider that they have migraine headaches.

ZECUITY is not used to prevent or decrease the number of migraine headaches you have.

It is not known if ZECUITY is safe and effective in children under 18 years of age.

Who should not use ZECUITY?

Do not use ZECUITY if you have:

• heart problems or a history of heart problems • had a stroke, transient ischemic attacks (TIAs), or problems with your blood circulation • narrowing of blood vessels to your legs, arms, stomach, or kidney (peripheral vascular disease) • uncontrolled high blood pressure • hemiplegic migraines or basilar migraines. If you are not sure if you have these types of migraines, ask your healthcare provider • taken any of the following medicines in the last 24 hours: o almotriptan (AXERT®) o eletriptan (RELPAX®) o frovatriptan (FROVA®) o naratriptan (AMERGE®) o rizatriptan (MAXALT®, MAXALT-MLT®) o sumatriptan and naproxen (TREXIMET®) o ergotamines (CAFERGOT®, ERGOMAR®, MIGERGOT®) o dihydroergotamine (D.H.E. 45®, MIGRANAL®)   Ask your healthcare provider if you are not sure if your medicine is listed above. • severe liver problems • an allergy to sumatriptan, the medicine in ZECUITY, or any of the components in ZECUITY TDS. See the end of this leaflet for a complete list of ingredients in ZECUITY.

What should I tell my healthcare provider before using ZECUITY?

Before you use ZECUITY, tell your healthcare provider about all of your medical conditions, including if you:

• have high blood pressure • have high cholesterol • have diabetes • smoke • are overweight • are a female who has gone through menopause • have heart problems or family history of heart problems or stroke • have liver problems • have had epilepsy or seizures • are not using effective birth control • have or have had any side effects caused by the use of electrical devices. Talk to your healthcare provider if you are not sure if you have a medical electronic device or sensitivities to electrical devices. • are pregnant or plan to become pregnant. It is not known if ZECUITY will harm your unborn baby. • are breastfeeding or plan to breastfeed. It is not known if the medicine in ZECUITY passes into your breast milk. You and your healthcare provider should decide if you will use ZECUITY or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

Using ZECUITY with certain other medicines can affect each other, causing serious side effects.

Especially tell your healthcare provider if you take anti-depressant medicines called:

• selective serotonin reuptake inhibitors (SSRIs) • serotonin norepinephrine reuptake inhibitors (SNRIs) • tricyclic antidepressants (TCAs) • monoamine oxidase inhibitors (MAOIs)

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 use ZECUITY?

• Read the Instructions for Use in the package that comes with your ZECUITY TDS for information about the right way to use ZECUITY TDS. • Certain people should apply their first dose of ZECUITY in their healthcare provider’s office or in another medical setting. Ask your healthcare provider if you should use your first dose in a medical setting. • ZECUITY is for use on the skin only. • Use ZECUITY exactly as your healthcare provider tells you to. • Apply 1 ZECUITY to your upper arm or thigh. • Do not apply ZECUITY to other areas of your body. Talk to your healthcare provider if you are not sure where to apply ZECUITY. • If your headache comes back or you only get some relief from your headache, you may apply a second ZECUITY to your other arm or thigh, no sooner than 2 hours after the activation of the previously applied ZECUITY. • Do not apply more than 2 ZECUITY in 24 hours.   • If you use too much ZECUITY, call your healthcare provider or go to the nearest hospital emergency room right away. • It is not known if using more than 4 ZECUITY in 1 month is safe.

What should I avoid while using ZECUITY?

• Do not bathe, shower, or swim while wearing ZECUITY.

  • ZECUITY 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. • You should remove ZECUITY before you have a Magnetic Resonance Imaging (MRI) procedure.

What are the possible side effects of ZECUITY?

See “What is the most important information I should know about ZECUITY?”

ZECUITY may cause serious side effects including:

• injury during a Magnetic Resonance Imaging (MRI). The ZECUITY TDS contains metal parts and must be removed before an MRI. • allergic contact dermatitis (ACD). Some people have had a serious skin reaction called allergic contact dermatitis (ACD) where ZECUITY is applied. Symptoms of ACD include: o itching, redness, or irritation of skin o blistering or peeling of your skin o warmth or tenderness of skin o blisters that ooze, drain, or crust over   You should stop using ZECUITY and call your healthcare provider if you have any of the symptoms of ACD. If you have or have had ACD while using ZECUITY and need to take sumatriptan by mouth or injection, your first dose of sumatriptan should be given in your healthcare provider’s office or in another medical setting.
• changes in color or sensation in your fingers and toes (Raynaud’s syndrome) • stomach and intestinal problems (gastrointestinal and colonic ischemic events). Symptoms of gastrointestinal and colonic ischemic events include: o sudden or severe stomach pain o stomach pain after meals o weight loss o nausea or vomiting o constipation or diarrhea o bloody diarrhea o fever • problems with blood circulation to your legs and feet (peripheral vascular ischemia). Symptoms of peripheral vascular ischemia include: o cramping and pain in your legs or hips o feeling of heaviness or tightness in your leg muscles o burning or aching pain in your feet or toes while resting o numbness, tingling, or weakness in your legs o cold feeling or color changes in 1 or both legs or feet • medication overuse headaches. Some people who use too many ZECUITY may have worse headaches (medication overuse headache). If your headaches get worse, your healthcare provider may decide to stop your treatment with sumatriptan. • serotonin syndrome. Serotonin syndrome is a rare but serious problem that can happen in people using ZECUITY, especially if ZECUITY is used with anti-depressant medicines called SSRIs or 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:

  o mental changes such as seeing things that are not there (hallucinations), agitation, or coma o fast heartbeat o changes in blood pressure o high body temperature o tight muscles o trouble walking o nausea, vomiting, or diarrhea • increases in blood pressure. You should not use ZECUITY if you have uncontrolled high blood pressure. • serious allergic reactions. Get medical help right away if you have any of these symptoms of a serious allergic reaction: o swelling of your face, lips, mouth, or tongue o trouble breathing o wheezing o severe itching o skin rash, redness, or swelling o dizziness or fainting o fast heartbeat or pounding in your chest (tachycardia) o sweating • seizures. Seizures have happened in people taking sumatriptan who have never had seizures before. Talk with your healthcare provider about your chance of having seizures while you take ZECUITY.

The most common side effects of ZECUITY include pain, tingling, itching, warmth, discomfort or a change in the skin color at the application site of ZECUITY.

Most people have some skin redness after removal of ZECUITY. This redness will usually go away in 24 hours.

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 ZECUITY. For more information, ask your healthcare provider or pharmacist.

Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store ZECUITY?

• Store ZECUITY at room temperature between 68°F to 77°F (20°C to 25°C). • Do not store ZECUITY in the refrigerator or freezer.

Keep ZECUITY and all medicines out of the reach of children.

General information about the safe and effective use of ZECUITY

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ZECUITY for a condition for which it was not prescribed. Do not give ZECUITY to other people, even if they have the same symptoms that you have. It may harm them.

This Patient Information leaflet summarizes the most important information about ZECUITY. If you would like more information, talk to your healthcare provider. You can ask your healthcare provider or pharmacist for information about ZECUITY that is written for healthcare professionals.

For more information, go to www.ZECUITY.com or call 1-855-ZECUITY.

What are the ingredients in ZECUITY?

Active ingredient: sumatriptan succinate

Inactive ingredients:

• Sumatriptan Reservoir Card and pad: purified water, basic butylated methacrylate copolymer (polyamine), lauric acid, adipic acid, methylparaben, and non-woven viscose pad. • Salt Reservoir Card and pad: purified water, hydroxypropylcellulose, sodium chloride, methylparaben, and non-woven viscose pad. • Iontophoretic device: medical grade adhesive fabric, foam and plastic dome containing an activation button, coin cell lithium batteries, and electronics.

This Patient Information has been approved by the U.S. Food and Drug Administration.

ZECUITY® is a registered trademark of Teva Pharmaceuticals International GmbH. The other brands listed are trademarks of their respective owners and are not trademarks of Teva Pharmaceuticals International GmbH. The makers of these brands are not affiliated with and do not endorse Teva Pharmaceuticals International GmbH or its affiliates or products.

Manufactured for Teva Pharmaceuticals International GmbH by LTS

Lohmann Therapie-Systeme AG, D-56626

Andernach, Germany

and by LTS Lohmann Therapy Systems Corp.,

West Caldwell, NJ 07006

Distributed by:

Teva Pharmaceuticals USA, Inc.

North Wales, PA 19454

©2016 Teva Pharmaceuticals USA, Inc.

All rights reserved.

ZECPL-002

Revised: February 2016

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