Xopenex

XOPENEX (levalbuterol HCl) Inhalation Solution is indicated for the treatment or prevention of bronchospasm in adults, adolescents, and children 6 years of age and older with reversible obstructive airway disease.

Dosage Forms And Strengths

XOPENEX Inhalation Solution is supplied in 3 mL unit-dose, low-density polyethylene (LDPE) vials as a clear, colorless, sterile, preservative-free, aqueous solution, in three different strengths of levalbuterol (0.31 mg, 0.63 mg, 1.25 mg). Each strength of XOPENEX Inhalation Solution is available in a shelf carton containing one or more foil pouches, each containing 12 unit-dose LDPE vials.

Storage And Handling

XOPENEX Inhalation Solution is supplied in 3 mL unit-dose, low-density polyethylene (LDPE) vials as a clear, colorless, sterile, preservative-free, aqueous solution, in three different strengths of levalbuterol (0.31 mg, 0.63 mg, 1.25 mg). Each strength of XOPENEX Inhalation Solution is available in a shelf-carton containing one or more foil pouches, each containing 12 unit-dose LDPE vials.

XOPENEX (levalbuterol HCl) Inhalation Solution, 0.31 mg (foil pouch label color green) contains 0.31 mg of levalbuterol (as 0.36 mg of levalbuterol HCl) and is available in cartons of 24 unit-dose LDPE vials (NDC 63402-511-24).

XOPENEX (levalbuterol HCl) Inhalation Solution, 0.63 mg (foil pouch label color yellow) contains 0.63 mg of levalbuterol (as 0.73 mg of levalbuterol HCl) and is available in cartons of 24 unit-dose LDPE vials (NDC 63402-512-24).

XOPENEX (levalbuterol HCl) Inhalation Solution, 1.25 mg (foil pouch label color red) contains 1.25 mg of levalbuterol (as 1.44 mg of levalbuterol HCl) and is available in cartons of 24 unit-dose LDPE vials (NDC 63402-513-24).

XOPENEX Inhalation Solution is also available as a concentrate in individually pouched 0.5 mL unit-dose vials containing 1.25 mg of levalbuterol (NDC 63402-515-30).

Store XOPENEX Inhalation Solution in the protective foil pouch at 20-25°C (68-77°F) [see USP Controlled Room Temperature]. Protect from light and excessive heat. Keep unopened vials in the foil pouch. Once the foil pouch is opened, the vials should be used within 2 weeks. Vials removed from the pouch, if not used immediately, should be protected from light and used within 1 week. Discard any vial if the solution is not colorless.

Manufactured for : Sunovion Pharmaceuticals Inc. Marlborough, MA 01752 USA For customer service, call 1-888-394-7377. To report adverse events, call 1-877-737-7226. For medical information, call 1-800-739-0565. March 2014

If you take too much Xopenex, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

Bronchodilator; synthetic sympathomimetic amine and relatively selective, short-acting β2-adrenergic agonist.216 b

• Importance of providing patient with a copy of the manufacturer’s patient information.216

• Importance of adequate understanding of proper storage, preparation, and inhalation techniques, including use of various delivery systems.216 b

• Importance of adherence to dosing schedules of levalbuterol and concomitant therapy, including not exceeding the recommended dose or frequency of use unless otherwise instructed by a clinician.216 b

• If decreased effectiveness occurs, contact a clinician immediately; do not increase the dose or frequency of administration.216 b

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.216

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., other inhaled agents) and OTC drugs.216

• Importance of informing patients of other important precautionary information. (See Cautions.)

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Fast heartbeat

• Chest pain or tightness
• dizziness
• feeling “faint”
• lightheadedness
• troubled breathing

• Cough
• difficult or labored breathing
• difficulty swallowing
• extra heartbeats
• fainting
• fast, pounding, slow, or irregular heartbeat or pulse
• hives, welts, itching, or rash
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• noisy breathing
• redness of the skin
• tightness in the chest
• unusual tiredness or weakness

Get emergency help immediately if any of the following symptoms of overdose occur:

• Chest pain
• dizziness
• dry mouth
• general feeling of discomfort or illness
• headache
• impaired consciousness
• irregular or fast heartbeat
• lightheadedness
• nausea
• nervousness
• seizures
• sleeplessness
• sweating
• tremor

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Accidental injury (in children 4 to 11 years of age)
• anxiety
• body aches or pain
• chills
• congestion
• cough or hoarseness
• dryness or soreness of the throat
• fever
• general aches and pains
• headache
• hoarseness
• increased cough
• leg cramps
• loss of appetite
• migraines or other headaches
• muscle tightness
• nervousness
• runny or stuffy nose

• Abdominal or stomach pain
• abnormal growth filled with fluid or semisolid material
• blemishes on the skin
• blood in the urine
• bloody nose
• burning, dry, or itching eyes
• burning or stinging of the skin
• cough producing mucus
• cramps
• diarrhea
• difficulty having a bowel movement (stool)
• discharge from the eye
• dry mouth or throat
• ear pain
• excessive tearing
• eye itch
• heavy menstrual bleeding
• muscle pain
• night sweats
• numbness or decreased sensitivity of the hand
• pain
• painful cold sores or blisters on the lips, nose, eyes, or genitals
• pimples
• redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid
• tingling sensation in the arms or legs
• vaginal yeast infection
• weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Do not run out of Xopenex.
• Do not take more of this medicine or use it more often than you have been told. Deaths have happened when too much of Xopenex was taken. Talk with your doctor.
• Call your doctor right away if your normal dose does not work well, if your signs get worse, or if you need to use this medicine more often than normal.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
• If you are 65 or older, use Xopenex with care. You could have more side effects.
• This medicine is not approved for use in children younger than 6 years of age. The chance of side effects may be raised in children younger than 6 years of age. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Use Xopenex as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Follow how to use as you have been told by the doctor or read the package insert.
• Keep out of your eyes.
• For breathing in only as a liquid (solution) by a special machine (nebulizer) into the lungs.
• Do not use if the solution is cloudy, leaking, or has particles.
• Do not use if solution changes color.
• Some of these products must be mixed with saline before use. Check with your doctor or pharmacist to see if your product needs to be mixed.
• Do not mix other drugs in nebulizer.

What do I do if I miss a dose?

• If you take this medicine on a regular basis, take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.
• Many times Xopenex is taken on an as needed basis. Do not take more often than told by the doctor.

Xopenex (levalbuterol HCl) Inhalation Solution is indicated for the treatment or prevention of bronchospasm in adults, adolescents, and children 6 years of age and older with reversible obstructive airway disease.

Xopenex Inhalation Solution is contraindicated in patients with a history of hypersensitivity to levalbuterol or racemic albuterol. Reactions have included urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema [see Warnings and Precautions (5.6)].

Carcinogenesis, Mutagenesis, Impairment of Fertility

Although there have been no carcinogenesis studies with levalbuterol HCl, racemic albuterol sulfate has been evaluated for its carcinogenic potential.

In a 2-year study in Sprague-Dawley rats, dietary administration of racemic albuterol sulfate resulted in a significant dose-related increase in the incidence of benign leiomyomas of the mesovarium at doses of 2 mg/kg/day and greater (approximately 4 times the MRDI dose of levalbuterol HCl for adults and approximately 5 times the MRDI dose of levalbuterol HCl for children on a mg/m2 basis). In an 18-month study in CD-1 mice and a 22-month study in the golden hamster, dietary administration of racemic albuterol sulfate showed no evidence of tumorigenicity. Dietary doses in CD-1 mice were up to 500 mg/kg/day (approximately 540 times the MRDI dose of levalbuterol HCl for adults and approximately 630 times the MRDI dose of levalbuterol HCl for children on a mg/m2 basis) and doses in the golden hamster study were up to 50 mg/kg/day (approximately 90 times the MRDI dose of levalbuterol HCl for adults on a mg/m2 basis and approximately 105 times the MRDI dose of levalbuterol HCl for children on a mg/m2 basis).

Levalbuterol HCl was not mutagenic in the Ames test or the CHO/HPRT Mammalian Forward Gene Mutation Assay. Levalbuterol HCl was not clastogenic in the in vivo micronucleus test in mouse bone marrow. Racemic albuterol sulfate was not clastogenic in an in vitro chromosomal aberration assay in CHO cell cultures.

No fertility studies have been conducted with levalbuterol hydrochloride. Reproduction studies in rats using racemic albuterol sulfate demonstrated no evidence of impaired fertility at oral doses up to 50 mg/kg/day (approximately 108 times the maximum recommended daily inhalation dose of levalbuterol HCl for adults on a mg/m2 basis).

See FDA-approved patient labeling (Patient Information and Instructions for Using Xopenex Inhalation Solution).

Patients should be given the following information:

Hypersensitivity

Query patients about previously experienced hypersensitivity to levalbuterol or racemic albuterol and counsel patients to report any hypersensitivity reactions to their physician.

Frequency of Use

Inform patients not to increase the dose or use Xopenex Inhalation Solution more frequently than recommended without consulting their physician. If patients find that treatment with Xopenex Inhalation Solution becomes less effective for symptomatic relief, symptoms become worse, or they need to use the product more frequently than usual, they should seek medical attention immediately.

Paradoxical Bronchospasm

Inform patients that Xopenex Inhalation Solution can produce paradoxical bronchospasm. Instruct patients to discontinue Xopenex Inhalation Solution if paradoxical bronchospasm occurs.

Concomitant Drug Use

Inform patients using Xopenex Inhalation Solution, that other inhaled drugs and asthma medications should be taken only as directed by their physician.

Common Adverse Reactions

Advise patients of the common adverse reactions of treatment with Xopenex Inhalation Solution including palpitations, chest pain, fast heart rate, headache, dizziness, tremor and nervousness.

Pregnancy

Advise patients who are pregnant or nursing to contact their physician about the use of Xopenex Inhalation Solution.

General Information on Storage and Use

Advise patients to store Xopenex Inhalation Solution in the foil pouch between 20°C to 25°C (68°F to 77°F) protected from light and excessive heat. Do not use after the expiration date stamped on the container. Store unused vials in the protective foil pouch. Once the foil pouch is opened, use the vials within 2 weeks. Use vials removed from the pouch, immediately, or protect from light and use within 1 week. Discard any vial if the solution is not colorless.

Advise patients not to mix Xopenex Inhalation Solution with other drugs in a nebulizer.

AKORN
Distributed by: Akorn, Inc.
Lake Forest, IL 60045

Manufactured for: Oak Pharmaceuticals, Inc.

For customer service, call 1-800-932-5676.
To report adverse events, call 1-800-932-5676.
For medical information, call 1-800-932-5676.

Xopenex is a registered trademark of Sunovion Pharmaceuticals Inc. and is used under license.

XP00N        January 2015
AKNX024-642R00

PATIENT INFORMATION

Xopenex®(pronounced zō-pen-eks)

(levalbuterol hydrochloride)

Inhalation Solution

0.31 mg, 0.63 mg, 1.25 mg

3 mL Unit-Dose Vials

Read this Patient Information before you start to use Xopenex Inhalation Solution and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.

What is Xopenex Inhalation Solution?

Xopenex Inhalation Solution is an inhaled prescription medicine used for the treatment or prevention of bronchospasm in people 6 years of age and older.

Xopenex Inhalation Solution has not been shown to be safe and effective in children younger than 6 years of age.

Xopenex Inhalation Solution is supplied in 3 mL unit-dose vials in three different strengths of levalbulterol (0.31 mg, 0.63 mg, 1.25 mg). The vials do not require dilution before use.

Who should not use Xopenex Inhalation Solution?

Do not use Xopenex Inhalation Solution if you are allergic to levalbuterol, racemic albuterol, or any of the ingredients in Xopenex. See the end of this leaflet for a complete list of ingredients in Xopenex Inhalation Solution.

What should I tell my doctor before using Xopenex Inhalation Solution?

Before you use Xopenex Inhalation Solution, tell your doctor if you have:

• had an allergic reaction to levalbuterol or racemic albuterol
• heart problems
• high blood pressure
• seizures
• diabetes
• thyroid problems
• any other medical conditions
• are pregnant or planning to become pregnant. It is not known if Xopenex Inhalation Solution will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.
• are breastfeeding or plan to breastfeed. It is not known if Xopenex Inhalation Solution passes into your breast milk. You and your doctor should decide if you will use Xopenex Inhalation Solution or breastfeed. You should not do both.

Tell your doctor about all the medicines you take including prescription and over-the-counter medicines, vitamins, and herbal supplements. Xopenex Inhalation Solution may affect the way other medicines work, and other medicines may affect how Xopenex Inhalation Solution works.

Especially tell your doctor if you take:

• other asthma medicines
• heart medicines
• medicines that increase urination (diuretics)
• antidepressants
• medicine to treat chronic obstructive pulmonary disease (COPD)

Ask your doctor if you are not sure if any of your medicines are the kinds listed above.

Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine.

How should I use Xopenex Inhalation Solution?

• Read the step-by-step Instructions for Using Xopenex Inhalation Solution at the end of this leaflet.
• Use Xopenex Inhalation Solution exactly as your doctor tells you to. Do not change your dose without talking to your doctor first.
• Your doctor will tell you how many times and when to use your Xopenex Inhalation Solution.
• An adult should help a child use Xopenex Inhalation Solution.
• Do not use your Xopenex Inhalation Solution more often than your doctor tells you to.
• Get medical help right away if Xopenex Inhalation Solution:
  • does not work as well for your asthma symptoms or
  • your asthma symptoms get worse or
  • you need to use your Xopenex Inhalation Solution more often than usual
• If you also use another medicine by inhalation, you should ask your doctor for instructions on when to use it while you are also using Xopenex Inhalation Solution.
• Do not mix Xopenex Inhalation Solution with other medicines in your nebulizer.
• Only use Xopenex Inhalation Solution if it is colorless. Throw away the Xopenex Inhalation Solution vial if the liquid medicine is not colorless.
• Do not use Xopenex Inhalation Solution after the expiration date on the vial.

What are the possible side effects of Xopenex Inhalation Solution?

Xopenex Inhalation Solution can cause serious side effects including:

• sudden shortness of breath (bronchospasm). Sudden shortness of breath can happen right away after using Xopenex Inhalation Solution.
• worsening asthma
• heart problems
• death. If you use too much Xopenex Inhalation Solution you can have heart or lung problems that can lead to death.
• serious allergic reactions. Call your doctor and stop using Xopenex Inhalation Solution right away if you have any symptoms of an allergic reaction such as:
  • swelling of the face, throat or tongue
  • hives
  • rash
  • breathing problems
• low potassium levels in your blood

Call your doctor or go to the nearest hospital emergency room right away if you have any of the serious side effects listed above or if you have worsening lung symptoms.

The most common side effects of Xopenex Inhalation Solution include:

• palpitations
• chest pain
• fast heart rate
• headache
• dizziness
• tremor
• nervousness

Tell your doctor if you have any side effects that bother you or that do not go away.

These are not all the possible side effects of Xopenex Inhalation Solution. For more information, ask your doctor or pharmacist.

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 Xopenex Inhalation Solution?

• Store unopened Xopenex Inhalation Solution vials in the protective foil pouch they come in between 68°F to 77°F (20°C to 25°C).
• Keep Xopenex Inhalation Solution away from light and heat.
• When a Xopenex Inhalation Solution foil pouch is opened, use the vials within 2 weeks.
• When Xopenex Inhalation Solution vials are removed from the foil pouch, use them right away or within 1 week.

Keep Xopenex Inhalation Solution and all medicines out of the reach of children.

General information about the safe and effective use of Xopenex Inhalation Solution.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Xopenex Inhalation Solution for a condition for which it was not prescribed. Do not give Xopenex Inhalation Solution 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 Xopenex Inhalation Solution. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Xopenex Inhalation Solution that is written for health professionals.

For customer service, call 1-800-932-5676.
To report adverse events, call 1-800-932-5676.
For medical information, call 1-800-932-5676.

What are the ingredients in Xopenex Inhalation Solution?

Active ingredient: levalbuterol hydrochloride

Inactive ingredients: sodium chloride, sulfuric acid, water and nitrogen

Xopenex Inhalation Solution vial (see Figure A):

Using your Xopenex Inhalation Solution:

Read the following Steps before using your Xopenex Inhalation Solution. If you have any questions, ask your doctor or pharmacist.

Step 1. Open the foil pouch by tearing the notched edge along the seam of the pouch (See Figure B). Remove 1 vial to be used right away. Keep the rest of the unused vials in the foil pouch to protect them from light and heat.

Step 2. Hold the vial in your hands. Make sure your thumb and finger cover the twist-off tabs below the X-top (See Figure C).

Step 3. While holding the top firmly between your thumb and finger, twist the body of the vial to open the vial (See Figure C).

Step 4. Throw away the top of the vial and squeeze the entire contents of the vial into the nebulizer reservoir (See Figure D).

Step 5. Connect the nebulizer reservoir to the mouthpiece (See Figure E.1) or face mask (See Figure E.2).

Step 6. Connect the nebulizer to the compressor (See Figure F).

Step 7. Sit in a comfortable, upright position. Place the mouthpiece in your mouth (See Figure G.1) or put on your face mask (See Figure G.2). Turn on the compressor.

Step 8. Breathe as calmly, deeply, and evenly as possible until no more mist is seen in the nebulizer reservoir. Your treatment will take about 5 to 15 minutes. When you do not see any mist in the nebulizer reservoir, your treatment is finished.

Step 9. Clean and store your nebulizer. See the manufacturer's instructions that come with your nebulizer for how to clean and store your nebulizer.

This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration.

AKORN
Distributed by: Akorn, Inc.
Lake Forest, IL 60045

Manufactured for: Oak Pharmaceuticals, Inc.

For customer service, call 1-800-932-5676.
To report adverse events, call 1-800-932-5676.
For medical information, call 1-800-932-5676.

Xopenex is a registered trademark of Sunovion Pharmaceuticals Inc. and is used under license.

XP00N     January 2015
AKNX024-642R00

Principal Display Panel Text for Pouch Label:

Xopenex® NDC 17478-172-12

(levalbuterol HCl)

Inhalation Solution 0.31 mg/3 mL* *Potency expressed as levalbuterol

Principal Display Panel Text for Carton Label:

NDC 17478-172-24

0.31 mg/3 mL

Xopenex®

(levalbuterol HCl) *Potency expressed as levalbuterol

Inhalation Solution For Oral Inhalation Only. Sterile Unit-Dose Vial

0.31 mg/3 mL* 24 x 3 mL Sterile Unit-Dose Vials

Rx only

Akorn Logo

Principal Display Panel Text for Pouch Label:

Xopenex® NDC 17478-173-12

(levalbuterol HCl)

Inhalation Solution 0.63 mg/3 mL* *Potency expressed as levalbuterol

Principal Display Panel Text for Carton Label:

NDC 17478-173-24

0.63 mg/3 mL

Xopenex®

(levalbuterol HCl) *Potency expressed as levalbuterol

Inhalation Solution For Oral Inhalation Only. Sterile Unit-Dose Vial

0.63 mg/3 mL* 24 x 3 mL Sterile Unit-Dose Vials

Rx only

Akorn Logo

Principal Display Panel Text for Pouch Label:

Xopenex® NDC 17478-174-12

(levalbuterol HCl)

Inhalation Solution 1.25 mg/3 mL* *Potency expressed as levalbuterol

Principal Display Panel Text for Carton Label:

NDC 17478-174-24

1.25 mg/3 mL

Xopenex®

(levalbuterol HCl) *Potency expressed as levalbuterol

Inhalation Solution For Oral Inhalation Only. Sterile Unit-Dose Vial

1.25 mg/3 mL* 24 x 3 mL Sterile Unit-Dose Vials

Rx only

Akorn Logo

You should not use Xopenex if you are allergic to levalbuterol or albuterol (Accuneb, ProAir, Proventil, Ventolin).

To make sure Xopenex is safe for you, tell your doctor if you have:

• heart disease, high blood pressure, or congestive heart failure;

• a seizure disorder;

• diabetes; or

• a thyroid disorder.

It is not known whether Xopenex will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether levalbuterol passes into breast milk or if it could affect a nursing baby. Tell your doctor if you are breast-feeding.

A Xopenex inhaler should not be given to a child younger than 4 years old. Xopenex solution in a nebulizer should not be given to a child younger than 6 years old.

Tell your doctor if you have used an MAO inhibitor in the past 14 days. MAO inhibitors include isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• any other inhaled medicines to treat asthma or COPD (chronic obstructive pulmonary disease);

• an antidepressant;

• a diuretic or "water pill"; or

• medicine to treat a heart condition.

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