Xopenex HFA (Page 4 of 4)

13.2 Animal Toxicology and/or Pharmacology

Propellant HFA-134a

In animals and humans, propellant HFA-134a was found to be rapidly absorbed and rapidly eliminated, with an elimination half-life of 3 to 27 minutes in animals and 5 to 7 minutes in humans. Time to maximum plasma concentration (tmax ) and mean residence time are both extremely short, leading to a transient appearance of HFA-134a in the blood with no evidence of accumulation. Based on studies in animals, the propellant HFA-134a had no detectable toxicological activity at amounts less than 380 times the maximum human exposure based on comparisons of AUC values. The toxicological effects observed at these very high doses included ataxia, tremors, dyspnea, or salivation, similar to effects produced by the structurally-related chlorofluorocarbons (CFCs) used in metered-dose inhalers, that were extensively used in the past.

14 CLINICAL STUDIES

14.1 Bronchospasm Associated with Asthma

Adults and Adolescent Patients 12 Years of Age and Older

The efficacy and safety of XOPENEX HFA were established in two 8-week, multicenter, randomized, double-blind, active- and placebo-controlled trials in 748 adults and adolescents with asthma between the ages of 12 and 81 years. In these two trials, XOPENEX HFA (403 patients) was compared to an HFA-134a placebo MDI (166 patients), and the trials included a marketed albuterol HFA-134a MDI (179 patients) as an active control. Serial forced expiratory volume in 1 second (FEV1 ) measurements demonstrated that 90 mcg (2 inhalations) of XOPENEX HFA produced significantly greater improvement in FEV1 over the pretreatment value than placebo. The results from one of the trials are shown in Figure 1 as the mean percent change in FEV1 from test-day baseline at Day 1 (n=445) and Day 56 (n=387). The results from the second trial were similar.

Figure 1: Percent Change in FEV 1 from Test-Day Baseline in Adults and Adolescents Aged 12 to 81 Years at Day 1 and Day 56

Figure 1
(click image for full-size original)

Figure 1
(click image for full-size original)

For XOPENEX HFA on Day 1, the median time to onset of a 15% increase in FEV1 ranged from 5.5 to 10.2 minutes and the median time to peak effect ranged from 76 to 78 minutes. In the responder population, on Day 1 the median duration of effect as measured by a 15% increase in FEV1 was 3 to 4 hours, with duration of effect in some patients of up to 6 hours.

Pediatric Patients 4 to 11 Years of Age

The efficacy and safety of XOPENEX HFA in children were established in a 4-week, multicenter, randomized, double-blind, active- and placebo-controlled trial in 150 pediatric patients with asthma between the ages of 4 and 11 years. In this trial, XOPENEX HFA (76 patients) was compared to a placebo HFA-134a MDI (35 patients), and the trial included a marketed albuterol HFA-134a MDI (39 patients) as an active control. Serial FEV1 measurements demonstrated that 90 mcg (2 inhalations) of XOPENEX HFA produced significantly greater improvement in FEV1 over the pretreatment value than placebo and were consistent with the efficacy findings in the adult studies.

For XOPENEX HFA, on Day 1 the median time to onset of a 15% increase in FEV1 was 4.5 minutes and the median time to peak effect was 77 minutes. In the responder population, the median duration of effect as measured by a 15% increase in FEV1 was 3 hours, with a duration of effect in some pediatric patients of up to 6 hours.

16 HOW SUPPLIED/STORAGE AND HANDLING

XOPENEX HFA inhalation aerosol is supplied as a pressurized aluminum canister in a box:

  • NDC 63402-510-01: Canister labeled with a net weight of 15 grams containing 200 metered actuations (or inhalations)

Each canister is fitted with a dose indicator and is supplied with a blue plastic actuator mouthpiece, a red mouthpiece cap, and patient’s instructions.

Shake well before using. Store between 20° and 25°C (68° and 77°F; see USP controlled room temperature). Protect from freezing temperatures and direct sunlight. Store inhaler with the actuator mouthpiece down.

Contents under pressure

Do not puncture or incinerate. Do not store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw container into fire or incinerator. Keep out of reach of children.

The blue actuator supplied with XOPENEX HFA should not be used with any other product canisters. Actuators from other products should not be used with a XOPENEX HFA canister. The correct amount of medication in each actuation cannot be assured after 200 actuations, even though the canister is not completely empty. When the dose indicator display window shows a red zone, approximately 20 inhalations are left, and a refill is required. The canister should be discarded when the dose indicator display window shows zero, indicating that 200 actuations have been used.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Patients should be given the following information:

Frequency of Use

The action of XOPENEX HFA should last for 4 to 6 hours. Do not use XOPENEX HFA more frequently than recommended. Instruct patients to not increase the dose or frequency of doses of XOPENEX HFA without consulting their physician. If patients find that treatment with XOPENEX HFA 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.

Priming, Cleaning and Storage

Priming: SHAKE WELL BEFORE USING. Patients should be instructed that priming XOPENEX HFA is essential to ensure appropriate levalbuterol content in each actuation. Patients should prime XOPENEX HFA before using for the first time and in cases where the inhaler has not been used for more than 3 days by releasing 4 test sprays into the air, away from the face.

Cleaning: To ensure proper dosing and prevent actuator orifice blockage, instruct patients to wash the actuator in warm water and air-dry thoroughly at least once a week. Patients should be informed that detailed cleaning instructions are included in the FDA-approved patient labeling.

Storage: Store canister between 20° and 25°C (68° and 77°F). Protect from freezing temperatures and direct sunlight.

Paradoxical Bronchospasm

Inform patients that XOPENEX HFA can produce paradoxical bronchospasm. Instruct patients to discontinue XOPENEX HFA if paradoxical bronchospasm occurs.

Concomitant Drug Use

While patients are using XOPENEX HFA, other inhaled drugs and asthma medications should be taken only as directed by the physician.

Common Adverse Reactions

Common adverse effects of treatment with inhaled beta-agonists include palpitations, chest pain, rapid heart rate, tremor, and nervousness.

Pregnancy

Patients who are pregnant or nursing should contact their physicians about the use of XOPENEX HFA.

General Information on Use

Effective and safe use of XOPENEX HFA includes an understanding of the way that it should be administered.

Shake the inhaler well immediately before each use.

Use XOPENEX HFA only with the actuator supplied with the product. When the dose indicator display window shows a red zone, approximately 20 inhalations are left, and a refill is required. Discard the inhaler when the dose indicator display window shows zero, indicating that 200 sprays have been used. Never immerse the canister in water to determine how full the canister is (“float test”).

In general, the technique for administering XOPENEX HFA to children is similar to that for adults. Children should use XOPENEX HFA under adult supervision, as instructed by the patient’s physician [advise the patient to read the FDA-approved patient labeling – (Patient Information and Instructions for Use)].

SUNOVION
Manufactured for
Sunovion Pharmaceuticals Inc.
Marlborough, MA 01752 USA

© 2017 Sunovion Pharmaceuticals Inc. All rights reserved.

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.

Revised February 2017901715R03

PATIENT INFORMATION XOPENEX HFA ® (zō-pen-eks hfa) (levalbuterol tartrate) inhalation aerosol, for oral inhalation use
What is XOPENEX HFA?
  • XOPENEX HFA is an inhaled prescription medicine used for the treatment or prevention of asthma in people 4 years of age and older.
  • XOPENEX HFA has not been shown to be safe and effective in children younger than 4 years of age.
Do not use XOPENEX HFA if you:
  • are allergic to levalbuterol, racemic albuterol or any of the ingredients in XOPENEX HFA. See the end of this Patient Information leaflet for a complete list of ingredients in XOPENEX HFA.
Before you use XOPENEX HFA, tell your doctor about all of your medical conditions, including if you:
  • have heart problems.
  • have high blood pressure.
  • have seizures.
  • have diabetes.
  • have thyroid problems.
  • are pregnant or plan to become pregnant. It is not known if XOPENEX HFA 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 HFA passes into your breast milk. Talk to your doctor about the best way to feed your baby if you use XOPENEX HFA.
Tell your doctor about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. XOPENEX HFA may affect the way other medicines work, and other medicines may affect how XOPENEX HFA works.Especially tell your doctor if you take:
  • other inhaled medicines or asthma medicines
  • heart medicines
  • medicines that increase urination (diuretics)
  • antidepressants
  • medicine to treat chronic obstructive pulmonary disease (COPD). Ask your doctor 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 doctor and pharmacist when you get a new medicine.
How should I use XOPENEX HFA?
  • Read the step-by-step Instructions for Use for XOPENEX HFA at the end of this Patient Information leaflet.
  • XOPENEX HFA is for oral inhalation use only.
  • Use XOPENEX HFA 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 HFA.
  • An adult should help a child use XOPENEX HFA. Your doctor should show you how your child should use XOPENEX HFA.
  • Do not use your XOPENEX HFA more often than your doctor tells you to.
  • Get medical help right away if XOPENEX HFA:
    • does not work as well for your asthma symptoms
    • your asthma symptoms get worse
    • you need to use XOPENEX HFA more often than usual
  • While you are using XOPENEX HFA, do not use other inhaled medicines and asthma medicines unless your doctor tells you to.
What are the possible side effects of XOPENEX HFA? XOPENEX HFA can cause serious side effects including:
  • sudden shortness of breath (bronchospasm). Sudden shortness of breath can happen right away after using XOPENEX HFA.
  • worsening asthma.
  • heart problems.
  • death. If you use too much XOPENEX HFA you can have heart or lung problems that can lead to death.
  • serious allergic reactions. Call your doctor and stop using XOPENEX HFA 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 HFA include:
  • accidental injury
  • bronchitis
  • dizziness
  • pain
  • sore throat
  • runny nose
  • vomiting
  • palpitations
  • chest pain
  • fast heart rate
  • tremors
  • nervousness
These are not all the possible side effects of XOPENEX HFA.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.You may also report side effects to Sunovion Pharmaceuticals Inc. at 1-877-737-7226.
How should I store XOPENEX HFA?
  • Store XOPENEX HFA at room temperature between 68°F to 77°F (20°C to 25°C).
  • Do not use or store XOPENEX HFA inhaler near heat or open flame. Temperatures above 120°F may cause the canister to burst.
  • Do not freeze XOPENEX HFA.
  • Keep XOPENEX HFA out of direct sunlight.
  • Do not put a hole in the XOPENEX HFA canister.
  • Store XOPENEX HFA with the mouthpiece down.
  • Throw away XOPENEX HFA when the dose indicator display window reaches zero “0”, showing that all 200 sprays (actuations) have been used.
  • Do not throw XOPENEX HFA into a fire or an incinerator.
Keep XOPENEX HFA and all medicines out of the reach of children.
General information about the safe and effective use of XOPENEX HFA Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use XOPENEX HFA for a condition for which it was not prescribed. Do not give XOPENEX HFA to other people, even if they have the same symptoms that you have. It may harm them.You can ask your pharmacist or doctor for information about XOPENEX HFA that is written for health professionals.
What are the ingredients in XOPENEX HFA? Active ingredient: levalbuterol tartrateInactive ingredients: propellant HFA-134a, Dehydrated Alcohol USP, Oleic Acid NF

Instructions for Use

XOPENEX HFA ® (zō-pen-eks hfa)

(levalbuterol tartrate)

inhalation aerosol, for oral inhalation use

Important Information:

  • For oral inhalation use only
  • Use XOPENEX HFA exactly as your doctor tells you to.
  • If you have any questions about the use of your inhaler, ask your doctor or pharmacist.

The parts of your XOPENEX HFA inhaler (See Figure 1):

Figure 1
(click image for full-size original)

Figure 1

  • XOPENEX HFA comes as a canister that fits into an actuator with a dose indicator.
    • Do not use the XOPENEX HFA actuator with a canister of medicine from any other inhaler.
    • Do not use the XOPENEX HFA canister with an actuator from any other inhaler.
  • The dose indicator display window will show you how many sprays of medicine you have left in your inhaler. A spray of medicine is released each time you press down on the center of the dose indicator.
  • It is important that you pay attention to the number of sprays left in your XOPENEX HFA inhaler by reading the dose indicator. You should also keep track of the number of sprays used from your inhaler.

Each canister of XOPENEX HFA contains enough medicine for you to spray your medicine 200 times (See Figure 2a).

  • The pointer will be pointing between 180 and 200 after you take 10 sprays. This means that there are 190 sprays of medicine left in the canister (See Figure 2b).
  • The pointer will be pointing to 180 after you take 10 more sprays. This means that there are 180 sprays of medicine left in the canister (See Figure 2c).
Figure 2a
Figure 2b
Figure 2c
Figure 2a Figure 2b Figure 2c
200 sprays 190 sprays 180 sprays
  • The dose indicator display window will continue to move after every 10 sprays. The number on the dose indicator display window will continue to change after every 20 sprays.
Figure 2d

Figure 2d

  • The dose indicator display window will change to red, as shown in the shaded area, when there are only 20 sprays of medicine left in your inhaler (See Figure 2d). You should refill your prescription or ask your doctor if you need another prescription for XOPENEX HFA.
  • When the number in the dose indicator display window reaches zero “0”, this means that 200 sprays of medicine have been used. Throw away your XOPENEX HFA inhaler.

Note: Do not place the canister under water to find out the amount of medicine left in the canister.

Preparing your XOPENEX HFA inhaler for use:

  • Your XOPENEX HFA inhaler should be at room temperature before you use it.
  • Shake the inhaler well before each use.

Priming your XOPENEX HFA inhaler:

Before you use XOPENEX HFA for the first time or if you have not taken your medicine for 3 days in a row, you must prime the inhaler.

  • Look at the dose indicator on top of the inhaler. Make sure that the pointer on the dose indicator is pointing to the “200” inhalation mark before you use your XOPENEX HFA inhaler for the first time.
  • Take the cap off the mouthpiece of the actuator (See Figure 3). Check inside the mouthpiece for objects before use.
Figure 3

Figure 3

  • Hold the inhaler in the upright position away from the face and shake the inhaler well (See Figure 4).
Figure 4

Figure 4

  • Press down fully on the center of the dose indicator to release a spray of medicine from the mouthpiece (See Figure 5). You may hear a soft click from the dose indicator as it counts down during use.
Figure 5
(click image for full-size original)

Figure 5

  • Avoid spraying in your eyes.
  • Repeat the priming steps 3 more times (See Figure 4 and Figure 5) to finish priming the inhaler.
  • After priming 4 times the first time you use your XOPENEX HFA inhaler, the dose indicator should be pointing to “200” and your inhaler is now ready to use.

If you do not use your XOPENEX HFA inhaler for more than 3 days, you will need to prime the inhaler again before use.

Using your XOPENEX HFA inhaler:

Step 1: Take the cap off the mouthpiece of the actuator (See Figure 3). Check inside the mouthpiece for objects. Make sure the canister fits firmly in the actuator.

Step 2: Shake the inhaler well for 5 seconds before use.

Step 3: Hold the inhaler upright with the mouthpiece pointing towards you. Before you put the mouthpiece in your mouth, breathe out through your mouth and push out as much air from your lungs as you can (See Figure 6).

Figure 6
(click image for full-size original)

Figure 6

Step 4: Put the mouthpiece in your mouth and close your lips around it.

Figure 7
(click image for full-size original)

Figure 7

Step 5: While breathing in deeply and slowly, press down on the center of the targeting rings (See Figure 7) until a spray of medicine has been released. Then stop pressing the dose indicator.

Step 6: When you have finished breathing in, remove the mouthpiece from your mouth. Close your mouth and hold your breath for 10 seconds if possible. Then breathe out gently.

Step 7: Wait about 1 minute, then shake the inhaler well. Repeat steps 3 through 6 to take your second spray of XOPENEX HFA.

Step 8: Put the cap back on the mouthpiece right away after use.

Make sure the cap snaps firmly into place.

Cleaning your XOPENEX HFA inhaler:

Figure 8

Figure 8

Clean the inhaler 1 time each week. It is very important to keep the actuator clean so that medicine will not build up and block the spray from the mouthpiece (See Figure 8).

To clean the actuator:

Step 1: Take the canister out of the actuator (See Figure 9). Do not clean the canister or let it get wet.

Figure 9
(click image for full-size original)

Figure 9

Step 2: Take the cap off the mouthpiece.

Step 3: Hold the actuator under the faucet and run warm water through it for at least 30 seconds. Turn the actuator upside down and rinse the actuator again through the mouthpiece for at least 30 seconds (See Figure 10).

Figure 10
(click image for full-size original)

Figure 10

Step 4: Shake off as much water from the actuator as you can.

Step 5: Look inside the actuator and mouthpiece to make sure any medicine build-up has been completely washed away. Medicine build-up is more likely to happen if the actuator is not allowed to air-dry completely.

Step 6: Let the actuator air-dry overnight. Do not put the canister back into the actuator if it is still wet.

Step 7: When the actuator is dry, put the canister back in the actuator and put the cap back on the mouthpiece. Make sure to firmly press the canister down in the actuator.

Note: If your actuator becomes blocked, it means that little or no medicine is coming out of the mouthpiece (See Figure 11). Repeat Steps 1 through 7 above in the section “To clean the actuator”.

Figure 11
(click image for full-size original)

Figure 11

If you need to use your inhaler before the plastic actuator is completely dry:

  • Shake off as much water from the actuator as you can.
  • Put the canister back into the actuator and shake the inhaler well.
  • To remove most of the water from your inhaler, press down on the center of the targeting rings 2 times to release a total of 2 sprays into the air away from your face.
  • Take your prescribed dose of medicine.
  • Repeat Steps 1 through 7 above in the section “To clean the actuator.

How should I store XOPENEX HFA?

  • Store XOPENEX HFA at room temperature between 68°F to 77°F (20°C to 25°C).
  • Do not use or store XOPENEX HFA inhaler near heat or open flame. Temperatures above 120°F may cause the canister to burst.
  • Do not freeze XOPENEX HFA.
  • Keep XOPENEX HFA out of direct sunlight.
  • Do not put a hole in the XOPENEX HFA canister.
  • Store XOPENEX HFA with the mouthpiece down.
  • Throw away XOPENEX HFA when the dose indicator display window reaches zero “0”, showing that all 200 sprays (actuations) have been used.
  • Do not throw XOPENEX HFA into a fire or incinerator.

Keep XOPENEX HFA and all medicines out of the reach of children.

For more information, go to www.XOPENEX.com.

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

SUNOVION
Manufactured for
Sunovion Pharmaceuticals Inc.
Marlborough, MA 01752 USA

© 2017 Sunovion Pharmaceuticals Inc. All rights reserved.

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.

Revised February 2017901715R03

PRINCIPAL DISPLAY PANEL – TRADE CANISTER LABEL – 45 MCG 200 ACTUATIONS

NDC 63402-510-01 Net Contents: 15 g

Xopenex HFA®

(levalbuterol tartrate)

Inhalation Aerosol

45 mcg/actuation

200 Metered Inhalations

FOR ORAL INHALATION WITH Xopenex HFA® ACTUATOR ONLY

Shake well before using.

Rx only

SUNOVION

PRINCIPAL DISPLAY PANEL – TRADE CANISTER LABEL – 45 MCG 200 ACTUATIONS
(click image for full-size original)

PRINCIPAL DISPLAY PANEL – TRADE CARTON — 45 MCG 200 ACTUATIONS

NDC 63402-510-01 Net Contents: 15g

Xopenex HFA®

(levalbuterol tartrate)

Inhalation Aerosol

45 mcg/actuation

200 Metered Inhalations

FOR ORAL INHALATION WITH Xopenex HFA® ACTUATOR ONLY

Shake well before using.

Rx only

SUNOVION

PRINCIPAL DISPLAY PANEL – TRADE CARTON -- 45 MCG 200 ACTUATIONS
(click image for full-size original)
XOPENEX HFA levalbuterol tartrate aerosol, metered
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:63402-510
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
levalbuterol tartrate (levalbuterol) levalbuterol 45 ug
Inactive Ingredients
Ingredient Name Strength
norflurane
alcohol
Oleic Acid
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:63402-510-01 1 INHALER in 1 CARTON contains a INHALER
1 200 AEROSOL, METERED in 1 INHALER This package is contained within the CARTON (63402-510-01)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA021730 12/01/2005
Labeler — Sunovion Pharmaceuticals Inc. (131661746)

Revised: 06/2020 Sunovion Pharmaceuticals Inc.

Page 4 of 4 1 2 3 4

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.