Albuterol Sulfate: Package Insert and Label Information (Page 3 of 4)

13.2 Animal Toxicology and/or Pharmacology

Preclinical

Intravenous studies in rats with albuterol sulfate have demonstrated that albuterol crosses the blood-brain barrier and reaches brain concentrations amounting to approximately 5% of the plasma concentrations. In structures outside the blood-brain barrier (pineal and pituitary glands), albuterol concentrations were found to be 100 times those in the whole brain.

Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when β-agonists and methylxanthines were administered concurrently. The clinical significance of these findings is unknown.

Propellant HFA-134a is devoid of pharmacological activity except at very high doses in animals (380 to 1300 times the maximum human exposure based on comparisons of AUC values), primarily producing ataxia, tremors, dyspnea, or salivation. These are similar to effects produced by the structurally related chlorofluorocarbons (CFCs), which have been used extensively in metered-dose inhalers.

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 (T_max ) and mean residence time are both extremely short leading to a transient appearance of HFA-134a in the blood with no evidence of accumulation.

14 CLINICAL STUDIES

14.1 Bronchospasm Associated with Asthma

Adult and Adolescent Patients 12 Years of Age and Older

In a 6-week, randomized, double-blind, placebo-controlled trial, albuterol sulfate (58 patients) was compared to a matched placebo HFA inhalation aerosol (58 patients) in asthmatic patients 12 to 76 years of age at a dose of 180 mcg albuterol four times daily. An evaluator-blind marketed active comparator HFA-134a albuterol inhaler arm (56 patients) was included.

Serial FEV₁ measurements, shown below as percent change from test-day baseline at Day 1 and at Day 43, demonstrated that two inhalations of albuterol sulfate produced significantly greater improvement in FEV₁ over the pre-treatment value than the matched placebo, as well as a comparable bronchodilator effect to the marketed active comparator HFA-134a albuterol inhaler.

FEV₁ as Mean Percent Change from Test-Day Pre-Dose in a

6-Week Clinical Trial

Day 1

Day 43

In this study, 31 of 58 patients treated with albuterol sulfate inhalation aerosol achieved a 15% increase in FEV₁ within 30 minutes post-dose on Day 1. In these patients, the median time to onset, median time to peak effect, and median duration of effect were 8.2 minutes, 47 minutes, and approximately 3 hours, respectively. In some patients, the duration of effect was as long as 6 hours.

In a placebo-controlled, single-dose, crossover study, albuterol sulfate inhalation aerosol, administered at albuterol doses of 90, 180 and 270 mcg, produced bronchodilator responses significantly greater than those observed with a matched placebo HFA inhalation aerosol and comparable to a marketed active comparator HFA-134a albuterol inhaler.

Pediatric Patients 4 to 11 Years of Age

In a 3-week, randomized, double-blind, placebo- controlled trial, the same formulation of albuterol as in albuterol sulfate inhalation aerosol (50 patients) was compared to a matched placebo HFA inhalation aerosol (45 patients) in asthmatic children 4 to 11 years of age at a dose of 180 mcg albuterol four times daily. Serial FEV₁ measurements, expressed as the maximum percent change from test-day baseline in percent predicted FEV₁ at Day 1 and at Day 22 observed within two hours post-dose, demonstrated that two inhalations of HFA albuterol sulfate produced significantly greater improvement in FEV₁ over the pre-treatment value than the matched placebo.

In this study, 21 of 50 pediatric patients treated with the same formulation of albuterol as in albuterol sulfate inhalation aerosol achieved a 15% increase in FEV₁ within 30 minutes post-dose on Day 1. In these patients, the median time to onset, median time to peak effect and median duration of effect were 10 minutes, 31 minutes, and approximately 4 hours, respectively. In some pediatric patients, the duration of effect was as long as 6 hours.

In a placebo-controlled, single-dose, crossover study in 55 pediatric patients 4 to 11 years of age, albuterol sulfate inhalation aerosol, administered at albuterol doses of 90 and 180 mcg, was compared with a matched placebo HFA inhalation aerosol. Serial FEV₁ measurements, expressed as the baseline-adjusted percent predicted FEV₁ observed over 6 hours post-dose, demonstrated that one and two inhalations of albuterol sulfate inhalation aerosol produced significantly greater bronchodilator responses than the matched placebo.

14.2 Exercise-Induced Bronchospasm

In a randomized, single-dose, crossover study in 24 adults and adolescents with exercise-induced bronchospasm (EIB), two inhalations of albuterol sulfate inhalation aerosol taken 30 minutes before exercise prevented EIB for the hour following exercise (defined as maintenance of FEV₁ within 80% of post-dose, pre-exercise baseline values) in 83% (20 of 24) of patients as compared to 25% (6 of 24) of patients when they received placebo.

Some patients who participated in these clinical trials were using concomitant steroid therapy.

16 HOW SUPPLIED/STORAGE AND HANDLING

Albuterol sulfate inhalation aerosol is supplied as a pressurized aluminum canister with a blue plastic actuator with a dose indicator and green dust cap each in boxes of one. Each canister contains 8.5 g of the formulation and provides 200 actuations (NDC 71205-732-85). Each actuation delivers 120 mcg of albuterol sulfate from the canister valve and 108 mcg of albuterol sulfate from the actuator mouthpiece (equivalent to 90 mcg of albuterol base).

SHAKE WELL BEFORE USE. Store between 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature.] Contents under pressure. Do not puncture or incinerate. Protect from freezing temperatures and prolonged exposure to direct sunlight. Exposure to temperatures above 120^o F may cause bursting. For best results, canister should be at room temperature before use. Avoid spraying in eyes. Keep out of reach of children.

See FDA-Approved Patient Labeling (17.9) for priming and cleaning instructions.

The blue actuator supplied with albuterol sulfate inhalation aerosol should not be used with the canister from any other inhalation aerosol products. The albuterol sulfate inhalation aerosol canister should not be used with the actuator from any other inhalation aerosol products.

Albuterol sulfate inhalation aerosol has a dose indicator attached to the actuator. Patients should never try to alter the numbers for the dose indicator or tamper with the dose indicator button mechanism. Discard the albuterol sulfate inhalation aerosol when the indicator displays 0 or after the expiration date on the product, whichever comes first. The labeled amount of medication in each actuation cannot be assured after the indicator displays 0, even though the canister is not completely empty and will continue to operate. Never immerse the canister into water to determine how full the canister is (“float test”).

Albuterol sulfate inhalation aerosol does not contain chlorofluorocarbons (CFCs) as the propellant.

17 PATIENT COUNSELING INFORMATION

See FDA-Approved Patient Labeling (17.9)

Patients should be given the following information:

17.1 Frequency of Use

The action of albuterol sulfate inhalation aerosol should last for 4 to 6 hours. Do not use albuterol sulfate inhalation aerosol more frequently than recommended. Instruct patients to not increase the dose or frequency of doses of albuterol sulfate inhalation aerosol without consulting the physician. If patients find that treatment with albuterol sulfate inhalation aerosol becomes less effective for symptomatic relief, symptoms become worse, and/or they need to use the product more frequently than usual, they should seek medical attention immediately.

17.2 Priming and Cleaning

Priming

Priming is essential to ensure appropriate albuterol content in each actuation.

Instruct patients to prime the inhaler before using for the first time and in cases where the inhaler has not been used for more than 2 weeks by releasing three sprays into the air, away from the face.

Cleaning

To ensure proper dosing and prevent actuator orifice blockage, instruct patients to wash the blue plastic actuator mouthpiece and dry thoroughly at least once a week. Instruct patients that if they have more than one albuterol sulfate inhaler, they should wash each one at separate times to prevent attaching the wrong canister to the wrong plastic actuator. In this way, they can be sure they will always know the correct number of remaining doses. Patients should be instructed to never attach a canister of medicine from any other inhaler to the albuterol sulfate inhalation aerosol actuator and never attach the albuterol sulfate inhalation aerosol canister to an actuator from any other inhaler. Patients should not remove the canister from the actuator except during cleaning because reattachment may release a dose into the air and the dose indicator will typically rotate during every 5 to 7 actuations (sprays) towards the next decreasing number. Detailed cleaning instructions are included in the illustrated Information for the Patient leaflet.

17.3 Dose Indicator

Patients should be informed that albuterol sulfate inhalation aerosol has a dose indicator attached to the actuator. When the patient receives the inhaler, new inhaler first shows “200” in the dose indicator window. The dose indicator will show the approximate number of actuations (sprays) of medicine remaining in the inhaler. As you use the inhaler, the dose indicator will typically rotate during every 5 to 7 actuations (sprays) towards the next decreasing number. The dose-indicator window displays the number of sprays left in the inhaler in units of twenty (e.g., 200, 180, 160, etc). When the dose indicator displays “40,” where the background changes from white to red to remind the patient to contact their pharmacist for a refill of medication or consult their physician for a prescription refill. The background color will be all red when the indicator approaches 20. The indicator will stop moving at “0”. Discard the inhaler once the dose indicator displays “0”. Patients should be informed to discard albuterol sulfate inhalation aerosol inhaler when the dose indicator displays 0 or after the expiration date on the product, whichever comes first.

17.4 Paradoxical Bronchospasm

Inform patients that albuterol sulfate inhalation aerosol can produce paradoxical bronchospasm. Instruct patients to discontinue albuterol sulfate inhalation aerosol if paradoxical bronchospasm occurs.

17.5 Concomitant Drug Use

While patients are taking albuterol sulfate inhalation aerosol, other inhaled drugs and asthma medications should be taken only as directed by a physician.

17.6 Common Adverse Events

Common adverse effects of treatment with inhaled albuterol include palpitations, chest pain, rapid heart rate, tremor, or nervousness.

17.7 Pregnancy

Patients who are pregnant or nursing should contact their physician about the use of albuterol sulfate inhalation aerosol.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to asthma medications during pregnancy [see USE IN SPECIFIC POPULATIONS (8.1)].

17.8 General Information on Use

Effective and safe use of albuterol sulfate inhalation aerosol includes an understanding of the way that it should be administered.

Shake well before each spray.

Use albuterol sulfate inhalation aerosol only with the actuator supplied with the product. Discard the albuterol sulfate inhalation aerosol inhaler when the dose indicator displays 0 or after the expiration date on the product, whichever comes first. Never immerse the canister in water to determine how full the canister is (“float test”).

In general, the technique for administering albuterol sulfate inhalation aerosol to children is similar to that for adults. Children should use albuterol sulfate inhalation aerosol under adult supervision, as instructed by the patient’s physician.

17.9 FDA-Approved Patient Labeling

See tear-off illustrated Information for the Patient leaflet.

Manufactured for:

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States

Manufactured by:

Lupin Limited

Pithampur (M.P.) — 454 775

India

Relabeled by:

Proficient Rx LP

Thousand Oaks, CA 91320

Revised: August 2021

Attention Pharmacist: Detach Patient’s Instructions for use from package insert and dispense with the product.

Patient Information

Albuterol Sulfate (al bue’ ter ol) (sul’ fate)

Inhalation Aerosol

Read this Patient Information before you start using albuterol sulfate inhalation aerosol and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

What is albuterol sulfate inhalation aerosol?

Albuterol sulfate inhalation aerosol is a prescription medicine used in people 4 years of age and older to:

• treat or prevent bronchospasm in people who have reversible obstructive airway disease

• prevent exercise induced bronchospasm

It is not known if albuterol sulfate inhalation aerosol is safe and effective in children under 4 years of age.

Who should not use albuterol sulfate inhalation aerosol?

Do not use albuterol sulfate inhalation aerosol if you are allergic to albuterol sulfate or any of the ingredients in albuterol sulfate inhalation aerosol. See the end of this leaflet for a complete list of ingredients in albuterol sulfate inhalation aerosol.

What should I tell my doctor before I use albuterol sulfate inhalation aerosol? Before you use albuterol sulfate inhalation aerosol, tell your doctor if you:

• have heart problems

• have high blood pressure (hypertension)

• have convulsions (seizures)

• have thyroid problems

• have diabetes

• have low potassium levels in your blood

• are pregnant or plan to become pregnant. It is not known if albuterol sulfate inhalation aerosol 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 albuterol sulfate passes into your breast milk. Talk to your doctor about the best way to feed your baby if you are using albuterol sulfate inhalation aerosol.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Albuterol sulfate inhalation aerosol and other medicines may affect each other and cause side effects. Albuterol sulfate inhalation aerosol may affect the way other medicines work, and other medicines may affect the way albuterol sulfate inhalation aerosol works.

Especially tell your doctor if you take:

• other inhaled medicines or asthma medicines

• beta blocker medicines

• diuretics

• digoxin

• monoamine oxidase inhibitors

• tricyclic antidepressants

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 albuterol sulfate inhalation aerosol?

• For detailed instructions, see “Instructions for Use ” at the end of this Patient Information.

• Use albuterol sulfate inhalation aerosol exactly as your doctor tells you to use it.

• If your child needs to use albuterol sulfate inhalation aerosol, watch your child closely to make sure your child uses the inhaler correctly. Your doctor will show you how your child should use albuterol sulfate inhalation aerosol.

• Each dose of albuterol sulfate inhalation aerosol should last up to 4 hours to 6 hours.

• Do not increase your dose or take extra doses of albuterol sulfate inhalation aerosol without first talking to your doctor.

• Get medical help right away if albuterol sulfate inhalation aerosol no longer helps your symptoms.

• Get medical help right away if your symptoms get worse or if you need to use your inhaler more often.

• While you are using albuterol sulfate inhalation aerosol, do not use other inhaled rescue medicines and asthma medicines unless your doctor tells you to do so.

• Call your doctor if your asthma symptoms like wheezing and trouble breathing become worse over a few hours or days. Your doctor may need to give you another medicine (for example, corticosteroids) to treat your symptoms.

What are the possible side effects of albuterol sulfate inhalation aerosol?

Albuterol sulfate inhalation aerosol may cause serious side effects, including:

• worsening trouble breathing, coughing and wheezing (paradoxical bronchospasm). If this happens stop using albuterol sulfate inhalation aerosol and call your doctor or get emergency help right away. Paradoxical bronchospasm is more likely to happen with your first use of a new canister of medicine.

• heart problems including faster heart rate and higher blood pressure

• possible death in people with asthma who use too much albuterol sulfate inhalation aerosol

• allergic reactions. Call your doctor right away if you have the following symptoms of an allergic reaction:

o itchy skin

o swelling beneath your skin or in your throat

o rash

o worsening trouble breathing

• low potassium levels in your blood

• worsening of other medical problems in people who also use albuterol sulfate inhalation aerosol including increases in blood sugar

The most common side effects of albuterol sulfate inhalation aerosol include:

• your heart feels like it is pounding or racing (palpitations)

• chest pain

• fast heart rate

• shakiness

• nervousness

• headache

• dizziness

• sore throat

• runny nose

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all of the possible side effects of albuterol sulfate inhalation aerosol. 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 albuterol sulfate inhalation aerosol?

• Store albuterol sulfate inhalation aerosol at room temperature between 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature.]

• Avoid exposure to extreme heat and cold.

• Shake the albuterol sulfate inhalation aerosol canister well before use.

• Do not puncture the albuterol sulfate inhalation aerosol canister.

• Do not store the albuterol sulfate inhalation aerosol canister near heat or a flame. Temperatures above 120° F may cause the canister to burst.

• Do not throw the albuterol sulfate inhalation aerosol canister into a fire or an incinerator.

• Avoid spraying albuterol sulfate inhalation aerosol in your eyes.

Keep albuterol sulfate inhalation aerosol and all medicines out of the reach of children. General Information about the safe and effective use of albuterol sulfate inhalation aerosol

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use albuterol sulfate inhalation aerosol for a condition for which it was not prescribed. Do not give albuterol sulfate inhalation aerosol to other people, even if they have the same symptoms that you have. It may harm them.

This Patient Information summarizes the most important information about albuterol sulfate inhalation aerosol. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about albuterol sulfate inhalation aerosol that is written for health professionals.

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

Instructions for Use

Albuterol Sulfate (al bue’ter ol) (sul’fate)

Inhalation Aerosol

Read this Instructions for Use before you start using albuterol sulfate inhalation aerosol and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

The Parts of Your Albuterol Sulfate inhalation aerosol Inhaler Device:

There are 2 main parts of your albuterol sulfate inhalation aerosol inhaler device including a:

• blue plastic actuator that sprays the medicine from the canister. See Figure A.

• protective green color dust cap that covers the mouthpiece of the actuator. See Figure A.

There is also a metal canister that holds the medicine. See Figure A.

There is also a dose indicator attached around the valve sitting of the actuator with a viewing window that shows you approximately how many sprays of medicine you have left. See Figure B.

You will see the number “200” in the dose indicator window on the actuator. See Figure B. The dose indicator will show the approximate number of actuations (sprays) of medicine remaining in the inhaler. Before you use the inhaler you will need to prime it first. See “Priming Your Albuterol Sulfate Inhalation Aerosol Device ” below.

Figure A

Figure B

Do not use the albuterol sulfate inhalation aerosol actuator with a canister of medicine from any other inhaler.

Do not use an albuterol sulfate inhalation aerosol canister with an actuator from any other inhaler, including another albuterol sulfate inhalation aerosol inhaler.

Priming Your Albuterol Sulfate Inhalation Aerosol Device:

Your albuterol sulfate inhalation aerosol device must be primed before you use it for the first time or if your device has not been used for more than 14 days in a row. Do not prime your albuterol sulfate inhalation aerosol device every day.

• Remove your albuterol sulfate inhalation aerosol device from its package.

• Remove the protective dust cap from the mouthpiece.

• Shake the inhaler well, and spray it into the air away from your face. See Figure C.

Figure C

• Shake and spray the inhaler like this 2 more times to finish priming it. The dose indicator on the actuator should show the number “200” after you prime the inhaler for the first time. See Figure D.

Figure D

Each Time You Use Your Albuterol Sulfate Inhalation Aerosol Device:

• Make sure the canister fits firmly in the plastic actuator.

• Look into the mouthpiece to make sure there are no foreign objects there, especially if the cap has not been used to cover the mouthpiece.

Reading the Dose Indicator on Your Albuterol Sulfate Inhalation Aerosol Actuator:

• The dose indicator will count down each time a spray is released. The dose-indicator window will show the number of sprays left in the inhaler in units of 20 sprays. For example, during every 5 to 7 sprays the dose indicator will count down by 20 towards the next decreasing number. See Figure E.

• When the dose indicator reaches “0”, it will stop moving. Throw away (discard) the inhaler when the dose indicator shows “0” and replace your Albuterol Sulfate Inhalation Aerosol device.

• The dose indicator cannot be reset and is permanently attached to the actuator. Do not change the numbers for the dose indicator.

• Do not remove the canister from the plastic actuator except during cleaning. Reattaching the canister to the actuator may accidently release a dose of albuterol sulfate inhalation aerosol into the air.

Figure E

Using Your Albuterol Sulfate Inhalation Aerosol Device:

Step 1. Shake the inhaler well before each spray. Take the cap off the mouthpiece of the actuator.

Step 2. Hold the inhaler with the mouthpiece down. See Figure F.

Figure F

Step 3. Breathe out through your mouth and push as much air from your lungs as you can. Put the mouthpiece in your mouth and close your lips around it. See Figure G.

Step 4. Push the top of the canister all the way down while you breathe in deeply and slowly through your mouth. See Figure G.

Figure G

Step 5. Right after the spray comes out, take your finger off the canister. After you have breathed in all the way, take the inhaler out of your mouth and close your mouth.

Step 6. Hold your breath as long as you can , up to 10 seconds, then breathe normally.

If your doctor has told you to use more sprays , wait 1 minute and shake the inhaler again. Repeat Steps 2 through Step 6.

Step 7. Put the cap back on the mouthpiece after every time you use the inhaler.

Make sure the cap snaps firmly into place.

Cleaning Your Albuterol Sulfate Inhalation Aerosol Device:

It is very important to keep the plastic actuator clean so the medicine will not build-up and block the spray. See Figure H and Figure I.

Figure H

Figure I

• Do not try to clean the metal canister or let it get wet. The inhaler may stop spraying if it is not cleaned correctly.

• If you have more than 1 albuterol sulfate inhalation aerosol inhaler, wash each device at separate times to prevent putting the wrong canister together with the wrong plastic actuator. This way you can be sure you will always know the correct number of remaining doses of albuterol sulfate inhalation aerosol.

• Wash the actuator at least 1 time each week as follows:

o Take the canister out of the actuator, and take the cap off the mouthpiece.

o Hold the actuator under the faucet and run warm water through it for about 30 seconds. See Figure J.

Figure J

o Turn the actuator upside down and run warm water through the mouthpiece for about 30 seconds. See Figure K.

Figure K

o Shake off as much water from the actuator as you can. Look into the mouthpiece to make sure any medicine build-up has been completely washed away. If there is any build-up, repeat the washing instructions.

o Let the actuator air-dry completely, such as overnight. See Figure L.

Figure L

o When the actuator is dry, put the canister in the actuator and make sure it fits firmly. Shake the inhaler well and spray it twice into the air away from your face. Put the cap back on the mouthpiece.

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

• Shake as much water off the actuator as you can.

• Put the canister in the actuator and make sure it fits firmly.

• Shake the inhaler well and spray it twice into the air away from your face.

• Take your albuterol sulfate inhalation aerosol dose as prescribed.

• Follow the Cleaning Instructions above.

Replacing Your Albuterol Sulfate Inhalation Aerosol Device

• There are approximately 40 sprays left when the dose indicator shows the number “40,” and the background color changes from white to red. See Figure M.

o The red background will remind you to refill your prescription or ask your doctor for another prescription for albuterol sulfate inhalation aerosol.

o The background color will be all red when the dose indicator approaches “20”.

o The dose indicator will stop moving at “0”. Throw away (discard) the inhaler once the dose indicator displays “0” See Figure N.

Figure M

Figure N

• Throw the albuterol sulfate inhalation aerosol inhaler away as soon as the dose indicator says “0” or after the expiration date on the albuterol sulfate inhalation aerosol packaging, whichever comes first. You should not keep using the inhaler after 200 sprays even though the canister may not be completely empty. You cannot be sure you will receive any medicine in each actuation (spray) once the dose indicator displays “0”.

• Do not use the inhaler after the expiration date on the albuterol sulfate inhalation aerosol packaging.

For more information about Albuterol Sulfate Inhalation Aerosol Device go to https://lupin.com/albuterol or call Lupin Pharmaceuticals, Inc. at 1-800-399-2561.

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

Manufactured for:

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States

Manufactured by:

Lupin Limited

Pithampur — (M.P.) — 454 775

India

Relabeled by:

Proficient Rx LP

Thousand Oaks, CA 91320

Revised: August 2021 ID# 268593