FDA package insert

HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
PROAIR HFA safely and effectively. See full prescribing information for
PROAIR HFA Inhalation Aerosol
PROAIR HFA (albuterol sulfate) INHALATION AEROSOL
Initial U.S. Approval: 1981

----------------------------INDICATIONS AND USAGE--------------------------PROAIR HFA Inhalation Aerosol is a beta2-adrenergic agonist indicated for:
•
Treatment or prevention of bronchospasm in patients 4 years of age and
older with reversible obstructive airway disease. (1.1)
•
Prevention of exercise-induced bronchospasm in patients 4 years of age
and older. (1.2)
----------------------DOSAGE AND ADMINISTRATION----------------------For oral inhalation only
•
Treatment or prevention of bronchospasm in adults and children 4 years
of age and older: 2 inhalations every 4 to 6 hours. In some patients, one
inhalation every 4 hours may be sufficient. (2.1)
•
Prevention of exercise-induced bronchospasm in adults and children 4
years of age and older: 2 inhalations 15 to 30 minutes before exercise.
(2.2)
•
Priming information: Prime PROAIR HFA before using for the first
time, or when the inhaler has not been used for more than 2 weeks. To
prime PROAIR HFA, release 3 sprays into the air away from the face.
Shake well before each spray. (2.3)
•
Cleaning information: At least once a week, wash the actuator with
warm water, shake off excess, and air dry thoroughly. (2.3)
•
PROAIR HFA inhaler should be discarded when the dose counter
displays 0 or after the expiration date on the product, whichever comes
first. (2.3)
---------------------DOSAGE FORMS AND STRENGTHS---------------------Inhalation Aerosol: Each actuation delivers 108 mcg of albuterol sulfate from
the actuator mouthpiece (equivalent to 90 mcg of albuterol base). Supplied in
8.5-g canister containing 200 actuations. (3)
-------------------------------CONTRAINDICATIONS-----------------------------Hypersensitivity to albuterol and any other PROAIR HFA Inhalation Aerosol
Components. (4)

-----------------------WARNINGS AND PRECAUTIONS-----------------------•
Life-threatening paradoxical bronchospasm may occur. Discontinue
PROAIR HFA immediately and treat with alternative therapy. (5.1)
•
Need for more doses of PROAIR HFA than usual may be a sign of
deterioration of asthma and requires reevaluation of treatment. (5.2)
•
PROAIR HFA is not a substitute for corticosteroids. (5.3)
•
Cardiovascular effects may occur. Use with caution in patients sensitive
to sympathomimetic drugs and patients with cardiovascular or
convulsive disorders. (5.4, 5.7)
•
Excessive use may be fatal. Do not exceed recommended dose. (5.5)
•
Immediate hypersensitivity reactions may occur. Discontinue PROAIR
HFA immediately. (5.6)
•
Hypokalemia and changes in blood glucose may occur. (5.7, 5.8)
------------------------------ADVERSE REACTIONS------------------------------Most common adverse reactions (≥3.0% and >placebo) are headache,
tachycardia, pain, dizziness, pharyngitis, and rhinitis. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Teva
Respiratory, LLC at 1-888-482-9522 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
------------------------------DRUG INTERACTIONS------------------------------•
Other short-acting sympathomimetic aerosol bronchodilators and
adrenergic drugs: May potentiate effect. (7)
•
Beta-blockers: May decrease effectiveness of PROAIR HFA and
produce severe bronchospasm. Patients with asthma should not
normally be treated with beta-blockers. (7.1)
•
Diuretics, or non-potassium sparing diuretics: May potentiate
hypokalemia or ECG changes. Consider monitoring potassium levels.
(7.2)
•
Digoxin: May decrease serum digoxin levels. Consider monitoring
digoxin levels. (7.3)
•
Monoamine oxidase (MAO) inhibitors and tricyclic antidepressants:
May potentiate effect of albuterol on the cardiovascular system.
Consider alternative therapy in patients taking MAOs or tricyclic
antidepressants. (7.4)
See 17 for PATIENT COUNSELING INFORMATION and FDAapproved patient labeling.
Revised: 02/2019

____________________________________________________________________________________________________________________________________

FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
1.1 Bronchospasm
1.2 Exercise-Induced Bronchospasm
2 DOSAGE AND ADMINISTRATION
2.1 Bronchospasm
2.2 Exercise-Induced Bronchospasm
2.3 Administration Information
3 DOSAGE FORMS & STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS & PRECAUTIONS
5.1 Paradoxical Bronchospasm
5.2 Deterioration of Asthma
5.3 Use of Anti-inflammatory Agents
5.4 Cardiovascular Effects
5.5 Do Not Exceed Recommended Dose
5.6 Immediate Hypersensitivity Reactions
5.7 Coexisting Conditions
5.8 Hypokalemia
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 Beta-Blockers
7.2 Diuretics
7.3 Digoxin
7.4 Monoamine Oxidase Inhibitors or Tricyclic
Antidepressants
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation

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8.4 Pediatric Use
8.5 Geriatric Use
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
14.1 Bronchospasm Associated with Asthma
14.2 Exercise-Induced Bronchospasm
16 HOW SUPPLIED/STORAGE & HANDLING
17 PATIENT COUNSELING INFORMATION
17.1 Frequency of Use
17.2 Priming and Cleaning
17.3 Dose Counter
17.4 Paradoxical Bronchospasm
17.5 Concomitant Drug Use
17.6 Common Adverse Events
17.7 Pregnancy
17.8 General Information on Use
17.9 FDA-Approved Patient Labeling
*Sections or subsections omitted from the full prescribing
information are not listed.

FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
1.1 Bronchospasm
PROAIR HFA Inhalation Aerosol is indicated for the treatment or prevention of
bronchospasm in patients 4 years of age and older with reversible obstructive airway
disease.
1.2 Exercise-Induced Bronchospasm
PROAIR HFA Inhalation Aerosol is indicated for the prevention of exerciseinduced bronchospasm in patients 4 years of age and older.

2 DOSAGE AND ADMINISTRATION
2.1 Bronchospasm
For treatment of acute episodes of bronchospasm or prevention of symptoms
associated with bronchospasm, the usual dosage for adults and children 4 years and
older is two inhalations repeated every 4 to 6 hours. More frequent administration or a
larger number of inhalations is not recommended. In some patients, one inhalation
every 4 hours may be sufficient.
2.2 Exercise-Induced Bronchospasm
The usual dosage for adults and children 4 years of age or older is two
inhalations 15 to 30 minutes before exercise.
2.3 Administration Information
Administer PROAIR HFA by oral inhalation only. Shake well before each spray.
To maintain proper use of this product and to prevent medication build-up and blockage,
it is important to follow the cleaning directions carefully.
Priming: 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: As with all HFA-containing albuterol inhalers, to maintain proper use
of this product and to prevent medication build-up and blockage, it is important to clean
the plastic mouthpiece regularly. The inhaler may cease to deliver medication if the
plastic actuator mouthpiece is not properly cleaned and dried. To clean: Wash the
plastic mouthpiece with warm running water for 30 seconds, shake off excess water, and
air dry thoroughly at least once a week. If the patient has more than one PROAIR
HFA inhaler, the patient should wash each one separately to prevent attaching the
wrong canister to the wrong plastic actuator. In this way, the patient can be sure
to always know the correct number of remaining doses. Never attach a canister of
medication from any other inhaler to the PROAIR HFA actuator and never attach
the PROAIR HFA canister to an actuator from any other inhaler. If the mouthpiece
becomes blocked, washing the mouthpiece will remove the blockage. If it is necessary
to use the inhaler before it is completely dry, shake off excess water, replace canister,
spray twice into the air away from face, and take the prescribed dose. After such use,
the mouthpiece should be rewashed and allowed to air dry thoroughly. [see FDAApproved Patient Labeling (17.9)].
Dose Counter: PROAIR HFA has a dose counter attached to the actuator.
When the patient receives the inhaler, a black dot will appear in the viewing window until
it has been primed 3 times, at which point the number 200 will be displayed. The dose
counter will count down each time a spray is released. When the dose counter reaches
20, the color of the numbers will change to red to remind the patient to contact their
pharmacist for a refill of medication or consult their physician for a prescription refill.

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When the dose counter reaches 0, the background will change to solid red. PROAIR
HFA inhaler should be discarded when the dose counter displays 0 or after the
expiration date on the product, whichever comes first.

3 DOSAGE FORMS & STRENGTHS
PROAIR HFA is an inhalation aerosol. PROAIR HFA is supplied as an 8.5 g/200
actuations pressurized aluminum canister with a red plastic actuator with a dose counter
and white dust cap each in boxes of one. 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).

4 CONTRAINDICATIONS
PROAIR HFA Inhalation Aerosol is contraindicated in patients with a history of
hypersensitivity to albuterol and any other PROAIR HFA Inhalation Aerosol components.
Rare cases of hypersensitivity reactions, including urticaria, angioedema, and rash have
been reported after the use of albuterol sulfate [see Warnings and Precautions (5.6)].

5 WARNINGS & PRECAUTIONS
5.1 Paradoxical Bronchospasm
PROAIR HFA Inhalation Aerosol can produce paradoxical bronchospasm that
may be life threatening. If paradoxical bronchospasm occurs, PROAIR HFA Inhalation
Aerosol should be discontinued immediately and alternative therapy instituted. It should
be recognized that paradoxical bronchospasm, when associated with inhaled
formulations, frequently occurs with the first use of a new canister.
5.2 Deterioration of Asthma
Asthma may deteriorate acutely over a period of hours or chronically over several
days or longer. If the patient needs more doses of PROAIR HFA Inhalation Aerosol than
usual, this may be a marker of destabilization of asthma and requires re-evaluation of
the patient and treatment regimen, giving special consideration to the possible need for
anti-inflammatory treatment, e.g., corticosteroids.
5.3 Use of Anti-inflammatory Agents
The use of beta-adrenergic-agonist bronchodilators alone may not be adequate
to control asthma in many patients. Early consideration should be given to adding antiinflammatory agents, e.g., corticosteroids, to the therapeutic regimen.
5.4 Cardiovascular Effects
PROAIR HFA Inhalation Aerosol, like other beta-adrenergic agonists, can
produce clinically significant cardiovascular effects in some patients as measured by
pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon
after administration of PROAIR HFA Inhalation Aerosol at recommended doses, if they
occur, the drug may need to be discontinued. In addition, beta-agonists have been
reported to produce ECG changes, such as flattening of the T wave, prolongation of the
QTc interval, and ST segment depression. The clinical significance of these findings is
unknown. Therefore, PROAIR HFA Inhalation Aerosol, like all sympathomimetic
amines, should be used with caution in patients with cardiovascular disorders, especially
coronary insufficiency, cardiac arrhythmias, and hypertension.
5.5 Do Not Exceed Recommended Dose
Fatalities have been reported in association with excessive use of inhaled
sympathomimetic drugs in patients with asthma. The exact cause of death is unknown,
but cardiac arrest following an unexpected development of a severe acute asthmatic
crisis and subsequent hypoxia is suspected.

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5.6 Immediate Hypersensitivity Reactions
Immediate hypersensitivity reactions may occur after administration of albuterol
sulfate, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm,
anaphylaxis, and oropharyngeal edema. The potential for hypersensitivity must be
considered in the clinical evaluation of patients who experience immediate
hypersensitivity reactions while receiving PROAIR HFA Inhalation Aerosol.
5.7 Coexisting Conditions
PROAIR HFA Inhalation Aerosol, like all sympathomimetic amines, should be
used with caution in patients with cardiovascular disorders, especially coronary
insufficiency, cardiac arrhythmias, and hypertension; in patients with convulsive
disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually
responsive to sympathomimetic amines. Clinically significant changes in systolic and
diastolic blood pressure have been seen in individual patients and could be expected to
occur in some patients after use of any beta-adrenergic bronchodilator. Large doses of
intravenous albuterol have been reported to aggravate preexisting diabetes mellitus and
ketoacidosis.
5.8 Hypokalemia
As with other beta-agonists, PROAIR HFA Inhalation Aerosol may produce
significant hypokalemia in some patients, possibly through intracellular shunting, which
has the potential to produce adverse cardiovascular effects. The decrease is usually
transient, not requiring supplementation.

6 ADVERSE REACTIONS
Use of PROAIR HFA may be associated with the following:
• Paradoxical bronchospasm [see Warnings and Precautions (5.1)]
• Cardiovascular Effects [see Warnings and Precautions (5.4)]
• Immediate hypersensitivity reactions [see Warnings and Precautions (5.6)]
• Hypokalemia [see Warnings and Precautions (5.8)]
6.1 Clinical Trials Experience
A total of 1090 subjects were treated with PROAIR HFA Inhalation Aerosol, or
with the same formulation of albuterol as in PROAIR HFA Inhalation Aerosol, during the
worldwide clinical development program.
Because clinical trials are conducted under widely varying conditions, adverse
reaction rates observed in the clinical trials of a drug cannot be directly compared to
rates in the clinical trials of another drug and may not reflect the rates observed in
practice.
Adult and Adolescents 12 Years of Age and Older: The adverse reaction
information presented in the table below concerning PROAIR HFA Inhalation Aerosol is
derived from a 6-week, blinded study which compared PROAIR HFA Inhalation Aerosol
(180 mcg four times daily) with a double-blinded matched placebo HFA-Inhalation
Aerosol and an evaluator-blinded marketed active comparator HFA-134a albuterol
inhaler in 172 asthmatic patients 12 to 76 years of age. The table lists the incidence of
all adverse events (whether considered by the investigator drug related or unrelated to
drug) from this study which occurred at a rate of 3% or greater in the PROAIR HFA
Inhalation Aerosol treatment group and more frequently in the PROAIR HFA Inhalation
Aerosol treatment group than in the matched placebo group. Overall, the incidence and
nature of the adverse events reported for PROAIR HFA Inhalation Aerosol and the
marketed active comparator HFA-134a albuterol inhaler were comparable.

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Adverse Experience Incidences (% of Patients) in a Six-Week Clinical Trial*
Body System/
PROAIR HFA
Marketed active
Matched Placebo
Adverse Event (as Preferred Term)
Inhalation
comparator
HFA-134a
Aerosol
HFA-134a
Inhalation Aerosol
(N = 58)
albuterol
(N = 58)
inhaler
(N = 56)
Body as a Whole
Headache
7
5
2
Cardiovascular
Tachycardia
3
2
0
Musculoskeletal
Pain
3
0
0
Nervous System
Dizziness
3
0
0
Respiratory System
Pharyngitis
14
7
9
Rhinitis
5
4
2
* This table includes all adverse events (whether considered by the investigator drug related or unrelated to drug) which
occurred at an incidence rate of at least 3.0% in the PROAIR HFA Inhalation Aerosol group and more frequently in the
PROAIR HFA Inhalation Aerosol group than in the placebo HFA Inhalation Aerosol group.

Adverse events reported by less than 3% of the patients receiving PROAIR HFA
Inhalation Aerosol but by a greater proportion of PROAIR HFA Inhalation Aerosol
patients than the matched placebo patients, which have the potential to be related to
PROAIR HFA Inhalation Aerosol, included chest pain, infection, diarrhea, glossitis,
accidental injury (nervous system), anxiety, dyspnea, ear disorder, ear pain, and urinary
tract infection.
In small cumulative dose studies, tremor, nervousness, and headache were the
most frequently occurring adverse events.
Pediatric Patients 4 to 11 Years of Age: Adverse events reported in a 3-week
pediatric clinical trial comparing the same formulation of albuterol as in PROAIR HFA
Inhalation Aerosol (180 mcg albuterol four times daily) to a matching placebo HFA
inhalation aerosol occurred at a low incidence rate (no greater than 2% in the active
treatment group) and were similar to those seen in adult and adolescent trials.
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of
PROAIR HFA. Because these reactions are reported voluntarily from a population of
uncertain size, it is not always possible to reliably estimate their frequency or establish a
causal relationship to drug exposure. Reports have included rare cases of aggravated
bronchospasm, lack of efficacy, asthma exacerbation (reported fatal in one case),
muscle cramps, and various oropharyngeal side-effects such as throat irritation, altered
taste, glossitis, tongue ulceration, and gagging.
The following adverse events have been observed in postapproval use of inhaled
albuterol: urticaria, angioedema, rash, bronchospasm, hoarseness, oropharyngeal
edema, and arrhythmias (including atrial fibrillation, supraventricular tachycardia,
extrasystoles). In addition, albuterol, like other sympathomimetic agents, can cause
adverse reactions such as: angina, hypertension or hypotension, palpitations, central
nervous system stimulation, insomnia, headache, nervousness, tremor, muscle cramps,
drying or irritation of the oropharynx, hypokalemia, hyperglycemia, and metabolic
acidosis.

7 DRUG INTERACTIONS
Other short-acting sympathomimetic aerosol bronchodilators should not be used
concomitantly with PROAIR HFA Inhalation Aerosol. If additional adrenergic drugs are

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to be administered by any route, they should be used with caution to avoid deleterious
cardiovascular effects.
7.1 Beta-Blockers
Beta-adrenergic-receptor blocking agents not only block the pulmonary effect of
beta-agonists, such as PROAIR HFA Inhalation Aerosol, but may produce severe
bronchospasm in asthmatic patients. Therefore, patients with asthma should not
normally be treated with beta-blockers. However, under certain circumstances, e.g., as
prophylaxis after myocardial infarction, there may be no acceptable alternatives to the
use of beta-adrenergic-blocking agents in patients with asthma. In this setting, consider
cardioselective beta-blockers, although they should be administered with caution.
7.2 Diuretics
The ECG changes and/or hypokalemia which may result from the administration
of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely
worsened by beta-agonists, especially when the recommended dose of the beta-agonist
is exceeded. Although the clinical significance of these effects is not known, caution is
advised in the coadministration of beta-agonists with non-potassium sparing diuretics.
Consider monitoring potassium levels.
7.3 Digoxin
Mean decreases of 16% and 22% in serum digoxin levels were demonstrated
after single dose intravenous and oral administration of albuterol, respectively, to normal
volunteers who had received digoxin for 10 days. The clinical significance of these
findings for patients with obstructive airway disease who are receiving albuterol and
digoxin on a chronic basis is unclear. Nevertheless, it would be prudent to carefully
evaluate the serum digoxin levels in patients who are currently receiving digoxin and
PROAIR HFA Inhalation Aerosol.
7.4 Monoamine Oxidase Inhibitors or Tricyclic Antidepressants
PROAIR HFA Inhalation Aerosol should be administered with extreme caution to
patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or
within 2 weeks of discontinuation of such agents, because the action of albuterol on the
cardiovascular system may be potentiated. Consider alternative therapy in patients
taking MAO inhibitors or tricyclic antidepressants.

8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in
women exposed to asthma medications during pregnancy. For more information, contact
the Mothers To Baby Pregnancy Studies conducted by the Organization of Teratology
Information Specialists at 1-877-311-8972 or visit http://mothertobaby.org/pregnancy­
studies/.
Risk Summary
There are no randomized clinical studies of use of albuterol during pregnancy.
Available data from published epidemiological studies and postmarketing case reports of
pregnancy outcomes following inhaled albuterol use do not consistently demonstrate a
risk of major birth defects or miscarriage. There are clinical considerations with use of
albuterol in pregnant women [see Clinical Considerations]. In animal reproduction
studies, when albuterol sulfate was administered subcutaneously to pregnant mice there

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was evidence of cleft palate at less than and up to 9 times the maximum recommended
human daily inhalation dose (MRHDID) [see Data].
The estimated background risk of major birth defects and miscarriage for the
indicated population(s) are unknown. In the U.S. general population, the estimated risk
of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4%
and 15 to 20%, respectively.
Clinical Considerations
Disease-Associated Maternal and/or Embryo/Fetal Risk
In women with poorly or moderately controlled asthma, there is an increased risk
of preeclampsia in the mother and prematurity, low birth weight, and small for gestational
age in the neonate. Pregnant women should be closely monitored and medication
adjusted as necessary to maintain optimal control.
Labor or Delivery
Because of the potential for beta-agonist interference with uterine contractility,
use of PROAIR HFA Inhalation Aerosol for relief of bronchospasm during labor should
be restricted to those patients in whom the benefits clearly outweigh the risk. PROAIR
HFA Inhalation Aerosol has not been approved for the management of pre-term labor.
Serious adverse reactions, including pulmonary edema, have been reported during or
following treatment of premature labor with beta2-agonists, including albuterol.
Data
Animal Data
In a mouse reproduction study, subcutaneously administered albuterol sulfate
produced cleft palate formation in 5 of 111 (4.5%) fetuses at an exposure nine-tenths of
the MRHDID for adults (on a mg/m2 basis at a maternal dose of 0.25 mg/kg) and in 10 of
108 (9.3%) fetuses at approximately 9 times the MRHDID (on a mg/m2 basis at a
maternal dose of 2.5 mg/kg). Similar effects were not observed at approximately oneeleventh the MRHDID for adults (on a mg/m2 basis at a maternal dose of 0.025 mg/kg).
Cleft palate also occurred in 22 of 72 (30.5%) fetuses from females treated
subcutaneously with isoproterenol (positive control).
In a rabbit reproduction study, orally administered albuterol sulfate induced
cranioschisis in 7 of 19 fetuses (37%) at approximately 750 times the MRHDID (on a
mg/m2 basis at a maternal dose of 50 mg/kg).
In a rat reproduction study, an albuterol sulfate/HFA-134a formulation
administered by inhalation did not produce any teratogenic effects at exposures
approximately 80 times the MRHDID (on a mg/m2 basis at a maternal dose of 10.5
mg/kg).
A study in which pregnant rats were dosed with radiolabeled albuterol sulfate
demonstrated that drug-related material is transferred from the maternal circulation to
the fetus.
8.2 Lactation
Risk Summary
There are no available data on the presence of albuterol in human milk, the
effects on the breastfed child, or the effects on milk production. However, plasma levels

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of albuterol after inhaled therapeutic doses are low in humans, and if present in breast
milk, albuterol has a low oral bioavailability [see Clinical Pharmacology (12.3)].
The developmental and health benefits of breastfeeding should be considered
along with the mother’s clinical need for albuterol and any potential adverse effects on
the breastfed child from albuterol or from the underlying maternal condition.
8.4 Pediatric Use
The safety and effectiveness of PROAIR HFA Inhalation Aerosol for the
treatment or prevention of bronchospasm in children 12 years of age and older with
reversible obstructive airway disease is based on one 6-week clinical trial in 116 patients
12 years of age and older with asthma comparing doses of 180 mcg four times daily with
placebo, and one single-dose crossover study comparing doses of 90, 180, and
270 mcg with placebo in 58 patients [see Clinical Studies (14.1)]. The safety and
effectiveness of PROAIR HFA Inhalation Aerosol for treatment of exercise-induced
bronchospasm in children 12 years of age and older is based on one single-dose
crossover study in 24 adults and adolescents with exercise-induced bronchospasm
comparing doses of 180 mcg with placebo [see Clinical Studies (14.2)].
The safety of PROAIR HFA Inhalation Aerosol in children 4 to 11 years of age is
based on one 3-week clinical trial in 50 patients 4 to 11 years of age with asthma using
the same formulation of albuterol as in PROAIR HFA Inhalation Aerosol comparing
doses of 180 mcg four times daily with placebo. The effectiveness of PROAIR HFA
Inhalation Aerosol in children 4 to 11 years of age is extrapolated from clinical trials in
patients 12 years of age and older with asthma and exercise-induced bronchospasm,
based on data from a single-dose study comparing the bronchodilatory effect of PROAIR
HFA 90 mcg and 180 mcg with placebo in 55 patients with asthma and a 3-week clinical
trial using the same formulation of albuterol as in PROAIR HFA Inhalation Aerosol in
95 asthmatic children 4 to 11 years of age comparing a dose of 180 mcg albuterol four
times daily with placebo [see Clinical Studies (14.1)].
The safety and effectiveness of PROAIR HFA Inhalation Aerosol in pediatric
patients below the age of 4 years have not been established.
8.5 Geriatric Use
Clinical studies of PROAIR HFA Inhalation Aerosol did not include sufficient
numbers of patients aged 65 and over to determine whether they respond differently
from younger patients. Other reported clinical experience has not identified differences
in responses between elderly and younger patients. 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 [see Warnings and Precautions (5.4, 5.7)].
All beta2-adrenergic agonists, including albuterol, are known to be substantially
excreted by the kidney, and the risk of toxic reactions may be greater in patients with
impaired renal function. Because elderly patients are more likely to have decreased
renal function, care should be taken in dose selection, and it may be useful to monitor
renal function.

10 OVERDOSAGE
The expected symptoms with overdosage are those of excessive beta­
adrenergic stimulation and/or occurrence or exaggeration of any of the symptoms listed
under ADVERSE REACTIONS, e.g., seizures, angina, hypertension or hypotension,
tachycardia with rates up to 200 beats per minute, arrhythmias, nervousness, headache,
tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and insomnia.

Reference ID: 4395126

Hypokalemia may also occur. As with all sympathomimetic medications, cardiac
arrest and even death may be associated with abuse of PROAIR HFA Inhalation
Aerosol.
Treatment consists of discontinuation of PROAIR HFA Inhalation Aerosol
together with appropriate symptomatic therapy. The judicious use of a cardioselective
beta-receptor blocker may be considered, bearing in mind that such medication can
produce bronchospasm. There is insufficient evidence to determine if dialysis is
beneficial for overdosage of PROAIR HFA Inhalation Aerosol.
The oral median lethal dose of albuterol sulfate in mice is greater than
2,000 mg/kg (approximately 6,800 times the maximum recommended daily inhalation
dose for adults on a mg/m2 basis and approximately 3,200 times the maximum
recommended daily inhalation dose for children on a mg/m2 basis). In mature rats, the
subcutaneous median lethal dose of albuterol sulfate is approximately 450 mg/kg
(approximately 3,000 times the maximum recommended daily inhalation dose for adults
on a mg/m2 basis and approximately 1,400 times the maximum recommended daily
inhalation dose for children on a mg/m2 basis). In young rats, the subcutaneous median
lethal dose is approximately 2,000 mg/kg (approximately 14,000 times the maximum
recommended daily inhalation dose for adults on a mg/m2 basis and approximately
6,400 times the maximum recommended daily inhalation dose for children on a mg/m 2
basis). The inhalation median lethal dose has not been determined in animals.

11 DESCRIPTION
The active ingredient of PROAIR HFA (albuterol sulfate) Inhalation Aerosol is
albuterol sulfate, a racemic salt, of albuterol. Albuterol sulfate has the chemical name
1-[(tert-butylamino) methyl]-4-hydroxy-m-xylene-,'-diol sulfate (2:1) (salt), and has
the following chemical structure:

The molecular weight of albuterol sulfate is 576.7, and the empirical formula is
(C13H21NO3)2•H2SO4. Albuterol sulfate is a white to off-white crystalline powder. It is
soluble in water and slightly soluble in ethanol. Albuterol sulfate is the official generic
name in the United States, and salbutamol sulfate is the World Health Organization
recommended generic name. PROAIR HFA Inhalation Aerosol is a pressurized
metered-dose aerosol unit with a dose counter. PROAIR HFA is for oral inhalation only.
It contains a microcrystalline suspension of albuterol sulfate in propellant HFA-134a (1,
1, 1, 2-tetrafluoroethane) and ethanol.
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. After priming, each actuation delivers 108 mcg albuterol sulfate, from the
actuator mouthpiece (equivalent to 90 mcg of albuterol base). Each canister provides
200 actuations (inhalations).
This product does not contain chlorofluorocarbons (CFCs) as the propellant.

12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Albuterol sulfate is a beta2-adrenergic agonist. The pharmacologic effects of
albuterol sulfate are attributable to activation of beta2-adrenergic receptors on airway

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smooth muscle. Activation of beta2-adrenergic receptors leads to the activation of
adenylcyclase and to an increase in the intracellular concentration of cyclic-3',
5’-adenosine monophosphate (cyclic AMP). This increase of cyclic AMP is associated
with the activation of protein kinase A, which in turn inhibits the phosphorylation of
myosin and lowers intracellular ionic calcium concentrations, resulting in muscle
relaxation. Albuterol relaxes the smooth muscle of all airways, from the trachea to the
terminal bronchioles. Albuterol acts as a functional antagonist to relax the airway
irrespective of the spasmogen involved, thus protecting against all bronchoconstrictor
challenges. Increased cyclic AMP concentrations are also associated with the inhibition
of release of mediators from mast cells in the airway. While it is recognized that beta2­
adrenergic receptors are the predominant receptors on bronchial smooth muscle, data
indicate that there are beta-receptors in the human heart, 10% to 50% of which are
cardiac beta2-adrenergic receptors. The precise function of these receptors has not
been established [see Warnings and Precautions (5.4)].
Albuterol has been shown in most controlled clinical trials to have more effect on
the respiratory tract, in the form of bronchial smooth muscle relaxation, than
isoproterenol at comparable doses while producing fewer cardiovascular effects.
However, inhaled albuterol, like other beta-adrenergic agonist drugs, can produce a
significant cardiovascular effect in some patients, as measured by pulse rate, blood
pressure, symptoms, and/or electrocardiographic changes [see Warnings and
Precautions (5.4)].
12.2 Pharmacokinetics
The systemic levels of albuterol are low after inhalation of recommended doses.
In a crossover study conducted in healthy male and female volunteers, high cumulative
doses of PROAIR HFA Inhalation Aerosol (1,080 mcg of albuterol base administered
over one hour) yielded mean peak plasma concentrations (Cmax) and systemic exposure
(AUCinf) of approximately 4,100 pg/mL and 28,426 pg/mL*hr, respectively compared to
approximately 3,900 pg/mL and 28,395 pg/mL*hr, respectively following the same dose
of an active HFA-134a albuterol inhaler comparator. The terminal plasma half-life of
albuterol delivered by PROAIR HFA Inhalation Aerosol was approximately 6 hours.
Comparison of the pharmacokinetic parameters demonstrated no differences between
the products.
The pharmacokinetic profile of PROAIR HFA Inhalation Aerosol was evaluated in a
two-way cross-over study in 11 healthy pediatric volunteers, 4 to 11 years of age. A single
dose administration of PROAIR HFA Inhalation Aerosol (180 mcg albuterol base) yielded a
least square mean (SE) Cmax and AUC0- of 1,100 (1.18) pg/mL and 5,120 (1.15) pg/mL*hr,
respectively. The least square mean (SE) terminal plasma half-life of albuterol delivered by
PROAIR HFA Inhalation Aerosol was 166 (7.8) minutes.
Metabolism and Elimination: Information available in the published literature
suggests that the primary enzyme responsible for the metabolism of albuterol in humans
is SULTIA3 (sulfotransferase). When racemic albuterol was administered either
intravenously or via inhalation after oral charcoal administration, there was a 3- to 4-fold
difference in the area under the concentration-time curves between the (R)- and (S)­
albuterol enantiomers, with (S)-albuterol concentrations being consistently higher.
However, without charcoal pretreatment, after either oral or inhalation administration the
differences were 8- to 24-fold, suggesting that the (R)-albuterol is preferentially
metabolized in the gastrointestinal tract, presumably by SULTIA3.
The primary route of elimination of albuterol is through renal excretion (80% to
100%) of either the parent compound or the primary metabolite. Less than 20% of the
drug is detected in the feces. Following intravenous administration of racemic albuterol,

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between 25% and 46% of the (R)-albuterol fraction of the dose was excreted as
unchanged (R)-albuterol in the urine.
Geriatric, Pediatric, Hepatic/Renal Impairment: No pharmacokinetic studies
for PROAIR HFA Inhalation Aerosol have been conducted in neonates or elderly
subjects.
The effect of hepatic impairment on the pharmacokinetics of PROAIR HFA
Inhalation Aerosol has not been evaluated.
The effect of renal impairment on the pharmacokinetics of albuterol was
evaluated in 5 subjects with creatinine clearance of 7 to 53 mL/min, and the results were
compared with those from healthy volunteers. Renal disease had no effect on the halflife, but there was a 67% decline in albuterol clearance. Caution should be used when
administering high doses of PROAIR HFA Inhalation Aerosol to patients with renal
impairment [see Use in Specific Populations (8.5)].

13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
In a 2-year study in Sprague-Dawley rats, albuterol sulfate caused a dose-related
increase in the incidence of benign leiomyomas of the mesovarium at and above dietary
doses of 2 mg/kg (approximately 15 times and 6 times the maximum recommended
human daily inhalation dose (MRHDID) for adults and children, respectively, on a mg/m2
basis). In another study this effect was blocked by the coadministration of propranolol, a
non-selective beta-adrenergic antagonist. In an 18-month study in CD-1 mice, albuterol
sulfate showed no evidence of tumorigenicity at dietary doses of up to 500 mg/kg
(approximately 1,900 times and 740 times the MRHDID for adults and children,
respectively, on a mg/m2 basis). In a 22-month study in Golden Hamsters, albuterol
sulfate showed no evidence of tumorigenicity at dietary doses of up to 50 mg/kg
(approximately 250 times and 100 times the MRHDID for adults and children,
respectively, on a mg/m2 basis).
Albuterol sulfate was not mutagenic in the Ames test or a mutation test in yeast.
Albuterol sulfate was not clastogenic in a human peripheral lymphocyte assay or in an
AH1 strain mouse micronucleus assay.
Reproduction studies in rats demonstrated no evidence of impaired fertility at
oral doses up to 50 mg/kg (approximately 380 times the MRHDID for adults on a mg/m2
basis).
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 -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 - 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.

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In animals and humans, propellant HFA-134a was found to be rapidly absorbed
and rapidly eliminated, with an elimination half-life of 3 - 27 minutes in animals and
5 - 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.

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, PROAIR HFA Inhalation Aerosol
(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 PROAIR HFA
Inhalation Aerosol 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

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Day 43

In this study, 31 of 58 patients treated with PROAIR HFA 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, PROAIR HFA 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 PROAIR HFA 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 PROAIR HFA 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, PROAIR HFA 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 PROAIR

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HFA 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 PROAIR HFA 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 & HANDLING
PROAIR HFA (albuterol sulfate) Inhalation Aerosol is supplied as a pressurized
aluminum canister with a red plastic actuator with a dose counter and white dust cap
each in boxes of one. Each canister contains 8.5 g of the formulation and provides 200
actuations (NDC 59310-579-22). 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 15° and 25°C (59° and 77°F).
Contents under pressure. Do not puncture or incinerate. Protect from freezing
temperatures and prolonged exposure to direct sunlight. Exposure to temperatures
above 120oF 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 red actuator supplied with PROAIR HFA Inhalation Aerosol should not be
used with the canister from any other inhalation aerosol products. The PROAIR HFA
Inhalation Aerosol canister should not be used with the actuator from any other
inhalation aerosol products.
PROAIR HFA inhaler has a dose counter attached to the actuator. Patients
should never try to alter the numbers for the dose counter or tamper with the pin
mechanism inside the actuator. Discard the PROAIR HFA inhaler when the counter
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 counter
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”).
PROAIR HFA 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 PROAIR HFA Inhalation Aerosol should last for 4 to 6 hours. Do
not use PROAIR HFA Inhalation Aerosol more frequently than recommended. Instruct
patients to not increase the dose or frequency of doses of PROAIR HFA Inhalation
Aerosol without consulting the physician. If patients find that treatment with PROAIR
HFA 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.

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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 red plastic actuator mouthpiece and dry thoroughly at least
once a week. Instruct patients that if they have more than one PROAIR HFA 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 PROAIR HFA actuator and never
attach the PROAIR HFA 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 counter will count down each time a spray
is released. Detailed cleaning instructions are included in the illustrated Information for
the Patient leaflet.
17.3 Dose Counter
Patients should be informed that PROAIR HFA has a dose counter attached to
the actuator. When the patient receives the inhaler, a black dot will appear in the
viewing window until it has been primed 3 times, at which point the number 200 will be
displayed. The dose counter will count down each time a spray is released. The dosecounter window displays the number of sprays left in the inhaler in units of two (e.g.,
200, 198, 196, etc). When the counter displays 20, the color of the numbers will change
to red to remind the patient to contact their pharmacist for a refill of medication or consult
their physician for a prescription refill. When the dose counter reaches 0, the
background will change to solid red. Patients should be informed to discard PROAIR
HFA inhaler when the dose counter displays 0 or after the expiration date on the
product, whichever comes first.
17.4 Paradoxical Bronchospasm
Inform patients that PROAIR HFA Inhalation Aerosol can produce paradoxical
bronchospasm. Instruct patients to discontinue PROAIR HFA Inhalation Aerosol if
paradoxical bronchospasm occurs.
17.5 Concomitant Drug Use
While patients are taking PROAIR HFA 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 PROAIR HFA 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 PROAIR HFA Inhalation Aerosol includes an
understanding of the way that it should be administered.
Shake well before each spray.
Use PROAIR HFA Inhalation Aerosol only with the actuator supplied with the
product. Discard the PROAIR HFA inhaler when the dose counter displays 0 or after the

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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 PROAIR HFA Inhalation Aerosol to
children is similar to that for adults. Children should use PROAIR HFA 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.
Mktd by: Teva Respiratory, LLC
Frazer, PA 19355
Mfd by: IVAX Pharmaceuticals Ireland

Waterford, Ireland

Copyright 2019, Teva Respiratory, LLC
All rights reserved.
The color red as used on the ProAir® HFA inhaler is a registered trademark of Teva
Respiratory, LLC

PROA-001

Attention Pharmacist:

Detach Patient’s Instructions for use from package insert and dispense with the

product.

-----------------------------------------------------------------------------------------------------------Patient Information
PROAIR® HFA (prō’ ār)
(albuterol sulfate)
Inhalation Aerosol
Read this Patient Information before you start using PROAIR HFA 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 PROAIR HFA?

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PROAIR HFA 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 PROAIR HFA is safe and effective in children under 4 years
of age.
Who should not use PROAIR HFA?
Do not use PROAIR HFA if you are allergic to albuterol sulfate or any of
the ingredients in PROAIR HFA. See the end of this leaflet for a complete list
of ingredients in PROAIR HFA.
What should I tell my doctor before I use PROAIR HFA?
Before you use PROAIR HFA, 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 PROAIR
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 PROAIR HFA
passes into your breast milk. Talk to your doctor about the best way to
feed your baby if you are using PROAIR HFA.
Tell your doctor about all the medicines you take, including prescription
and non-prescription medicines, vitamins, and herbal supplements.
PROAIR HFA and other medicines may affect each other and cause side
effects. PROAIR HFA may affect the way other medicines work, and other
medicines may affect the way PROAIR HFA works.
Especially tell your doctor if you take:
• other inhaled medicines or asthma medicines
• beta blocker medicines
• diuretics
• digoxin
• monoamine oxidase inhibitors
• tricyclic antidepressants

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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 PROAIR HFA?
•
•
•
•
•
•
•
•
•

For detailed instructions, see “Instructions for Use” at the end of
this Patient Information.
Use PROAIR HFA exactly as your doctor tells you to use it.
If your child needs to use PROAIR HFA, watch your child closely to
make sure your child uses the inhaler correctly. Your doctor will show
you how your child should use PROAIR HFA.
Each dose of PROAIR HFA should last up to 4 hours to 6 hours.
Do not increase your dose or take extra doses of PROAIR HFA without
first talking to your doctor.
Get medical help right away if PROAIR HFA 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 PROAIR HFA, 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 PROAIR HFA?
PROAIR HFA may cause serious side effects, including:
• worsening trouble breathing, coughing and wheezing
(paradoxical bronchospasm). If this happens stop using PROAIR
HFA 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

PROAIR HFA

• 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

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o rash
o worsening trouble breathing
• low potassium levels in your blood
• worsening of other medical problems in people who also use
PROAIR HFA including increases in blood sugar
The most common side effects of PROAIR HFA 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 PROAIR HFA. 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 PROAIR HFA?
• Store PROAIR HFA at room temperature between 59º F and 77º F (15º
C and 25º C).
• Avoid exposure to extreme heat and cold.
• Shake the PROAIR HFA canister well before use.
• Do not puncture the PROAIR HFA canister.
• Do not store the PROAIR HFA canister near heat or a flame.

Temperatures above 120° F may cause the canister to burst.

• Do not throw the PROAIR HFA canister into a fire or an incinerator.
• Avoid spraying PROAIR HFA in your eyes.
Keep PROAIR HFA and all medicines out of the reach of children.
General Information about the safe and effective use of PROAIR HFA
Medicines are sometimes prescribed for purposes other than those listed in a
Medication Guide. Do not use PROAIR HFA for a condition for which it was
not prescribed. Do not give PROAIR HFA 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
PROAIR HFA. If you would like more information, talk with your doctor. You
can ask your pharmacist or doctor for information about PROAIR HFA that is
written for health professionals.
For more information, go to www.ProAirHFA.com or call 1-888-482-9522.

Reference ID: 4395126

What are the ingredients in PROAIR HFA?
Active ingredient: albuterol sulfate

Inactive ingredients: propellant HFA-134a and ethanol.

Instructions for Use
PROAIR® HFA (prō’ ār)
(albuterol sulfate)
Inhalation Aerosol
Read this Instructions for Use before you start using PROAIR HFA 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 PROAIR HFA Inhaler Device:
There are 2 main parts of your PROAIR HFA inhaler device including a:
• red plastic actuator that sprays the medicine from the canister. See
Figure A.
• protective 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 counter attached to the back of the actuator with a
viewing window that shows you how many sprays of medicine you have left.
See Figure B.
You will see a black dot in the viewing window on the actuator until the
device has been primed 3 times. See Figure B and “Priming Your PROAIR
HFA Device” below.

Figure A

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Figure B

• Do not use the PROAIR HFA actuator with a canister of medicine from
any other inhaler.
• Do not use a PROAIR HFA canister with an actuator from any other
inhaler, including another PROAIR HFA inhaler.
Priming Your PROAIR HFA Device:
Your PROAIR 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 PROAIR HFA device every day.
• Remove your PROAIR HFA 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 counter on the actuator should display the number 200 after
you prime the actuator for the first time. See Figure D.

Figure D
Each Time You Use Your PROAIR HFA Device:
• Make sure the canister fits firmly in the plastic actuator.

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• 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 Counter on Your PROAIR HFA Actuator
• The dose counter will count down each time a spray is released. The
dose counter window shows the number of sprays left in your inhaler
in units of 2 sprays. For example, there are 190 sprays left if the arrow
is exactly opposite the number 190, or 189 sprays left if the arrow
points between 190 and 188. See Figure D.
• When the dose counter reaches 0, it will continue to show 0 and you
should replace your PROAIR HFA device.
• The dose counter cannot be reset and is permanently attached to the
actuator. Never change the numbers for the dose counter or touch
the pin inside the actuator.
• Do not remove the canister from the plastic actuator except during
cleaning. Reattaching the canister to the actuator may accidently
release a dose of PROAIR HFA into the air. The dose counter will count
down each time a spray is released.
Using Your PROAIR HFA 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 E.

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

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Figure F
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 PROAIR HFA Device:
It is very important to keep the plastic actuator clean so the
medicine will not build-up and block the spray. See Figure G and Figure
H.

Figure G

Figure H

• 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 PROAIR HFA inhaler, wash each device at
separate times to prevent putting the wrong canister together with the

Reference ID: 4395126

wrong plastic actuator. This way you can be sure you will always know
the correct number of remaining doses of PROAIR HFA.
• 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 I.

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

Figure J
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
K.

Reference ID: 4395126

Figure K
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 PROAIR HFA dose as prescribed.
• Follow the Cleaning Instructions above.
Replacing Your PROAIR HFA Device
• When the dose counter on the actuator says the number 20, the
color of the numbers will change to red. The red numbers are to
remind you to refill your prescription or ask your doctor for another
prescription for PROAIR HFA. When the dose counter reaches 0, the
background color will change to solid red.
• Throw the PROAIR HFA inhaler away as soon as the dose counter
says 0 or after the expiration date on the PROAIR HFA 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 after using 200
sprays.
• Do not use the inhaler after the expiration date on the PROAIR HFA
packaging.

This Patient Information and Instructions for Use has been approved by the
U.S. Food and Drug Administration.
Marketed by Teva Respiratory, LLC
Frazer, PA 19355

Reference ID: 4395126

Manufactured by IVAX Pharmaceuticals Ireland
Waterford, Ireland
Revised 06/2016

Reference ID: 4395126