ProAir HFA

ProAir HFA is part of the drug class:

• Inhaled Selective beta 2 adrenoreceptor agonists

Proair HFA may cause serious side effects, including:

• worsening trouble breathing, coughing and wheezing (paradoxical bronchospasm). If this happens stop using albuterol 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:
  • itchy skin
  • swelling beneath your skin or in your throat
  • rash
  • worsening trouble breathing
• low potassium levels in your blood
• worsening of other medical problems in people who also use albuterol including increases in blood sugar

Do not use this medication if you are allergic to albuterol sulfate or any of the ingredients in Proair HFA. 

Inhalational:

• Do not use the inhaler after the expiration date, which is on the packaging it comes in.
• Store between 15° and 25° C (59° and 77° F). Avoid exposure to extreme heat and cold. For best results, canister should be at room temperature. Store the inhaler with the mouthpiece down. Shake well before each spray.
• Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw container into fire or incinerator.
• It is very important to keep the plastic actuator clean so the medicine will not build-up and block the spray. Do not try to clean the metal canister or let it get wet. The inhaler may stop spraying if it is not cleaned correctly. Wash the actuator at least once a week with warm water and let it air-dry completely.
• As with all aerosol medications, it is recommended 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. Prime by releasing four “test sprays” into the air, away from your face.

A) Albuterol aerosol spray

• Before you reach 200 sprays, you should refill your prescription or ask your doctor if you need another prescription for Proair HFA.
• Throw the inhaler away when you have used 200 sprays. You should not keep using the inhaler after 200 sprays even though the canister may not be completely empty because you cannot be sure you will receive any medicine.

B) Albuterol aerosol spray- with dose counter

• Discard the inhaler when the counter reads 000 or 12 months after it is taken out of the foil pouch, whichever comes first.
• When the counter reads 020, contact your pharmacist for a refill or talk to your doctor to determine whether a prescription refill is needed.
• Never try to alter the numbers or remove the counter from the metal canister.
• Never immerse the canister in water to determine the amount of drug remaining in the canister.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• wheezing, choking, or other breathing problems after using this medicine;

• chest pain, fast heart rate, pounding heartbeats or fluttering in your chest;

• pain or burning when you urinate;

• high blood sugar--increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss; or

• low potassium--leg cramps, constipation, irregular heartbeats, fluttering in your chest, extreme thirst, increased urination, numbness or tingling, muscle weakness or limp feeling.

Common side effects may include:

• back pain, body aches;

• headache, dizziness;

• feeling nervous;

• nausea, diarrhea, upset stomach; or

• sore throat, sinus pain, stuffy runny nose.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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

• any other inhaled medicines or bronchodilators;

• digoxin;

• a diuretic or "water pill";

• an antidepressant--amitriptyline, desipramine, imipramine, doxepin, nortriptyline, and others;

• a beta blocker--atenolol, carvedilol, labetalol, metoprolol, propranolol, sotalol, and others; or

• an MAO inhibitor--isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others.

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

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.

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.

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 FDA-Approved 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. 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.

Other short-acting sympathomimetic aerosol bronchodilators should not be used concomitantly with ProAir HFA Inhalation Aerosol. If additional adrenergic drugs are to be administered by any route, they should be used with caution to avoid deleterious cardiovascular effects.

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.

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.

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.

  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.

The active ingredient of ProAir HFA (albuterol sulfate) Inhalation Aerosol is albuterol sulfate, a racemic salt, of albuterol. Albuterol sulfate has the chemical name α1-[(tert-butylamino) methyl]-4-hydroxy-m-xylene-α,α'-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.

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 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)].

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, 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 half-life, 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)].

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 120°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 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.