ProAir RespiClick

Dosage Forms And Strengths

PROAIR RESPICLICK is a multi-dose breath-actuated dry powder inhaler that meters 117 mcg of albuterol sulfate (equivalent to 97 mcg of albuterol base) from the device reservoir and delivers 108 mcg of albuterol sulfate (equivalent to 90 mcg of albuterol base) from the mouth piece per actuation. Each inhaler is supplied for 200 inhalation doses. PROAIR RESPICLICK inhalation powder is supplied as a white dry powder inhaler with a red cap in a sealed foil pouch.

Storage And Handling

PROAIR RESPICLICK inhalation powder is supplied as a white dry powder inhaler with a red cap sealed in a foil pouch in boxes of one. Each inhaler contains 0.65g of the formulation and provides 200 actuations (NDC 59310-580-20).

Store at room temperature (between 15° and 25°C; 59° and 77°F). Avoid exposure to extreme heat, cold, or humidity.

Keep out of reach of children.

PROAIR RESPICLICK inhaler has a dose counter. Patients should never try to alter the numbers for the dose counter. Discard the inhaler 13 months after opening the foil pouch, 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 inhaler is not completely empty and will continue to operate [see PATIENT INFORMATION].

Marketed by: Teva Respiratory, LLC, Horsham, PA 19044. Manufactured by: Teva Pharmaceutical Industries Ltd., Jerusalem, Israel. Revised: Apr 2016

Rinse with water if this medicine gets in your eyes.

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.

You should not use this medicine if you are allergic to albuterol. You should not use ProAir RespiClick if you are allergic to milk proteins.

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

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

• a heart rhythm disorder;

• a seizure disorder such as epilepsy;

• diabetes;

• overactive thyroid; or

• low levels of potassium in your blood.

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

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

Albuterol inhalation is not approved for use by anyone younger than 4 years old.

Rinse with water if this medicine gets in your eyes.

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.

In the U.S.

• Accuneb
• ProAir HFA
• Proair Respiclick
• Proventil
• Proventil HFA
• ReliOn Ventolin HFA
• Ventolin
• Ventolin HFA

In Canada

• Alti-Salbutamol Inhalation Aerosol
• Apo-Salvent
• Salbutamol
• Salbutamol Nebuamp
• Salbutamol Respirator Solution
• Ventolin Inhaler
• Ventolin Nebules P.F.
• Ventolin Respirator
• Ventolin Rotacaps

Available Dosage Forms:

• Aerosol Powder
• Solution
• Capsule
• Powder
• Suspension

Therapeutic Class: Bronchodilator

Pharmacologic Class: Sympathomimetic

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of low potassium levels like muscle pain or weakness, muscle cramps, or a heartbeat that does not feel normal.
• If you are not able to get the breathing attack under control. Get help right away.
• Chest pain or pressure or a fast heartbeat.
• Very nervous and excitable.
• Very bad headache.
• Very bad dizziness or passing out.
• Peak flow measurement low.
• Pain when passing urine.
• Trouble passing urine.
• This medicine may sometimes cause very bad breathing problems. This may be life-threatening. When this happens with a puffer (inhaler) or with liquid for breathing in, most of the time it happens right after a dose and after the first use of a new canister or vial of ProAir Respiclick (albuterol inhalation powder). If you have trouble breathing, breathing that is worse, wheezing, or coughing, get medical help right away.

Use of ProAir Respiclick is contraindicated in patients with a history of hypersensitivity to albuterol and/or severe hypersensitivity to milk proteins. Rare cases of hypersensitivity reactions, including urticaria, angioedema, and rash have been reported after the use of albuterol sulfate. There have been reports of anaphylactic reactions in patients using inhalation therapies containing lactose [see Warnings and Precautions (5.6)].

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 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).

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.

Bronchospasm Associated with Asthma

Adult and Adolescent Patients 12 Years of Age and Older

In two 12-week, randomized, double-blind, placebo-controlled studies of identical design (Study 1 and Study 2), ProAir Respiclick (153 patients) was compared to a matched placebo dry powder inhaler (163 patients) in asthmatic patients 12 to 76 years of age at a dose of 180 mcg albuterol four times daily. Patients were maintained on inhaled corticosteroid treatment. Serial FEV1 measurements, shown below in Figure 1 as average of the mean changes from test-day baseline at Day 1 and Day 85, demonstrated that two inhalations of ProAir Respiclick produced significantly greater improvement in FEV1 AUC0‑6hr over the pre-treatment value than placebo in Study 1. Consistent results were observed in Study 2.

In Study 1, 44 of 78 patients treated with ProAir Respiclick achieved a 15% increase in FEV1 within 30 minutes post‑dose on Day 1. The median time to onset was 5.7 minutes, and median duration of effect as measured by a 15% increase was approximately 2 hours. Consistent results were observed in Study 2. In a double‑blind, randomized, placebo–controlled, single‑dose crossover study evaluating ProAir Respiclick and ProAir HFA in 71 adult and adolescent subjects ages 12 and older with persistent asthma, ProAir Respiclick had bronchodilator efficacy that was significantly greater than placebo at administered doses of 90 and 180 mcg.

Pediatric Patients 4 to 11 Years of Age

In a 3‑week, randomized, double‑blind, placebo-controlled trial, ProAir Respiclick (92 patients) was compared to a matched placebo (92 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 baseline-adjusted percent-predicted FEV1 AUC0‑6h over the 3‑week treatment period, demonstrated that 2 inhalations of ProAir Respiclick produced significantly greater improvement in FEV1 over the pre-treatment value than the matched placebo.

In this study, 48 of 92 patients treated with ProAir Respiclick achieved a 15% increase in FEV1 within 30 minutes post-dose on Day 1. The median time to onset was 5.9 minutes, and the median duration of effect as measured by a 15% increase was approximately 1 hour.

In a placebo-controlled, single-dose, crossover study in 61 patients 4 to 11 years of age, ProAir Respiclick, administered at albuterol doses of 90 and 180 mcg, was compared with a matched placebo and with albuterol HFA MDI. ProAir Respiclick provided similar bronchodilation when administered as one or two inhalations (baseline-adjusted percent-predicted serial FEV1 observed over 6 hours post-dose), whereas two inhalations from albuterol HFA MDI provided significantly greater bronchodilation compared to a single inhalation.

Exercise-Induced Bronchospasm

In a randomized, single-dose, crossover study in 38 adult and adolescent patients with exercise-induced bronchospasm (EIB), two inhalations of ProAir Respiclick taken 30 minutes before exercise prevented EIB for the hour following exercise (defined as the maintenance of FEV1 within 80% of post-dose, pre-exercise baseline values) in 97% (37 of 38) of patients as compared to 42% (16 of 38) of patients when they received placebo.

Patients who participated in these clinical trials were allowed to use concomitant steroid therapy.