For Oral Inhalation Only
DESCRIPTION
The active component of MAXAIR AUTOHALER (pirbuterol acetate) is (R,S)α6-{[(1,1-dimethylethyl)amino]methyl}-3-hydroxy-2,6-pyridinedimethanol monoacetate salt, a beta-2 adrenergic bronchodilator, having the following chemical structure:
Pirbuterol acetate is a white, crystalline racemic mixture of two optically active isomers. It is a powder, freely soluble in water, with a molecular weight of 300.3 and empirical formula of C12H20N2O3•C2H4O2.
MAXAIR AUTOHALER is a pressurized metered-dose aerosol unit for oral inhalation. It provides a fine-particle suspension of pirbuterol acetate in the propellant mixture of trichloromonofluoromethane and dichlorodifluoromethane, with sorbitan trioleate. Each actuation delivers 253 mcg of pirbuterol (as pirbuterol acetate) from the valve and 200 mcg of pirbuterol (as pirbuterol acetate) from the mouthpiece. The unit is breath-actuated such that the medication is delivered automatically during inspiration without the need for the patient to coordinate actuation with inspiration. Each 14.0 g canister provides 400 inhalations and each 2.8 g canister provides 80 inhalations.
As with all aerosol medications, it is recommended to prime (test) MAXAIR AUTOHALER before using for the first time. MAXAIR AUTOHALER should also be primed if it has not been used in 48 hours. As described in the priming procedure, use the test fire slide to release two priming sprays into the air away from yourself and other people. (See “Patient's Instructions For Use” portion of this package insert.)
Pirbuterol acetate is a white, crystalline racemic mixture of two optically active isomers. It is a powder, freely soluble in water, with a molecular weight of 300.3 and empirical formula of C12H20N2O3•C2H4O2.MAXAIR AUTOHALER is a pressurized metered-dose aerosol unit for oral inhalation. It provides a fine-particle suspension of pirbuterol acetate in the propellant mixture of trichloromonofluoromethane and dichlorodifluoromethane, with sorbitan trioleate. Each actuation delivers 253 mcg of pirbuterol (as pirbuterol acetate) from the valve and 200 mcg of pirbuterol (as pirbuterol acetate) from the mouthpiece. The unit is breath-actuated such that the medication is delivered automatically during inspiration without the need for the patient to coordinate actuation with inspiration. Each 14.0 g canister provides 400 inhalations and each 2.8 g canister provides 80 inhalations.
As with all aerosol medications, it is recommended to prime (test) MAXAIR AUTOHALER before using for the first time. MAXAIR AUTOHALER should also be primed if it has not been used in 48 hours. As described in the priming procedure, use the test fire slide to release two priming sprays into the air away from yourself and other people. (See “Patient's Instructions For Use” portion of this package insert.)
CLINICAL PHARMACOLOGY
In vitro studies and in vivo pharmacologic studies have demonstrated that pirbuterol has a preferential effect on beta-2 adrenergic receptors compared with isoproterenol. While it is recognized that beta-2 adrenergic receptors are the predominant receptors in bronchial smooth muscle, data indicate that there is a population of beta-2 receptors in the human heart, existing in a concentration between 10-50%. The precise function of these receptors has not been established (see WARNINGS section).
The pharmacologic effects of beta adrenergic agonist drugs, including pirbuterol, are at least in part attributable to stimulation through beta adrenergic receptors of intracellular adenyl cyclase, the enzyme which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3′,5′-adenosine monophosphate (c-AMP). Increased c-AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.
Bronchodilator activity of pirbuterol was manifested clinically by an improvement in various pulmonary function parameters (FEV1, MMF, PEFR, airway resistance [RAW] and conductance [GA/Vtg]).
The pharmacologic effects of beta adrenergic agonist drugs, including pirbuterol, are at least in part attributable to stimulation through beta adrenergic receptors of intracellular adenyl cyclase, the enzyme which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3′,5′-adenosine monophosphate (c-AMP). Increased c-AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.
Bronchodilator activity of pirbuterol was manifested clinically by an improvement in various pulmonary function parameters (FEV1, MMF, PEFR, airway resistance [RAW] and conductance [GA/Vtg]).
INDICATIONS AND USAGE
MAXAIR AUTOHALER is indicated for the prevention and reversal of bronchospasm in patients 12 years of age and older with reversible bronchospasm including asthma. It may be used with or without concurrent theophylline and/or corticosteroid therapy.
CONTRAINDICATIONS
MAXAIR AUTOHALER is contraindicated in patients with a history of hypersensitivity to pirbuterol or any of its ingredients.
WARNINGS
PRECAUTIONS
ADVERSE REACTIONS
The following rates of adverse reactions to pirbuterol are based on single- and multiple-dose clinical trials involving 761 patients, 400 of whom received multiple doses (mean duration of treatment was 2.5 months and maximum was 19 months).
The following were the adverse reactions reported more frequently than 1 in 100 patients:
CNS: nervousness (6.9%), tremor (6.0%), headache (2.0%), dizziness (1.2%).
Cardiovascular: palpitations (1.7%), tachycardia (1.2%).
Respiratory: cough (1.2%).
Gastrointestinal: nausea (1.7%).
The following adverse reactions occurred less frequently than 1 in 100 patients and there may be a causal relationship with pirbuterol:
CNS: depression, anxiety, confusion, insomnia, weakness, hyperkinesia, syncope.
Cardiovascular: hypotension, skipped beats, chest pain.
Gastrointestinal: dry mouth, glossitis, abdominal pain/cramps, anorexia, diarrhea, stomatitis, nausea and vomiting.
Ear, Nose and Throat: smell/taste changes, sore throat.
Dermatological: rash, pruritus.
Other: numbness in extremities, alopecia, bruising, fatigue, edema, weight gain, flushing.
Other adverse reactions were reported with a frequency of less than 1 in 100 patients but a causal relationship between pirbuterol and the reaction could not be determined: migraine, productive cough, wheezing, and dermatitis.
The following rates of adverse reactions during three-month controlled clinical trials involving 310 patients are noted. The table does not include mild reactions.
The following were the adverse reactions reported more frequently than 1 in 100 patients:
CNS: nervousness (6.9%), tremor (6.0%), headache (2.0%), dizziness (1.2%).
Cardiovascular: palpitations (1.7%), tachycardia (1.2%).
Respiratory: cough (1.2%).
Gastrointestinal: nausea (1.7%).
The following adverse reactions occurred less frequently than 1 in 100 patients and there may be a causal relationship with pirbuterol:
CNS: depression, anxiety, confusion, insomnia, weakness, hyperkinesia, syncope.
Cardiovascular: hypotension, skipped beats, chest pain.
Gastrointestinal: dry mouth, glossitis, abdominal pain/cramps, anorexia, diarrhea, stomatitis, nausea and vomiting.
Ear, Nose and Throat: smell/taste changes, sore throat.
Dermatological: rash, pruritus.
Other: numbness in extremities, alopecia, bruising, fatigue, edema, weight gain, flushing.
Other adverse reactions were reported with a frequency of less than 1 in 100 patients but a causal relationship between pirbuterol and the reaction could not be determined: migraine, productive cough, wheezing, and dermatitis.
The following rates of adverse reactions during three-month controlled clinical trials involving 310 patients are noted. The table does not include mild reactions.
| Reaction | Pirbuterol | Metaproterenol |
| N=157 | N=153 | |
| Central Nervous System | ||
| tremors | 1.3% | 3.3% |
| nervousness | 4.5% | 2.6% |
| headache | 1.3% | 2.0% |
| weakness | .0% | 1.3% |
| drowsiness | .0% | 0.7% |
| dizziness | 0.6% | .0% |
| Cardiovascular | ||
| palpitations | 1.3% | 1.3% |
| tachycardia | 1.3% | 2.0% |
| Respiratory | ||
| chest pain/tightness | 1.3% | .0% |
| cough | .0% | 0.7% |
| Gastrointestinal | ||
| nausea | 1.3% | 2.0% |
| diarrhea | 1.3% | 0.7% |
| dry mouth | 1.3% | 1.3% |
| vomiting | .0% | 0.7% |
| Dermatological | ||
| skin reaction | .0% | 0.7% |
| rash | .0% | 1.3% |
| Other | ||
| bruising | 0.6% | .0% |
| smell/taste change | 0.6% | .0% |
| backache | .0% | 0.7% |
| fatigue | .0% | 0.7% |
| hoarseness | .0% | 0.7% |
| nasal congestion | .0% | 0.7% |
OVERDOSAGE
The expected symptoms with overdosage are those of excessive beta-stimulation and/or any of the symptoms uled 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. Hypokalemia may also occur. As with all sympathomimetic aerosol medication, cardiac arrest and even death may be associated with abuse of MAXAIR AUTOHALER.
Treatment consists of discontinuation of pirbuterol 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.
The oral median lethal dose of pirbuterol dihydrochloride in mice and rats is greater than 2000 mg/kg (approximately 3400 and 6800 times the maximum recommended daily inhalation dose for adults on a mg/m2 basis).
Treatment consists of discontinuation of pirbuterol 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.
The oral median lethal dose of pirbuterol dihydrochloride in mice and rats is greater than 2000 mg/kg (approximately 3400 and 6800 times the maximum recommended daily inhalation dose for adults on a mg/m2 basis).
DOSAGE AND ADMINISTRATION
The usual dose for adults and children 12 years and older is two inhalations (400 mcg) repeated every 4-6 hours. One inhalation (200 mcg) repeated every 4-6 hours may be sufficient for some patients.
A total daily dose of 12 inhalations should not be exceeded.
If a previously effective dosage regimen fails to provide the usual relief, medical advice should be sought immediately as this is often a sign of seriously worsening asthma which would require reassessment of therapy.
A total daily dose of 12 inhalations should not be exceeded.
If a previously effective dosage regimen fails to provide the usual relief, medical advice should be sought immediately as this is often a sign of seriously worsening asthma which would require reassessment of therapy.
HOW SUPPLIED
MAXAIR AUTOHALER, box of one, is supplied in a pressurized aluminum canister with a light blue plastic breath-activated actuator and a light blue mouthpiece cover. DO NOT USE WITH OTHER CANISTERS OR MOUTHPIECES. Each actuation delivers 253 mcg of pirbuterol (as pirbuterol acetate) from the valve and 200 mcg of pirbuterol (as pirbuterol acetate) from the mouthpiece.
Canister net span weight 14.0 g, 400 inhalations (NDC 0089-0815-21) and canister net span weight 2.8 g, 80 inhalations (Hospital Pack: NDC 0089-0817-10, Sample Pack: NDC 0089-0815-08).
The correct amount of medication in each canister cannot be assured after 80 actuations from the 2.8 g canister and 400 actuations from the 14.0 g canister, even though the canister is not completely empty. The canister should be discarded when the labeled numbers of actuations have been used.
Note: The indented statement below is required by the Federal government's Clean Air Act for all products containing or manufactured with chlorofluorocarbons (CFC's).
WARNING: Contains trichloromonofluoromethane and dichlorodifluoromethane, substances which harm public health and environment by destroying ozone in the upper atmosphere.
A notice similar to the above WARNING has been placed in the “Patient's Instructions For Use” portion of this package insert under the Environmental Protection Agency's (EPA's) regulations. The patient's warning states that the patient should consult his or her physician if there are questions about alternatives.
Rx only
Store between 15° and 30°C (59° to 86°F). Failure to use this product within this temperature range may result in improper dosing. For optimal results, the canister should be at room temperature before use. Shake well before using.
The spans of MAXAIR AUTOHALER are under pressure. Do not puncture. Do not use or store near heat or open flame. Exposure to temperature above 120°F may cause bursting. Never throw container into fire or incinerator. Keep out of reach of children. Avoid spraying in eyes.
The light blue plastic actuator supplied with MAXAIR AUTOHALER should not be used with any other product canisters, and actuators from other product should not be used with MAXAIR AUTOHALER canister.
3M Pharmaceuticals
Northridge, CA 91324 3
654800 JULY 2003
Canister net span weight 14.0 g, 400 inhalations (NDC 0089-0815-21) and canister net span weight 2.8 g, 80 inhalations (Hospital Pack: NDC 0089-0817-10, Sample Pack: NDC 0089-0815-08).
The correct amount of medication in each canister cannot be assured after 80 actuations from the 2.8 g canister and 400 actuations from the 14.0 g canister, even though the canister is not completely empty. The canister should be discarded when the labeled numbers of actuations have been used.
Note: The indented statement below is required by the Federal government's Clean Air Act for all products containing or manufactured with chlorofluorocarbons (CFC's).
WARNING: Contains trichloromonofluoromethane and dichlorodifluoromethane, substances which harm public health and environment by destroying ozone in the upper atmosphere.
A notice similar to the above WARNING has been placed in the “Patient's Instructions For Use” portion of this package insert under the Environmental Protection Agency's (EPA's) regulations. The patient's warning states that the patient should consult his or her physician if there are questions about alternatives.
Rx only
Store between 15° and 30°C (59° to 86°F). Failure to use this product within this temperature range may result in improper dosing. For optimal results, the canister should be at room temperature before use. Shake well before using.
The spans of MAXAIR AUTOHALER are under pressure. Do not puncture. Do not use or store near heat or open flame. Exposure to temperature above 120°F may cause bursting. Never throw container into fire or incinerator. Keep out of reach of children. Avoid spraying in eyes.
The light blue plastic actuator supplied with MAXAIR AUTOHALER should not be used with any other product canisters, and actuators from other product should not be used with MAXAIR AUTOHALER canister.
3M Pharmaceuticals
Northridge, CA 91324 3
654800 JULY 2003
