The active component of PROVENTIL HFA (albuterol sulfate) Inhalation Aerosol is albuterol sulfate, USP racemic α¹[(tert-Butylamino)methyl]-4-hydroxy-m-xylene-α, α-diol sulfate (2:1)(salt), a relatively selective beta₂-adrenergic bronchodilator having the following chemical structure:

Albuterol sulfate is the official generic name in the United States. The World Health Organization recommended name for the drug is salbutamol sulfate. 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 solid. It is soluble in water and slightly soluble in ethanol. PROVENTIL HFA Inhalation Aerosol is a pressurized metered-dose aerosol unit for oral inhalation. It contains a microcrystalline suspension of albuterol sulfate in propellant HFA-134a (1,1,1,2-tetrafluoroethane), ethanol, and oleic acid.

Each actuation delivers 120 mcg albuterol sulfate, USP from the valve and 108 mcg albuterol sulfate, USP from the mouthpiece (equivalent to 90 mcg of albuterol base from the mouthpiece). Each canister provides 200 inhalations. 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 by releasing four "test sprays" into the air, away from the face.

This product does not contain chlorofluorocarbons (CFCs) as the propellant.

Inhalation Aerosol and Capsules for Inhalation: Albuterol inhalation aerosol is indicated for the prevention and relief of bronchospasm in patients 4 years of age and older with reversible obstructive airway disease and for the prevention of exercise-induced bronchospasm in patients 4 years of age and older. The capsules for inhalation formulation is particularly useful in patients who are unable to properly use the pressurized aerosol form of albuterol or who prefer an alternative formulation.

Albuterol inhalation aerosol can be used with or without concomitant steroid therapy.

Inhalation Solution: Albuterol inhalation solution is indicated for the relief of bronchospasm in patients 2 years of age or older with reversible obstructive airway disease and acute attacks of bronchospasm.

Inhalation Aerosol

For treatment of acute episodes of bronchospasm or prevention of asthmatic symptoms, the usual dosage for adults and children 4 years of age and older is two inhalations repeated every 4 to 6 hours; in some patients, one inhalation every 4 hours may be sufficient. More frequent administration or a larger number of inhalations are not recommended. It is recommended to "test spray" albuterol inhalation aerosol. Do this by spraying four times into the air before using for the first time and when the inhaler has not been used for a prolonged period of time (i.e., more than 4 weeks).

The use of albuterol inhalation aerosol can be continued as medically indicated to control recurring bouts of bronchospasm. During this time most patients gain optimal benefit from regular use of the inhaler. Safe usage for periods extending over several years has been documented.

If a previously effective dosage regimen fails to provide the usual response, this may be a marker of destabilization of asthma and requires reevaluation of the patient and the treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment (e.g., corticosteroids).

Exercise-Induced Bronchospasm Prevention: The usual dosage for adults and children 4 years and older is two inhalations 15 minutes before exercise.

For treatment, see above.

Inhalation Solution, 0.5%

To avoid microbial contamination, proper aseptic techniques should be used each time the bottle is opened. Precautions should be taken to prevent contact of the dropper tip of the bottle with any surface, including the nebulizer reservoir and associated ventilatory equipment. In addition, if the solution changes color or becomes cloudy, it should not be used.

Children 2 to 12 Years of Age: For children 2 to 12 years of age, initial dosing should be based upon body weight (0.1 to 0.15 mg/kg per dose), with subsequent dosing triated to achieve the desired clinical response. Dosing should not exceed 2.5 mg three to four times daily by nebulization. TABLE 5 outlines approximate dosing according to body weight.

The appropriate volume of the 0.5% inhalation solution should be diluted in sterile normal saline solution to a total volume of 3 ml prior to administration via nebulization.

Adults and Children Over 12 Years of Age: The usual dosage for adults and children 12 years of age and older is 2.5 mg of albuterol administered three to four times daily by nebulization. More frequent administration or higher doses are not recommended. To administer 2.5 mg of albuterol, dilute 0.5 ml of the 0.5% inhalation solution with 2.5 ml of sterile normal saline solution. The wflow rate is regulated to suit the particular nebulizer so that albuterol inhalation solution will be delivered over approximately 5 to 15 minutes.

The use of albuterol sulfate inhalation solution 0.5% can be continued as medically indicated to control recurring bouts of bronchospasm. During this time most patients gain optimal benefit from regular use of the inhalation solution.

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 that would require reassessment of therapy.

Drug compatibility (physical and chemical), efficacy, and safety of albuterol inhalation solution 0.5% when mixed with other drugs in a nebulizer have not been established.

Inhalation Solution, 0.083%

Adults and Children 2 to 12 Years of Age: The usual dosage for adults and children weighing at least 15 kg is 2.5 mg of albuterol (one Ventolin Nebule) administered three to four times daily by nebulization. Children weighing less than 15 kg who require less than 2.5 mg/dose (i.e., less than a full Ventolin Nebule) should use albuterol inhalation solution 0.5% instead of 0.083%. More frequent administration or higher doses are not recommended. To administer 2.5 mg of albuterol, administer the contents of one sterile unit dose Nebule (3 ml of 0.083% inhalation solution) by nebulization. The wflow rate is regulated to suit the particular nebulizer so that albuterol inhalation solution 0.083% will be delivered over approximately 5 to 15 minutes.

The use of albuterol inhalation solution 0.083% can be continued as medically indicated to control recurring bouts of bronchospasm. During this time most patients gain optimal benefit from regular use of the inhalation solution.

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 that would require reassessment of therapy.

Drug compatibility (physical and chemical), efficacy, and safety of albuterol inhalation solution 0.083% when mixed with other drugs in a nebulizer have not been established.

Capsules for Inhalation

The usual dosage of capsules for inhalation for adults and children 4 years of age and older is the contents of one 200-mcg capsule inhaled every 4 to 6 hours using a Rotahaler inhalation device. In some patients, the contents of two 200 mcg capsules inhaled every 4 to 6 hours may be required. Larger doses or more frequent administration is not recommended.

The use of albuterol capsules for inhalation can be continued as medically indicated to control recurring bouts of bronchospasm. During this time most patients gain optimal benefit from regular use of the albuterol capsules for inhalation formulation.

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 that would require reassessment of therapy.

Exercise-Induced Bronchospasm Prevention: The usual dosage of albuterol capsules for inhalation for adults and children 4 years of age and older is the contents of one 200-mcg capsule inhaled using a Rotahaler 15 minutes before exercise.

Ventolin Inhalation Aerosol

Supplied in 6.8-g canisters containing 80 metered inhalations and in 17-g canisters containing 200 metered inhalations. Each actuation delivers 100 mcg of albuterol from the valve and 90 mcg of albuterol from the mouthpiece. Each canister is supplied with a blue oral adapter and patient's instructions. Also available, Ventolin inhalation aerosol refill 17-g canister only with patient's instructions.

The blue adapter supplied with Ventolin inhalation aerosol should not be used with any other product canisters, and adapters from other products should not be used with Ventolin inhalation aerosol canister. The correct amount of medication in each canister cannot be assured after 80 actuations from the 6.8-g canister and 200 actuations from the 17.0-g canister, even though the canister is not completely empty. The canister should be discarded when the labelled number of actuations have been used.

Storage: Store between 15-30°C (59-86°F). As with most inhaled medications in aerosol canisters, the therapeutic effect of this medication may decrease when the canister is cold, for best results, the canister should be at room temperature before use. Shake well before using.

Note the indented statement below is required by the Federal government Clean Air Act for all products containing chlorofluorocarbons.

WARNING: This product 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 instruction leaflet pursuant to regulations of the U.S. Environmental Protection Agency (EPA). The patient's warning states that the patient should consult his or her physician if there are questions about alternatives.

Ventolin Inhalation Solution, 0.5%

Supplied as 20 ml with accompanying calibrated dropper.

Storage: Store between 2-25°C (36-77°F).

Ventolin Nebules Inhalation Solution, 0.083%

Contained in sterile, plastic dose nebules of 3 ml each.

Storage: Protect from light. Store in refrigerator between 2-8°C (36-46°F). Ventolin Nebules Inhalation Solution may be held at room temperature for up to 2 weeks before use. (Nebules must be used within 2 weeks of removal from refrigerator; record date the nebules are removed from the refrigerator in the space provided on the product carton.) Discard if solution becomes discolored. (Note:Ventolin Nebules inhalation solution is colorless.)

Ventolin Rotacaps for Inhalation

The 200-mcg capsule is light blue and clear with "VENTOLIN 200" printed on the blue cap and "GLAXO" printed on the clear body.

Ventolin Rotacaps for inhalation are supplied in a kit containing 100 capsules and one Rotahaler inhalation device with patient's instructions. Also available, Ventolin Rotacaps for inhalation refill with patient's instructions.

Storage: Store between 2-30°C (36-86°F). Replace cap securely after each opening.

Cases of urticaria, angioedema, rash, bronchospasm, hoarseness, oropharyngeal edema, and arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles) have been reported after the use of albuterol.

Inhalation Aerosol

The adverse reactions to albuterol are similar in nature to reactions to other sympathomimetic agents, although the incidence of certain cardiovascular effects is lower with albuterol.

In addition, albuterol, like other sympathomimetic agents, can cause adverse reactions such as hypertension, angina, vertigo, central nervous system stimulation, sleeplessness, and unusual taste.

Inhalation Solutions

The results of clinical trials with albuterol inhalation solution in 135 patients showed the following side effects that were considered probably or possibly drug related.

Central Nervous System: Tremors (20%), dizziness (7%), nervousness (4%), headache (3%), sleeplessness (1%).

Gastrointestinal: Nausea (4%), dyspepsia (1%).

Ear, Nose and Throat: Nasal congestion (1%), pharyngitis (<1%).

Cardiovascular: Tachycardia (1%), hypertension (1%).

Respiratory: Bronchospasm (8%), cough (4%), bronchitis (4%), wheezing (1%).

No clinically relevant laboratory abnormalities related to albuterol inhalation solution administration were determined in these studies.

Capsules for Inhalation

The adverse reactions to albuterol are similar in nature to reactions to other sympathomimetic agents, although the incidence of certain cardiovascular effects is lower with albuterol. Results of clinical trials with albuterol capsules for inhalation 200 mcg in 172 patients aged 12 years and older (adults) and 129 patients aged 4 to 12 years (children) are shown in TABLE 3 and TABLE 4.

In addition, albuterol, like other sympathomimetic agents, can cause adverse reactions such as hypertension, angina, vertigo, and CNS stimulation.

Other short-acting sympathomimetic aerosol bronchodilators (and for inhalation solutions, epinephrine) should not be used concomitantly with albuterol. If additional adrenergic drugs are to be administered by any route, they should be used with caution to avoid deleterious cardiovascular effects.

Monoamine Oxidase Inhibitors or Tricyclic Antidepressants: Albuterol 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 vascular system may be potentiated.

Beta-Blockers: Beta-adrenergic receptor blocking agents not only block the pulmonary effect of beta-agonists, such as albuterol, 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), cardioselective beta-blockers could be considered, although they should be administered with caution.

Diuretics: The ECG changes and/or hypokalemia that may result from the administration of nonpotassium-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 nonpotassium-sparing diuretics.

Digoxin: Mean decreases of 16% to 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 albuterol.

Paradoxical Bronchospasm: Albuterol can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, albuterol 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 or vial. Solutions: Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs and with the home use of nebulizers. It is therefore essential that the physician instruct the patient in the need for further evaluation if his/her asthma becomes worse.

Cardiovascular Effects: Albuterol, like all other beta-adrenergic agonists, can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon after administration of albuterol at recommended doses, if they occur, the drug may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T wave, prolongation of the QT_c interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, albuterol, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

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 albuterol than usual, this may be a marker of destabilization of asthma and requires reevaluation of the patient and treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, (e.g., corticosteroids).

Immediate Hypersensitivity Reactions: Immediate hypersensitivity reactions may occur after administration of albuterol, as demonstrated by rare cases or urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema and, for inhalation aerosol and capsules for inhalation, anaphylaxis.

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 anti-inflammatory agents (e.g., corticosteroids).

Additional Information for Inhalation Aerosol: The contents of albuterol inhalation aerosol are under pressure. 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. Keep out of reach of children.

Additional Information for Inhalation Solution 0.05%: Microbial Contamination: To avoid microbial contamination, proper aseptic technique should be used each time the bottle is opened. Precautions should be taken to prevent contact of the dropper tip of the bottle with any surface, including the nebulizer reservoir and associated ventilatory equipment. In addition, if the solution changes color or becomes cloudy, it should not be used.

Additional Information for Inhalation Capsules: Inhalation of capsule particles may result if damage to the capsule has occurred from handling by the patient.

General

Albuterol, as with 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. Large doses of intravenous albuterol have been reported to aggravate preexisting diabetes mellitus and ketoacidosis. As with other beta-agonists, albuterol 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. Inhalation Aerosol and Inhalation Solutions: 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.

Additional Information for Inhalation Aerosol: Although there have been no reports concerning the use of albuterol inhalation aerosol during labor and delivery, it has been reported that high doses of albuterol administered intravenously inhibit uterine contractions. Although this effect is extremely unlikely as a consequence of aerosol use, it should be kept in mind.

Additional Information for Inhalation Solution: Repeated dosing with 0.15 mg/kg of albuterol inhalation solution in children aged 5 to 17 years who were initially normokalemic has been associated with an asymptomatic decline of 20% to 25% in serum potassium levels.

Information for the Patient

See PATIENT INFORMATION section.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

In a 2-year study in Sprague-Dawley rats, albuterol sulfate caused a significant dose-related increase in the incidence of benign leiomyomas of the mesovarium at dietary doses of 2.0, 10, and 50 mg/kg. [Inhalation Solutions: Approximately 2, 8, and 40 times, respectively, the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 3/5, 3, and 15 times, respectively, the maximum recommended daily inhalation dose in children on a mg/m² basis.] [Capsules for Inhalation: Approximately 7, 35 and 170 times, respectively, the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 3, 15 and 80 times, respectively, the maximum recommended daily dose in children on a mg/m² basis.] [Inhalation Aerosol: Approximately 15, 70 and 340 times, respectively, the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 6, 30 and 160 times, respectively, the maximum recommended daily inhalation dose for children 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 tumorgenicity at dietary doses of up to 500 mg/kg. [Inhalation Solutions: Approximately 200 times the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 75 times the maximum recommended daily inhalation dose for children on a mg/m² basis.] [Capsules for Inhalation: Approximately 850 times the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 400 times the maximum recommended daily inhalation dose for children on a mg/m² basis.] [Inhalation Aerosol: Approximately 1700 times the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 800 times the maximum recommended daily inhalation dose for children on a mg/m² basis.] In a 22-month study in the Golden hamster, albuterol sulfate showed no evidence of tumorgenicity at dietary doses of up to 50 mg/kg [approximately 25 times for adults, 10 times for children [inhalation solution], 120 times for adults, and 55 times for children [capsules for inhalation] and 225 times for adults and 110 times for children [inhalation aerosol] the maximum recommended daily inhalation dose a mg/m² basis).

Albuterol sulfate was not mutagenic in the Ames test with or without metabolic activation using tester strains S. typhimurium TA1537, TA1538, and TA98 or E. coli WP2, WP2uvrA, and WP67. No forward mutation was seen in yeast strain S. cerevisiae S9 nor any mitotic gene conversion in yeast strain S. cerevisiae JD1 with or without metabolic activation. Fluctuation assays in S. typhimurium TA98 and E. coli WP2, both with metabolic activation, were negative. Albuterol sulfate was not clastogenic in a human peripheral lymphocyte assay or in an AH1 strain mouse micronucleus assay at intraperitoneal doses of up to 200 mg/kg.

Reproduction studies in rats demonstrated no evidence of impaired fertility at oral doses up to 50 mg/kg approximately 40 times [inhalation solution], 170 times [capsules for inhalation] and 340 times [inhalation aerosol] the maximum recommended daily inhalation dose for adults on a mg/m² basis.

Pregnancy, Teratogenic Effects, Pregnancy Category C

Albuterol has been shown to be teratogenic in mice. A study in CD-1 mice at subcutaneous doses of 0.025, 0.25, and 2.5 mg/kg (approximately 2/25, 1.0, and 8.0 [inhalation aerosol]; 1/100, 1/10, and 1.0 [inhalation solution]; 1/25, 2/5, and 4 [capsules for inhalation] times, respectively, the maximum recommended daily inhalation dose for adults on a mg/m² basis), showed cleft palate formation in 5 of 111 (4.5%) fetuses at 0.25 mg/kg and in 10 of 108 (9.3%) fetuses at 2.5 mg/kg. The drug did not induce cleft palate formation at the lowest dose, 0.025 mg/kg. Cleft palate also occurred in 22 of 72 (30.5%) fetuses from females treated with 2.5 mg/kg of isoproterenol (positive control) subcutaneously (approximately 1.0 time [solution], 4 times [capsules] and 8 times [inhalation aerosol] the maximum recommended daily inhalation dose for adults on a mg/m² basis).

A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7 of 19 (37%) fetuses when albuterol was administered orally at a 50-mg/kg dose (approximately to 80 [inhalation solution] 340 [capsules for inhalation] 680 [inhalation aerosol] times the maximum recommended daily inhalation dose for adults on a mg/m² basis.

There are no adequate and well-controlled studies in pregnant women. Albuterol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

During worldwide marketing experience, various congenital anomalies, including cleft palate and limb defects, have been rarely reported in the offspring of patients being treated with albuterol. Some of the mothers were taking multiple medications during their pregnancies. No consistent pattern of defects can be discerned, and a relationship between albuterol use and congenital anomalies has not been established.

Labor and Delivery

Because of the potential for beta-agonist interference with uterine contractility, use of albuterol for relief of bronchospasm during labor should be restricted to those patients in whom the benefits clearly outweigh the risk.

Tocolysis: Albuterol has not been approved for the management of preterm labor. The benefit:risk ratio when albuterol is administered for tocolysis has not been established. Serious adverse reactions, including maternal pulmonary edema, have been reported during or following treatment of premature labor with beta₂-agonists, including albuterol.

Nursing Mothers

It is not known whether this drug is excreted in human milk after inhalation of recommended doses. Because of the potential for tumorigenicity shown for albuterol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Inhalation Aerosol and Capsules for Inhalation: Safety and effectiveness in children below 4 years of age have not been established.

Inhalation Solution: The safety and effectiveness of albuterol inhalation solution have been established in children 2 years of age and older. Use of albuterol inhalation solution in these age-groups is supported by evidence from adequate and well-controlled studies of inhalation solution in adults; the likelihood that the disease course, pathophysiology, and the drug's effect in pediatric and adult patients are substantially similar; and published reports of trials in pediatric patients 3 years of age or older. The recommended dose for the pediatric population is based upon three published dose comparison studies of efficacy and safety in children 5 to 17 years, and on the safety profile in both adults and pediatric patients at doses equal to or higher than the recommended doses. The safety and effectiveness of albuterol inhalation solution in children below 2 years of age have not been established.

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/min, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and sleeplessness.) Hypokalemia may also occur. Inhalation Solution Only: In isolated cases in children 2 to 12 years of age, tachycardia with rates >200 beats/min has been observed.

As with all sympathomimetic medications, cardiac arrest and even death may be associated with abuse of albuterol. Treatment consists of discontinuation of albuterol together with appropriate symptomatic therapy. The judicious use of a cardioselective beta-recptor 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 albuterol.

The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/kg (approximately 810 times the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 300 times the maximum recommended daily inhalation dose for children on a mg/m² basis for inhalation solution, and approximately 6800 times the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 3200 times the maximum recommended daily inhalation dose for children on a mg/m² basis for inhalation aerosol or approximately 3400 times the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 1600 times the maximum recommended daily inhalation dose for children on a mg/m² basis for inhalation capsules). In mature rats, the subcutaneous median lethal dose of albuterol sulfate is approximately 450 mg/kg (approximately 365 times the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 135 times the maximum recommended daily inhalation dose for children on a mg/m² basis for inhalation solution and approximately 3000 times the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 1400 times the maximum recommended daily inhalation dose for children on a mg/m² basis for inhalation aerosol or approximately 1500 times the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 1700 times the maximum recommended daily inhalation dose for children on a mg/m² basis for inhalation capsules). In small young rats, the subcutaneous median lethal dose is approximately 2000 mg/kg (approximately 1600 times the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 600 times the maximum recommended daily inhalation dose for children on a mg/m² basis for inhalation solution and approximately 14,000 times the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 6400 times the maximum recommended daily inhalation dose for children on a mg/m² basis for inhalation aerosol or approximately 6800 times the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 3200 times the maximum recommended daily inhalation dose for children on a mg/m² basis for inhalation capsules). The inhalational median lethal dose has not been determined in animals.

Dialysis is not appropriate treatment for overdosage of albuterol capsules for inhalation.

Albuterol formulations are contraindicated in patients with a history of hypersensitivity to albuterol or any of the formulation components.

In vitro studies and in vivo pharmacologic studies have demonstrated that albuterol has a preferential effect on beta₂-adrenergic receptors compared with isoproterenol. While it is recognized that beta₂-adrenergic receptors are the predominant receptors in bronchial smooth muscle, data indicate that there is a population of beta₂-receptors in the human heart existing in a concentration between 10% and 50%. The precise function of these receptors has not been established (see WARNINGS).

The pharmacologic effects of beta-adrenergic agonist drugs, including albuterol, are at least in party attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic- 3¢, 5¢-adenosine monophosphate (cyclic AMP). Increased cyclic 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.

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.

Controlled clinical studies and other clinical experience have shown that 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.

Albuterol is longer acting than isoproterenol in most patients by any route of administration because it is not a substrate for the cellular uptake processes for catecholamines nor for catechol-O-methyl transferase.

Additional Information for Inhalation Aerosol: The effects of rising doses of albuterol and isoproterenol aerosols were studied in volunteers and asthmatic patients. Results in normal volunteers indicated that albuterol is one half to one quarter as active as isoproterenol in producing increases in heart rate. In asthmatic patients similar cardiovascular differentiation between the two drugs was also seen.

Pharmacokinetics

Inhalation Aerosol and Capsules for Inhalation: Because of its gradual absorption from the bronchi, systemic levels of albuterol inhalation aerosol are low after inhalation of recommended doses. Studies undertaken with four subjects administered tritiated albuterol resulted in maximum plasma concentrations occurring within 2 to 4 hours. Due to the sensitivity of the assay method, the metabolic rate and half-life of elimination of albuterol in plasma could not be determined. However, urinary excretion provided data indicating that albuterol has an elimination half-life of 3.8 hours. Approximately 72% of the inhaled dose is excreted within 24 hours in the urine, and consists of 28% as unchanged drug and 44% as metabolite.

Inhalation Solution: Studies in asthmatic patients have shown that less than 20% of a single albuterol dose was absorbed following either intermittent positive-pressure breathing (IPPB) or nebulizer administration; the remaining amount was recovered from the nebulizer and apparatus and expired air. Most of the absorbed dose was recovered in the urine 24 hours after drug administration. Following a 3-mg dose of nebulized albuterol in adults, the maximal albuterol plasma levels at 0.5 hours were 2.1 ng/ml (range, 1.4 to 3.2 ng/ml). There was a significant dose-related response in FEV₁ (forced expiratory volume in 1 second) and peak flow rate. It has been demonstrated that following oral administration of 4 mg of albuterol, the elimination half-life was 5 to 6 hours.

Preclinical

Intravenous studies in rats with albuterol sulfate have demonstrated that albuterol crosses the blood-brain barrier and reaches brain concentrations amounting to approximately 5.0% of the plasma concentrations. In structures outside the 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 beta-agonists and methylxanthines were administered concurrently. The clinical significance of these findings is unknown.

CLINICAL STUDIES

Inhalation Aerosol

In controlled clinical trials involving adults with asthma, the onset of improvement in pulmonary function was within 15 minutes, as determined by both MMEF (maximum midexpiratory wflow rate) and FEV₁ (forced expiratory volume in 1 second). MMEF measurements also showed that near maximum improvement in pulmonary function generally occurs within 60 to 90 minutes following two inhalations of albuterol and that clinically significant improvement generally continues for 3 to 4 hours in most patients. Some patients showed a therapeutic response (defined by maintaining FEV₁ values 15% or more above baseline) that was still apparent at 6 hours. Continued effectiveness of albuterol was demonstrated over a 13-week period in these same trials.

In controlled clinical trials involving children 4 to 12 years of age, FEV₁ measurements showed that maximum improvement in pulmonary function occurs within 30 to 60 minutes. The onset of clinically significant (³15%) improvement in FEV₁ was observed as soon as 5 minutes following 180 mcg of albuterol in 18 of 30 (60%) children in a controlled dose-ranging study. Clinically significant improvement in FEV₁ continued in the majority of patients for 2 hours and in 33% to 47% for 4 hours among 56 patients receiving inhalation aerosol in one pediatric study. In a second study among 48 patients receiving inhalation aerosol, clinically significant improvement continued in the majority for up to 1 hour and in 23% to 40% for 4 hours. In addition, at least 50% of the patients in both studies achieved an improvement in FEF_25%-75% (forced expiratory wflow rate between 25% and 75% of the forced vital capacity) of at least 20% for 2 to 5 hours. Continued effectiveness of albuterol was demonstrated over the 12-week study period.

In other clinical studies in adults and children, two inhalations of albuterol inhalation aerosol taken approximately 15 minutes before exercise prevented exercise-induced bronchospasm, as demonstrated by the maintenance of FEV₁ within 80% of baseline values in the majority of patients. One study in adults also evaluated the duration of the prophylactic effect to repeated exercise challenges, which was evident at 4 hours in the majority of patients and at 6 hours in approximately one third of the patients.

Inhalation Solution

In controlled clinical trials in adults, most patients exhibited an onset of improvement in pulmonary function within 5 minutes as determined by FEV₁. FEV₁ measurements also showed that the maximum average improvement in pulmonary function usually occurred at approximately 1 hour following inhalation of 2.5 mg of albuterol by compressor-nebulizer and remained close to peak for 2 hours. Clinically significant improvement in pulmonary function (defined as maintenance of a 15% or more increase in FEV₁ over baseline values) continued for 3 to 4 hours in most patients, with some patients continuing up to 6 hours.

Published reports of trials in asthmatic children aged 3 years or older have demonstrated significant improvement in either FEV₁ or PEFR within 2 to 20 minutes following single doses of albuterol inhalation solution. An increase of 15% or more in baseline FEV₁ has been observed in children aged 5 to 11 years up to 6 hours after treatment with doses of 0.10 mg/kg or higher of albuterol inhalation solution. Single doses of 3, 4, or 10 mg resulted in improvement in baseline PEFR that was comparable in extent and duration to a 2-mg dose, but doses above 3 mg were associated with heart rate increases of more than 10%.

Capsules for Inhalation

In single, dose-range, crossover trials with albuterol capsules for inhalation in patients 12 years of age and older, the onset of improvement in pulmonary function was within 5 minutes as determined by a 15% increase in forced expiratory volume in 1 second (FEV₁) following administration of either a 200- or 400-mcg dose. Maximum increases in FEV₁ occurred within 60 minutes following inhalation of either dose. The duration of effect (defined as an increase in FEV₁ of 15% or greater in a single-dose study) was 1 to 2 hours after the 200-mcg dose and 3 to 4 hours after the 400 mcg dose. In a single-dose study, an increase in forced expiratory flow rate between 25% and 75% of the forced vital capacity (FEF_25%-75%) of 20% or greater continued for 3 to 4 hours after the 200-mcg dose and for 3 to 6 hours following the 400 mcg dose. A therapeutic response continued for 4 hours in the majority of patients and for 6 hours in 38% of the patients following the 400-mcg dose. Twenty-two percent of the patients receiving the 200-mcg dose had a duration of effect of 8 hours.

In 12-week, double-blind, comparative evaluations in patients 12 years of age and older of one 200-mcg albuterol capsule for inhalation versus two inhalations of albuterol inhalation aerosol, the two dosage regimens were found to be clinically comparable. Based on a 15% or more increase in FEV₁ determinations, both provided a therapeutic response that persisted for 2 or 3 hours in 50% of 231 patients aged 12 years and older. Similar results were found in two controlled, 12-week clinical trials involving 204 children aged 4 to 11 years. Both formulations produced a therapeutic response (defined as maintenance of mean increase over baseline of at least 15% in FEV₁, or 20% in FEF_{25%- 75%}). Therapeutic improvement of FEF_25%-75% persisted for 3 to 5 hours in over 50% of the children throughout the study. Continued effectiveness and safety of albuterol capsules for inhalation were demonstrated over the 12-week study periods in both adults and children.

In other clinical studies in adults and children, one 200-mcg albuterol capsule for inhalation taken approximately 15 minutes before exercise prevented exercise-induced bronchospasm, as demonstrated by the maintenance of FEV₁ within 80% of baseline values in the majority of patients. One study in adults also evaluated the duration of the prophylactic effect to repeated exercise challenges, which was evident at 4 hours in the majority of patients and at 6 hours in approximately one third of the patients.

The action of albuterol may last up to 6 hours or longer. Albuterol should not be used more frequently than recommended. Do not increase the dose or frequency of albuterol without consulting your physician. If you find that treatment with albuterol becomes less effective for symptomatic relief, your symptoms become worse, and/or you need to use the product more frequently than usual, you should seek medical attention immediately. While you are using albuterol, other inhaled drugs and asthma medications should be taken only as directed by your physician. Common adverse effects include palpitations, chest pain, rapid heart rate, and tremor or nervousness. If you are pregnant or nursing, contact your physician about use of albuterol. Effective and safe use of albuterol includes an understanding of the way that it should be administered.

Additional Information for Inhalation Aerosol: In general, the technique for administering albuterol inhalation aerosol to children is similar to that for adults, since children's smaller ventilatory exchange capacity automatically provides proportionally smaller aerosol intake. Children should use albuterol aerosol under adult supervision, as instructed by the patient's physician. (See PATIENT PACKAGE INSERT.)

Additional Information for Inhalation Solutions: Drug compatibility (physical and chemical), efficacy, and safety of albuterol inhalation solution when mixed with other drugs in a nebulizer have not been established. 0.05% Solution Only: To avoid microbial contamination, proper aseptic techniques should be used each time the bottle is opened. Precautions should be taken to prevent contact of the dropper tip of the bottle with any surface, including the nebulizer reservoir and associated ventilatory equipment. In addition, if the solution changes color or becomes cloudy, it should not be used.

See PATIENT PACKAGE INSERT.

Additional Information for Capsules for Inhalation: Children should use albuterol capsules for inhalation under adult supervision, as instructed by the patient's physician.

See PATIENT PACKAGE INSERT.

PATIENT PACKAGE INSERT

Ventolin Inhalation Aerosol

Before using your Ventolin inhalation aerosol, read complete instructions carefully.

Children should use Ventolin inhalation aerosol under adult supervision, as instructed by the patient's doctor.

The blue adapter supplied with Ventolin inhalation aerosol should not be used with any other product canisters, and adapters from other products should not be used with a Ventolin inhalation aerosol canister. The refill canister is to be used only with the blue Ventolin inhalation aerosol adapter.

1. SHAKE THE INHALER WELL immediately before each use. Then remove the cap from the mouthpiece; the strap on the cap will stay attached to the actuator. If the strap is removed from the actuator and lost, the inhaler mouthpiece should be inspected for the presence of foreign objects before each use. Make sure the cannister is fully and firmly inserted into the actuator.

2. BREATHE OUT FULLY THROUGH THE MOUTH, expelling as much air from your lungs as possible. Place the mouthpiece fully into the mouth, holding the inhaler in its upright position and closing the lips around it.

3. WHILE BREATHING IN DEEPLY AND SLOWLY THROUGH THE MOUTH. FULLY DEPRESS THE TOP OF THE METAL CANISTER with your index finger.

4. HOLD YOUR BREATH AS LONG AS POSSIBLE. Before breathing out, remove the inhaler from your mouth and release your finger from the canister.

5. Wait one minute and SHAKE the inhaler again. Repeat steps 2 through 4 for each inhalation prescribed by your doctor.

6. CLEANSE THE INHALER THOROUGHLY AND FREQUENTLY. Remove the metal canister and cleanse the plastic case and cap by rinsing thoroughly in warm, running water at least once a day. After thoroughly drying the plastic case and cap, gently replace the canister into the case with a twisting motion and put the cap back on the mouthpiece.

7. As with all aerosol medications, it is recommended to "test spray" the inhaler into the air before using for the first time and when the inhaler has not been used for a prolonged period of time (i.e., more than 4 weeks).

8. DISCARD THE CANISTER AFTER YOU HAVE USED THE LABELED NUMBER OF INHALATIONS. The correct amount of medication in each inhalation cannot be assured after 80 actuations from the 6.8-g canister and 200 actuations from the 17.0-g canister, even though the canister is not completely empty. The canister should be discarded when the labeled number of actuations have been used. Before you reach the specific number of actuations, you should consult your physician to determine whether a refill is needed. Just as you should not take extra doses without consulting your physician, you also should not stop using Ventolin inhalation aerosol without consulting your physician.

Note the statement below is required by the Federal government Clean Air Act for all products containing chlorofulorocarbons.

This product contains trichloromonofluoromethane and dichlorodifluoromethane, substances which harm the environment by depleting ozone in the upper atmosphere.

Your doctor has determined that this product is likely to help your personal health. USE THIS PRODUCT AS DIRECTED UNLESS INSTRUCTED TO DO OTHERWISE BY YOUR DOCTOR. If you have any questions about alternatives, consult your doctor.

Ventolin Inhalation Solution, 0.5%*

*Potency expressed as albuterol.

Read complete instructions carefully before using.

1. Draw the appropriate volume of Ventolin inhalation solution into the specially marked dropper that comes with each multidose bottle. For children 12 years of age and under, the volume is based upon body weight. Use the dropper volume prescribed by your doctor.

2. Squeeze the solution into the nebulizer reservoir through the appropriate opening, taking care not to touch the tip of the dropper.

3. Add sterile normal saline solution, as your doctor has directed. A general guideline for the amount of saline to add is: For children using 0.25 ml or 1.25 mg of Ventolin inhalation solution, add 2.75 ml of sterile normal saline. For children or adults using 0.5 ml or 2.5 mg of Ventolin inhalation solution, add 2.5 mg of sterile normal saline.

4. Gently swirl the nebulizer to mix the contents and connect it with the mouthpiece or face mask.

5. Connect the nebulizer to the compressor.

6. Sit in a comfortable, upright position; place the mouthpiece in your mouth (or put on the face mask); and turn on the compressor.

7. Breathe as calmly, deeply, and evenly as possible until no more mist is formed in the nebulizer chamber (about 5 to 15 minutes). At this point, the treatment is finished.

8. Clean the nebulizer (see manufacturer's instructions).

Note: Use only as directed by your doctor. More frequent administration or higher doses are not recommended.

To avoid microbial contamination, proper aseptic techniques should be used each time the bottle is opened. Precautions should be taken to prevent contact of the dropper tip of the bottle with any surface, including the nebulizer reservoir and associated ventilatory equipment. In addition, if the solution changes color or becomes cloudy, it should not be used.

The safety and effectiveness of Ventolin inhalation solution have not been determined when one or more drugs are mixed with it in a nebulizer. Check with your doctor before mixing any medications in your nebulizer.

Store between 2-25°C (36-77°F).

Ventolin Nebules Inhalation Solution, 0.083%*

*Potency expressed as albuterol.

Read complete instructions carefully before using.

1. Twist open the top of one Nebule unit-of-use container and squeeze the entire contents into the nebulizer reservoir.

2. Connect the nebulizer reservoir to the mouthpiece or face mask.

3. Connect the nebulizer to the compressor.

4. Sit in a comfortable, upright position; place the mouthpiece in your mouth (or put on the face mask); and turn on the compressor.

5. Breathe as calmly, deeply, and evenly as possible until no more mist is formed in the nebulizer chamber (about 5 to 15 minutes). At this point, the treatment is finished.

6. Clean the nebulizer (see manufacturer's instructions).

Note: Use only as directed by your doctor. More frequent administration or higher doses are not recommended.

The safety and effectiveness of Ventolin Nebules inhalation solution 0.083% have not been determined when one or more drugs are mixed with it in a nebulizer. Check with your doctor before mixing any medications in your nebulizer.

Protect from light. Store in a refrigerator between 2-8°C (36-46°F). Ventolin Nebules inhalation solution may be held at room temperature for up to 2 weeks before use. (Nebules must be used within 2 weeks of removal from refrigerator; record date the nebules are removed from the refrigerator in the space provided on the product carton.) Discard if solution becomes discolored. (Note: Ventolin Nebules inhalation solution is colorless.)

Ventolin Rotacaps Capsules for Inhalation

Instructions for Administration of Ventolin for Inhalation with the Rotahaler Inhalation Device

Note: Ventolin Rotacaps for inhalation should be stored in a dry place and not exposed to temperature extremes. Ventolin Rotacaps for inhalation should be stored below 86°F. Do not remove Ventolin Rotacaps for inhalation from the original packaging until you are ready to use the Rotahaler inhalation device.

Bottle Packs: Store Ventolin Rotacaps for inhalation capsules in the original bottle. You may transfer a daily supply of capsules to the smaller, reusable bottle that fits into the carrying case. Do not remove capsules from the bottle until you are ready to use the Rotahaler inhalation device.

Hospital Unit Dose Pack: To remove a capsule from a unit dose blister pack, tear off one section of the paper backing starting at the corner marked "PEEL."

The Ventolin Rotacaps for inhalation capsules appear partially filled; the partial filling of dry powder facilitates the delivery of the medication.

Children should use Ventolin Rotacaps for inhalation capsules under adult supervision, as instructed by the patient's doctor.

Preparing the Rotahaler For Use:

1. Remove the Rotahaler from its container and check to be sure it is clean and dry. Inspect the mouthpiece for the presence of foreign objects before each use.

2. Keeping the Rotahaler upright (vertical), hold the darker colored end in one hand and turn the lighter colored end as far as it will go in either direction.

3. Take a Ventolin Rotacaps for inhalation capsule from its pack and insert the clear (thinner) end into the raised octagonal hole located in the lighter colored end of the Rotahaler inhalation device. This will force the previously used capsule shell into the Rotahaler chamber. Push the new capsule in until it is level with the top of the hole. (Note: When first using or after washing the Rotahaler, the raised octagonal hole will be empty).

4. Hold the Rotahaler level (horizontally) with the white dot uppermost and turn the lighter colored end (the end where the capsule was inserted) as far as it will go in the opposite direction. This will open the capsule.

YOUR ROTAHALER IS NOW READY FOR USE. KEEP LEVEL.

Using the Rotahaler:

5. Keep the Rotahaler level. Breathe out fully. Raise the Rotahaler to your mouth and gently place the mouthpiece (darker colored end) between your teeth and lips. Avoid inserting the Rotahaler beyond teeth.

6. Firmly grasp the Rotahaler on the dark blue portion prior to inhalation (breathing in) to avoid accidental inhalation of the device.

7. Breathe in through your mouth as quickly and as deeply as you can.

8. Hold your breath briefly; then remove the Rotahaler from your mouth and exhale.

9. If a dose of two capsules is recommended by your doctor, repeat steps 2 through 8.

After Using the Rotahaler:

1. After each use, pull the two halves of the Rotahaler apart and throw away the loose capsule shells.

2. Reassemble the Rotahaler and replace it in its container.

Care of Your Rotahaler: Keep the Rotahaler clean and dry at all times. Once every 2 weeks wash the two halves of your Rotahaler in warm water. Make sure that the empty capsule shell is removed from the raised octagonal hole before washing your inhaler.

Dry your Rotahaler thoroughly before reassembling it. Avoid excessive heat.

Dosage: Use only as directed by your doctor.

Warnings: The action of Ventolin Rotacaps for inhalation capsules may last for 6 hours or longer. Ventolin Rotacaps for inhalation capsules should not be used more frequently than recommended. Do not increase the dose or frequency of Ventolin Rotacaps for inhalation capsules without consulting your doctor. If you find that treatment with Ventolin Rotacaps for inhalation capsules becomes less effective for symptomatic relief, your symptoms become worse, and/or you need to use the product more frequently than usual, you should seek medical attention immediately. While taking Ventolin Rotacaps for inhalation capsules, other inhaled drugs and asthma medicines should be used only as directed by your doctor.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

ALBUTEROL (SALBUTAMOL) HFA INHALER - ORAL

(al-BUE-ter-ol)(sal-BUE-tah-mol)

COMMON BRAND NAME(S): Proventil HFA, Ventolin HFA

USES: Albuterol (also known as salbutamol) is used to prevent and treat wheezing and shortness of breath caused by breathing problems (e.g., asthma, chronic obstructive pulmonary disease). It is also used to prevent asthma brought on by exercise. Albuterol belongs to a class of drugs known as bronchodilators. It works in the airways by opening breathing passages and relaxing muscles. Controlling symptoms of breathing problems can decrease time lost from work or school.

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start using this medication and each time you get a refill. Follow the illustrated directions for use of the inhaler. If any of the information is unclear, consult your doctor or pharmacist.

Follow the instructions for test sprays in the air (priming) if you are using a new canister, or if you have not used it for 2 weeks or longer, or if the inhaler has been dropped. Avoid spraying the medication in your eyes.

Before each dose, shake the inhaler well. Inhale this medication by mouth, usually every 4 to 6 hours as needed or as directed by your doctor. Dosage is based on your medical condition and response to treatment. Do not increase your dose or use it more frequently than prescribed without your doctor's approval.

If you are using this medication to prevent asthma brought on by exercise, inhale 2 puffs 15 to 30 minutes before exercise or as directed by your doctor.

If you find it difficult to use this inhaler correctly, it may help to use a spacer device with this inhaler. Ask your doctor or pharmacist for more information.

Clean and dry the inhaler at least once a week as directed in the Patient Information Leaflet. It should also be cleaned anytime it appears to be clogged or is not working properly.

If you use other asthma drugs (including inhaled medications), ask your doctor about how to properly use this medication with your other asthma medicines.

If this medication stops working well, or if your breathing symptoms become worse, or if you need to use this medication more frequently than usual, seek immediate medical attention.

Keep track of the number of inhalations you use, and discard the inhaler after you have used the labeled number of inhalations on the product package. Test sprays used to prime the inhaler should also be counted.

SIDE EFFECTS: Nervousness, shaking (tremor), mouth/throat dryness or irritation, cough, dizziness, headache, trouble sleeping, or nausea may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: fast/pounding heartbeat, muscle cramps/weakness.

Seek immediate medical attention if any of these rare but very serious side effects occur: chest pain, irregular heartbeat.

Rarely, this medication has caused severe (rarely fatal), sudden worsening of breathing problems/asthma (paradoxical bronchospasm). If you experience sudden wheezing, seek immediate medical attention.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using albuterol, tell your doctor or pharmacist if you are allergic to it; or if you have had a serious reaction to similar drugs (e.g., metaproterenol, terbutaline); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart problems (e.g., irregular heartbeat, angina, heart attack), high blood pressure, diabetes, low levels of potassium in the blood, seizure, overactive thyroid (hyperthyroidism).

This drug may make you dizzy. Use caution while driving, using machinery, or doing any activity that requires alertness. Limit alcoholic beverages.

Before having surgery, tell your doctor or dentist that you are using this medication.

Caution is advised when using this drug in older adults since they may be more sensitive to its effects, especially the effects on the heart.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Avoid taking MAO inhibitors (e.g., furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine) within 2 weeks before, during, or after treatment with this medication. In some cases a serious, possibly fatal drug interaction may occur.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: adrenaline-like drugs (e.g., ephedrine, epinephrine), beta blockers (e.g., atenolol, propranolol), digoxin, tricyclic antidepressants (e.g., amitriptyline, nortriptyline), "water pills" (diuretics such as furosemide, hydrochlorothiazide).

Check the labels on all your medicines (e.g., cough-and-cold products, diet aids) because they may contain ingredients that could increase heart rate or blood pressure. Ask your pharmacist about using those products safely.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: fast/pounding/irregular heartbeat, severe shaking (tremors), seizures.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., pulmonary function tests, blood pressure, levels of potassium in the blood) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Avoid allergens/irritants such as smoke, pollen, pet dander, dust, or molds that may worsen breathing problems.

Learn to use a peak flow meter, use it daily, and promptly report worsening breathing problems (such as readings in the yellow/red range, increased use of quick-relief inhalers).

Ask your doctor or pharmacist whether you should have an annual flu shot.

MISSED DOSE: If you are using this medication on a prescribed schedule and miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-77 degrees F (15-25 degrees C) away from light and moisture. It is best to store the inhaler with the mouthpiece down. Do not puncture the canister or expose it to high heat or open flame. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.