Home Page Main Page  Previous   Next 

Albuterol  (0115)
[ al-byoo'-ter-ole ]
Ingredients: Albuterol
Indications: Asthma; Bronchospasm, exercise- induced
Pregnancy Category: C
FDA Approved: 1981- 12- 01
Classes: Adrenergic agonists; Bronchodilators; Orphan Drugs; WHO Formulary
HCFA Jcodes: J7618, J7619, J7620
Brand Names: Accuneb - US ; Aerolin - Brazil, Chile, Greece ; Airhexal - Philippines ; Airomir - Australia, Canada, France, Hong-kong, Malaysia, Singapore, Taiwan, Thailand ; Almotex - Philippines ; Asmacaire - Philippines ; Asmadil - AFRICA(Except South-africa ) ; Asmalin Pulmoneb - Philippines ; Asmasal - Thailand ; Asmatol - Argentina ; Asmaven - England ; Asmavent - Canada ; Asmidon - Japan ; Asmol CFC-Free - Australia ; Asmol Uni-Dose - New-zealand ; Asmovent - Malaysia ; Assal - Mexico ; Asthalin - India ; Azmasol - Singapore ; Broncho-Spray - Germany ; Broncovaleas - Italy ; Bronter - Colombia ; Brytolin - Philippines ; Butahale - Singapore ; Buto-Asma - Singapore, Spain, Thailand ; Butomix - Peru ; Butotal - Chile ; Buventol - Singapore, Taiwan ; Buventol Easyhaler - France, Indonesia, Thailand ; Cletal - Philippines ; Cobutolin - England ; Cybutol - Hong-kong ; Dilatamol - Indonesia ; Emplusal - Philippines ; Epaq Inhaler - Australia ; Exafil - Mexico ; Farcolin - MIDDLEEAST ; Glisend - Indonesia ; Grafalin - Indonesia ; Hivent DS - Philippines ; Krosalburol - Ecuador ; Libretin - Philippines ; Medolin - Singapore ; Mozal - Taiwan ; Novosalmol - Canada ; Parasma - Colombia ; Proventil - US ; Proventil HFA - US ; Proventil Repetabs - US ; Provexel NS - Philippines ; Prox-S - Philippines ; Pulmol-S - Peru ; Respax - AUSTRALIA; New-zealand ; Respreve - Hong-kong ; Sabutol - Singapore ; Salbetol - India ; Salbron - Indonesia ; Salbulin - Costa-rica, Dominican-republic, El-salvador, England, Guatemala, Honduras, Panama ; Salbutalan - Mexico ; Salbutan - Venezuela ; Salbutin - MIDDLEEAST(Except Israel ) ; Salbutol - Korea, Peru ; Salbutron SR - Korea ; Salbuven - Indonesia ; Salbuvent - Norway ; Salda - Thailand ; Salden - Costa-rica, Ecuador, El-salvador, Guatemala, Honduras, Nicaragua, Panama ; Salmaplon - India ; Salmol - China ; Salmundin Retard - Germany ; Salomol - Taiwan ; Sedalin - Philippines ; Sultanol - Austria, Germany, Japan ; Suprasma - Indonesia ; Teoden - Brazil ; Tobybron - Indonesia ; Venalax - Philippines ; Vencronyl - Philippines ; Venetlin - Japan ; Ventilan - Colombia, Portugal ; Ventilastin Novolizer - Germany ; Ventimax - South-africa ; Ventodisks - China ; Ventol - MIDDLEEAST(Except Israel ) ; Ventolin - US; Argentina, Belgium, Bulgaria, Canada, China, Costa-rica, Czech-republic, Ecuador, El-salvador, Guatemala, Honduras, Hong-kong, Hungary, Indonesia, Ireland, Italy, Malaysia, Mexico, Netherlands, Nicaragua, Panama, Paraguay, Peru, Philippines, Spain, Switzerland, Taiwan, Thailand, Uruguay, Venezuela ; Ventolin CFC-Free - Australia ; Ventoline - Denmark, Finland, France, Norway, Sweden ; Ventolin HFA - US ; Ventolin Rotacaps - US ; Volmax - MIDDLEEAST, US; China, Ecuador, Hong-kong, New-zealand ; Vospire - US ; Zebu - Thailand ; Zenmolin - MIDDLEEAST; Hong-kong ; Zibil - Mexico ;
DEA schedules: (none)
Cost of therapy: $5.24 ( Asthma ; Generic Tablets (Phys. Total Care) ; 2 mg ; 4 tablet(s)/day ; 30 day supply )
$6.76 ( Asthma ; Generic Tablets (Phys. Total Care) ; 4 mg ; 4 tablets/day ; 30 day supply )
$21.35 ( Asthma ; Generic Aerosol ; 90 mcg;17 gm ; 8 inhalation(s)/day ; 25 day supply )
$38.39 ( Asthma ; Ventolin Aerosol ; 90 mcg;17 gm ; 8 inhalation(s)/day ; 25 day supply )
$62.38 ( Asthma ; Proventil ; 2 mg ; 4 tablet(s)/day ; 30 day supply )
$104.12 ( Asthma ; Proventil ; 4 mg ; 4 tablets/day ; 30 day supply )
$167.00 ( Asthma ; Volmax Extended-Release ; 4 mg ; 4 tablet(s)/day ; 30 day supply )

Administration Route:Oral

DESCRIPTION
 
Note: The trade names have been used throughout this monograph for clarity.

Ventolin Tablets
  Ventolin tablets contain albuterol sulfate, the racemic form of albuterol and a relatively selective beta2 - adrenergic bronchodilator. Albuterol sulfate has the chemical name (±)α1- [( tert - butylamino)methyl]- 4- hydroxy- m - xylene- α, α′- diol sulfate (2:1)(salt).
Albuterol sulfate has a molecular weight of 576.7, and the empirical formula is (C13 H21 NO3 )2 ·H2 SO4 . Albuterol sulfate is a white crystalline powder, soluble in water and slightly soluble in ethanol.
The World Health Organization recommended name for albuterol base is salbutamol.
Each Ventolin tablet contains 2 or 4 mg of albuterol as 2.4 or 4.8 mg, respectively, of albuterol sulfate for oral administration. Each tablet also contains the inactive ingredients corn starch, lactose, and magnesium stearate.

Ventolin Syrup
  Ventolin syrup contains albuterol sulfate, the racemic form of albuterol, a relatively selective beta2 - adrenergic bronchodilator. Albuterol sulfate has the chemical name α1- [( tert - butylamino)methyl]- 4- hydroxy- m - xylene- α, α′- diol sulfate (2:1)(salt).
The molecular weight of albuterol sulfate is 576.7, and the empirical formula is (C13 H21 NO3 )2 ·H2 SO4 . Albuterol sulfate is a white crystalline powder, soluble in water and slightly soluble in ethanol. The World Health Organization's recommended name for albuterol base is salbutamol.
Ventolin syrup for oral administration contains 2 mg of albuterol as 2.4 mg of albuterol sulfate in each teaspoonful (5 ml). The inactive ingredients for Ventolin syrup include: citric acid anhydrous; FD&C yellow no. 6; flavor strawberry artificial F- 8636; hydroxypropyl methylcellulose 2906 or 2910; saccharin; sodium benzoate; sodium citrate dihydrate; and water purified. The pH of the syrup is between 3.0 and 4.5.

Volmax Extended-Release Tablets
  Volmax (albuterol sulfate) extended- release tablets contain albuterol sulfate, the racemic form of albuterol and a relatively selective beta2 - adrenergic bronchodilator, in an extended- release formulation. Albuterol sulfate has the chemical name (±) α1 - [( tert - butylamino)methyl]- 4- hydroxy- m - xylene- α, α′- diol sulfate (2:1) (salt).
Albuterol sulfate has a molecular weight of 576.7, and the molecular formula is (C13 H21 NO3 )2 ·H2 SO4 . Albuterol sulfate is a white crystalline powder, soluble in water and slightly soluble in ethanol.
The World Health Organization recommended name for albuterol base is salbutamol.
Each Volmax extended- release tablet for oral administration contains 4 mg or 8 mg of albuterol as 4.8 mg or 9.6 mg, respectively, of albuterol sulfate in a nondeformable cellulosic material that serves as the rate- controlling membrane. Each tablet also contains the inactive ingredients cellulose acetate, croscarmellose sodium, FD&C blue no. 1 (4 mg tablet only), hydroxypropyl cellulose (8 mg tablet only), hydroxypropyl methylcellulose, magnesium stearate, povidone, silica, sodium chloride, and titanium dioxide.

CLINICAL PHARMACOLOGY
 

Ventolin Tablets
  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 part 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.
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.

Preclinical
  Intravenous (IV) 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 are administered concurrently. The clinical significance of these findings is unknown.

Pharmacokinetics
  Albuterol is rapidly absorbed after oral administration of 4 mg Ventolin tablets in normal volunteers. Maximum plasma concentrations of about 18 ng/ ml of albuterol are achieved within 2 hours, and the drug is eliminated with a half- life of about 5 hours.
In other studies, the analysis of urine samples of patients given 8 mg of tritiated albuterol orally showed that 76% of the dose was excreted over 3 days, with the majority of the dose being excreted within the first 24 hours. Sixty percent (60%) of this radioactivity was shown to be the metabolite. Feces collected over this period contained 4% of the administered dose.

Ventolin Syrup
  The primary action of beta- adrenergic drugs, including albuterol, is to stimulate adenyl cyclase, the enzyme which catalyzes the formation of cyclic- 3′, 5′- adenosine monophosphate (cyclic AMP) from adenosine triphosphate (ATP) in beta- adrenergic cells. The cyclic AMP thus formed mediates the cellular responses. 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.
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.
In controlled clinical trials, albuterol has been shown 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 ECG 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.

Preclinical
  Intravenous (IV) studies in rats with albuterol sulfate have demonstrated that albuterol crosses the blood- brain barrier and reaches brain concentrations that are amounting to approximately 5.0% 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 beta- agonists and methylxanthines are administered concurrently. The clinical significance of these findings is unknown.

Pharmacokinetics
  Albuterol is rapidly and well absorbed following oral administration. After oral administration of 10 ml of Ventolin syrup (4 mg albuterol) in normal volunteers, maximum plasma albuterol concentrations of about 18 ng/ ml are achieved within 2 hours, and the drug is eliminated with a half- life of about 5- 6 hours.
In other studies, the analysis of urine samples of patients given 8 mg of tritiated albuterol orally showed that 76% of the dose was excreted over 3 days, with the majority of the dose being excreted within the first 24 hours. Sixty percent (60%) of this radioactivity was shown to be the metabolite. Feces collected over this period contained 4% of the administered dose.

Volmax Extended-Release Tablets
  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 indicates 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, Volmax Extended- Release Tablets .)
The pharmacologic effects of beta- adrenergic agonist drugs, including albuterol, are at least in part attributable to stimulation through beta- adrenergic receptors on 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.
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.

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 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 occurence 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.

Pharmacokinetics and Disposition
  In a single- dose study comparing one 8 mg Volmax extended- release tablet with two 4 mg immediate- release Ventolin (albuterol sulfate) tablets in 17 normal adult volunteers, the extent of availability of Volmax extended- release tablets was shown to be about 80% of Ventolin tablets with or without food. In addition, lower mean peak plasma concentration and longer time to reach the peak level were observed with Volmax extended- release tablets as compared with Ventolin tablets. The single- dose study results also showed that food decreases the rate of absorption of albuterol from Volmax extended- release tablets without altering the extent of bioavailability. In addition, the study indicated that food causes a more gradual increase in the fraction of the available dose absorbed from the extended- release formulation as compared with the fasting condition.
In another single- dose study in adults, 8 mg and 4 mg Volmax extended- release tablets were shown to deliver dose- proportional plasma concentrations in the fasting state. Definitive studies for the effect of food on 4 mg Volmax extended- release tablets have not been conducted. However, since food lowers the rate of absorption of 8 mg Volmax extended- release tablets, it is expected that food reduces the rate of absorption of 4 mg Volmax extended- release tablets also.
Volmax extended- release tablets have been formulated to provide duration of action of up to 12 hours. In an 8 day, multiple- dose, crossover study, 15 normal adult male volunteers were given 8 mg Volmax extended- release tablets every 12 hours or 4 mg Ventolin (albuterol sulfate) tablets every 6 hours. Each dose of Volmax extended- release tablets and the corresponding doses of Ventolin tablets were administered in the postprandial state. Steady- state plasma concentrations were reached within 2 days for both formulations. Fluctuations (Cmax - Cmin / Caverage ) in plasma concentrations were similar for Volmax extended- release tablets administered at 12 hour intervals and Ventolin tablets administered every 6 hours. In addition, the relative bioavailability of Volmax extended- release tablets was approximately 100% of the immediate- release tablet at steady state. A summary of these results is shown in TABLE 1 .
TABLE 1    Mean Values at Steady State
  Volmax Ventolin
Cmax 13.7 ng/ ml 13.9 ng/ ml
Cmin 8.1 ng/ ml 8.1 ng/ ml
Tmax 6.0 hours 2.6 hours
T½ 9.3 hours 7.2 hours
AUC 134 ng·h/ ml 132 ng·h/ ml

Pharmacokinetic studies of 4 and 8 mg Volmax extended- release tablets have not been conducted in pediatric patients. Bioavailability of 4 and 8 mg Volmax extended- release tablets in pediatric patients relative to 2 and 4 mg immediate- release albuterol has been extrapolated from adult studies showing comparability at steady- state dosing and reduced bioavailability after single dose administration.

CLINICAL STUDIES
 

Ventolin Tablets
  In controlled clinical trials in patients with asthma, the onset of improvement in pulmonary function, as measured by maximum midexpiratory flow rate (MMEF), was within 30 minutes after a dose of Ventolin tablets, with peak improvement occurring between 2 and 3 hours. In controlled clinical trials in which measurements were conducted for 6 hours, clinically significant improvement (defined as maintaining a 15% or more increase in forced expiratory volume in 1 second [FEV1 ] and a 20% or more increase in MMEF over baseline values) was observed in 60% of patients at 4 hours and in 40% at 6 hours. In other single- dose, controlled clinical trials, clinically significant improvement was observed in at least 40% of the patients at 8 hours. No decrease in the effectiveness of Ventolin tablets was reported in patients who received long- term treatment with the drug in uncontrolled studies for periods up to 6 months.

Ventolin Syrup
  In controlled clinical trials in patients with asthma, the onset of improvement in pulmonary function, as measured by maximal midexpiratory flow rate (MMEF) and forced expiratory volume in 1 second (FEV1 ), was within 30 minutes after a dose of Ventolin syrup. Peak improvement of pulmonary function occurred between 2 and 3 hours. In a controlled clinical trial involving 55 children, clinically significant improvement (defined as maintenance of mean values over baseline of 15% or 20% or more in the FEV1 and MMEF, respectively) continued to be recorded up to 6 hours. No decrease in the effectiveness was reported in one uncontrolled study of 32 children who took Ventolin syrup for a 3 month period.

INDICATIONS AND USAGE
 

Ventolin Tablets
  Ventolin tablets are indicated for the relief of bronchospasm in adults and children 6 years of age and older with reversible obstructive airway disease.

Ventolin Syrup
  Ventolin syrup is indicated for the relief of bronchospasm in adults and children 2 years of age and older with reversible obstructive airway disease.

Volmax Extended-Release Tablets
  Volmax extended- release tablets are indicated for the relief of bronchospasm in adults and children 6 years of age and older with reversible obstructive airway disease.

CONTRAINDICATIONS
 

Ventolin Tablets
  Ventolin tablets are contraindicated in patients with a history of hypersensitivity to albuterol or any of its components.

Ventolin Syrup
  Ventolin syrup is contraindicated in patients with a history of hypersensitivity to albuterol or any of its components.

Volmax Extended-Release Tablets
  Volmax extended- release tablets are contraindicated in patients with a history of hypersensitivity to albuterol or any of its components.

WARNINGS
 

Ventolin Tablets
 

Paradoxical Bronchospasm
  Ventolin tablets can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, Ventolin tablets should be discontinued immediately and alternative therapy instituted.

Cardiovascular Effects
  Ventolin tablets, 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 Ventolin tablets 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 QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, Ventolin tablets, 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 Ventolin tablets 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.

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.

Immediate Hypersensitivity Reactions
  Immediate hypersensitivity reactions may occur after administration of albuterol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema. Albuterol, like other beta- adrenergic agonists, can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/ or electrocardiographic changes.
Rarely, erythema multiforme and Stevens- Johnson syndrome have been associated with the administration of oral albuterol sulfate in children.

Ventolin Syrup
 

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 Ventolin syrup than usual, this may be a marker of destabilization of asthma and requires re- evaluation of the patient and the treatment regimen, giving special consideration to the possible need for anti- inflammatory treatment, e.g., corticosteroids.

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.

Cardiovascular Effects
  Ventolin syrup, 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 Ventolin syrup 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 QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, Ventolin syrup, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Paradoxical Bronchospasm
  Ventolin syrup can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, Ventolin syrup should be discontinued immediately and alternative therapy instituted.

Immediate Hypersensitivity Reactions
  Immediate hypersensitivity reactions may occur after administration of albuterol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema.
Rarely, erythema multiforme and Stevens- Johnson syndrome have been associated with the administration of oral albuterol sulfate in children.

Volmax Extended-Release Tablets
  Immediate hypersensitivity reactions may occur after administration of albuterol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema.

Cardiovascular Effects
  Volmax extended- release tablets, 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 Volmax extended- release tablets 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 QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, Volmax extended- release tablets, 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 Volmax extended- release tablets than usual, 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.

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.

Paradoxical Bronchospasm
  Volmax extended- release tablets can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, Volmax extended- release tablets should be discontinued immediately and alternative therapy instituted.
Rarely, erythema multiforme and Stevens- Johnson syndrome have been associated with the administration of oral albuterol in children.

PRECAUTIONS
 

Ventolin Tablets
 

General
  Albuterol, as with all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, hypertension, and cardiac arrhythmia; in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines. Clinically significant changes in systolic and diastolic blood pressure have been seen in individual patients and could be expected to occur in some patients after use of any beta- adrenergic bronchodilator.
Large doses of IV 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.

Information for the Patient
  The action of Ventolin tablets may last up to 8 hours or longer. Ventolin tablets should not be taken more frequently than recommended. Do not increase the dose or frequency of Ventolin tablets without consulting your physician. If you find that treatment with Ventolin tablets becomes less effective for symptomatic relief, your symptoms get worse, and/ or you need to take the product more frequently than usual, you should seek medical attention immediately. While you are taking Ventolin tablets, other asthma medications and inhaled drugs 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 Ventolin tablets. Effective and safe use of Ventolin tablets includes an understanding of the way that it should be administered.

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 (approximately ½, 3, and 15 times, respectively, the maximum recommended daily oral dose for adults on a mg/ m2basis or 2/ 5, 2, and 10 times, respectively, the maximum recommended daily oral dose for children on a mg/ m2basis). 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 65 times the maximum recommended daily oral dose for adults on a mg/ m2basis or approximately 50 times the maximum recommended daily oral dose for children on a mg/ m2basis). In a 22 month study in the Golden hamster, albuterol sulfate showed no evidence of tumorigenicity at dietary doses of up to 50 mg/ kg (approximately 8 times the maximum recommended daily oral dose for adults on a mg/ m2basis or approximately 7 times the maximum recommended daily oral dose for children on a mg/ m2basis).
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 15 times the maximum recommended daily oral dose for adults on a mg/ m2basis).

Pregnancy, Teratogenic Effects, Pregnancy Category C
  Albuterol has been shown to be teratogenic in mice. A study in CD- 1 mice at subcutaneous (SC) doses of 0.025, 0.25, and 2.5 mg/ kg (approximately 3/ 1000, 3/ 100, and 3/ 10 times, respectively, the maximum recommended daily oral dose for adults on a mg/ m2basis) 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 3/ 10 times the maximum recommended daily oral dose for adults on a mg/ m2basis).
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 25 times the maximum recommended daily oral dose for adults on a mg/ m2basis).
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.

Use in Labor and Delivery
  Because of the potential for beta- agonist interference with uterine contractility, use of Ventolin tablets 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. 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
  Safety and effectiveness in children below 6 years of age have not been established.

Ventolin Syrup
 

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. Clinically significant changes in systolic and diastolic blood pressure have been seen and could be expected to occur in some patients after use of any beta- adrenergic bronchodilator.
Large doses of IV albuterol have been reported to aggravate pre- existing diabetes 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.

Information for the Patient
  The action of Ventolin syrup may last up to 6 hours or longer. Ventolin syrup should not be taken more frequently than recommended. Do not increase the dose or frequency of doses of Ventolin syrup without consulting your physician. If you find that treatment with Ventolin syrup becomes less effective for symptomatic relief, your symptoms become worse, and/ or you need to take the product more frequently than usual, you should seek medical attention immediately. While you are taking Ventolin syrup, 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, tremor, or nervousness. If you are pregnant or nursing, contact your physician about the use of Ventolin syrup. Effective use of Ventolin syrup includes an understanding of the way that it should be administered.

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 and above dietary doses of 2 mg/ kg (corresponding to less than the maximum recommended daily oral dose for adults and children on a mg/ m2basis). In another study, this effect was blocked by the coadministration of propranolol, a nonselective beta- adrenergic antagonist.
In an 18 month study in CD- 1 mice, albuterol sulfate showed no evidence of tumorigenicity at dietary doses up to 500 mg/ kg (approximately 65 times the maximum recommended daily oral dose for adults on a mg/ m2basis and approximately 50 times the maximum recommended daily oral dose for children on a mg/ m2basis). In a 22 month study in the Golden Hamster, albuterol sulfate showed no evidence of tumorigenicity at dietary doses up to 50 mg/ kg (approximately 8 times the maximum recommended daily oral dose for adults and children on a mg/ m2basis).
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.
Reproduction studies in rats demonstrated no evidence of impaired fertility at oral doses of albuterol sulfate up to 50 mg/ kg (approximately 15 times the maximum recommended daily oral dose for adults on a mg/ m2basis).

Pregnancy, Teratogenic Effects, Pregnancy Category C
  Albuterol sulfate has been shown to be teratogenic in mice. A study in CD- 1 mice at subcutaneous (SC) doses at and above 0.25 mg/ kg (corresponding to less than the maximum recommended daily oral dose for adults on a mg/ m2basis), induced cleft palate formation in 5 of 111 (4.5%) fetuses. At a SC dose of 2.5 mg/ kg (corresponding to less than the maximum recommended daily oral dose for adults on a mg/ m2basis), albuterol sulfate induced cleft palate formation in 10 of 108 (9.3%) fetuses. The drug did not induce cleft palate formation when administered at a SC dose of 0.025 mg/ kg (significantly less than the maximum recommended daily oral dose for adults on a mg/ m2basis). Cleft palate also occurred in 22 of 72 (30.5%) fetuses from females treated with 2.5 mg/ kg of isoproterenol (positive control) administered subcutaneously.
A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7 of 19 (37%) fetuses when albuterol was administered orally at a dose of 50 mg/ kg (approximately 25 times the maximum recommended daily oral dose for adults on a mg/ m2basis).
Studies in pregnant rats with tritiated albuterol demonstrated that approximately 10% of the circulating maternal drug is transferred to the fetus. Disposition in the fetal lungs is comparable to maternal lungs, but fetal liver disposition is 1% of the maternal liver levels.
There are no adequate and well- controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, 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 reported in the offspring of patients being treated with albuterol. Some of the mothers were taking multiple medications during their pregnancies. Because no consistent pattern of defects can be discerned, a relationship between albuterol use and congenital anomalies has not been established.

Use in Labor and Delivery
 

Use in Labor
  Because of the potential for beta- agonist interference with uterine contractility, use of Ventolin syrup 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. 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
  Safety and effectiveness in children below the age of 12 years have not been established.

Volmax Extended-Release Tablets
 

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. Clinically significant changes in systolic and diastolic blood pressure have been seen and could be expected to occur in some patients after use of any beta- adrenergic bronchodilator.
In controlled clinical trials in adults, patients treated with Volmax extended- release tablets had increases in selected serum chemistry values and decreases in selected hematologic values. Increases in SGPT were more frequent among patients treated with Volmax extended- release tablets (12 of 247 patients, 4.9%) than among the theophylline (6 of 188 patients, 3.2%) and placebo (1 of 138 patients, 0.7%) groups. Increases in serum glucose concentration were also more frequent among patients treated with Volmax extended- release tablets (23 of 234 patients, 9.8%) than among theothephylline (11 of 173 patients, 6.45%) and placebo (3 of 129 patients, 2.3%) groups. Increases in SGOT were also more frequent among patients treated with Volmax extended- release tablets (10 of 248 patients, 4%) and theophylline (5 of 193, 2.6%) than among patients treated with placebo. Decreases in white blood cell counts were more frequent in patients treated with Volmax extended- release tablets (10 of 247 patients, 4%) compared with patients receiving theophylline (2 of 185 patients, 1.1%) and patients receiving placebo (1 of 141 patients, 0.7%). Decreases in hemoglobin and hematocrit were more frequent in patients receiving Volmax extended- release tablets (16 of 228 patients, 7.0%, and 17 of 230 patients, 7.4%, respectively) than in patients receiving theophylline (5 of 171 patients, 2.9%, and 9 of 173 patients, 5.2%, respectively) and patients receiving placebo (5 of 129 patients, 3.9%, and 3 of 132 patients, 2.3%, respectively). The clinical significance of these results is unknown.
Large doses of intravenous albuterol have been reported to aggravate pre- existing 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.
As with any other nondeformable material, caution should be used when administering Volmax extended- release tablets to patients with pre- existing gastrointestinal narrowing from any cause. There have been rare reports of gastrointestinal obstruction in such patients occurring in association with ingestion of products containing delivery systems similar to that contained in Volmax extended- release tablets.

Information for the Patient
  Each Volmax extended- release tablet contains a small hole that is part of the unique extended- release system. Volmax extended- release tablets must be swallowed whole with the aid of liquids. DO NOT CHEW OR CRUSH THESE TABLETS.
The outer coating of the tablet is not absorbed and is excreted in the feces; in some instances the empty outer coating may be noticeable in the stool.
The action of Volmax extended- release tablets should last up to 12 hours or longer. Volmax extended- release tablets should not be used more frequently than recommended. Do not increase the dose or frequency of Volmax extended- release tablets without consulting your physician. If you find that treatment with Volmax extended- release tablets 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 Volmax extended- release tablets, 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, tremor or nervousness. If you are pregnant or nursing, contact your physician about use of Volmax extended- release tablets. Effective and safe use of Volmax extended- release tablets includes an understanding of the way that it should be administered.

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, (approximately 1/ 2, 3, and 15 times, respectively, the maximum recommended daily oral dose for adults on a mg/ m2basis, or, approximately 2/ 5, 2, and 10 times, respectively, the maximum recommended daily oral dose for children on a mg/ m2basis). In another study this effect was blocked by the coadministration of propranolol, a non- selective beta- adrenergic antagonist. In a 18 month study in CD- 1 mice, albuterol sulfate showed no evidence of tumorigenicity at dietary doses of up to 500 mg/ kg (approximately 65 times the maximum recommended daily oral dose for adults on a mg/ m2basis, or, approximately 50 times the maximum recommended daily oral dose for children on a mg/ m2basis). In a 22 month study in the Golden hamster, albuterol sulfate showed no evidence of tumorigenicity at dietary doses of 50 mg/ kg (approximately 7 times the maximum recommended daily oral dose for adults and children on a mg/ m2basis).
Albuterol sulfate was not mutagenic in the Ames test with or without metabolic activation using tester strains S. typhimurium TA 1537, TA 1538, 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 15 times the maximum recommended daily oral dose for adults on a mg/ m2basis).

Pregnancy, Teratogenic Effects, Pregnancy Category C
  Albuterol Sulfate has been shown to be teratogenic in mice. A study in CD- 1 mice at subcutaneous (SC) doses of 0.025, 0.25, and 2.5 mg/ kg (approximately 3/ 1000, 3/ 100, and 3/ 10 times the maximum recommended daily oral dose for adults on a mg/ m2basis), 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 of females treated with 2.5 mg/ kg of isoproterenol (positive control) subcutaneously (approximately 3/ 10 times the maximum recommended daily oral dose for adults on a mg/ m2basis). A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7/ 19 fetuses (37%) when albuterol sulfate was administered orally at a 50 mg/ kg dose (approximately 25 times the maximum recommended daily oral dose for adults on a mg/ m2basis).
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 Volmax extended- release tablets for relief of bronchospasm during labor should be restricted to those patients in whom the benefits clearly outweigh the risks.

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

Nursing Mothers
  It is not known whether albuterol is excreted in human milk. Because of the potential for tumorigenicity shown for albuterol in 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
  The safety and effectiveness of Volmax extended- release tablets have been established in pediatric patients 6 years of age or older. Use of Volmax extended- release tablets in these age groups is supported by evidence from adequate and well- controlled studies of Volmax extended- release tablets in adults; the likelihood that the disease course, pathophysiology, and the drug's effect in pediatric and adult patients are substantially similar; the established safety and effectiveness of immediate- release albuterol tablets in pediatric patients 6 years of age and older; and clinical trials that support the safety of Volmax extended- release tablets in pediatric patients over 6 years of age. The recommended dose of Volmax extended- release tablets for the pediatric population is based upon the recommended pediatric dosing of immediate- release albuterol tablets and pharmacokinetic studies in adults showing comparable bioavailability at steady- state dosing and reduced bioavailability after single dose administration. Safety and effectiveness in pediatric patients below 6 years of age have not been established.

DRUG INTERACTIONS
 

Ventolin Tablets
  The concomitant use of Ventolin tablets and other oral sympathomimetic agents is not recommended since such combined use may lead to deleterious cardiovascular effects. This recommendation does not preclude the judicious use of an aerosol bronchodilator of the adrenergic stimulant type in patients receiving Ventolin tablets. Such concomitant use, however, should be individualized and not given on a routine basis. If regular coadministration is required, then alternative therapy should be considered.

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 Ventolin tablets, but may produce severe bronchospasm in patients with asthma. 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- 22% in serum digoxin levels were demonstrated after single- dose IV 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.

Ventolin Syrup
  The concomitant use of Ventolin syrup and other oral sympathomimetic agents is not recommended since such combined use may lead to deleterious cardiovascular effects. This recommendation does not preclude the judicious use of an aerosol bronchodilator of the adrenergic stimulant type in patients receiving Ventolin syrup. Such concomitant use, however, should be individualized and not given on a routine basis. If regular coadministration is required, then alternative therapy should be considered.

Beta-Blockers
  Beta- adrenergic receptor blocking agents not only block the pulmonary effect of beta- agonists, such as Ventolin syrup, but may produce severe bronchospasm in patients with asthma. 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- 22% in serum digoxin levels were demonstrated after single dose IV 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.

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.

Volmax Extended-Release Tablets
  The concomitant use of Volmax extended- release tablets and other oral sympathomimetic agents is not recommended since such combined use may lead to deleterious cardiovascular effects. This recommendation does not preclude the judicious use of an aerosol bronchodilator of the adrenergic stimulant type in patients receiving Volmax extended- release tablets. Such concomitant use, however, should be individualized and not given on a routine basis. If regular coadministration is required, then alternative therapy should be considered.

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 Volmax extended- release tablets, 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 nonpotasssium- 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.

Digoxin
  Mean decreases of 16- 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.

ADVERSE REACTIONS
 

Ventolin Tablets
  In clinical trials, the most frequent adverse reactions to Ventolin tablets are shown in TABLE 2 .
TABLE 2    Percent Incidence of Adverse Reactions
Reaction Percent Incidence
Central Nervous System
  Nervousness 20%
  Tremor 20%
  Headache 7%
  Sleeplessness 2%
  Weakness 2%
  Dizziness 2%
  Drowsiness <1%
  Restlessness <1%
  Irritability <1%
Cardiovascular
  Tachycardia 5%
  Palpitations 5%
  Chest discomfort <1%
  Flushing <1%
Musculoskeletal
  Muscle cramps 3%
Gastrointestinal
  Nausea 2%
Genitourinary
  Difficulty in micturition <1%

Cases of urticaria, angioedema, rash, bronchospasm, oropharyngeal edema, and arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles) have been reported after the use of Ventolin tablets.
In addition, albuterol, like other sympathomimetic agents, can cause adverse reactions such as hypertension, angina, vomiting, vertigo, central nervous system stimulation, unusual taste, and drying or irritation of the oropharynx.
The reactions are generally transient in nature, and it is usually not necessary to discontinue treatment with Ventolin tablets. In selected cases, however, dosage may be reduced temporarily; after the reaction has subsided, dosage should be increased in small increments to the optimal dosage.

Ventolin Syrup
  The adverse reactions to albuterol are similar in nature to those of other sympathomimetic agents. In clinical trials, the most frequent adverse reactions to Ventolin syrup in adults and older children are shown in TABLE 3 .
TABLE 3    Percent Incidence of Adverse Reactions in Adults and Children (6- 12 Years of Age)
Adverse Event Percent Incidence
Central Nervous System
  Tremor 10%
  Nervousness 9%
  Shakiness 9%
  Headache 4%
  Dizziness 3%
  Excitement 2%
  Hyperactivity 2%
  Sleeplessness 1%
  Disturbed sleep <1%
  Irritable behavior <1%
  Dilated pupils <1%
  Weakness 1%
Cardiovascular
  Tachycardia 1%
  Palpitations <1%
  Sweating <1%
  Chest pain <1%
Ear, Nose, and Throat
  Epistaxis 1%
Gastrointestinal
  Increased appetite 3%
  Epigastric pain <1%
  Stomachache <1%
Musculoskeletal
  Muscle spasm <1%
Respiratory
  Cough <1%

In clinical trials, the following adverse reactions to Ventolin syrup were noted more frequently in young children 2- 6 years of age than in adults and older children (see TABLE 4 ).
TABLE 4    Percent Incidence of Adverse Reactions Noted More Frequently in Children 2- 6 Years of Age Than in Older Children and Adults
Adverse Event Percent Incidence
Central Nervous System
  Excitement 20%
  Nervousness 15%
  Hypokinesia 4%
  Sleeplessness 2%
  Emotional lability 1%
  Fatigue 1%
Cardiovascular
  Tachycardia 2%
  Pallor 1%
Gastrointestinal
  Gastrointestinal symptoms 2%
  Loss of appetite 1%
Ophthalmologic
  Conjunctivitis 1%

Cases of urticaria, angioedema, rash, bronchospasm, oropharyngeal edema, and arrhythmias (including atrial fibrillation, supraventricular tachycardia, and extrasystoles) have been reported after the use of Ventolin syrup.
In addition, albuterol, like other sympathomimetic agents, can cause adverse reactions such as angina, central nervous system stimulation, drying or irritation of the oropharynx, hypertension, nausea, unusual taste, vertigo, and vomiting.
The reactions are generally transient in nature, and it is usually not necessary to discontinue treatment with Ventolin syrup. In selected cases, however, dosage may be reduced temporarily; after the reaction has subsided, dosage should be increased in small increments to the optimal dosage.

Volmax Extended-Release Tablets
  The adverse reactions to albuterol are similar in nature to reactions to other sympathomimetic agents. The most frequent adverse reactions to albuterol are nervousness, tremor, headache, tachycardia, and palpitations. Less frequent adverse reactions are muscle cramps, insomnia, nausea, weakness, dizziness, drowsiness, flushing, restlessness, irritability, chest discomfort, and difficulty in micturition.
Rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema have been reported after the use of albuterol.
In addition, albuterol, like other sympathomimetic agents, can cause adverse reactions such as hypertension, angina, vomiting, vertigo, central nervous system stimulation, unusual taste, and drying or irritation of the oropharynx.
In controlled clinical trials of adult patients conducted in the US, the following incidence of adverse events was reported (see TABLE 5 ).
TABLE 5   
  Volmax Theophylline Other Beta- Agonists Placebo
Event (n=330) (n=197) (n=20) (n=178)
Tremor 24.2% 6.1% 35.0% 1.1%
Headache 18.8% 26.9% 35.0% 20.8%
Nervousness 8.5% 5.1% 10.0% 2.8%
Nausea/ vomiting 4.2% 19.8% 5.0% 3.9%
Tachycardia 2.7% 0.5% 5.0% 0%
Muscle cramps 2.7% 0.5% 5.0% 0.6%
Palpitations 2.4% 0.5% 0% 1.1%
Insomnia 2.4% 6.1% 0% 1.7%
Dizziness 1.5% 2.0% 0% 5.1%
Somnolence 0.3% 1.0% 0% 0.6%

A trend was observed among patients treated with Volmax extended- release tablets toward increasing frequency of muscle cramps with increasing patient age (12- 20 years, 1.2%; 21- 30 years, 2.6%; 31- 40 years, 6.9%; 41- 50 years, 6.9%), compared with no such events in the placebo group. Also observed was an increasing frequency of tremor with increasing patient age (12- 20 years, 29.4%; 21- 30 years, 29.9%; 31- 40 years, 27.6%; 41- 50 years, 37.9%), compared to 2.9% or less in the placebo group.
The reactions are generally transient in nature, and it is usually not necessary to discontinue treatment with Volmax extended- release tablets.

OVERDOSAGE
 

Ventolin Tablets
  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/ minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and sleeplessness. Hypokalemia may also occur. As with all sympathomimetic medications, cardiac arrest and even death may be associated with abuse of Ventolin tablets. Treatment consists of discontinuation of Ventolin tablets together with appropriate symptomatic therapy. The judicious use of a cardioselective beta- receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of Ventolin tablets.
The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/ kg (approximately 250 times the maximum recommended daily oral dose for adults on a mg/ m2basis or approximately 200 times the maximum recommended daily oral dose for children on a mg/ m2basis. In mature rats, the subcutaneous median lethal dose of albuterol sulfate is approximately 450 mg/ kg (approximately 110 times the maximum recommended daily oral dose for adults on a mg/ m2basis or approximately 90 times the maximum recommended daily oral dose for children on a mg/ m2basis). In small young rats, the subcutaneous median lethal dose is approximately 2000 mg/ kg (approximately 500 times the maximum recommended daily oral dose for adults on a mg/ m2basis or approximately 400 times the maximum recommended daily oral dose for children on a mg/ m2basis).

Ventolin Syrup
  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., angina, hypertension, tachycardia with rates up to 200 beats/ minute, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, and insomnia. In addition, seizures, hypotension, arrhythmias, malaise, and hypokalemia may also occur. As with all sympathomimetic medications, cardiac arrest and even death may be associated with abuse of Ventolin syrup. Treatment consists of discontinuation of Ventolin syrup together with appropriate symptomatic therapy. The judicious use of a cardioselective beta- receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of Ventolin syrup.
The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/ kg (approximately 250 times the maximum recommended daily oral dose for adults on a mg/ m2basis and approximately 200 times the maximum recommended daily oral dose for children on a mg/ m2basis). In mature rats, the subcutaneous (SC) median lethal dose of albuterol sulfate is approximately 450 mg/ kg (approximately 110 times the maximum recommended daily oral dose for adults on a mg/ m2basis and approximately 90 times the maximum recommended daily oral dose for children on a mg/ m2basis). In small young rats, the SC median lethal dose is approximately 2000 mg/ kg (approximately 510 times the maximum recommended daily oral dose for adults on a mg/ m2basis and approximately 400 times the maximum recommended daily oral dose for children on a mg/ m2basis).

Volmax Extended-Release Tablets
  The expected symptoms with overdosage are those of excessive beta- adrenergic stimulation and/ or occurrence or exaggeration of any of the symptoms listed under ADVERSE REACTIONS , e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats per minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and insomnia. Hypokalemia may also occur. As with all sympathomimetic aerosol medications, cardiac arrest and even death may be associated with abuse of Volmax extended- release tablets.
Treatment consists of discontinuation of Volmax extended- release tablets together with appropriate symptomatic therapy. The judicious use of a cardioselective beta- receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of Volmax extended- release tablets.
The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/ kg (approximately 250 times the maximum recommended daily oral dose for adults on a mg/ m2basis, or, approximately 200 times the maximum recommended daily oral dose for children on a mg/ m2basis). In mature rats, the subcutaneous median lethal dose of albuterol sulfate is approximately 450 mg/ kg (approximately 110 times the maximum recommended daily oral dose for adults on a mg/ m2basis, or, approximately 90 times the maximum recommended daily oral dose for children on a mg/ m2basis). In small young rats, the subcutaneous median lethal dose is approximately 2000 mg/ kg (approximately 500 times the maximum recommended daily oral dose for adults on a mg/ m2basis, or, approximately 400 times the maximum recommended daily oral dose for children on a mg/ m2basis).

DOSAGE AND ADMINISTRATION
 

Ventolin Tablets
  The following dosages of Ventolin tablets are expressed in terms of albuterol base.
Usual Dosage:
Adults and children over 12 years of age: The usual starting dosage for adults and children 12 years and older is 2 or 4 mg three or four times a day.
Children 6- 12 years of age: The usual starting dosage for children 6- 12 years of age is 2 mg three or four times a day.

Dose Adjustment:
Adults and children over 12 years of age: For adults and children 12 years and older, a dosage above 4 mg four times a day should be used only when the patient fails to respond. If a favorable response does not occur with the 4 mg initial dosage, it should be cautiously increased stepwise up to a maximum of 8 mg four times a day as tolerated.
Children 6- 12 years of age who fail to respond to the initial starting dosage of 2 mg four times a day: For children from 6- 12 years of age who fail to respond to the initial starting dosage of 2 mg four times a day, the dosage may be cautiously increased stepwise, but not to exceed 24 mg/ day (given in divided doses).

The total daily dose should not exceed 32 mg in adults and children 12 years and older.

Elderly Patients and Those Sensitive to Beta-Adrenergic Stimulators
  An initial dosage of 2 mg three or four times a day is recommended for elderly patients and for those with a history of unusual sensitivity to beta- adrenergic stimulators. If adequate bronchodilatation is not obtained, dosage may be increased gradually to as much as 8 mg three or four times a day.

Ventolin Syrup
  The following dosages of Ventolin syrup are expressed in terms of albuterol base.
Usual Dosage:
Adults and pediatric patients over 12 years of age: The usual starting dosage for adults and children over 12 years of age is 2 mg (1 teaspoonful) or 4 mg (2 teaspoonfuls) 3 or 4 times a day.
Pediatric patients 6- 12 years of age: The usual starting dosage for children 6- 12 years of age is 2 mg (1 teaspoonful) 3 or 4 times a day.
Pediatric patients 2- 6 years of age: Dosing in children 2- 6 years of age should be initiated at 0.1 mg/ kg of body weight 3 times a day. The starting dosage should not exceed 2 mg (1 teaspoonful) 3 times a day.

Dose Adjustment:
Adults and pediatric patients over 12 years of age: For adults and children over 12 years of age, a dosage above 4 mg four times a day should be used only when the patient fails to respond to this dosage. If a favorable response does not occur with the 4 mg initial dosage, it may be cautiously increased stepwise as tolerated, but not to exceed 8 mg four times a day (total daily dose should not exceed 32 mg).
Pediatric patients 6- 12 years of age who fail to respond to the initial starting dosage of 2 mg four times a day: For children 6- 12 years of age who fail to respond to the initial starting dosage of 2 mg four times a day, the dosage may be cautiously increased stepwise as tolerated but not to exceed 6 mg four times a day (total daily dose should not exceed 24 mg).
Pediatric patients 2- 6 years of age who do not respond satisfactorily to the initial dosage: For children 2- 6 years of age who do not respond satisfactorily to the initial starting dosage, the dosage may be increased stepwise to 0.2 mg/ kg of body weight 3 times a day as tolerated, but not to exceed a maximum of 4 mg (2 teaspoonfuls) given 3 times a day (total daily dose should not exceed 12 mg).

Elderly Patients and Those Sensitive to Beta-Adrenergic Stimulators
  The initial dosage should be restricted to 2 mg three or four times a day. If adequate bronchodilation is not obtained, dosage may be increased gradually as tolerated to as much as 8 mg three or four times per day (total daily dose should not exceed 32 mg).

Volmax Extended-Release Tablets
  The following dosages of Volmax extended- release tablets are expressed in terms of albuterol base:
Usual Dosage:
Adults and children over 12 years of age: The usual recommended dosage for adults and pediatric patients over 12 years of age is 8 mg every 12 hours. In some patients, 4 mg every 12 hours may be sufficient.
Children 6 to 12 years of age: The usual recommended dosage for children 6 through 12 years of age is 4 mg every 12 hours.

Dosage Adjustment in Adults and Children Over 12 Years of Age
  In unusual circumstances, such as adults of low body weight, it may be desirable to use a starting dosage of 4 mg every 12 hours and progress to 8 mg every 12 hours according to response.
If control of reversible airway obstruction is not achieved with the recommended doses in patients on otherwise optimized asthma therapy, the doses may be cautiously increased stepwise under the control of the supervising physician to a maximum dose of 32 mg/ day in divided doses ( i.e., q12h).

Dosage Adjustment in Children 6–12 Years of Age
  If control of reversible airway obstruction is not achieved with the recommended doses in patients on otherwise optimized asthma therapy, the doses may be cautiously increased stepwise under the control of the supervising physician to a maximum dose of 24 mg/ day in divided doses ( i.e., every 12 hours).

Switching From Oral Ventolin Products
  Patients currently maintained on Ventolin (albuterol sulfate) tablets or Ventolin (albuterol sulfate) syrup can be switched to Volmax extended- release tablets. For example, the administration of one 4 mg Volmax extended- release tablet every 12 hours is comparable to one 2 mg Ventolin tablet every 6 hours. Multiples of this regimen up to the maximum recommended daily dose also apply.
Each Volmax extended- release tablet contains a small hole that is part of the unique extended- release system. Volmax extended- release tablets must be swallowed whole with the aid of liquids. DO NOT CHEW OR CRUSH THESE TABLETS.

HOW SUPPLIED
 

Ventolin Tablets
  Ventolin tablets are available as follows:
2 mg of albuterol as the sulfate: White, round, compressed tablets impressed with the product name ("VENTOLIN") and the number "2" on one side and scored on the other with "GLAXO" impressed on each side of the score.
4 mg of albuterol as the sulfate: White, round, compressed tablets impressed with the product name ("VENTOLIN") and the number "4" on one side and scored on the other with "GLAXO" impressed on each side of the score.


Storage: Store between 2 and 25°C (36 and 77°F). Replace cap securely after each opening.

Ventolin Syrup
  Ventolin syrup, a clear orange- yellow liquid with a strawberry flavor, contains 2 mg albuterol as the sulfate per 5 ml.

Storage: Store between 2 and 30°C (36 and 86°F). Dispense in tight, light­resistant containers.

Volmax Extended-Release Tablets
  Volmax extended- release tablets are available in:
4 mg: Light blue, hexagonal tablets printed with "Volmax" on one side and the number "4" on the other in dark blue ink.
8 mg: White, hexagonal tablets printed with "Volmax" on one side and the number "8" on the other in dark blue ink.


Storage: Store refrigerated, 2- 8°C (36- 46°F).

Administration Route:Inhalation

DESCRIPTION
 
Note: The trade name has been used throughout this monograph for clarity.

Ventolin Inhalation Aerosol
  Bronchodilator Aerosol.
For Oral Inhalation Only.
The active component of Ventolin inhalation aerosol is albuterol, racemic (α1- [( tert - butylamino)methyl]- 4- hydroxy- m - xylene- α, α′- diol) and a relatively selective beta2 - adrenergic bronchodilator.
Albuterol is the official generic name in the US. The World Health Organization recommended name for the drug is salbutamol. The molecular weight of albuterol is 239.3, and the empirical formula is C13 H21 NO3 . Albuterol is a white to off- white crystalline solid. It is soluble in ethanol, sparingly soluble in water, and very soluble in chloroform.
Ventolin inhalation aerosol is a pressurized metered- dose aerosol unit for oral inhalation. It contains a microcrystalline (95% ≤10 μm) suspension of albuterol in propellants (trichloromonofluoromethane and dichlorodifluoromethane) with oleic acid. Each actuation delivers 100 μg of albuterol from the valve and 90 μg of albuterol from the mouthpiece. Each 6.8 g canister provides 80 inhalations and each 17 g canister provides 200 inhalations.

Ventolin HFA Inhalation Aerosol
  Bronchodilator Aerosol.
For Oral Inhalation Only.
The active component of Ventolin HFA (albuterol sulfate HFA inhalation aerosol) is albuterol sulfate, the racemic form of albuterol and a relatively selective beta2 - adrenergic bronchodilator. Albuterol sulfate has the chemical name α1- [( tert - butylamino)methyl]- 4- hydroxy- m - xylene- α, α′- diol sulfate (2:1)(salt).
Albuterol sulfate has a molecular weight of 576.7, and the empirical formula is (C13 H21 NO3 )2 ·H2 SO4 . Albuterol sulfate is a white crystalline powder, soluble in water and slightly soluble in ethanol.
The World Health Organization recommended name for albuterol base is salbutamol.
Ventolin HFA 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). It contains no other excipients.
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 4 test sprays into the air, away from the face. After priming with 4 actuations, each actuation delivers 120 μg of albuterol sulfate in 75 mg of suspension from the valve and 108 μg of albuterol sulfate from the mouthpiece (equivalent to 90 μg of albuterol base from the mouthpiece). Each 18 g canister provides 200 inhalations.
This product does not contain chlorofluorocarbons (CFCs) as the propellant.

Ventolin Inhalation Solution, 0.5%
  *Potency expressed as albuterol.
The active component of Ventolin inhalation solution is albuterol sulfate, the racemic form of albuterol and a relatively selective beta2 - adrenergic bronchodilator (see CLINICAL PHARMACOLOGY ). It has the chemical name α1- [( tert - butylamino)methyl]- 4- hydroxy- m - xylene- α, α′- diol sulfate (2:1)(salt).
Albuterol sulfate has a molecular weight of 576.7, and the empirical formula is (C13 H21 NO3 )2 ·H2 SO4 . Albuterol sulfate is a white crystalline powder, soluble in water and slightly soluble in ethanol.
The World Health Organization recommended name for albuterol base is salbutamol.
Ventolin inhalation solution, 0.5% is in concentrated form. Dilute the appropriate volume of the solution (see DOSAGE AND ADMINISTRATION ) with sterile normal saline solution to a total volume of 3 ml and administer by nebulization.
Each milliliter of Ventolin inhalation solution contains 5 mg of albuterol (as 6 mg of albuterol sulfate) in an aqueous solution containing benzalkonium chloride; sulfuric acid is used to adjust the pH to between 3 and 5. Ventolin inhalation solution contains no sulfiting agents. It is supplied in a 20 ml amber glass bottle.
Ventolin inhalation solution is a clear, colorless to light yellow solution.

Ventolin Nebules Inhalation Solution, 0.083%
  *Potency expressed as albuterol.
Ventolin Nebules inhalation solution is a relatively selective beta2 - adrenergic bronchodilator (see CLINICAL PHARMACOLOGY ). Albuterol sulfate, the racemic form of albuterol, has the chemical name α1- [( tert - butylamino)methyl]- 4- hydroxy- m - xylene- α, α′- diol sulfate (2:1)(salt).
Albuterol sulfate has a molecular weight of 576.7, and the empirical formula is (C13 H21 NO3 )2 ·H2 SO4 . Albuterol sulfate is a white crystalline powder, soluble in water and slightly soluble in ethanol.
The World Health Organization recommended name for albuterol base is salbutamol.
Ventolin Nebules inhalation solution requires no dilution before administration by nebulization.
Each milliliter of Ventolin Nebules inhalation solution contains 0.83 mg of albuterol (as 1 mg of albuterol sulfate) in an isotonic, sterile, aqueous solution containing sodium chloride; sulfuric acid is used to adjust the pH to between 3 and 5. Ventolin Nebules inhalation solution contains no sulfiting agents or preservatives.
Ventolin Nebules inhalation solution is a clear, colorless solution.

Ventolin Rotacaps for Inhalation
  FOR ORAL INHALATION ONLY.
For Use With the Rotahaler Inhalation Device.
Ventolin Rotacaps for inhalation contain a dry powder presentation of albuterol sulfate intended for oral inhalation only. Each light blue and clear, hard gelatin capsule contains a mixture of 200 μg of microfine (95% ≤10 μm) albuterol (as the sulfate) with 25 mg of lactose.
The contents of each capsule are inhaled using a specially designed plastic device for inhaling powder called the Rotahaler. When turned, this device opens the capsule and facilitates dispersion of the albuterol sulfate into the airstream created when the patient inhales through the mouthpiece.
Ventolin Rotacaps for inhalation are an alternative inhalation form of albuterol to the metered- dose pressurized inhaler.
The active component of Ventolin Rotacaps for inhalation is albuterol sulfate, the racemic form of albuterol and a relatively selective beta2 - adrenergic bronchodilator. It has the chemical name α1- [( tert - butylamino)methyl]- 4- hydroxy- m - xylene- α, α′- diol sulfate (2:1)(salt).
Albuterol sulfate has a molecular weight of 576.7, and the empirical formula is (C13 H21 NO3 )2 ·H2 SO4 . Albuterol sulfate is a white crystalline powder, soluble in water and slightly soluble in ethanol.
The World Health Organization recommended name for albuterol base is salbutamol.

CLINICAL PHARMACOLOGY
 

Ventolin Inhalation Aerosol
  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.
The pharmacologic effects of beta- adrenergic agonist drugs, including albuterol, are at least in part 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.
The effects of rising doses of albuterol and isoproterenol aerosols were studied in volunteers and patients with asthma. Results in normal volunteers indicated that albuterol is one- half to one- quarter as active as isoproterenol in producing increases in heart rate. In patients with asthma similar cardiovascular differentiation between the 2 drugs was also seen.

Preclinical
  Intravenous (IV) 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 are administered concurrently. The clinical significance of these findings is unknown.

Pharmacokinetics
  Because of its gradual absorption from the bronchi, systemic levels of albuterol are low after inhalation of recommended doses. Studies undertaken with 4 subjects administered tritiated albuterol resulted in maximum plasma concentrations occurring within 2- 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.

Ventolin HFA Inhalation Aerosol
 

Mechanism of Action
  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% of cardiac beta- adrenergic receptors. The precise function of these receptors has not been established (see WARNINGS, Cardiovascular Effects ).
Activation of beta2 - adrenergic receptors on airway smooth muscle 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 leads to the activation of protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation. Albuterol relaxes the smooth muscles 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.
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.

Preclinical
  Intravenous (IV) 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 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 beta- agonists and methylxanthines are administered concurrently. The clinical significance of these findings is unknown.
Propellant HFA- 134a is devoid of pharmacological activity except at very high doses in animals (380- 1300 times the maximum human exposure based on comparisons of AUC values), primarily producing ataxia, tremors, dyspnea, or salivation. These are similar to effects produced by the structurally related chlorofluorocarbons (CFCs), which have been used extensively in metered- dose inhalers.
In animals and humans, propellant HFA- 134a was found to be rapidly absorbed and rapidly eliminated, with an elimination half- life of 3- 27 minutes in animals and 5- 7 minutes in humans. Time to maximum plasma concentration (Tmax ) and mean residence time are both extremely short, leading to a transient appearance of HFA- 134a in the blood with no evidence of accumulation.

Pharmacokinetics
  The systemic levels of albuterol are low after inhalation of recommended doses. A study conducted in 12 healthy male and female subjects using a higher dose (1080 μg of albuterol base) showed that mean peak plasma concentrations of approximately 3 ng/ ml occurred after dosing when albuterol was delivered using propellant HFA- 134a. The mean time to peak concentrations (Tmax ) was delayed after administration of Ventolin HFA (Tmax = 0.42 hours) as compared to CFC- propelled albuterol inhaler (Tmax = 0.17 hours). Apparent terminal plasma half- life of albuterol is approximately 4.6 hours. No further pharmacokinetic studies for Ventolin HFA were conducted in neonates, children, or elderly subjects.

Ventolin Inhalation Solution, 0.5%
  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 part 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.

Pharmacokinetics
  Studies in patients with asthma 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 within 24 hours after drug administration. Following a 3 mg dose of nebulized albuterol in adults, the maximum albuterol plasma levels at 0.5 hours were 2.1 ng/ ml (range, 1.4- 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- 6 hours.

Preclinical
  Intravenous (IV) 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 are administered concurrently. The clinical significance of these findings is unknown.

Ventolin Nebules Inhalation Solution, 0.083%
  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 10- 50% of the beta- receptors in the human heart may be beta2 - receptors. The precise function of these receptors has not been established.
The pharmacologic effects of beta- adrenergic agonist drugs, including albuterol, are at least in part 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.

Pharmacokinetics
  Studies in patients with asthma have shown that less than 20% of a single albuterol dose was absorbed following either IPPB (intermittent positive- pressure breathing) 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 maximum albuterol plasma levels at 0.5 hours were 2.1 ng/ ml (range, 1.4- 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- 6 hours.

Preclinical
  Intravenous (IV) 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 are administered concurrently. The clinical significance of these findings is unknown.

Ventolin Rotacaps for Inhalation
  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 part 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 normal cellular uptake processes for catecholamines nor for catechol- O - methyl transferase.

Pharmacokinetics
  Studies undertaken with 4 subjects administered tritiated albuterol from a metered- dose aerosol inhaler resulted in maximum plasma concentrations occurring within 2- 4 hours. Due to the sensitivity of the assay method, the metabolic rate and half- life 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.

Preclinical
  Intravenous (IV) 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 are administered concurrently. The clinical significance of these findings is unknown.

CLINICAL STUDIES
 

Ventolin 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 flow rate) and FEV1 (forced expiratory volume in 1 second). MMEF measurements also showed that near maximum improvement in pulmonary function generally occurs within 60- 90 minutes following 2 inhalations of albuterol and that clinically significant improvement generally continues for 3- 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- 12 years of age, FEV1 measurements showed that maximum improvement in pulmonary function occurs within 30- 60 minutes. The onset of clinically significant (≥15%) improvement in FEV1 was observed as soon as 5 minutes following 180 μg 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- 47% for 4 hours among 56 patients receiving inhalation aerosol in 1 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- 40% for 4 hours. In addition, at least 50% of the patients in both studies achieved an improvement in FEF25- 75% (forced expiratory flow rate between 25 and 75% of the forced vital capacity) of at least 20% for 2- 5 hours. Continued effectiveness of albuterol was demonstrated over the 12 week study period.
In other clinical studies in adults and children, 2 inhalations of Ventolin 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.

Ventolin HFA Inhalation Aerosol
  In a 12 week, randomized, double- blind study, Ventolin HFA (101 patients) was compared to CFC 11/ 12- propelled albuterol (99 patients) and an HFA- 134a placebo inhaler (97 patients) in adolescent and adult patients 12- 76 years of age with mild to moderate asthma. Serial forced expiratory volume in 1 second (FEV1 ) measurements [as percent change from test- day baseline at Day 1 (n=297) and at Week 12 (n=249)] demonstrated that 2 inhalations of Ventolin HFA produced significantly greater improvement in FEV1 over the pretreatment value than placebo. Patients taking the HFA- 134a placebo inhaler also took Ventolin HFA for asthma symptom relief on an as- needed basis.
In the responder population (≥15% increase in FEV1 within 30 minutes postdose) treated with Ventolin HFA, the mean time to onset of a 15% increase in FEV1 over the pretreatment value was 5.4 minutes, and the mean time to peak effect was 56 minutes. The mean duration of effect as measured by a 15% increase in FEV1 over the pretreatment value was approximately 4 hours. In some patients, duration of effect was as long as 6 hours.
A second 12 week randomized, double- blind study was conducted to evaluate the efficacy and safety of switching patients from CFC 11/ 12- propelled albuterol to Ventolin HFA. During the 3 week run- in phase of the study, all patients received CFC 11/ 12- propelled albuterol. During the double- blind treatment phase, Ventolin HFA (91 patients) was compared to CFC 11/ 12- propelled albuterol (100 patients) and an HFA- 134a placebo inhaler (95 patients) in adolescent and adult patients with mild to moderate asthma. Serial FEV1 measurements demonstrated that 2 inhalations of Ventolin HFA produced significantly greater improvement in pulmonary function than placebo. The switching from CFC 11/ 12- propelled albuterol inhaler to Ventolin HFA did not reveal any clinically significant changes in the efficacy profile.
In the 2 adult studies, the efficacy results from Ventolin HFA were significantly greater than placebo and were clinically comparable to those achieved with albuterol CFC 11/ 12- propelled albuterol, although small numerical differences in mean FEV1 response and other measures were observed. Physicians should recognize that individual responses to beta- adrenergic agonists administered via different propellants may vary and that equivalent responses in individual patients should not be assumed.
In a 2 week, randomized, double- blind study, Ventolin HFA was compared to CFC 11/ 12- propelled albuterol and an HFA- 134a placebo inhaler in 135 pediatric patients (4- 11 years old) with mild to moderate asthma. Serial pulmonary function measurements demonstrated that 2 inhalations of Ventolin HFA produced significantly greater improvement in pulmonary function than placebo and that there were no significant differences between the groups treated with Ventolin HFA and CFC 11/ 12- propelled albuterol. In the responder population treated with Ventolin HFA, the mean time to onset of a 15% increase in peak expiratory flow rate (PEFR) over the pretreatment value was 7.8 minutes, and the mean time to peak effect was approximately 90 minutes. The mean duration of effect as measured by a 15% increase in PEFR over the pretreatment value was greater than 3 hours. In some patients, duration of effect was as long as 6 hours.
One controlled clinical study in adult patients with asthma (n=24) demonstrated that 2 inhalations of Ventolin HFA taken approximately 30 minutes prior to exercise significantly prevented exercise- induced bronchospasm (as measured by maximum percentage fall in FEV1 following exercise) compared to an HFA- 134a placebo inhaler. In addition, Ventolin HFA was shown to be clinically comparable to a CFC 11/ 12- propelled albuterol inhaler for this indication.
Some patients who participated in these clinical trials were using concomitant steroid therapy.

Ventolin Inhalation Solution, 0.5%
  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- 4 hours in most patients, with some patients continuing up to 6 hours.
Published reports of trials in children with asthma aged 3 years or older have demonstrated significant improvement in either FEV1 or PEFR within 2- 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- 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%.

Ventolin Nebules Inhalation Solution, 0.083%
  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- 4 hours in most patients, with some patients continuing up to 6 hours.
Published reports of trials in children with asthma aged 3 years or older have demonstrated significant improvement in either FEV1 or PEFR within 2- 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- 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%.

Ventolin Rotacaps for Inhalation
  In single, dose- range, crossover trials with Ventolin Rotacaps 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 μg 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- 2 hours after the 200 μg dose and 3- 4 hours after the 400 μg dose. In a single- dose study, an increase in forced expiratory flow rate between 25 and 75% of the forced vital capacity (FEF25- 75% ) of 20% or greater continued for 3- 4 hours after the 200 μg dose and for 3- 6 hours following the 400 μg 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 μg dose. Twenty- two percent (22%) of the patients receiving the 200 μg 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 μg Ventolin Rotacaps for inhalation capsule versus 2 inhalations of Ventolin (albuterol) inhalation aerosol, the 2 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 2 controlled, 12 week clinical trials involving 204 children aged 4- 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 FEF25- 75% ). Therapeutic improvement of FEF25- 75% persisted for 3- 5 hours in over 50% of the children throughout the study. Continued effectiveness and safety of Ventolin Rotacaps 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 μg Ventolin Rotacaps for inhalation capsule 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.

INDICATIONS AND USAGE
 

Ventolin Inhalation Aerosol
  Ventolin 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.
Ventolin inhalation aerosol can be used with or without concomitant steroid therapy.

Ventolin HFA Inhalation Aerosol
  Ventolin HFA is indicated for the treatment or prevention of bronchospasm in adults and children 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.

Ventolin Inhalation Solution, 0.5%
  Ventolin inhalation solution is indicated for the relief of bronchospasm in patients 2 years of age and older with reversible obstructive airway disease and acute attacks of bronchospasm.

Ventolin Nebules Inhalation Solution, 0.083%
  Ventolin Nebules inhalation solution is indicated for the relief of bronchospasm in patients 2 years of age and older with reversible obstructive airway disease and acute attacks of bronchospasm.

Ventolin Rotacaps for Inhalation
  Ventolin Rotacaps for inhalation are 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 Ventolin Rotacaps 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. Ventolin Rotacaps for inhalation can be used with or without concomitant steroid therapy.

CONTRAINDICATIONS
 

Ventolin Inhalation Aerosol
  Ventolin inhalation aerosol is contraindicated in patients with a history of hypersensitivity to albuterol or any of its components.

Ventolin HFA Inhalation Aerosol
  Ventolin HFA is contraindicated in patients with a history of hypersensitivity to albuterol or any other components of Ventolin HFA.

Ventolin Inhalation Solution, 0.5%
  Ventolin inhalation solution is contraindicated in patients with a history of hypersensitivity to albuterol or any of its components.

Ventolin Nebules Inhalation Solution, 0.083%
  Ventolin Nebules inhalation solution is contraindicated in patients with a history of hypersensitivity to albuterol or any of its components.

Ventolin Rotacaps for Inhalation
  Ventolin Rotacaps for inhalation are contraindicated in patients with a history of hypersensitivity to albuterol or any of its components.

WARNINGS
 

Ventolin Inhalation Aerosol
 

Paradoxical Bronchospasm
  Ventolin inhalation aerosol can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, Ventolin inhalation aerosol should be discontinued immediately and alternative therapy instituted. It should be recognized that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister or vial.

Cardiovascular Effects
  Ventolin inhalation aerosol, 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 Ventolin inhalation aerosol 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 QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, Ventolin inhalation aerosol, 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 Ventolin inhalation aerosol 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.

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.

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

Ventolin HFA Inhalation Aerosol
 

Paradoxical Bronchospasm
  Inhaled albuterol sulfate can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, Ventolin HFA 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.

Cardiovascular Effects
  Ventolin HFA, like all other beta- adrenergic agonists, can produce clinically significant cardiovascular effects in some patients as measured by pulse rate, blood pressure, and/ or symptoms. Although such effects are uncommon after administration of Ventolin HFA 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 QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, Ventolin HFA, 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 Ventolin HFA 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.

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, to the therapeutic regimen.

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

Do Not Exceed Recommended Dose
  Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. The exact cause of death is unknown, but cardiac arrest following an unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected.

Ventolin Inhalation Solution, 0.5%
 

Paradoxical Bronchospasm
  Ventolin inhalation solution can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, Ventolin inhalation solution 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.
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
  Ventolin inhalation solution, 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 Ventolin inhalation solution 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 QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, Ventolin inhalation solution, 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 Ventolin inhalation solution 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 of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema.

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.

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.

Ventolin Nebules Inhalation Solution, 0.083%
 

Paradoxical Bronchospasm
  Ventolin Nebules inhalation solution can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, Ventolin Nebules inhalation solution 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.

Cardiovascular Effects
  Ventolin Nebules inhalation solution, 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 Ventolin Nebules inhalation solution 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 QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, Ventolin Nebules inhalation solution, 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 Ventolin Nebules inhalation solution 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 of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema.

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.

Ventolin Rotacaps for Inhalation
 

Paradoxical Bronchospasm
  Ventolin Rotacaps for inhalation can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, Ventolin Rotacaps for inhalation should be discontinued immediately and alternative therapy instituted.

Cardiovascular Effects
  Ventolin Rotacaps for inhalation, 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 Ventolin Rotacaps for inhalation 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 QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, Ventolin Rotacaps for inhalation, 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 Ventolin Rotacaps for inhalation 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 of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema.

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.
Inhalation of capsule particles may result if damage to the capsule has occurred from handling by the patient.

PRECAUTIONS
 

Ventolin Inhalation Aerosol
 

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. Clinically significant changes in systolic and diastolic blood pressure have been seen in individual patients and could be expected to occur in some patients after use of any beta- adrenergic bronchodilator.
Large doses of IV 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.
Although there have been no reports concerning the use of Ventolin 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.

Information for the Patient
  The action of Ventolin inhalation aerosol may last up to 6 hours or longer. Ventolin inhalation aerosol should not be used more frequently than recommended. Do not increase the dose or frequency of Ventolin inhalation aerosol without consulting your physician. If you find that treatment with Ventolin inhalation aerosol 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 Ventolin inhalation aerosol, 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 Ventolin inhalation aerosol. Effective and safe use of Ventolin inhalation aerosol includes an understanding of the way that it should be administered.
In general, the technique for administering Ventolin 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 Ventolin inhalation aerosol under adult supervision, as instructed by the patient's physician.
See illustrated Patient's Instructions for Use distributed with the prescription.

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 (approximately 15, 70, and 340 times, respectively, the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 6, 30, and 160 times, respectively, the maximum recommended daily inhalation dose for children on a mg/ m2basis). 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 1700 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 800 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). In a 22 month study in the Golden hamster, albuterol sulfate showed no evidence of tumorigenicity at dietary doses of up to 50 mg/ kg (approximately 225 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 110 times the maximum recommended daily inhalation dose for children on a mg/ m2basis).
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 340 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis).

Pregnancy, Teratogenic Effects, Pregnancy Category C
  Albuterol sulfate 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 times, respectively, the maximum recommended daily inhalation dose for adults on a mg/ m2basis), 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) subcutaneous (approximately 8 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis).
A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7 of 19 (37%) fetuses when albuterol sulfate was administered orally at a 50 mg/ kg dose (approximately 680 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis).
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.

Use in Labor and Delivery
  Because of the potential for beta- agonist interference with uterine contractility, use of Ventolin inhalation aerosol 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. 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
  Safety and effectiveness in children below 4 years of age have not been established.

Geriatric Use
  Clinical studies of Venolin inhalation aerosol did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Ventolin HFA Inhalation Aerosol
 

General
  Albuterol sulfate, as with all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, hypertension, and cardiac arrhythmia; in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines. Clinically significant changes in systolic and diastolic blood pressure have been seen in individual patients and could be expected to occur in some patients after use of any beta- adrenergic bronchodilator.
Large doses of IV 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.

Information for the Patient
  See illustrated Patient's Instructions for Use distributed with the prescription. SHAKE WELL BEFORE USING.
Patients should be given the following information:
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 4 test sprays into the air, away from the face.
KEEPING THE PLASTIC ACTUATOR CLEAN IS VERY IMPORTANT TO PREVENT MEDICATION BUILD- UP AND BLOCKAGE. THE ACTUATOR SHOULD BE WASHED, SHAKEN TO REMOVE EXCESS WATER, AND AIR- DRIED THOROUGHLY AT LEAST ONCE A WEEK. THE INHALER MAY CEASE TO DELIVER MEDICATION IF NOT PROPERLY CLEANED.
The actuator should be cleaned (with the canister removed) by running warm water through the top and bottom for 30 seconds at least once a week. Do not attempt to clean the metal canister or allow the metal canister to become wet. Never immerse the metal canister in water. The actuator must be shaken to remove excess water, then air- dried thoroughly (such as overnight). Blockage from medication build- up or improper medication delivery may result from failure to clean and thoroughly air- dry the actuator.
If the actuator should become blocked (little or no medication coming out of the mouthpiece), the blockage may be removed by washing the actuator as described above.
If it is necessary to use the inhaler before it is completely dry, shake excess water off the plastic actuator, replace canister, shake well, test spray twice away from face, and take the prescribed dose. After such use, the actuator should be rewashed and allowed to air- dry thoroughly.
The action of Ventolin HFA should last up to 4- 6 hours. Ventolin HFA should not be used more frequently than recommended. Do not increase the dose or frequency of doses of Ventolin HFA without consulting your physician. If you find that treatment with Ventolin HFA 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 Ventolin HFA, other inhaled drugs and asthma medications should be taken only as directed by your physician.
Common adverse effects of treatment with inhaled albuterol include palpitations, chest pain, rapid heart rate, tremor, and nervousness. If you are pregnant or nursing, contact your physician about use of Ventolin HFA. Effective and safe use of Ventolin HFA includes an understanding of the way that it should be administered.
Use Ventolin HFA only with the actuator supplied with the product. Discard the canister after 200 sprays have been used or 3 months after removal from the moisture- protective foil pouch, whichever comes first. Never immerse the canister into water to determine how full the canister is ("float test").
In general, the technique for administering Ventolin HFA to children is similar to that for adults. Children should use Ventolin HFA under adult supervision, as instructed by the patient's physician. (See Patient's Instructions for Use distributed with the prescription.)

Carcinogenesis, Mutagenesis, and 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 2.0 mg/ kg (approximately 14 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis and approximately 6 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). 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 1700 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis and approximately 800 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). 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 225 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis and approximately 110 times the maximum recommended daily inhalation dose for children on a mg/ m2basis).
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 of albuterol sulfate up to 50 mg/ kg (approximately 340 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis).

Pregnancy, Teratogenic Effects, Pregnancy Category C
  Albuterol sulfate has been shown to be teratogenic in mice. A study in CD- 1 mice given albuterol sulfate subcutaneously showed cleft palate formation in 5 of 111 (4.5%) fetuses at 0.25 mg/ kg (less than the maximum recommended daily inhalation dose for adults on a mg/ m2basis) and in 10 of 108 (9.3%) fetuses at 2.5 mg/ kg (approximately 8 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis). The drug did not induce cleft palate formation at a dose of 0.025 mg/ kg (less than the maximum recommended daily inhalation dose for adults on a mg/ m2basis). Cleft palate also occurred in 22 of 72 (30.5%) fetuses from females treated subcutaneously with 2.5 mg/ kg of isoproterenol (positive control).
A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7 of 19 fetuses (37%) when albuterol sulfate was administered orally at a 50 mg/ kg dose (approximately 680 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis).
In an inhalation reproduction study in New Zealand white rabbits, albuterol sulfate/ HFA- 134a formulation exhibited enlargement of the frontal portion of the fetal fontanelles at and above inhalation doses of 0.0193 mg/ kg (less than the maximum recommended daily inhalation dose for adults on a mg/ m2basis).
A study in which pregnant rats were dosed with radiolabeled albuterol sulfate demonstrated that drug- related material is transferred from the maternal circulation to the fetus.
There are no adequate and well- controlled studies of Ventolin HFA or albuterol sulfate in pregnant women. Ventolin HFA 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 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.

Use in Labor and Delivery
  Because of the potential for beta- agonist interference with uterine contractility, use of Ventolin HFA 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
  Plasma levels of albuterol sulfate and HFA- 134a after inhaled therapeutic doses are very low in humans, but it is not known whether the components of Ventolin HFA are excreted in human milk. Because of the potential for tumorigenicity shown for albuterol in animal studies and lack of experience with the use of Ventolin HFA by nursing mothers, 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. Caution should be exercised when albuterol sulfate is administered to a nursing woman.

Pediatric Use
  Results from a 2 week, randomized study in pediatric patients 4- 11 years old with mild to moderate asthma have shown that Ventolin HFA is safe and effective in this population. Safety and effectiveness in children below 4 years of age have not been established.

Geriatrics
  Clinical studies of Ventolin HFA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Ventolin Inhalation Solution, 0.5%
 

General
  Albuterol, as with all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, hypertension, and cardiac arrhythmia; in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines. Clinically significant changes in systolic and diastolic blood pressure have been seen in individual patients and could be expected to occur in some patients after use of any beta- adrenergic bronchodilator.
Large doses of IV 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.
Repeated dosing with 0.15 mg/ kg of albuterol inhalation solution in children aged 5- 17 years who were initially normokalemic has been associated with an asymptomatic decline of 20- 25% in serum potassium levels.

Information for the Patient
  The action of Ventolin inhalation solution may last up to 6 hours or longer. Ventolin inhalation solution should not be used more frequently than recommended. Do not increase the dose or frequency of Ventolin inhalation solution without consulting your physician. If you find that treatment with Ventolin inhalation solution 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 Ventolin inhalation solution, 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 Ventolin inhalation solution. Effective and safe use of Ventolin inhalation solution includes an understanding of the way that it should be administered.
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.
Drug compatibility (physical and chemical), efficacy, and safety of Ventolin inhalation solution when mixed with other drugs in a nebulizer have not been established.
See illustrated Patient's Instructions for Use distributed with the prescription.

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 (approximately 2, 8, and 40 times, respectively, the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 3/ 5, 3, and 15 times, respectively, the maximum recommended daily inhalation dose in children on a mg/ m2basis). 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 200 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 75 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). In a 22 month study in the Golden hamster, albuterol sulfate showed no evidence of tumorigenicity at dietary doses of up to 50 mg/ kg (approximately 25 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 10 times the maximum recommended daily inhalation dose for children on a mg/ m2basis).
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 the maximum recommended daily inhalation dose for adults on a mg/ m2basis).

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 1/ 100, 1/ 10, and 1.0 times, respectively, the maximum recommended daily inhalation dose for adults on a mg/ m2basis) 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 the maximum recommended daily inhalation dose for adults on a mg/ m2basis).
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 80 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis).
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.

Use in Labor and Delivery
  Because of the potential for beta- agonist interference with uterine contractility, use of Ventolin inhalation solution 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. 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
  The safety and effectiveness of Ventolin inhalation solution have been established in children 2 years of age and older. Use of Ventolin inhalation solution in these age- groups is supported by evidence from adequate and well- controlled studies of Ventolin 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- 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 Ventolin inhalation solution in children below 2 years of age have not been established.

Ventolin Nebules Inhalation Solution, 0.083%
 

General
  Albuterol, as with all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, hypertension, and cardiac arrhythmia; in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines. Clinically significant changes in systolic and diastolic blood pressure have been seen in individual patients and could be expected to occur in some patients after use of any beta- adrenergic bronchodilator.
Large doses of IV 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.
Repeated dosing with 0.15 mg/ kg of albuterol inhalation solution in children aged 5- 17 years who were initially normokalemic has been associated with an asymptomatic decline of 20- 25% in serum potassium levels.

Information for the Patient
  The action of Ventolin Nebules inhalation solution may last up to 6 hours or longer. Ventolin Nebules inhalation solution should not be used more frequently than recommended. Do not increase the dose or frequency of Ventolin Nebules inhalation solution without consulting your physician. If you find that treatment with Ventolin Nebules inhalation solution 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 Ventolin Nebules inhalation solution, 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 Ventolin Nebules inhalation solution. Effective and safe use of Ventolin Nebules inhalation solution includes an understanding of the way that it should be administered.
Drug compatibility (physical and chemical), efficacy, and safety of Ventolin Nebules inhalation solution when mixed with other drugs in a nebulizer have not been established.
See illustrated Patient's Instructions for Use distributed with the prescription.

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 (approximately 2, 8, and 40 times, respectively, the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 3/ 5, 3, and 150 times, respectively, the maximum recommended daily inhalation dose in children on a mg/ m2basis). 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 up to 500 mg/ kg (approximately 200 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 75 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). In a 22 month study in the Golden hamster, albuterol sulfate showed no evidence of tumorigenicity at dietary doses up to 50 mg/ kg (approximately 25 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 10 times the maximum recommended daily inhalation dose for children on a mg/ m2basis).
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 the maximum recommended daily inhalation dose for adults on a mg/ m2basis).

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 1/ 100, 1/ 10, and 1.0 times, respectively, the maximum recommended daily inhalation dose for adults on a mg/ m2basis) 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 the maximum recommended daily inhalation dose for adults on a mg/ m2basis).
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 80 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis).
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.

Use in Labor and Delivery
  Because of the potential for beta- agonist interference with uterine contractility, use of Ventolin Nebules inhalation solution 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. 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
  The safety and effectiveness of Ventolin Nebules inhalation solution have been established in children 2 years of age and older. Use of Ventolin Nebules inhalation solution in these age- groups is supported by evidence from adequate and well- controlled studies of Ventolin Nebules 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 3 published dose comparison studies of efficacy and safety in children 5- 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 Ventolin Nebules inhalation solution in children below 2 years of age have not been established.

Ventolin Rotacaps for Inhalation
 

General
  Albuterol, as with all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, hypertension, and cardiac arrhythmia; in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines. Clinically significant changes in systolic and diastolic blood pressure have been seen in individual patients and could be expected to occur in some patients after use of any beta- adrenergic bronchodilator. 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.

Information for the Patient
  The action of Ventolin Rotacaps for inhalation may last for up to 6 hours or longer. Ventolin Rotacaps for inhalation should not be used more frequently than recommended. Do not increase the dose or frequency of Ventolin Rotacaps for inhalation without consulting your physician. If you find that treatment with Ventolin Rotacaps for inhalation 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 Ventolin Rotacaps for inhalation, 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 Ventolin Rotacaps for inhalation. Effective and safe use of Ventolin Rotacaps for inhalation includes an understanding of the way that it should be administered.
Children should use Ventolin Rotacaps for inhalation under adult supervision, as instructed by the patient's physician.
See illustrated Patient's Instructions for Use distributed with the prescription.

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 (approximately 7, 35, and 170 times, respectively, the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 3, 15, and 80 times, respectively, the maximum recommended daily inhalation dose in children on a mg/ m2basis). 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 850 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 400 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). In a 22 month study in the Golden hamster, albuterol sulfate showed no evidence of tumorigenicity at dietary doses of up to 50 mg/ kg (approximately 120 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 55 times the maximum recommended daily inhalation dose for children on a mg/ m2basis).
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 170 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis).

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 1/ 25, 2/ 5, and 4 times, respectively, the maximum recommended daily inhalation dose for adults on a mg/ m2basis) 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 4 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis.
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 340 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis).
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.

Use in Labor and Delivery
  Because of the potential for beta- agonist interference with uterine contractility, use of Ventolin Rotacaps for inhalation 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
  Safety and effectiveness in children below 4 years of age have not been established.

DRUG INTERACTIONS
 

Ventolin Inhalation Aerosol
  Other short- acting sympathomimetic aerosol bronchodilators 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 Ventolin inhalation aerosol, but may produce severe bronchospasm in patients with asthma. 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- 22% in serum digoxin levels were demonstrated after single- dose IV 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.

Ventolin HFA Inhalation Aerosol
  Other short- acting sympathomimetic aerosol bronchodilators 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
  Ventolin HFA 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 Ventolin HFA, but may produce severe bronchospasm in patients with asthma. 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 should 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- 22% in serum digoxin levels were demonstrated after single- dose IV 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.

Ventolin Inhalation Solution, 0.5%
  Other short- acting sympathomimetic aerosol bronchodilators or 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 Ventolin inhalation solution, but may produce severe bronchospasm in patients with asthma. 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- 22% in serum digoxin levels were demonstrated after single- dose IV 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.

Ventolin Nebules Inhalation Solution, 0.083%
  Other short- acting sympathomimetic aerosol bronchodilators or 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 Ventolin Nebules inhalation solution, but may produce severe bronchospasm in patients with asthma. 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- 22% in serum digoxin levels were demonstrated after single- dose IV 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.

Ventolin Rotacaps for Inhalation
  Other short- acting sympathomimetic aerosol bronchodilators 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 Ventolin Rotacaps for inhalation, but may produce severe bronchospasm in patients with asthma. 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- 22% in serum digoxin levels were demonstrated after single- dose IV 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.

ADVERSE REACTIONS
 

Ventolin 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 (see TABLE 6 and TABLE 7 ).
TABLE 6    Percent Incidence of Adverse Reactions in Patients ≥12 Years of Age in a 13 Week Clinical Trial*
Reaction Albuterol Isoproterenol
Tremor <15% <15%
Nausea <15% <15%
Tachycardia 10% 10%
Palpitations <10% <15%
Nervousness <10% <15%
Increased blood pressure <5% <5%
Dizziness <5% <5%
Heartburn <5% <5%
* A 13 week double- blind study compared albuterol and isoproterenol inhalation aerosols in 147 patients with asthma.

TABLE 7    Percent Incidence of Adverse Reactions in Children 4- 11 Years of Age in a 12 Week Trial*
Reaction Percent Incidence
Central Nervous System
  Headache 3%
  Nervousness 1%
  Lightheadedness <1%
  Tremor <1%
  Agitation 1%
  Nightmares 1%
  Hyperactivity 1%
  Aggressive behavior 1%
Gastrointestinal
  Nausea and/ or vomiting 6%
  Stomachache 3%
  Diarrhea 1%
Oropharyngeal
  Throat irritation 6%
  Discoloration of teeth 1%
Respiratory
  Epistaxis 3%
  Cough 2%
Musculoskeletal
  Muscle cramp 1%
* A 12 week double- blind trial in 104 patients aged 4- 11 years.

Cases of urticaria, angioedema, rash, bronchospasm, hoarseness, oropharyngeal edema, and arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles) have been reported after the use of Ventolin inhalation aerosol.
In addition, albuterol, like other sympathomimetic agents, can cause adverse reactions such as hypertension, angina, vertigo, central nervous system stimulation, sleeplessness, and unusual taste.

Ventolin HFA Inhalation Aerosol
  Adverse reaction information concerning Ventolin HFA is derived from two 12 week, randomized, double- blind studies in 610 adolescent and adult patients with asthma that compared Ventolin HFA, a CFC 11/ 12- propelled albuterol inhaler, and an HFA- 134a placebo inhaler. TABLE 8 lists the incidence of all adverse events (whether considered by the investigator to be related or unrelated to drug) from these studies that occurred at a rate of 3% or greater in the group treated with Ventolin HFA and more frequently in the group treated with Ventolin HFA than in the HFA- 134a placebo inhaler group. Overall, the incidence and nature of the adverse events reported for Ventolin HFA and a CFC 11/ 12- propelled albuterol inhaler were comparable. Results in a 2 week pediatric clinical study (n=135) showed that the adverse event profile was generally similar to that of the adult.
TABLE 8    Adverse Experience Incidence (% of Patients) in 2 Large 12 Week Adolescent and Adult Clinical Trials*
  Ventolin HFA CFC 11/ 12- Propelled Albuterol Inhaler Placebo HFA- 134a
Adverse Event Type (n=202) (n=207) (n=201)
Ear, Nose, and Throat
  Throat irritation 10% 6% 7%
  Upper respiratory inflammation 5% 5% 2%
Lower Respiratory
  Viral respiratory infections 7% 4% 4%
  Cough 5% 2% 2%
Musculoskeletal
  Musculoskeletal pain 5% 5% 4%
* This table includes all adverse events (whether considered by the investigator to be drug- related or unrelated to drug) that occurred at an incidence rate of at least 3.0% in the group treated with Ventolin HFA and more frequently in the group treated with Ventolin HFA than in the HFA- 134a placebo inhaler group.

Adverse events reported by less than 3% of the adolescent and adult patients receiving Ventolin HFA and by a greater proportion of patients receiving Ventolin HFA than receiving HFA- 134a placebo inhaler and that have the potential to be related to Ventolin HFA include diarrhea, laryngitis, oropharyngeal edema, cough, lung disorders, tachycardia, and extrasystoles. Palpitation and dizziness have also been observed with Ventolin HFA.
Cases of urticaria, angioedema, rash, bronchospasm, hoarseness, and arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles) have been reported after the use of albuterol.
In addition, albuterol, like other sympathomimetic agents, can cause adverse reactions such as hypertension, angina, vertigo, central nervous system stimulation, sleeplessness, headache, and drying or irritation of the oropharynx.

Ventolin Inhalation Solution, 0.5%
  The results of clinical trials with Ventolin inhalation solution in 135 patients showed the following side effects that were considered probably or possibly drug related (see TABLE 9 ).
TABLE 9    Percent Incidence of Adverse Reactions
Reaction n=135
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 Ventolin inhalation solution administration were determined in these studies.
Cases of urticaria, angioedema, rash, bronchospasm, hoarseness, oropharyngeal edema, and arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles) have been reported after the use of Ventolin inhalation solution.

Ventolin Nebules Inhalation Solution, 0.083%
  The results of clinical trials with Ventolin (albuterol sulfate) inhalation solution, 0.5% in 135 patients showed the following side effects that were considered probably or possibly drug related (see TABLE 10 ).
TABLE 10    Percent Incidence of Adverse Reactions
Reaction n=135
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 Ventolin inhalation solution administration were determined in these studies.
Cases of urticaria, angioedema, rash, bronchospasm, hoarseness, oropharyngeal edema, and arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles) have been reported after the use of Ventolin Nebules inhalation solution.

Ventolin Rotacaps 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 Ventolin Rotacaps for inhalation 200 μg in 172 patients aged 12 years and older (adults) and 129 patients aged 4- 12 years (children) are shown in TABLE 11 and TABLE 12 .
TABLE 11    Percent Incidence of Adverse Reactions in Patients ≥12 Years of Age
Reaction Percent Incidence
Central Nervous System
  Headache 2%
  Nervousness 1%
  Tremor 1%
  Sleeplessness <1%
  Dizziness <1%
  Lightheadedness <1%
Digestive System
  Throat irritation 2%
  Burning in the stomach <1%
  Dry mouth <1%
  Bad taste <1%
Respiratory System
  Coughing 5%
  Bronchospasm 1%

TABLE 12    Percent Incidence of Adverse Reactions in Children 4- 12 Years of Age
Reaction Percent Incidence
Central Nervous System
  Headache 5%
  Dizziness <1%
  Hyperactivity <1%
Gastrointestinal
  Nausea and/ or vomiting 4%
  Stomachache 2%
  Diarrhea <1%
Respiratory System
  Epistaxis 2%
  Hoarseness 2%
  Nasal congestion 2%
  Cough 2%
Oropharyngeal
  Throat irritation 2%
  Unusual taste 2%

Cases of urticaria, angioedema, rash, bronchospasm, hoarseness, oropharyngeal edema, and arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles) have been reported after the use of Ventolin Rotacaps for inhalation.
In addition, albuterol, like other sympathomimetic agents, can cause adverse reactions such as hypertension, angina, vertigo, and CNS stimulation.

OVERDOSAGE
 

Ventolin Inhalation Aerosol
  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/ minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and sleeplessness. Hypokalemia may also occur.
As with all sympathomimetic aerosol medications, cardiac arrest and even death may be associated with abuse of Ventolin inhalation aerosol. Treatment consists of discontinuation of Ventolin inhalation aerosol together with appropriate symptomatic therapy. The judicious use of a cardioselective beta- receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of Ventolin inhalation aerosol.
The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/ kg (approximately 6800 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 3200 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). In mature rats, the subcutaneous median lethal dose of albuterol sulfate is approximately 450 mg/ kg (approximately 3000 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 1400 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). In small young rats, the subcutaneous median lethal dose is approximately 2000 mg/ kg (approximately 14, 000 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 6400 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). The inhalation median lethal dose has not been determined in animals.

Ventolin HFA Inhalation Aerosol
  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/ minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and sleeplessness. Hypokalemia may also occur.
As with all sympathomimetic aerosol medications, cardiac arrest and even death may be associated with abuse of Ventolin HFA. Treatment consists of discontinuation of Ventolin HFA together with appropriate symptomatic therapy. The judicious use of a cardioselective beta- receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of Ventolin HFA.
The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/ kg (approximately 6800 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis and approximately 3200 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). In mature rats, the subcutaneous median lethal dose of albuterol sulfate is approximately 450 mg/ kg (approximately 3000 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis and approximately 1400 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). In young rats, the subcutaneous median lethal dose is approximately 2000 mg/ kg (approximately 14, 000 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis and approximately 6400 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). The inhalation median lethal dose has not been determined in animals.

Ventolin Inhalation Solution, 0.5%
  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/ minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and sleeplessness. Hypokalemia may also occur. In isolated cases in children 2- 12 years of age, tachycardia with rates >200 beats/ minute has been observed.
As with all sympathomimetic medications, cardiac arrest and even death may be associated with abuse of Ventolin inhalation solution. Treatment consists of discontinuation of Ventolin inhalation solution together with appropriate symptomatic therapy. The judicious use of a cardioselective beta- receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of Ventolin inhalation solution.
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/ m2basis or approximately 300 times the maximum recommended daily dose for children on a mg/ m2basis). In mature rats, the subcutaneous (SC) 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/ m2basis or approximately 135 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). In small young rats, the SC median lethal dose is approximately 2000 mg/ kg (approximately 1600 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 600 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). The inhalational median lethal dose has not been determined in animals.

Ventolin Nebules Inhalation Solution, 0.083%
  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/ minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and sleeplessness. Hypokalemia may also occur. In isolated cases in children 2- 12 years of age, tachycardia with rates >200 beats/ minute has been observed.
As with all sympathomimetic medications, cardiac arrest and even death may be associated with abuse of Ventolin Nebules inhalation solution. Treatment consists of discontinuation of Ventolin Nebules inhalation solution together with appropriate symptomatic therapy. The judicious use of a cardioselective beta- receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of Ventolin Nebules inhalation solution.
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/ m2basis or approximately 300 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). In mature rats, the subcutaneous (SC) 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/ m2basis or approximately 135 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). In small young rats, the SC median lethal dose is approximately 2000 mg/ kg (approximately 1600 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 600 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). The inhalation median lethal dose has not been determined in animals.

Ventolin Rotacaps for Inhalation
  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/ minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and sleeplessness. Hypokalemia may also occur. As with all sympathomimetic medications, cardiac arrest and even death may be associated with abuse of Ventolin Rotacaps for inhalation. Treatment consists of discontinuation of Ventolin Rotacaps for inhalation together with appropriate symptomatic therapy. The judicious use of a cardioselective beta- receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of Ventolin Rotacaps for inhalation.
The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/ kg (approximately 3400 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 1600 times the maximum recommended daily dose for children on a mg/ m2basis). In mature rats, the subcutaneous median lethal dose of albuterol sulfate is approximately 450 mg/ kg (approximately 1500 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 700 times the maximum recommended daily dose for children on a mg/ m2basis). In small young rats, the subcutaneous median lethal dose is approximately 2000 mg/ kg (approximately 6800 times the maximum recommended daily inhalation dose for adults on a mg/ m2basis or approximately 3200 times the maximum recommended daily inhalation dose for children on a mg/ m2basis). The inhalational median lethal dose has not been determined in animals.
Dialysis is not appropriate treatment for overdosage of Ventolin Rotacaps for inhalation.

DOSAGE AND ADMINISTRATION
 

Ventolin 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 2 inhalations repeated every 4- 6 hours; in some patients, 1 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" Ventolin inhalation aerosol. Do this by spraying 4 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 Ventolin 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 2 inhalations 15 minutes before exercise.
For treatment, see above.

Ventolin HFA Inhalation Aerosol
 

Adult and Pediatric Asthma
  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 2 inhalations repeated every 4- 6 hours; in some patients, 1 inhalation every 4 hours may be sufficient. More frequent administration or a larger number of inhalations is not recommended. 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 4 test sprays into the air, away from the face.
Ventolin HFA can also be used to relieve acute symptoms of asthma. The use of Ventolin HFA can be continued as medically indicated to control recurring bouts of bronchospasm. 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.
Safe usage of albuterol for periods extending over several years has been documented.

Exercise-Induced Bronchospasm Prevention
  The usual dosage for adults and children 4 years and older is 2 inhalations 15- 30 minutes before exercise. For treatment, see above.

Cleaning
  To maintain proper use of this product, it is important that the actuator be washed and dried thoroughly at least once a week. The inhaler may cease to deliver medication if not properly cleaned and dried thoroughly. See PRECAUTIONS, Information for the Patient . Keeping the plastic actuator clean is very important to prevent medication build- up and blockage. If the actuator becomes blocked with drug, washing the actuator will remove the blockage.

Ventolin 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 2-12 Years of Age
  For children 2- 12 years of age, initial dosing should be based upon body weight (0.1- 0.15 mg/ kg/ dose), with subsequent dosing titrated to achieve the desired clinical response. Dosing should not exceed 2.5 mg three to four times daily by nebulization. TABLE 13 outlines approximate dosing according to body weight.
TABLE 13   
Approximate Weight Dose Volume of Inhalation Solutions
10- 15 kg 22- 33 lb 1.25 mg 0.25 ml
>15 kg >33 lb 2.5 mg 0.5 ml

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 over 12 years of age is 2.5 mg of albuterol administered 3- 4 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 flow rate is regulated to suit the particular nebulizer so that Ventolin inhalation solution will be delivered over approximately 5- 15 minutes.
The use of Ventolin inhalation solution 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 Ventolin inhalation solution when mixed with other drugs in a nebulizer have not been established.

Ventolin Nebules Inhalation Solution, 0.083%
 

Adults and Children 2-12 Years of Age
  The usual dosage for adults and for children weighing at least 15 kg is 2.5 mg of albuterol (1 nebule) administered 3- 4 times daily by nebulization. Children weighing less than 15 kg who require less than 2.5 mg/ dose ( i.e., less than a full nebule) should use Ventolin inhalation solution instead of Ventolin Nebules inhalation solution. More frequent administration or higher doses are not recommended. To administer 2.5 mg of albuterol, administer the entire contents of 1 sterile unit dose nebule (3 ml of 0.083% inhalation solution) by nebulization. The flow rate is regulated to suit the particular nebulizer so that Ventolin Nebules inhalation solution will be delivered over approximately 5- 15 minutes.
The use of Ventolin Nebules inhalation solution 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 Ventolin Nebules inhalation solution when mixed with other drugs in a nebulizer have not been established.

Ventolin Rotacaps for Inhalation
  The usual dosage of Ventolin Rotacaps for inhalation for adults and children 4 years of age and older is the contents of one 200 μg capsule inhaled every 4- 6 hours using a Rotahaler inhalation device. In some patients, the contents of two 200 μg capsules inhaled every 4- 6 hours may be required. Larger doses or more frequent administration is not recommended.
The use of Ventolin Rotacaps 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 Ventolin Rotacaps 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 Ventolin Rotacaps for inhalation for adults and children 4 years of age and older is the contents of one 200 μg capsule inhaled using a Rotahaler 15 minutes before exercise.

HOW SUPPLIED
 

Ventolin Inhalation Aerosol
  Ventolin inhalation aerosol is supplied in 6.8 g canisters containing 80 metered inhalations and in 17 g canisters containing 200 metered inhalations. Each actuation delivers 100 μg of albuterol from the valve and 90 μg 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 a 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 labeled number of actuations have been used.

Storage
  Store between 15 and 30°C (59 and 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 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 US 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 HFA Inhalation Aerosol
  Ventolin HFA (albuterol sulfate HFA inhalation aerosol) is supplied as a pressurized aluminum canister with a blue plastic actuator and a blue strapcap packaged within a moisture- protective foil pouch. The moisture- protective foil pouch also contains a desiccant that should be discarded when the pouch is opened.
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 4 test sprays into the air, away from the face. After priming with 4 actuations, each actuation delivers 120 μg of albuterol sulfate in 75 mg of suspension from the valve and 108 μg of albuterol sulfate from the mouthpiece (equivalent to 90 μg of albuterol base from the mouthpiece). The canister is labeled with a net weight of 18 g and contains 200 metered inhalations.
The blue actuator supplied with Ventolin HFA should not be used with any other product canisters, and actuators from other products should not be used with a Ventolin HFA canister. The correct amount of medication in each canister cannot be assured after 200 actuations, even though the canister is not completely empty. The canister should be discarded when 200 actuations have been used or 3 months after removal from the moisture- protective foil pouch, whichever comes first. Never immerse the canister into water to determine how full the canister is ("float test").

Contents 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. Avoid spraying in eyes.

Storage
  Store between 15 and 25°C (59 and 77°F). Store canister with mouthpiece down. For best results, the canister should be at room temperature before use. SHAKE WELL BEFORE USING.
Ventolin HFA does not contain chlorofluorocarbons (CFCs) as the propellant.

Ventolin Inhalation Solution, 0.5%
  Ventolin inhalation solution 0.5% is supplied in bottles of 20 ml with accompanying calibrated dropper.

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

Ventolin Nebules Inhalation Solution, 0.083%
  Ventolin Nebules inhalation solution, 0.083% is contained in plastic, sterile, unit dose Nebules of 3 ml each supplied in foil pouches.

Storage: Protect from light. Store in refrigerator between 2 and 8°C (36 and 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
  Ventolin Rotacaps for inhalation, 200 μg, are light blue and clear, with "Ventolin 200" printed on the blue cap and "GLAXO" printed on the clear body.
Also available, Ventolin Rotacaps for inhalation refill.

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

PRODUCT IDENTIFICATION
  Albuterol , tablet , 2 mg [ Mylan Pharmaceuticals Inc ]
Albuterol , tablet , 2 mg [ UDL Laboratories Inc ]
Albuterol , tablet , 4 mg [ Mylan Pharmaceuticals Inc ]
Albuterol , tablet , 4 mg [ UDL Laboratories Inc ]
Albuterol , tablet, extended release , 4 mg [ Schering-Plough Corporation ]
Albuterol , tablet, extended release , 4 mg [ *Muro Pharmaceuticals Inc ]
Albuterol , tablet, extended release , 8 mg [ *Muro Pharmaceuticals Inc ]
Albuterol , tablet , 4 mg [ Warrick Pharmaceuticals Corporation ]

PATIENT DRUG CONSULT HANDOUT
  Albuterol (aerosal)
Albuterol (inhalation)
Albuterol (nebulizer)
Albuterol (oral)

PRODUCT LISTING - RATED THERAPEUTICALLY EQUIVALENT
 
aerosol - inhalation - 90 mcg/ inh -
7.0 gm $18.40 Ventolin
GlaxoSmithKline 		00173046300
17.0 gm $19.79 GENERIC
Dey Laboratories 		49502033327
17.0 gm $20.00 GENERIC
Pliva Inc 		50111080132
17.0 gm $20.00 GENERIC
Alpharma USPD 		00472126463
17.0 gm $21.50 GENERIC
Major Pharmaceuticals Inc 		00904507934
17.0 gm $28.70 GENERIC
Andrx Pharmaceuticals 		62037079444
17.0 gm $35.09 Ventolin
Physicians Total Care 		54868190300
17.0 gm $35.35 Ventolin
GlaxoSmithKline 		00173032198
17.0 gm $37.30 Ventolin
Pharma Pac 		52959058801
17.0 gm $38.39 Ventolin
Physicians Total Care 		54868073001
17.0 gm $39.90 GENERIC
Pharma Pac 		52959009403
aerosol with adapter - inhalation - 90 mcg/ inh -
17.0 gm $12.75 GENERIC
Dey Laboratories 		49502033317
17.0 gm $29.79 GENERIC
Pliva Inc 		50111080131
17.0 gm $29.79 GENERIC
IVAX Corporation 		00172439018
17.0 gm $30.00 Ventolin
Southwood Pharmaceuticals Inc 		58016609901
17.0 gm $35.06 Ventolin
Allscripts Healthcare Solutions 		54569100300
17.0 gm $38.35 Ventolin
GlaxoSmithKline 		00173032188
powder - compounding - 100% -
25.0 gm $54.11 GENERIC
Paddock Laboratories Inc 		00574051225
100.0 gm $192.38 GENERIC
Paddock Laboratories Inc 		00574051201
solution - inhalation - 0.083% -
3.0 ml x 25.0 $8.89 GENERIC
IVAX Corporation 		00172640544
3.0 ml x 60.0 $21.11 GENERIC
IVAX Corporation 		00172640549
3.0 ml x 30.0 $24.00 GENERIC
Nephron Pharmaceuticals 		00487950101
3.0 ml x 30.0 $24.00 GENERIC
Nephron Pharmaceuticals 		00487950103
3.0 ml x 24.0 $29.04 GENERIC
Warrick Pharmaceuticals Corporation 		59930151701
3.0 ml x 25.0 $30.25 GENERIC
Dey Laboratories 		49502069724
3.0 ml x 25.0 $30.25 GENERIC
Dey Laboratories 		49502069703
3.0 ml x 25.0 $30.25 GENERIC
Hi- Tech Pharmacal Company Inc 		50383074225
3.0 ml x 25.0 $30.50 GENERIC
Qualitest Pharmaceuticals Inc 		00603100540
3.0 ml x 60.0 $31.00 GENERIC
Aslung Pharmaceuticals LP 		65271000205
3.0 ml x 25.0 $31.00 GENERIC
Nephron Pharmaceuticals 		00487950125
3.0 ml x 25.0 $31.00 GENERIC
Alpharma USPD 		00472083123
3.0 ml x 25.0 $31.25 GENERIC
Major Pharmaceuticals Inc 		00904773117
3.0 ml x 25.0 $32.60 GENERIC
Sandoz Inc 		00781915093
3.0 ml x 30.0 $36.30 GENERIC
Dey Laboratories 		49502069733
3.0 ml x 30.0 $37.06 GENERIC
Alpharma USPD 		00472083130
3.0 ml x 60.0 $48.00 GENERIC
Nephron Pharmaceuticals 		00487950160
3.0 ml x 25.0 $51.25 Proventil
Schering- Plough Corporation 		00085020901
3.0 ml x 25.0 $57.84 Proventil
Schering- Plough Corporation 		00085180601
3.0 ml x 60.0 $72.60 GENERIC
Dey Laboratories 		49502069760
3.0 ml x 60.0 $72.60 GENERIC
Warrick Pharmaceuticals Corporation 		59930151702
3.0 ml x 60.0 $74.40 GENERIC
Alpharma USPD 		00472083160
3.0 ml x 60.0 $75.00 GENERIC
Morton Grove Pharmaceuticals Inc 		60432009406
solution - inhalation - 0.5% -
0.5 ml x 30.0 $27.00 GENERIC
Nephron Pharmaceuticals 		00487990130
20.0 ml $7.23 GENERIC
IVAX Corporation 		00182601465
20.0 ml $12.50 GENERIC
Qualitest Pharmaceuticals Inc 		00603100643
20.0 ml $14.65 GENERIC
Major Pharmaceuticals Inc 		00904765855
20.0 ml $14.99 GENERIC
Dey Laboratories 		49502010501
20.0 ml $14.99 GENERIC
Warrick Pharmaceuticals Corporation 		59930164702
20.0 ml $16.50 GENERIC
Hi- Tech Pharmacal Company Inc 		50383074120
20.0 ml $16.71 GENERIC
Alpharma USPD 		00472083230
20.0 ml $16.71 GENERIC
Alpharma USPD 		00472083220
20.0 ml $17.00 GENERIC
Bausch and Lomb 		24208034720
20.0 ml $22.05 Ventolin
Pharma Pac 		52959058900
20.0 ml $22.50 Proventil
Schering- Plough Corporation 		00085020802
20.0 ml $22.50 Proventil
Allscripts Healthcare Solutions 		54569198900
20.0 ml $23.44 Proventil
Schering- Plough Corporation 		00085133601
20.0 ml $23.58 Ventolin
Physicians Total Care 		54868347900
syrup - oral - 2 mg/ 5 ml -
5.0 ml x 50.0 $62.60 GENERIC
UDL Laboratories Inc 		51079076110
120.0 ml $11.07 GENERIC
Alpharma USPD 		00472082504
180.0 ml $29.20 GENERIC
Pharma Pac 		52959015306
240.0 ml $19.38 GENERIC
Alpharma USPD 		00472082508
473.0 ml $30.79 GENERIC
Teva Pharmaceuticals USA 		00093066116
480.0 ml $26.40 GENERIC
Watson Pharmaceuticals 		52544041916
480.0 ml $27.90 GENERIC
Major Pharmaceuticals Inc 		00904768116
480.0 ml $30.79 GENERIC
Qualitest Pharmaceuticals Inc 		00603100758
480.0 ml $34.99 GENERIC
Par Pharmaceutical Inc 		49884041133
480.0 ml $39.60 GENERIC
Hi- Tech Pharmacal Company Inc 		50383074016
480.0 ml $40.15 GENERIC
Alpharma USPD 		00472082516
tablet - oral - 2 mg -
20.0's $8.95 GENERIC
Pharma Pac 		52959042520
20.0's $16.27 GENERIC
PD- RX Pharmaceuticals 		55289036320
24.0's $17.50 GENERIC
PD- RX Pharmaceuticals 		55289036324
30.0's $8.10 GENERIC
Heartland Healthcare Services 		61392056730
30.0's $8.10 GENERIC
Heartland Healthcare Services 		61392056739
30.0's $8.55 GENERIC
PD- RX Pharmaceuticals 		55289036330
30.0's $15.59 Proventil
PD- RX Pharmaceuticals 		55289000930
30.0's $17.31 Ventolin
PD- RX Pharmaceuticals 		55289080930
31.0's $8.37 GENERIC
Heartland Healthcare Services 		61392056731
32.0's $8.64 GENERIC
Heartland Healthcare Services 		61392056732
45.0's $12.15 GENERIC
Heartland Healthcare Services 		61392056745
60.0's $16.20 GENERIC
Heartland Healthcare Services 		61392056765
60.0's $16.20 GENERIC
Heartland Healthcare Services 		61392056760
60.0's $31.19 Proventil
PD- RX Pharmaceuticals 		55289000960
90.0's $24.30 GENERIC
Heartland Healthcare Services 		61392056790
90.0's $24.30 GENERIC
Heartland Healthcare Services 		61392056795
100.0's $14.14 GENERIC
UDL Laboratories Inc 		51079065720
100.0's $24.90 GENERIC
Major Pharmaceuticals Inc 		00904287660
100.0's $25.38 GENERIC
Major Pharmaceuticals Inc 		00904287661
100.0's $28.05 GENERIC
Sandoz Inc 		00781167101
100.0's $31.14 GENERIC
United Research Laboratories/ Mutual Pharmaceutical Company 		00677135901
100.0's $31.14 GENERIC
Mylan Pharmaceuticals Inc 		00378025501
100.0's $31.14 GENERIC
United Research Laboratories/ Mutual Pharmaceutical Company 		53489017601
100.0's $48.92 Proventil
Schering- Plough Corporation 		00085025202
500.0's $39.31 GENERIC
United Research Laboratories/ Mutual Pharmaceutical Company 		00677135905
500.0's $112.90 GENERIC
Major Pharmaceuticals Inc 		00904287640
500.0's $135.00 GENERIC
Heartland Healthcare Services 		61392056751
500.0's $154.17 GENERIC
United Research Laboratories/ Mutual Pharmaceutical Company 		53489017605
500.0's $154.18 GENERIC
Mylan Pharmaceuticals Inc 		00378025505
500.0's $197.45 Proventil
Schering- Plough Corporation 		00085025203
2000.0's $540.00 GENERIC
Heartland Healthcare Services 		61392056754
3000.0's $810.00 GENERIC
Heartland Healthcare Services 		61392056756
10000.0's $2700.00 GENERIC
Heartland Healthcare Services 		61392056791
tablet - oral - 4 mg -
30.0's $11.87 GENERIC
Heartland Healthcare Services 		61392057030
30.0's $11.87 GENERIC
Heartland Healthcare Services 		61392057039
30.0's $19.72 GENERIC
PD- RX Pharmaceuticals 		55289004530
30.0's $25.61 Ventolin
PD- RX Pharmaceuticals 		55289081030
31.0's $12.26 GENERIC
Heartland Healthcare Services 		61392057031
32.0's $12.66 GENERIC
Heartland Healthcare Services 		61392057032
45.0's $17.80 GENERIC
Heartland Healthcare Services 		61392057045
60.0's $23.73 GENERIC
Heartland Healthcare Services 		61392057060
60.0's $23.73 GENERIC
Heartland Healthcare Services 		61392057065
90.0's $35.60 GENERIC
Heartland Healthcare Services 		61392057095
90.0's $35.60 GENERIC
Heartland Healthcare Services 		61392057090
100.0's $17.94 GENERIC
UDL Laboratories Inc 		51079065820
100.0's $35.30 GENERIC
Major Pharmaceuticals Inc 		00904287760
100.0's $36.38 GENERIC
Major Pharmaceuticals Inc 		00904287761
100.0's $41.30 GENERIC
Sandoz Inc 		00781167201
100.0's $45.76 GENERIC
Mylan Pharmaceuticals Inc 		00378057201
100.0's $45.76 GENERIC
United Research Laboratories/ Mutual Pharmaceutical Company 		53489017701
100.0's $74.40 Proventil
Schering- Plough Corporation 		00085057302
100.0's $86.77 Proventil
Physicians Total Care 		54868030801
500.0's $164.60 GENERIC
Major Pharmaceuticals Inc 		00904287740
500.0's $197.78 GENERIC
Heartland Healthcare Services 		61392057051
500.0's $224.19 GENERIC
United Research Laboratories/ Mutual Pharmaceutical Company 		53489017705
500.0's $224.20 GENERIC
Mylan Pharmaceuticals Inc 		00378057205
500.0's $294.85 Proventil
Schering- Plough Corporation 		00085057303
2000.0's $791.10 GENERIC
Heartland Healthcare Services 		61392057054
3000.0's $1186.65 GENERIC
Heartland Healthcare Services 		61392057056
10000.0's $3955.50 GENERIC
Heartland Healthcare Services 		61392057091
tablet, extended release - oral - 8 mg -
100.0 $218.42 Volmax
Muro Pharmaceuticals Inc 		00451039950

PRODUCT LISTING - RATED NOT THERAPEUTICALLY EQUIVALENT
 
aerosol - inhalation - 90 mcg/ inh -
17.0 gm $31.49 Proventil
Schering- Plough Corporation 		00085061403
17.0 gm $36.41 Proventil
Physicians Total Care 		54868104101
17.0 gm $36.83 Proventil
Pharma Pac 		52959029300
17.0 gm $38.86 Proventil
Allscripts Healthcare Solutions 		54569005200
aerosol with adapter - inhalation - 90 mcg/ inh -
6.0 gm $14.96 Proventil
Prescript Pharmaceuticals 		00247008486
17.0 gm $8.38 GENERIC
Warrick Pharmaceuticals Corporation 		59930156001
17.0 gm $22.95 GENERIC
Major Pharmaceuticals Inc 		00904507834
17.0 gm $32.39 Proventil
Prescript Pharmaceuticals 		00247008417
17.0 gm $43.06 Proventil
Schering- Plough Corporation 		00085061402
aerosol with adapter - inhalation - 108 mcg/ inh -
6.7 gm $34.65 Proventil HFA
Pharma Pac 		52959056901
6.7 gm $43.96 Proventil HFA
Schering- Plough Corporation 		00085113201
18.0 gm $37.63 Ventolin HFA
GlaxoSmithKline 		00173068200
tablet, extended release - oral - 4 mg -
15.0 $17.21 Proventil Repetabs
PD- RX Pharmaceuticals 		55289063415
20.0 $20.12 Proventil Repetabs
Allscripts Healthcare Solutions 		54569038702
30.0 $41.75 Volmax
Physicians Total Care 		55289049830
60.0 $65.52 Volmax
Allscripts Healthcare Solutions 		54569417801
60.0 $70.70 Proventil Repetabs
PD- RX Pharmaceuticals 		55289063460
100.0 $91.45 Proventil Repetabs
Schering- Plough Corporation 		00085043102
100.0 $109.21 Volmax
Muro Pharmaceuticals Inc 		00451039850
100.0 $114.55 Proventil Repetabs
Schering- Plough Corporation 		00085043104
180.0 $113.96 Proventil Repetabs
Allscripts Healthcare Solutions 		54569858900
500.0 $425.90 Proventil Repetabs
Schering- Plough Corporation 		00085043103

PRODUCT LISTING - EQUIVALENTS NOT AVAILABLE
 
aerosol - inhalation - 90 mcg/ inh -
17.0 gm $8.18 GENERIC
Physicians Total Care 		54868373900
17.0 gm $26.67 GENERIC
Prescript Pharmaceuticals 		00247034817
17.0 gm $28.75 GENERIC
Allscripts Healthcare Solutions 		54569424500
17.0 gm $29.95 GENERIC
Direct Dispensing Inc 		57866005101
aerosol with adapter - inhalation - 90 mcg/ inh -
17.0 gm $15.18 GENERIC
Physicians Total Care 		54868370900
17.0 gm $21.35 GENERIC
Southwood Pharmaceuticals Inc 		58016656901
capsule - inhalation - 200 mcg -
24.0 $24.55 Ventolin Rotacaps
GlaxoSmithKline 		00173038903
96.0 $42.66 Ventolin Rotacaps
Physicians Total Care 		54868264901
100.0 $37.92 Ventolin Rotacaps
Allscripts Healthcare Solutions 		54569374100
powder - compounding - 100% -
5.0 gm $11.50 GENERIC
A- A Spectrum Healthcare Products 		49452022601
5.0 gm $17.25 GENERIC
Gallipot Inc 		51552004405
10.0 gm $19.00 GENERIC
Medisca Inc 		38779018501
10.0 gm $19.00 GENERIC
Medisca Inc 		38779018401
25.0 gm $29.29 GENERIC
A- A Spectrum Healthcare Products 		49452022602
25.0 gm $38.00 GENERIC
Medisca Inc 		38779018425
25.0 gm $38.00 GENERIC
Medisca Inc 		38779018525
100.0 gm $93.69 GENERIC
A- A Spectrum Healthcare Products 		49452022603
100.0 gm $123.00 GENERIC
Medisca Inc 		38779018510
100.0 gm $123.00 GENERIC
Medisca Inc 		38779018410
500.0 gm $563.50 GENERIC
Medisca Inc 		38779018450
500.0 gm $563.50 GENERIC
Medisca Inc 		38779018550
solution - inhalation - 0.021% -
3.0 ml x 25.0 $41.50 Accuneb
Dey Laboratories 		49502069203
solution - inhalation - 0.042% -
3.0 ml x 25.0 $41.50 Accuneb
Dey Laboratories 		49502069303
solution - inhalation - 0.083% -
3.0 ml x 25.0 $30.50 GENERIC
RxElite 		66794000125
3.0 ml x 25.0 $34.63 GENERIC
Allscripts Healthcare Solutions 		54569389900
3.0 ml x 30.0 $36.60 GENERIC
RxElite 		66794000130
3.0 ml x 60.0 $73.20 GENERIC
RxElite 		66794000160
solution - inhalation - 0.5% -
3.0 ml x 25.0 $15.09 GENERIC
Physicians Total Care 		54868247201
20.0 ml $9.27 GENERIC
Physicians Total Care 		54868340700
20.0 ml $15.53 GENERIC
Southwood Pharmaceuticals Inc 		58016640401
20.0 ml $17.00 GENERIC
Allscripts Healthcare Solutions 		54569390000
20.0 ml $22.64 GENERIC
Pharma Pac 		52959074120
syrup - oral - 2 mg/ 5 ml -
118.0 ml $11.06 GENERIC
Allscripts Healthcare Solutions 		54569489900
118.25 ml $6.65 GENERIC
Allscripts Healthcare Solutions 		54569370001
120.0 ml $7.90 GENERIC
Alpharma USPD 		63874070912
120.0 ml $19.97 GENERIC
Pharma Pac 		52959015303
480.0 ml $7.36 GENERIC
Physicians Total Care 		54868288700
480.0 ml $10.96 GENERIC
Alpharma USPD 		63874070948
480.0 ml $33.10 GENERIC
Pharma Pac 		52959015309
tablet - oral - 2 mg -
4.0's $3.52 GENERIC
Prescript Pharmaceuticals 		00247026404
6.0's $3.59 GENERIC
Prescript Pharmaceuticals 		00247026406
12.0's $4.34 GENERIC
Southwood Pharmaceuticals Inc 		58016047312
15.0's $3.95 GENERIC
Prescript Pharmaceuticals 		00247026415
15.0's $5.42 GENERIC
Southwood Pharmaceuticals Inc 		58016047315
15.0's $13.77 GENERIC
Alpharma USPD 		63874037715
20.0's $3.78 GENERIC
Alpharma USPD 		63874037720
20.0's $4.15 GENERIC
Prescript Pharmaceuticals 		00247026420
20.0's $7.23 GENERIC
Southwood Pharmaceuticals Inc 		58016047320
24.0's $4.82 GENERIC
Alpharma USPD 		63874037724
24.0's $8.68 GENERIC
Southwood Pharmaceuticals Inc 		58016047324
30.0's $2.73 GENERIC
Physicians Total Care 		54868107303
30.0's $4.54 GENERIC
Prescript Pharmaceuticals 		00247026430
30.0's $7.90 GENERIC
Allscripts Healthcare Solutions 		54569340900
30.0's $10.85 GENERIC
Southwood Pharmaceuticals Inc 		58016047330
32.0's $4.62 GENERIC
Prescript Pharmaceuticals 		00247026432
50.0's $3.44 GENERIC
Physicians Total Care 		54868107306
60.0's $3.78 GENERIC
Physicians Total Care 		54868107304
90.0's $32.55 GENERIC
Southwood Pharmaceuticals Inc 		58016047390
100.0's $4.36 GENERIC
Physicians Total Care 		54868107302
100.0's $5.62 GENERIC
Alpharma USPD 		63874037701
100.0's $36.17 GENERIC
Southwood Pharmaceuticals Inc 		58016047300
120.0's $5.90 GENERIC
Physicians Total Care 		54868107305
tablet - oral - 4 mg -
4.0's $3.67 GENERIC
Prescript Pharmaceuticals 		00247026504
10.0's $4.57 GENERIC
Allscripts Healthcare Solutions 		54569287402
12.0's $6.47 GENERIC
Southwood Pharmaceuticals Inc 		58016060312
15.0's $4.54 GENERIC
Prescript Pharmaceuticals 		00247026515
15.0's $8.09 GENERIC
Southwood Pharmaceuticals Inc 		58016060315
20.0's $4.94 GENERIC
Prescript Pharmaceuticals 		00247026520
20.0's $10.79 GENERIC
Southwood Pharmaceuticals Inc 		58016060320
24.0's $6.08 GENERIC
Alpharma USPD 		63874037824
24.0's $12.94 GENERIC
Southwood Pharmaceuticals Inc 		58016060324
30.0's $3.10 GENERIC
Physicians Total Care 		54868107403
30.0's $5.74 GENERIC
Prescript Pharmaceuticals 		00247026530
30.0's $13.72 GENERIC
Allscripts Healthcare Solutions 		54569287400
30.0's $16.17 GENERIC
Southwood Pharmaceuticals Inc 		58016060330
60.0's $4.53 GENERIC
Physicians Total Care 		54868107407
60.0's $27.45 GENERIC
Allscripts Healthcare Solutions 		54569287401
100.0's $5.63 GENERIC
Physicians Total Care 		54868107405
100.0's $11.19 GENERIC
Alpharma USPD 		63874037801
100.0's $53.92 GENERIC
Southwood Pharmaceuticals Inc 		58016060300
120.0's $6.95 GENERIC
Physicians Total Care 		54868107406
500.0's $208.82 GENERIC
Alpharma USPD 		63874037850
tablet, extended release - oral - 4 mg -
100.0 $108.13 Vospire
Odyssey Pharmaceutical 		65473075401
tablet, extended release - oral - 8 mg -
60.0 $131.05 Volmax
Allscripts Healthcare Solutions 		54569417201
100.0 $216.26 Vospire
Odyssey Pharmaceutical 		65473075801

Copyright © 2006 Mosby Inc.,an Elsevier imprint. All Rights Reserved.
Click here for important legal information about Mosby's Drug Consult.