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Search #ABSTRACT#
Introduction
Asthma is among the most common chronic conditions in the US, affecting an
estimated 17 million people, causing over 1.5 million emergency room visits, accounting
for approximately 500,000 hospitalizations, and causing more than 5,500 deaths
each year.
The prevalence of asthma has been increasing since the early 1980s for all age, sex,
and racial groups. Specifically, the overall age-adjusted prevalence of asthma increased
75% from 1980 to 1994, and among children up to four years of age, the prevalence
increased 160% in the same period (from 22.2 to 57.8 per 1,000 individuals in the
population).
Among the entire population, hospitalizations with asthma as the primary diagnosis
have declined in recent years, but the rate of hospitalization among children has continued
to increase. The reason for this increase among children is not known.
The overall cost of asthma in the US in 1998 was $11.3 billion. Direct costs, primarily
due to hospitalization, accounted for $7.5 billion, while indirect costs, which included
factors such as loss of work time, loss of school time, and loss of productivity were
$3.8 billion.
The overall cost of asthma in the US in 1998 was $11.3 billion. Direct costs, primarily
due to hospitalization, accounted for $7.5 billion, while indirect costs, which included
factors such as loss of work time, loss of school time, and loss of productivity were
$3.8 billion.
Clearly, asthma represents an important and growing healthcare challenge in the
US, especially for children.
Questions And Answers For Healthcare Professionals
1. Why is AccuNeb the right choice for relief of bronchospasm
in patients 2 to 12 years of age with asthma?
AccuNeb (albuterol sulfate) Inhalation Solution is the first and only premixed, premeasured, lower-concentration albuterol designed for
pediatric patients.
more....
Description
2. What is AccuNeb?
The active component in AccuNeb Inhalation Solution is albuterol sulfate (1.25 mg/3 mL and 0.63 mg/3 mL, potency expressed as albuterol, equivalent to 1.5 mg and 0.75 mg albuterol sulfate).
more....
3. How is AccuNeb different from other bronchodilators?
AccuNeb (albuterol sulfate) Inhalation Solution is the first and only premixed, premeasured, lower-concentration albuterol designed for pediatric patients.
more....
Clinical Pharmacology
4. What is the mechanism of action for AccuNeb?
The prime action of beta-adrenergic drugs is to stimulate adenyl cyclase, the enzyme which catalyzes the formation of cyclic-3´,5´-adenosine monophosphate (cyclic AMP) from adenosine triphosphate (ATP).
more....
5. What are the pharmacokinetic characteristics of AccuNeb?
Studies in asthmatic patients have shown that less than 20% of a single albuterol dose was absorbed following either intermittent positive-pressure breathing (IPPB) or nebulizer administration; the remaining amount was recovered from the nebulizer and apparatus, and expired air.
more....
Efficacy Profile
6. What studies were performed to evaluate the efficacy of AccuNeb?
The clinical efficacy of albuterol in the management of asthma has been well documented in clinical studies.
more....
Indications/Usage
7. What is the approved indication for AccuNeb?
AccuNeb is indicated for the relief of bronchospasm in patients 2 to 12 years of age with asthma (reversible obstructive airway disease).
Safety Profile
8. What are the contraindications for AccuNeb?
AccuNeb is contraindicated in patients with a history of hypersensitivity to any of its components.
9. What adverse reactions are associated with administration of AccuNeb?
Adverse reaction information concerning AccuNeb was derived from the 4-week controlled clinical trial described above.
more....
10. What are the symptoms of overdosage of AccuNeb?
The expected symptoms with overdosage are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of symptoms such as 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, insomnia, and exaggeration of the pharmacological effects listed above in the Adverse Reactions table.
more....
Dosage & Administration
11. What is the recommended dosage and administration for AccuNeb?
The usual starting dosage for patients 2 to 12 years of age is 1.25 mg or 0.63 mg of AccuNeb administered 3 or 4 times daily, as needed, by nebulization.
more....
How Supplied
12. How is AccuNeb supplied?
AccuNeb (albuterol sulfate) Inhalation Solution is supplied as a 3-mL, clear, colorless, sterile, preservative-free, aqueous solution in two different strengths, 0.63 mg and 1.25 mg, of albuterol (equivalent to 0.75 mg of albuterol sulfate or 1.5 mg of albuterol sulfate per 3 mL) in unit-dose low-density polyethylene (LDPE) vials.
more....
13. How should AccuNeb be stored?
Store between 2°C and 25°C (36°F - 77°F). Protect from light and excessive heat.
more....
1.Why is AccuNeb the right choice for relief of bronchospasm
in patients 2 to 12 years of age with asthma?
AccuNeb (albuterol sulfate) Inhalation Solution is the first and only
premixed, premeasured, lower-concentration albuterol designed for
pediatric patients.
AccuNeb is a sterile, preservative-free albuterol available in two lower-dose
concentrations: 1.25 mg and 0.63 mg (equivalent to 1.5 mg and 0.75 mg albuterol sulfate).
The National Asthma Education and Prevention Program (NAEPP) Expert Panel
recommends the use of 0.05 mg/kg (minimum of 1.25 mg, maximum of 2.5 mg)
nebulized albuterol for children. AccuNeb is the only albuterol inhalation solution
that can be used to follow these guidelines that does not require mixing or dilution.
AccuNeb provides unit-dose convenience.
AccuNeb is premeasured to assure fast, accurate dosing.
Easy-to-open vials with TwistFlex™ tops are tamper evident and help reduce
cross-contamination.
AccuNeb has proven efficacy.
In a 4-week clinical trial of 349 children ages 6 to 12 with moderately severe
asthma, both the 1.25 mg and 0.63 mg strengths of AccuNeb produced significant
improvements in FEV1 compared to placebo.
Patients 6 to 12 years of age with more severe asthma (baseline FEV1 less than
60% predicted), weight >40 kg, or patients 11 to 12 years of age may achieve a better
initial response with the 1.25 mg dose.
2. What is AccuNeb?
The active component in AccuNeb Inhalation Solution is albuterol sulfate (1.25
mg/3 mL and 0.63 mg/3 mL, potency expressed as albuterol, equivalent to 1.5 mg and
0.75 mg albuterol sulfate).
AccuNeb™ (albuterol sulfate) inhalation solution is a sterile, clear, colorless solution
of the sulfate salt of racemic albuterol, albuterol sulfate. Albuterol sulfate is a relatively
selective beta2-adrenergic bronchodilator. The chemical name for albuterol sulfate is
a1 [(tert-butylamino) methyl]-4-hydroxy-m-xylene-a, a´-diol sulfate (2:1) (salt), and its
established chemical structure is as follows:
The molecular weight of albuterol sulfate is 576.7 and the empirical formula is
(C13H21NO3)2·H2SO4. Albuterol sulfate is a white crystalline powder, soluble in
water and slightly soluble in ethanol. The World Health Organization recommended
name for albuterol is salbutamol.
AccuNeb (albuterol sulfate) inhalation solution is supplied in two strengths in unit-dose
vials. Each unit-dose vial contains either 0.75 mg of albuterol sulfate (equivalent to
0.63 mg of albuterol) or 1.50 mg of albuterol sulfate (equivalent to 1.25 mg of albuterol)
with sodium chloride and sulfuric acid in a 3-mL isotonic, sterile, aqueous solution.
Sodium chloride is added to adjust isotonicity of the solution and sulfuric acid is added
to adjust pH of the solution to 3.5.
3. How is AccuNeb different from other bronchodilators?
AccuNeb (albuterol sulfate) Inhalation Solution is the first and only premixed,
premeasured, lower-concentration albuterol designed for pediatric patients.
The National Asthma Education and Prevention Program (NAEPP) Expert Panel
recommends the use of 0.05 mg/kg (minimum of 1.25 mg, maximum of 2.5 mg) nebulized
albuterol for children.AccuNeb is the only albuterol inhalation solution that can be used
to follow these guidelines that does not require mixing or dilution.
4. What is the mechanism of action for AccuNeb?
The prime action of beta-adrenergic drugs is to stimulate adenyl cyclase, the enzyme
which catalyzes the formation of cyclic-3´,5´-adenosine monophosphate (cyclic AMP)
from adenosine triphosphate (ATP). The cyclic AMP thus formed mediates the cellular
responses. 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, recent data indicate that 10% to 50% of the beta-receptors
in the human heart may be beta2-receptors. The precise function of these
receptors, however, is not yet established. 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.
5. What are the pharmacokinetic characteristics of AccuNeb?
Studies in asthmatic patients have shown that less than 20% of a single albuterol
dose was absorbed following either intermittent positive-pressure breathing (IPPB) or
nebulizer administration; the remaining amount was recovered from the nebulizer and
apparatus, and expired air. Most of the absorbed dose was recovered in urine collected
during the 24 hours after drug administration. Following oral administration of 4 mg
albuterol, the elimination half-life was five to six hours. Following a 3-mg dose of
nebulized albuterol in adults, the mean maximum albuterol plasma level at 0.5 hours
was 2.1 ng/mL (range, 1.4 to 3.2 ng/mL). The pharmacokinetics of albuterol following
administration of 0.63 mg or 1.25 mg albuterol sulfate inhalation solution by nebulization
have not been determined in children 2 to 12 years old.
6. What studies were performed to evaluate the efficacy of AccuNeb?
The clinical efficacy of albuterol in the management of asthma has been well
documented in clinical studies. Albuterol provides prompt relief of acute airflow
obstruction and its accompanying symptoms such as cough, chest tightness, shortness
of breath, and wheezing. As such, albuterol and the other beta2-agonists are the therapy
of choice for quick-relief of asthma exacerbations.
The safety and efficacy of AccuNeb was evaluated in a 4-week, multi-center,
randomized, double-blind, placebo-controlled, parallel group study in 349 children
6 to 12 years of age with mild-to-moderate asthma.5 The design, results, and conclusion
of the study are summarized in the following table.
AccuNeb Study Summary
| Title: |
Reduced doses of nebulized albuterol are effective for maintenance treatment of children with asthma. |
| Authors: |
James Kemp, University of California at San Diego; Anjuli Seth Nayak, University
of Illinois College of Medicine, Peoria; Michael Noonan, Oregon Health Sciences
University, Portland; Joseph Oren, Clinicom: Clinical Communications and Research
Consultancy, San Francisco; Allan Kaplan, PDCS Inc., Boca Raon, FL; Paul
Covington, PPD Development, Inc., Wilmington, SC. |
| Source: |
Dey, data on file. |
| Purpose: |
To determine the safety and efficacy of half and quarter-strength unit-doses of
albuterol sulfate inhalation solution in the treatment of moderately severe asthma
in children.. |
| Study Design: |
Prospective, multicenter, randomized, double-blind, placebo-controlled parallel-group
study of children with moderately severe asthma. Patients were randomly
assigned to receive a unit-dose of either 1.25 mg or 0.63 mg nebulized albuterol
inhalation solution or placebo 3 times a day for 4 weeks. Spirometry and various
safety endpoints were measured pre-dose and for 6 hours post-dose on Day 1 and
Day 28 of the trial. |
| Patients: |
A total of 349 children, ages 6 to 12, with moderately severe asthma were
randomized and 288 completed the double-blind 4-week treatment period. |
| Efficacy Results: |
The primary efficacy endpoint was the area under the percent change from pre-dose
FEV1 versus time curve for the initial dosing visit (Day 1) and the final dosing visit
(Day 28). Compared to placebo, both unit-doses of albuterol produced significant
improvement in FEV1 after the initial dose and after 4 weeks of TID treatment. |
| Safety: |
During the study, 47% of patients reported adverse events. The majority of events
were considered by the investigators to be unrelated to the study medication. The
safety profiles of the albuterol doses were comparable and similar to placebo.
Beta2 -agonist related events, such as tremors, were higher in the albuterol groups
than in the placebo group. |
| Conclusion: |
This study demonstrated the efficacy of albuterol sulfate solution at doses 75% to
50% lower than previously available unit-doses. Both dose levels are safe in children
6 to 12 years of age. |
Efficacy, as measured by the mean percent change from baseline in the area under
the 6-hour curve for FEV1, was demonstrated for both active treatment regimens (n=112
[1.25 mg group] and n=110 [0.63 mg group]) compared with placebo (n=110) on day 1
and day 28. Figures 2 and 3 illustrate the mean percentage change from pre-dose FEV1
on day 1 and day 28, respectively. The mean baseline FEV1 for all patients was 1.49 L.
7. What is the approved indication for AccuNeb?
AccuNeb is indicated for the relief of bronchospasm in patients 2 to 12 years of age
with asthma (reversible obstructive airway disease).
8. What are the contraindications for AccuNeb?
AccuNeb is contraindicated in patients with a history of hypersensitivity to any of its
components.
9. What adverse reactions are associated with administration of AccuNeb?
Adverse reaction information concerning AccuNeb was derived from the 4-week
controlled clinical trial described above. Adverse events reported in >1% of patients
receiving AccuNeb and more frequently than in patients receiving placebo are listed
on the table below.
Adverse Events
ADVERSE EVENTS WITH AN INCIDENCE OF >1% OF PATIENTS RECEIVING ACCUNEB AND GREATER THAN PLACEBO (EXPRESSED AS % OF TREATMENT GROUP)
| |
1.25 mg AccuNeb (N=115) |
0.63 mg AccuNeb Placebo (N=117) |
Placebo (N=117) |
| Asthma Exacerbation |
13 |
11.1 |
8.5 |
| Otitis Media |
4.3 |
0.9 |
0 |
| Allergic Reaction |
0.9 |
3.4 |
1.7 |
| Gastroenteritis |
0.9 |
3.4 |
0.9 |
| Flu Syndrome |
2.6 |
2.6 |
1.7 |
| Lymphadenopathy |
2.6 |
0.9 |
1.7 |
| Skin/Appendage Infection |
1.7 |
0 |
0 |
| Urticaria |
1.7 |
0.9 |
0 |
| Migraine |
0.9 |
1.7 |
0 |
| Chest Pain |
0.9 |
1.7 |
0 |
| Bronchitis |
0.9 |
1.7 |
0.9 |
| Nausea |
1.7 |
0.9 |
0.9 |
There was one case of ST segment depression in the 1.25 mg AccuNeb treatment group.No clinically relevant laboratory abnormalities related to AccuNeb administration were seen in the study.
10. What are the symptoms of overdosage of AccuNeb?
The expected symptoms with overdosage are those of excessive beta-adrenergic
stimulation and/or occurrence or exaggeration of symptoms such as 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, insomnia, and exaggeration of the pharmacological effects listed above in the
Adverse Reactions table. Hypokalemia may also occur. As with all sympathomimetic
aerosol medications, cardiac arrest and even death may be associated with abuse of
AccuNeb. Treatment consists of discontinuation of AccuNeb 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 AccuNeb.
The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/kg
(approximately 580 times the maximum recommended daily inhalation dose of
AccuNeb on a mg/mbasis). The subcutaneous median lethal dose of albuterol sulfate
in mature rats and small young rats is approximately 450 mg/kg and 2000 mg/kg,
respectively (approximately 260 and 1200 times the maximum recommended daily
inhalation dose of AccuNeb on a mg/mbasis). The inhalation median lethal dose has
not been determined in animals.
11. What is the recommended dosage and administration for AccuNeb?
The usual starting dosage for patients 2 to 12 years of age is 1.25 mg or 0.63 mg of
AccuNeb administered 3 or 4 times daily, as needed, by nebulization. More frequent
administration is not recommended.
To administer 1.25 mg or 0.63 mg of albuterol, use the entire contents of one
unit-dose vial (3 mL of 1.25mg or 0.63 mg inhalation solution) by nebulization. Adjust
nebulizer flow rate to deliver AccuNeb over 5 to 15 minutes.
The use of AccuNeb can be continued as medically indicated to control recurring
bouts of bronchospasm. During this time most patients gain optimum benefit from
regular use of the inhalation solution.
Patients 6 to 12 years of age with more severe asthma (baseline FEV1 less than 60%
predicted), weight >40 kg, or patients 11 to 12 years of age may achieve a better initial
response with the 1.25 mg dose.
AccuNeb has not been studied in the setting of acute attacks of bronchospasm. A
2.5-mg dose of albuterol provided by a higher concentration product (2.5-mg albuterol
per 3 mL) may be more appropriate for treating acute exacerbations, particularly in
children 6 years old and above.
If a previously effective dosage regimen fails to provide the usual relief, medical
advice should be sought immediately, as this is often a sign of seriously worsening
asthma which would require reassessment of therapy.
The drug compatibility (physical and chemical), clinical efficacy and safety of
AccuNeb solution, when mixed with other drugs in a nebulizer have not been established.
The safety and efficacy of AccuNeb have been established in clinical trials when
administered using the Pari LC Plus™ nebulizer and Pari PRONEB™ compressor. The
safety and efficacy of AccuNeb when administered with other nebulizer systems have
not been established.
AccuNeb should be administered via jet nebulizer connected to an air compressor
with adequate air flow, equipped with a mouthpiece or suitable face mask.
12. How is AccuNeb supplied?
AccuNeb (albuterol sulfate) Inhalation Solution is the first and only premixed,
premeasured, lower-concentration albuterol designed for pediatric patients.
AccuNeb (albuterol sulfate) Inhalation Solution is supplied as a 3-mL, clear,
colorless, sterile, preservative-free, aqueous solution in two different strengths, 0.63 mg
and 1.25 mg, of albuterol (equivalent to 0.75 mg of albuterol sulfate or 1.5 mg of
albuterol sulfate per 3 mL) in unit-dose low-density polyethylene (LDPE) vials. Each
unit-dose LDPE vial is protected in a foil-pouch, and each foil pouch contains 5 unit-dose
LDPE vials. Each strength of AccuNeb (albuterol sulfate) Inhalation Solution is available
in a shelf carton containing multiple foil pouches.
AccuNeb™ (albuterol sulfate) Inhalation Solution, 0.63 mg (potency expressed as
albuterol) contains 0.75 mg albuterol sulfate per 3 mL in unit-dose vial and is available
in the following packaging configuration.
NDC 49502-692-03 5 foil pouches, each containing 5 vials, total 25 vials per carton
AccuNeb™ (albuterol sulfate) Inhalation Solution, 1.25 mg (potency expressed as
albuterol) contains 1.50 mg albuterol sulfate per 3 mL in unit-dose vials and is available
in the following packaging configuration.
NDC 49502-693-03 5 foil pouches, each containing 5 vials, total 25 vials per carton.
13. How should AccuNeb be stored?
AccuNeb (albuterol sulfate) Inhalation Solution is the first and only premixed,
premeasured, lower-concentration albuterol designed for pediatric patients.
Store between 2°C and 25°C (36°F - 77°F). Protect from light and excessive heat.
Store between 2°C and 25°C (36°F - 77°F). Protect from light and excessive heat.
Store unit-dose vials in protective foil pouch at all times. Once removed from the
foil pouch, use vial(s) within one week. Discard the vial if the solution is not colorless.
Keep out of reach of children.
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