Have severe COPD? Learn how to manage your symptoms.

Corticosteroids (Inhalation-Local)

This monograph includes information on the following:

1) Beclomethasone
2) Budesonide
3) Flunisolide
4) Triamcinolone

Note: See also individual monograph, Fluticasone (Inhalation-Local)—Introductory Version .



INN:
Beclomethasone—Beclometasone


JAN:
Beclomethasone—Beclometasone dipropionate

VA CLASSIFICATION
Primary: RE110
Secondary: RE190

Commonly used brand name(s): AeroBid3; AeroBid-M3; Azmacort4; Beclodisk1; Becloforte1; Beclovent1; Beclovent Rotacaps1; Bronalide3; Pulmicort Nebuamp2; Pulmicort Respules2; Pulmicort Turbuhaler2; QVAR1; Vanceril1; Vanceril 84 mcg Double Strength1.

Other commonly used names for beclomethasone are
beclomethasone dipropionate, beclometasone, and beclometasone dipropionate . {01}
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Anti-inflammatory (inhalation)—

antiasthmatic—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.


Accepted

Asthma, bronchial, chronic (treatment)—Beclomethasone, budesonide, flunisolide, and triamcinolone are indicated as primary maintenance treatment in patients with persistent symptoms of chronic bronchial asthma. {93} {112} Treatment with inhaled corticosteroids is indicated in asthmatic patients whose conditions require anti-inflammatory treatment and in patients dependent on oral corticosteroids who may benefit from a gradual withdrawal from oral corticosteroids to decrease the likelihood of side effects {163} {164} {165} {166} {167}. Regular, continuous use of inhaled corticosteroids controls chronic airway inflammation, decreases airway hyperresponsiveness, prevents asthma symptoms, reduces the frequency of asthma exacerbations, and reduces hospital admissions for asthma{188}{190}{191}. Clinical studies have also reported that regular use with inhaled corticosteroids is associated with decreased mortality.{188}{190}{192} Inhaled corticosteroids are effective in all types of asthma and in patients of all ages. {93} {111}{188}
—Initiation of therapy with daily doses of inhaled corticosteroids shortly after a diagnosis of chronic asthma (even if mild) may prevent irreversible structural changes in the airways resulting from uncontrolled inflammation, may decrease {125} progression of severe disease, and may reduce the need for administration of systemic corticosteroids {09} {72} {102} {107} {111} {112} {113} {119}.
—Information comparing dose-related systemic effects or the ratios of local to systemic activity of beclomethasone, budesonide, flunisolide, and triamcinolone is limited. {112} {117} {118} However, since conclusive evidence is lacking and further studies are needed, the concept of individualized dose titration in each patient to identify{188} the lowest effective dose of an inhaled corticosteroid to achieve and maintain the desired clinical control of asthma {112} seems prudent {128}.
—Because of the potent anti-inflammatory effects of inhaled corticosteroids {124} {128} {131} and the potential morbidity and mortality associated with theophylline treatment {124} {125} {126}, inhaled corticosteroids in conventional low doses are preferred to theophylline as first-line therapy for chronic asthma. {28} {50} {72} {100} {128}
—Guidelines for the treatment of asthma: {188}{193}
—Children aged 5 years and younger—Preferred treatment for mild asthma (more than 2 symptoms per week but less than 1 symptom per day) is a low-dose inhaled corticosteroid. Alternative treatment may consist of cromolyn or a leukotriene receptor antagonist. Preferred treatment with moderate asthma (greater than 1 symptom per night) is a low-dose inhaled corticosteroid and long-acting inhaled beta-adrenergic bronchodilator. Alternative treatment may consist of a low-dose inhaled corticosteroid and either a leukotriene receptor antagonist or theophylline. Preferred treatment with severe asthma (continual symptoms throughout the day) is a high-dose inhaled corticosteroid and a long-acting inhaled beta-adrenergic bronchodilator. {188}{193}
—Children older than 5 years of age—Preferred treatment for mild asthma (more than 2 symptoms per week but less than 1 symptom per day) is a low-dose inhaled corticosteroid. Alternative treatment may consist of cromolyn, a leukotriene receptor antagonist, nedocromil, or theophylline. Preferred treatment with moderate asthma (greater than 1 symptom per night) is a low-to-medium dose inhaled corticosteroid and a long-acting inhaled beta-adrenergic bronchodilator. Alternative treatment may consist of a low-dose inhaled corticosteroid and either a leukotriene receptor antagonist or theophylline. Preferred treatment with severe asthma (continual symptoms throughout the day) is a high-dose inhaled corticosteroid and a long-acting inhaled beta-adrenergic bronchodilator.{188}{193}
—Budesonide dry-powder inhalers are indicated for use in [ children 3 months to 6 years of age]1and older.{184}Budesonide inhalation suspension is indicated for the maintenance treatment of asthma and as prophylactic therapy in children 12 months to 8 years of age. {185}

Acceptance not established
Use in children younger than 3 months of age for the treatment of asthma has not been established{184}.

Unaccepted
Corticosteroid inhalation therapy does not relieve acute bronchospasm and is not indicated for the primary treatment of status asthmaticus or other acute asthmatic episodes requiring more intensive or rapid treatment measures. {05} {06} {07} {08} {13} {14} {15} {16} {17} {18} {19} {20} {21} {22} {50} {51} {62} {67} {74} {75}{185}Oral corticosteroids are more effective than inhaled corticosteroids for the treatment of acute asthmatic episodes.{188}{194}

Corticosteroid inhalation therapy is not indicated in the treatment of nonasthmatic bronchitis. {05} {06} {07} {13} {14} {18} {19} {21} {22} {50} {51} {62} {67} {74} {75}

Dexamethasone inhalation is not recommended for use in asthma {103} because it {125} {128} has demonstrated a significantly higher incidence of systemic effects with no additional benefit over other inhaled corticosteroids. {50} {53} The high ratio of systemic glucocorticoid activity to local anti-inflammatory activity of inhaled dexamethasone may be {129} due to its greater water solubility and longer metabolic half-life after absorption {126} {130} relative to the other inhaled corticosteroids. {50} {51} {72}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Beclomethasone dipropionate: 521.05 {01} {76}
    Budesonide: 430.54 {76}
    Flunisolide: 443.52 {179}
    Triamcinolone acetonide: 434.5 {01} {74} {76}

Mechanism of action/Effect:

In the treatment of chronic bronchial asthma, orally inhaled corticosteroids have many probable sites of action. {59} {126} The net effect is to reduce the chronic inflammation in asthmatic airways.

The potent anti-inflammatory action may be due to an inhibition of the secretion of growth factors, endothelial activating and other cytokines from lymphocytes, eosinophils, macrophages, fibroblasts, and mast cells. The results are decreased influx of inflammatory cells into the bronchial walls, due in part to inhibition of expression of adhesion molecules on the endothelium and in the tissue. Decreased activation and survival of eosinophils in the lung tissue and a reduction in numbers of mast cells are further effects. {126}

Corticosteroids may inhibit release of mediators from basophils and enzymes from macrophages. There is decreased permeability through vasoconstriction and direct inhibition of endothelial cell contraction. {126}

Beta-adrenergic-receptor numbers may be increased, which results in an enhanced response to beta-adrenergic bronchodilators and reduced down-regulation of beta-receptors after prolonged beta-agonist exposure. {111} {126}

Inhaled corticosteroids also inhibit mucus secretion in airways, possibly by a direct action on submucosal gland cells and an indirect inhibitory effect caused by the reduction in inflammatory mediators that stimulate mucus secretion. {111} The amount and viscosity of sputum are reduced. {126}

The effect of inhaled corticosteroids on bronchial asthma is to block {150} the late inflammatory response to inhaled allergens and reduce over time the response to nonspecific triggers such as exercise. Bronchial wall inflammation and edema are reduced, sputum production is diminished, and the airways become less hyperresponsive to direct and indirect challenges. {111} {126}

Absorption:

Beclomethasone, budesonide, and flunisolide are rapidly absorbed from the lungs and gastrointestinal tract. Triamcinolone is absorbed more slowly.

Without the use of a spacer, approximately 10 to 25% of an inhaled corticosteroid dose is deposited in the airways {05} {06} {07} {13} {14} {15} {50}; the remainder is deposited in the mouth and throat, and swallowed. {05} {06} {07} {13} {14} {15} A greater percentage of the inhaled dose may reach the respiratory tract with the use of a spacer device. {27} {29} {31} {43} {50} {132} The Budesonide powder for inhalation does not require the use of a spacer device. {168}The budesonide inhalation suspension requires the use of a jet nebulizer device. In asthmatic children 4 to 6 years of age, the total absolute bioavailability (i.e. lung and oral) is approximately 6% of the labeled dose, delivered via jet nebulizer.{185}

Volume of distribution (VolD)

—Budesonide inhalation suspension: 3 liters per kilogram of body weight (L/kg) in children 4 to 6 years of age; approximately the same as in healthy adults.{185}

Biotransformation:


For beclomethasone dipropionate:

Rapidly transformed in the lungs to beclomethasone monopropionate, an active metabolite, which is significantly more potent topically than beclomethasone dipropionate. {72} {111} {124} {130}



For budesonide, flunisolide, and triamcinolone acetonide:

Absorbed unchanged. Those portions of each drug absorbed through the lungs or absorbed after being swallowed are rapidly and extensively transformed to inactive metabolites in the liver. {124}


Half-life:

For budesonide—120 to 180 minutes (plasma). {127} {143}

For flunisolide—90 to 120 minutes (plasma). {56} {127} {143}

For triamcinolone—88 minutes (plasma). {163}

Note: The plasma half-life of the inhaled corticosteroids does not correspond well with the biologic half-life. {163}


Onset of action:

Improvement in the control of asthma symptoms following inhalation of budesonide suspension can occur within 2 to 8 days of beginning treatment.{185}

Maximum {126} improvement in pulmonary function and symptoms may take up to 4 to 6 {185}weeks, while reduction in airway hyperresponsiveness occurs gradually over a period of weeks to months. {111}Response depends on disease severity and the daily dose of the inhaled corticosteroid.{188} Some patients fail to normalize their airway hyperresponsiveness despite years of treatment.{188}

Time to peak concentration:

The peak plasma concentration of inhaled budesonide suspension occurred 10 to 30 minutes after start of nebulization.{185}

Elimination:
    Fecal and renal.


Precautions to Consider

Carcinogenicity

Studies in animals showed no evidence of carcinogenicity for beclomethasone or triamcinolone. {163} {169} Studies in mice and rats on oral flunisolide showed an increase in pulmonary adenomas in mice but not in rats. Female rats showed an increased incidence of mammary adenocarcinoma. {164} Studies of budesonide in mice showed no evidence of carcinogenesis. However, studies in rats showed an increase in gliomas in male rats at higher doses. No changes were found in female rats at higher doses or in male and female rats at lower doses. {170} Two additional studies on male rats with budesonide at higher doses did not show an increase in glioma incidence but an increased incidence in hepatocellular tumors occurred. {170}

Mutagenicity

Studies with budesonide have been performed using six different test systems: Ames Salmonella/microsome plate test, mouse micronucleus test, mouse lymphoma test, chromosome aberration test in human lymphocytes, sex-linked recessive lethal test in Drosophila melanogaster, and DNA repair analysis in rat hepatocyte culture. Budesonide was not found to be mutagenic. {170} There have been no mutagenesis studies carried out with triamcinolone. {163}

Pregnancy/Reproduction
Fertility—
In animal studies performed in rats and dogs, some impairment of fertility was seen for beclomethasone, budesonide, and flunisolide at high doses. When lower doses were evaluated, no impairment of fertility was noted. {164} {169} {170} Triamcinolone showed no evidence of impaired fertility in animal studies. {163}

Pregnancy—
Chronic administration of systemic corticosteroids to pregnant women has shown decreased birth weights and a slight increase in the incidence of premature deliveries.

The use of conventional doses of inhaled corticosteroids by pregnant asthmatic women has not been reported to be associated with an increased incidence of congenital abnormalities in the newborn. {72} {99} {144} Inhaled corticosteroids may be used during pregnancy when clinically necessary, since poorly controlled asthma and loss of pulmonary function and hypoxia {134} present a greater risk to the mother and may cause fetal hypoxia. {72} {99} {111} If inhaled corticosteroids are effective before pregnancy, it is advisable to continue regular maintenance dosing during pregnancy.

In animal studies, decreases in fetal survival and weight have been demonstrated with systemic corticosteroids. {144} All of the inhaled corticosteroids have been shown to be teratogenic in animal studies. {163} {164} {165} {166} {167} {169} Rodents appear to be more susceptible to the teratogenic effects of glucocorticoids than humans. {163} {170}

Beclomethasone is the preferred inhaled corticosteroid during pregnancy in the U.S. because of more extensive clinical experience with its use than with flunisolide or triamcinolone. {124} {144}

Beclomethasone; Budesonide inhalation suspension; Flunisolide; Triamcinolone —FDA Pregnancy Category C. {62} {66} {67} {74} {163} {164} {169} {170}{196}

Budesonide inhalation powder—FDA Pregnancy Category B{188}{195}

Postpartum —
Infants whose mothers were treated with substantial doses of inhaled corticosteroids during pregnancy should be monitored for signs of hypoadrenalism. {164} {166} {167}

Breast-feeding

It is not known whether inhaled corticosteroids are distributed into breast milk. {62} {65} {74} {75} However, problems in humans have not been documented. Although systemic corticosteroids are distributed into breast milk, it is unlikely that inhaled corticosteroids would reach significant quantities in maternal serum, and the concentration in breast milk would probably be of minor clinical significance. {72}

Pediatrics

Orally inhaled corticosteroids are valuable and highly effective therapies in the management of asthma in pediatric patients. The Food and Drug Administration (FDA) and its advisory committees consider these products to be safe and effective in children when used according to their labeling guidelines. {180} Clinical studies have shown that inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients. {180}{197} In these studies (over a period of about 1 year), the mean reduction in growth velocity was approximately one centimeter (cm) per year (range 0.3 to 1.8 cm). {180} This reduction appears to be related to the dose and the duration of exposure to the inhaled corticosteroid. {180} This effect was observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression, which suggests that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than are some commonly used tests of HPA axis function. {180}

However, recent clinical trials have reported that while there is a slowing of growth velocity during the first 12 months of therapy, children treated with inhaled corticosteroids attain their predicted adult height at maturity. {188}{197}{198}{199}Studies comparing inhaled corticosteroid use in asthma to placebo have found no significant difference in adult height. Conflicting data comparing the adult height in children who were asthmatic and nonasthmatics exists. Some data indicates that asthmatic children, regardless of treatment, attained a lower adult height than nonasthmatic children. {198} Other data indicates that attained adult height of patients with asthma is not different from adult height in nonasthmatics patients, regardless of treatment with inhaled corticosteroids. {199}

In general, it is recommended that the growth of pediatric patients receiving orally inhaled corticosteroids should be monitored routinely, for example, via stadiometry. {180}{188}The potential effects on growth velocity of prolonged treatment with inhaled corticosteroids should be weighed against the clinical benefits obtained and the availability of safe and effective noncorticosteroid treatment alternatives. {180} To minimize the systemic effects of orally inhaled corticosteroids, the dose should be titrated to the lowest effective dose for the patient. {180}

Use of prolonged, high daily doses of inhaled corticosteroids may cause a reduction in secretion of endogenous cortisol, although there have been no reports of clinically significant adrenal insufficiency in children treated with inhaled corticosteroids only. {111} However, monitoring for the possibility of some suppression of the hypothalamic-pituitary-adrenal axis may be advisable in children receiving prolonged treatment. {82} {108} {109} {111}

Using a spacer device with beclomethasone, flunisolide, and triamcinolone (budesonide can not be used with a spacer device) {167}, rinsing the mouth after inhalations, using the lowest possible doses, and reducing doses after favorable responses have been obtained appear to minimize the risk of adverse systemic and local side effects. {109} A spacer device may enhance inhalation techniques and thus improve intrapulmonary delivery of inhaled corticosteroids and increase compliance in pediatric patients. {72}

Children who are taking systemic corticosteroids in immunosuppressant doses may be more susceptible to infectious diseases, especially chickenpox and measles. Chickenpox and measles may be more serious or possibly fatal in children on immunosuppressant doses of corticosteroids. {167} Although it is highly unlikely that inhaled corticosteroids in usual doses would be associated with an increased risk of serious infection {65} {73}, some precautions are advisable for children who are taking larger than usual doses of inhaled corticosteroids and who have not had these diseases. Particular care should be taken to avoid exposure to chickenpox and measles and to immunize at an early age against infectious diseases for which there are vaccines, such as measles. {62} {65} {66} {67} {75} {124} {161} If the child is exposed to chickenpox, preventative treatment with varicella zoster immune globulin (VZIG) may be appropriate. If the child is exposed to measles, pooled intramuscular immunoglobulin (IG) for prophylaxis may be indicated. Treatment with antiviral medications may be used if chickenpox should develop. {163} {164} {165} {166} {167}


Geriatrics


Appropriate studies on the relationship of age to the effects of inhaled corticosteroids have not been performed in the geriatric population. However, in studies that have included patients over 65 years of age, geriatrics-specific problems that would limit the usefulness of this medication in the elderly have not been documented. {52} {94}

Drug interactions and/or related problems
Significant drug interactions are unlikely to occur with usual doses of inhaled corticosteroids. Although there are no defined drug interactions with inhaled corticosteroids {151}, if these medications are used in high doses for a long time and systemic absorption occurs, some of the interactions seen with systemic corticosteroids have a potential to occur. {136} (See Corticosteroids—Glucocorticoid Effects [Systemic] .)


Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values

Note: The following values may be affected with chronic use of larger-than-recommended doses of inhalation corticosteroids. {62} {65} {90}

Adrenal function and
Hypothalamic-pituitary-adrenal (HPA) axis function as assessed by 24-hour urinary free cortisol, morning serum cortisol concentration, or short tetracosactrin cortisol test {82} {85}    (may be decreased if significant absorption of inhaled corticosteroid occurs, especially in children {05} {06} {07} {08} {13} {14} {16} {17} {75})


Glucose, blood or urine    (high-dose therapy may be associated with an increase in fasting insulin, peak glucose, and insulin to glucose ratios after glucose tolerance tests {111})


Hematologic status    (neutrophils and total white blood cell count may be increased; eosinophils and lymphocytes may be decreased; clinical relevance of these systemic effects may be insignificant {114})


Osteocalcin, serum    (may be decreased in children and adults taking inhaled corticosteroids; however, decrease may also be seen in asthma patients not taking corticosteroids {69} {109} {120})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Cirrhosis    (may cause the effects of the corticosteroids to be enhanced {166})


Glaucoma    (may increase intraocular pressure {166})


Hypothyroidism    (may cause the effects of the corticosteroids to be enhanced {166})


Infections, untreated systemic, including bacterial, fungal, parasitic, or viral {163} {164} {167} {169} {170}    (use with caution, if at all; {163} {164} {169} {170} however, if the infection is an upper respiratory viral infection, the patient should continue therapy with the inhaled corticosteroid. In patients who have a history of asthma control deteriorating quickly during viral respiratory infection, prompt treatment with a short course of systemic corticosteroids should be considered {167} {182})


Osteoporosis    (may be exacerbated in postmenopausal women taking high doses over a prolonged time {128} and not receiving an estrogen supplement. {16} {17} {72} The daily dose of corticosteroid should be adjusted to the minimum required to maintain good control of asthma symptoms and estrogen replacement therapy may be considered {166})

    (clinical studies have shown that cumulative inhaled corticosteroid doses have an inverse relationship with bone-mineral density at the lumbar spine and proximal femur{188}{200})


Tuberculosis    (may be reactivated during prolonged inhaled corticosteroid therapy unless chemoprophylaxis is administered concurrently; asthmatic patients with a positive Mantoux test who are using inhaled corticosteroids should be carefully monitored for manifestation or reactivation, especially in countries with a high incidence of tuberculosis {91}; inhaled corticosteroids should be avoided or used with great caution in patients with drug-resistant pulmonary tuberculosis or atypical tuberculosis {130})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Adrenal function assessment    (may be advisable periodically during, and for several months following, transfer of a patient from systemic to inhalation corticosteroid therapy {05} {06} {07} {13} {14} {18} {19} {21} {22} {25} {64} {66} {74})

    (may be advisable every year during treatment in both children and adults if dosing guidelines are exceeded, especially if systemic corticosteroids are used concurrently or prior to inhaled corticosteroids {123})


Growth and development in children    (careful monitoring of growth, for example via stadiometry, is recommended periodically during therapy with inhaled corticosteroids {180})


Inhalation technique    (frequent assessment of inhalation technique and patient education on the importance of continuous prophylactic treatment with inhaled corticosteroids is recommended to ensure compliance, enhance delivery of medication to lungs, and reduce local and systemic side effects)


Intraocular pressure    (periodic assessment is advisable in patients, such as the elderly, who may be at risk for glaucoma; patients who have glaucoma should be monitored prior to initiating treatment with inhaled corticosteroids and at appropriate intervals {166})


Pulmonary function assessment {72} {74}    (periodic assessment is advisable during, and for several months following, transfer of a patient from systemic to inhalation corticosteroid therapy {64} {66} {74}; frequent pulmonary function monitoring may be necessary {155} in some patients for as long as 4 to 8 months after discontinuation of oral corticosteroids {72} {148}; daily outpatient peak expiratory flow rate [PEFR] measurements are {149} useful in following the course of asthma and the patient's response to therapy {93} {124} {134} {149})


Signs of systemic absorption    (patients on high doses of inhaled corticosteroids should be assessed periodically for signs of increased bruising, weight gain, cushingoid features, acneform lesions, and cataracts {166})




Side/Adverse Effects

Note: Some clinically important cases of growth suppression have been reported for orally inhaled corticosteroids. {180} {182} See also Pediatrics section.
Use of corticosteroids in immunosuppressant doses is associated with a higher risk of infection, with the potential for those infections to be of a more serious nature. {164} {165} {166} {169} {170} Care should be taken in adults and children to avoid exposure to viral infections, especially chickenpox and measles, if the patient has not already had the disease or been immunized against it. {163} {164} {165} {166} {167} {169} {170} Infections such as ear, eye, flu-like, sinus, urinary tract, viral, and yeast infections have occurred in a small number of patients on inhaled corticosteroids. {163} {164} {169} {170} Transfer of patients from systemic to inhalation corticosteroid therapy may unmask allergic conditions which were previously suppressed, such as conjunctivitis, eczema, and rhinitis, due to a lower level of systemic corticosteroids. {163} {164} {165} {166} {167} {169}
Pulmonary infiltrates with eosinophilia have occurred in patients receiving inhaled corticosteroids. While this effect probably occurs as a result of withdrawal of the systemic corticosteroid, a causative role of the inhaled corticosteroids or their vehicles cannot be ruled out. {164} {165} {166} {167} {169} {183}


Those indicating need for medical attention
Incidence less frequent
    
Bruising {167} {170}
    
chest pain {164} {169}
    
cystitis {163} (burning or pain while urinating; blood in urine; frequent urge to urinate)
    
edema {163} {164} (swelling of face, fingers, ankles, feet, or lower legs; weight gain)
    
fatigue {164} {167} (unusual tiredness or weakness)
    
itching, rash, or hives {163} {164} {167} {169}
    
malaise {164} (general feeling of discomfort or illness)
    
oropharyngeal candidiasis or thrush {149} {150} {152} {153} {154} {155} {156} {157} {158} {160} (creamy white, curd-like patches in mouth or throat; pain when eating or swallowing)
    
palpitations or tachycardia {164} {169} (irregular or fast heartbeat)
    
sinus problems {163} {164} {166} {169} {170}
    
stomach or abdominal pain {163} {164} {170}
    
vertigo {164} (dizziness; sense of constant movement of self or surroundings)
    
weight gain {163} {164} {170}

Incidence rare
    
Adrenal insufficiency {166} {167} {169} (unusual tiredness or weakness; feeling faint; loss of appetite; nausea or vomiting; diarrhea; increased skin pigmentation )
    
bronchospasm {65} {67} {74} {75} (shortness of breath; troubled breathing; tightness in chest; wheezing)
    
cataracts {166} {169} (blurred vision or other changes in vision)
    
esophageal candidiasis (pain or burning in chest)
    
fever {164} {169}
    
gastroenteritis {170} (diarrhea; nausea; stomach pain)
    
growth inhibition {166} {169} —in children
    
hypercorticism {169} {170} (increased fat deposits in face, neck, and trunk)
    
hyperglycemia {169} (frequent urination; unusual thirst)
    
hypersensitivity reactions, such as angioedema (swelling of face, lips or eyelids), bronchospasm (severe wheezing or troubled breathing), rash
or urticaria (hives){165}{166}{169}{170}
    
hypertension {164} (high blood pressure)
    
loss of smell or taste {164} {166}
    
menstrual disturbances {164} (menstrual changes)
    
numbness {164}
    
pneumonia {164}
    
psychological disturbances, such as aggressive reactions {170} , anxiety {164} {170} , behavioral changes {167} , depression {164} {167} {169} {170} , psychosis {170} , and restlessness {137} (mood or mental changes)
    
rectal hemorrhage {169} (bleeding from rectum or bloody stools)
    
syncope {164} {170} (fainting)


Note: If use of this medication causes bronchospasm , the medication should be immediately discontinued and replaced with an alternative therapy. {166} {167}



Those occurring principally during long-term use indicating need for medical attention
    
Osteoporosis {166} (pain in back, ribs, arms, or legs)


Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Cold-like symptoms {164} {169}
    
cough {62} {65} {66} {67} {74} {75} {83}
    
dry mouth or throat {163} {164} {166} {167}
    
headache {66} {67}
    
laryngitis, pharyngitis, or dysphonia {27} {32} {43} {58} {62} {65} {66} {71} {72} {74} {163} {164} {170} (sore throat, hoarseness, or voice changes)
    
throat irritation {66} {67}

Incidence less frequent
    
Constipation or diarrhea {163} {164} {167} {169}
    
insomnia {164} {169} {170} (trouble in sleeping)
    
nausea or vomiting {66} {67} {163} {164} {170}
    
unpleasant taste {65} {66} {67}

Incidence rare
    
Epistaxis {164} (nosebleeds)





Overdose

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute
    
Suppression of hypothalamic-pituitary-adrenal (HPA) function {166} — the potential for toxicity is low {166}

Chronic
    
Adrenal suppression and hypercorticism {166}


Treatment of overdose
For acute overdose, no emergency action is required. Inhaled corticosteroid therapy should be continued at recommended doses to control asthma. HPA function should return to normal range within one or two days. {166}

For chronic overdose, treatment consists of decreasing the dose of the inhaled corticosteroid {172} and then returning to the inhaled corticosteroid therapy slowly{188}.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Corticosteroids (Inhalation) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to corticosteroids





Use in children—Use of inhaled corticosteroids may result in decreased growth velocity and reduced cortisol secretion; monitoring of growth and development and adrenal function is important. Except for budesonide powder for inhalation, the use of a spacer is necessary for better compliance and improved airway delivery. Budesonide inhalation suspension should be administered via jet nebulizer connected to an air compressor. Ultrasonic nebulizers are not recommended. Exposure to chickenpox or measles should be avoided


Proper use of this medication
» Not using to relieve acute asthma attack; continuing use even if using other medication for asthma attack

» Importance of not using more medication than the amount prescribed

» Compliance with therapy by using every day in regularly spaced doses; patients who are not taking systemic corticosteroids when inhalation therapy started may require up to 4 to 6 weeks for initial improvement and several months for full benefits

Gargling and rinsing mouth with water after each dose; not swallowing rinse water

» Reading patient instructions carefully; checking frequently with health care professional for proper use of inhaler nebulizer

» Proper dosing
Missed dose: Using as soon as possible; using any remaining doses for that day at regularly spaced intervals

Checking with pharmacist to determine availability of refills for aerosol inhalers; saving inhaler if refills available

» Proper storage
The canister should be stored at room temperature for best results. The dose delivered may be decreased if the canister is cold.

For beclomethasone, flunisolide, or triamcinolone inhalation aerosol dosage form
Testing or priming the inhaler before using first time

Proper administration technique

Proper administration technique with use of spacer device

Proper cleaning procedure for inhaler

For beclomethasone capsule for inhalation dosage form
» Not swallowing capsules; medication not effective if swallowed

Proper loading technique for inhaler

Proper administration technique

Proper cleaning procedure for inhaler

For beclomethasone powder for inhalation dosage form
Proper loading technique for inhaler

Proper administration technique

Proper cleaning procedure for inhaler

For budesonide powder for inhalation dosage form
Proper loading technique for inhaler

Prime inhaler before initial use

Proper administration technique

For budesonide suspension for inhalation dosage form
Using in a power-operated nebulizer with an adequate flow rate and equipped with face mask or mouthpiece

Preparation of medication for use in nebulizer

Proper administration technique

Proper cleaning procedure for nebulizer

Precautions while using this medication
» Checking with physician if:

• Unusual physical stress occurs, such as surgery, injury, or infections


• Exposure to the chickenpox or measles occurs


• Asthma attack is not responsive to bronchodilator


• Any sign indicating possible mouth, throat, or lung infection occurs


• Symptoms do not improve or condition becomes worse


Carrying medical identification card stating that supplemental systemic corticosteroid therapy may be required in emergency situations, periods of unusual stress, or acute asthma attack

» Caution if any kind of surgery or emergency treatment is required; informing physician or dentist in charge that inhalation corticosteroid is being used

Avoid spraying in eyes

For patients receiving systemic corticosteroid therapy
» Importance of not discontinuing systemic corticosteroid therapy without physician's advice; carefully reducing dose or discontinuing treatment if so directed

» Importance of regular visits to physician during time that systemic corticosteroid therapy is being withdrawn; obtaining physicians instructions to follow if severe asthma attack occurs, medical or surgical treatment is needed, or symptoms of corticosteroid withdrawal occur


Side/adverse effects
Signs of potential side effects, especially bruising; chest pain; cystitis; dysphonia; edema; fatigue; itching, rash, or hives; malaise; oropharyngeal candidiasis or thrush; palpitations or tachycardia; sinus problems; stomach or abdominal pain; vertigo; weight gain; adrenal insufficiency; bronchospasm; cataracts; esophageal candidiasis; fever; gastroenteritis; growth inhibition; hypercorticism; hyperglycemia; hypersensitivity reactions such as angioedema, bronchospasm, rash, or urticaria; hypertension; menstrual disturbances; numbness; pneumonia; psychological disturbances such as, aggressive reactions, anxiety, behavioral changes, depression, psychosis, and restlessness; rectal hemorrhage; syncope; and osteoporosis


General Dosing Information
Pharmacologic doses of inhaled corticosteroids should be carefully titrated to minimum effective doses to control asthma symptoms and prevent systemic effects. This is especially important for pediatric patients. {180} See also Pediatrics section.

Gargling {136} {138} and rinsing the mouth with water after each dose are recommended to help prevent hoarseness, throat irritation, and oral candidiasis; {05} {06} {07} {08} {12} {13} {14} {15} {18} {19} {20} {21} {22} {26} {62} {65} {66} {67} {68} {74} {75} {114} the rinse water should not be swallowed. {08} {15} Rinsing the mouth without swallowing can also significantly reduce the amount of inhaled corticosteroid absorbed from the gastrointestinal tract. {87}

The use of a spacer device with a metered dose inhaler may decrease the incidence of some adverse effects, especially oropharyngeal candidiasis and dysphonia. {72} {111} By reducing {124} the need for proper coordination of timing of inhalation with activation of the inhaler and reducing the velocity and mean diameter of the aerosol particles {130}, a spacer reduces the amount of medication deposited in the upper airways and increases the amount deposited in the lower respiratory tract. This enhances the local efficacy of the inhaled corticosteroid without significantly increasing systemic activity. {72} {111} Budesonide powder for inhalation can not be used with a spacer device. {168}

Some patients may require relatively high doses of inhaled corticosteroids to prevent severe asthma relapse. For this purpose, the highly concentrated beclomethasone aerosol inhalation product available outside the U.S. facilitates the clinical use of high doses. {92} The risk of local side effects, such as thrush and oropharyngeal candidiasis,{188} may be minimized by twice-daily dosing and the use of a spacer device. However, these measures do not eliminate the risk of systemic side effects associated with prolonged use of high doses. {72}

Patients whose asthma is controlled by their usual dose of inhaled corticosteroids may require temporary emergency use of systemic corticosteroids if their asthma control is rapidly deteriorating. The use of peak flow monitoring at home once or twice daily will provide objective information to the patient and the physician when this is necessary. {132}

A short-acting inhaled bronchodilator is necessary to provide relief for the acute symptoms of asthma, such as bronchospasm. {166}

Patients who use bronchodilators should administer the bronchodilator prior to the inhaled corticosteroid to enhance penetration of the corticosteroid into the bronchial tree. The inhaled bronchodilator should be used several minutes before the inhaled corticosteroid to allow time for bronchodilation and to reduce the potential for toxicity from fluorocarbon propellants of the inhaled corticosteroid. {166}

If inhaled corticosteroid therapy requires discontinuation, the dosing regimen should be tapered off gradually and not stopped abruptly. {166} {167}

It is recommended that the 250-mcg-per-metered-spray product of beclomethasone be used only when the total daily dose is between 500 mcg and 1000 mcg. {166}

For patients also receiving systemic corticosteroid therapy
Caution is required when transferring patients from systemic corticosteroids to inhaled corticosteroids. {05} {06} {07} {08} {13} {14} {15} {16} {17} {18} {19} {21} {22} {62} {74} {163} {164} {165} {166} {167} {169} {170} Deaths due to severe asthma relapse or possibly {130} adrenal insufficiency have occurred in asthmatic patients during and after the transfer. {20} {66} {67} {163} {164} {165} {166} {167} {169} {170}

When transferring a patient from systemic corticosteroid therapy to inhaled corticosteroid therapy, the patient's asthmatic condition should be relatively stable. {163} {164} {165} {167} {169} When initiating the transfer, the patient should add the inhaled corticosteroid to existing systemic therapy. {163} {164} {165} {169} After a week to ten days of concurrent therapy, the systemic agent should be withdrawn gradually by reducing the daily or alternate-daily dose. {163} {164} {165} {167} {169} The reductions should be made at intervals of 1 to 2 weeks, depending on how well the patient responds to the withdrawal. A slow rate of withdrawal is strongly urged. As a rule, the reductions should not exceed 2.5 mg of prednisone or its equivalent at one time. {163} {164} {165} {167} {169} {170}

Some patients may not be able to discontinue use of systemic corticosteroids. {08} A minimal oral maintenance dose may be required along with the inhaled corticosteroid. {08} {15} {20}

Continued monitoring of the patient for signs of adrenal insufficiency is recommended following complete withdrawal of systemic corticosteroid therapy. Recovery of adrenal function may require up to 12 months in some patients, depending on the dosage and duration of systemic therapy. {05} {06} {07} {08} {13} {14} {15} {16} {17} {18} {19} {20} {21} {22} {62} {66} {67} {74} {163} {164} {165} {166} {167} {169} {170}

During the period of hypothalamic-pituitary-adrenal (HPA) function recovery, the patient may show signs of adrenal insufficiency when exposed to stressors, such as trauma, surgery, or infections, especially gastroenteritis or other conditions which involve a loss of electrolytes over a short period of time. While the inhaled corticosteroid may control the symptoms of asthma during these episodes, it does not supply a sufficient amount of systemic corticosteroids to cope with these emergencies. Therefore, patients who have had systemic corticosteroid therapy withdrawn recently should be instructed to resume large doses of systemic corticosteroid for these periods of stress, or for an acute asthma attack, and to contact their physician for further instruction. {163} {164} {165} {166} {167} {169} {170}

Severe asthma relapse may occur upon withdrawal of the systemic corticosteroid. Reinstitution of systemic therapy may be required if a severe asthma attack occurs. Frequent pulmonary function monitoring (peak expiratory flow rate measurements) {134} may be needed for some patients for as long as 4 to 8 months after discontinuation of the systemic corticosteroid. {62} {66} {67} {72} {74}

A syndrome of pseudo-rheumatism (consisting of joint or muscle pain, joint swelling, peripheral edema, lethargy, anorexia, and nausea) may occur when systemic corticosteroid is withdrawn. This syndrome can be avoided or minimized {130} if the dosage of systemic corticosteroids is reduced slowly, using an alternate-day regimen. If the syndrome occurs, the symptoms may be alleviated by treatment with acetaminophen or {150} nonsteroidal anti-inflammatory drugs (NSAIDs) in asthmatic patients who are not sensitive to NSAIDs {133}. Resumption of systemic corticosteroid therapy may not be required. {62} {66} {67} {68} {72}

For treatment of adverse effects
For laryngeal or pharyngeal candidiasis—Recommended treatment includes:

   • Administration of an oral or systemic antifungal medication.
   • Change in frequency of inhaled corticosteroid dosing from four to two times a day without decreasing the total daily dose. This may allow recovery and clearing of thrush or prevent its occurrence while maintaining therapeutic efficacy.
   • Discontinuation of the inhaled corticosteroid is rarely necessary. {72} {111}

BECLOMETHASONE


Inhalation Dosage Forms

BECLOMETHASONE DIPROPIONATE INHALATION AEROSOL

Usual adult and adolescent dose
Antiasthmatic


For the 42- or 50-mcg-per-metered-spray products:
Oral inhalation, 2 inhalations (84 or 100 mcg) three or four times a day. Alternatively, a dosage of 4 inhalations two times a day has been shown to be effective for some patients. {80} {165}

For severe asthma: Oral inhalation, initially, 12 to 16 inhalations a day. Dosage should then be decreased according to the patient's response. {80} {165} {178}



For the 84-mcg-per-metered-spray product:
Oral inhalation, 2 inhalations (168 mcg) two times a day {78} {169}.

For severe asthma: Oral inhalation, initially, 6 to 8 inhalations a day. Dosage should then be decreased according to the patient's response {78} {169}.



Usual adult and adolescent prescribing limits
For the 42- or 50-mcg-per-metered-spray products—20 inhalations (840 or 1000 mcg) per day {80} {165} {178}.

For the 84-mcg-per-metered-spray product—10 inhalations (840 mcg) per day {78} {169}.

Usual pediatric dose
Antiasthmatic


Children up to 6 years of age:
Dosage has not been established.



Children 6 to 12 years of age:


For the 42- or 50-mcg-per-metered-spray products—
Oral inhalation, 1 or 2 inhalations three or four times a day. Alternatively, a dosage of 4 inhalations two times a day has been shown to be effective for some patients. {80} {165} {178}



For the 84-mcg-per-metered-spray product—
Oral inhalation, 2 inhalations two times a day. {78} {169}




Children older than 12 years of age:
See Usual adult and adolescent dose .


Note: The 250-mcg-per-metered-spray product is not recommended for children up to 16 years of age. {166}



Usual pediatric prescribing limits
For the 42- or 50-mcg-per-metered-spray products—10 inhalations (420 or 500 mcg per day. {62} {165} {178}

For the 84-mcg-per-metered-spray product—5 inhalations (420 mcg) per day. {78} {169}

Strength(s) usually available
U.S.—


42 mcg (0.042 mg) per metered spray (Rx) [Beclovent{177}{178}] [Vanceril{165}]


84 mcg (0.084 mg) per metered spray (Rx) [Vanceril 84 mcg Double Strength{169} (chlorofluorocarbons)]

Note: The 84-mcg-per-metered spray must be primed by spraying twice into the air before the initial use and when the product has not been used for more than 7 days. {169}
Each 6.7 gram canister contains medication for 80 inhalations. {177} Each 16.8 gram canister contains medication for about 200 inhalations. {165} {178}


Canada—


50 mcg (0.05 mg) per metered spray (Rx) [Beclovent{174}] [Vanceril]


250 mcg (0.25 mg) per metered spray (Rx) [Becloforte{166}]

Note: The 50-mcg-per-metered-spray product is available in two sizes that contain medication for 80 or 200 inhalations per canister. {174}
The 250-mcg-per-metered-spray product is available in two sizes that contain medication for 80 or 200 inhalations per canister. {173}


Packaging and storage:
Store between 15° and 30° C (59° and 86° F). If medication is not used within this range of temperature, the dose may not be accurate. {165}

Auxiliary labeling:
   • Shake well before using {62}.
   • For oral inhalation only.
   • Store away from heat and direct sunlight. {62}

Note: Include patient instructions when dispensing.
Demonstrate administration technique.


Additional information:
In Canada, metered dose inhalers are labeled according to the amount of beclomethasone delivered at the valve; in the U.S., metered dose inhalers are labeled according to the amount of beclomethasone delivered at the mouthpiece or actuator. Thus, 50 mcg of beclomethasone delivered at the valve is equivalent to 42 mcg delivered at the mouthpiece. {95}

These products contains dichlorodifluoromethane and trichloromonofluoromethane, substances that harm public health and the environment by destroying ozone in the upper atmosphere.


BECLOMETHASONE DIPROPIONATE HFA INHALATION AEROSOL

Usual adult and adolescent dose
Antiasthmatic


For the 40-mcg-per-metered-spray product:
For patients who have previously used bronchodilators alone—{188}Oral inhalation, 1 (40 mcg) or 2 (80 mcg) inhalations twice daily. {186}

For patients who have previously used inhaled corticosteroids— Oral inhalation, 1 (40 mcg) to 4 (160 mcg) inhalations twice daily. {186}{188}



For the 50-mcg-per-metered-spray product:
Mild asthma—{188}Oral inhalation, 1 (50 mcg) or 2 (100 mcg) inhalations twice daily. {187}

Moderate asthma—Oral inhalation 2 (100 mcg) to 5 (250 mcg) inhalations twice daily. {187}



For the 80-mcg-per-metered-spray product:
For patients who have previously used bronchodilators alone—{188}Oral inhalation, 1 inhalation (80 mcg) two times a day. {186}

For patients who have previously used inhaled corticosteroids—{188} Oral inhalation, 1 or 2 inhalations (80 or 160 mcg) two times a day. {186}



For the 100-mcg-per-metered-spray product:
Severe asthma—{188}Oral inhalation, 3 (300 mcg) or 4 (400 mcg) inhalations twice daily. {187}


Note: The prescribing information in Canada includes a suggested conversion of doses for patients switching from CFC-beclomethasone dipropionate (CFC-BDP) to HFA-beclomethasone dipropionate (HFA-BDP). {187}
For patients using 200 mcg per day of CFC-BDP, use 100 mcg per day of HFA-BDP. {187}
For patients using 400 to 500 mcg per day of CFC-BDP, use 200 mcg per day of HFA-BDP. {187}
For patients using 600 to 750 mcg per day of CFC-BDP, use 300 mcg per day of HFA-BDP. {187}
For patients using 800 to 1000 mcg per day of CFC-BDP, use 400 mcg per day of HFA-BDP. {187}



Usual adult and adolescent prescribing limits
For the 40 mcg-per-metered-spray product—16 inhalations (640 mcg) per day. {186}

For the 50 mcg-per-metered-spray product—10 inhalations (500 mcg) per day. {187}

For the 80-mcg-per-metered-spray product—8 inhalations (640 mcg) per day. {186}.

For the 100 mcg-per-metered-spray product—8 inhalations (800 mcg) per day. {187}

Usual pediatric dose
Antiasthmatic
Children up to 5 years of age: Dosage has not been established.

Children 5 to 11 years of age: Oral inhalation, 1 (40 mcg) inhalation twice daily. {189}

Children older than 12 years of age: See Usual adult and adolescent dose.


Usual pediatric prescribing limits
For the 40 mcg-per-metered-spray product—2 inhalations (80 mcg) per day.

Strength(s) usually available
U.S.—


40 mcg (0.04 mg) per metered spray (Rx) [QVAR{186}]


80 mcg (0.08 mg) per metered spray (Rx) [QVAR{186} (tetrafluoroethane) (ethanol)]

Note: The 40-mcg-per-metered spray and 80-mcg-per-metered spray must be primed by spraying twice into the air (avoid eyes and face) before the initial use and when the product has not been used for more than 10 days. Each 7.3 gram canister contains medication for 100 inhalations{186}


Canada—


50 mcg (0.05 mg) per metered spray (Rx) [QVAR{187}] [QVAR]


100 mcg (0.1 mg) per metered spray (Rx) [QVAR{187}]

Note: The 50-mcg-per-metered-spray product is available in two sizes that contain medication for 100 (6.5 grams) and 200 (12.4 grams) inhalations per canister. {187}
The 100-mcg-per-metered-spray product is available in two sizes that contain medication for 100 (6.5 grams) and 200 (12.4 grams) inhalations per canister. {187}


Packaging and storage:
Store between 25° C (77° F). Excursions permitted between 15° and 30° C (59° and 86° F). If medication is not used within this range of temperature, the dose may not be accurate. {186}.

Auxiliary labeling:
   • For oral inhalation only.
   • Store away from heat and direct sunlight. {186}
   • Store the canister on the concave end with the plastic actuator on top {186}
   • Exposure to temperatures above 49° C (120° F) may cause bursting. {186}

Note: Include patient instructions when dispensing.
Shaking the canister prior to administration is not necessary for this aerosol solution formulation.
Demonstrate administration technique.


Additional information:
In Canada, metered dose inhalers are labeled according to the amount of beclomethasone delivered at the valve; in the U.S., metered dose inhalers are labeled according to the amount of beclomethasone delivered at the mouthpiece or actuator. {186} Thus, 50 mcg of beclomethasone dipropionate delivered at the valve is equivalent to 40 mcg delivered at the mouthpiece and 100 mcg of beclomethasone dipropionate delivered at the valve is equivalent to 80 mcg delivered at the mouthpiece. {187}

While the beclomethasone dipropionate HFA was developed for use without a spacer device being necessary, the AeroChamber® is a suitable device for use with beclomethasone dipropionate HFA metered dose inhaler to maintain the extrafine particle fraction. {187}{188}


BECLOMETHASONE DIPROPIONATE FOR INHALATION (CAPSULES)

Usual adult dose
Antiasthmatic
Oral inhalation, 200 mcg (0.2 mg) three or four times a day. Dosage should then be decreased according to patient response; many patients may be maintained on 400 mcg (0.4 mg) a day. {08} {09} {10} {77} {174}


Usual adult prescribing limits
1000 mcg (1 mg) per day. {174}

Usual pediatric dose
Antiasthmatic
Children up to 6 years of age: Dosage has not been established. {77} {174}

Children 6 to 14 years of age: Oral inhalation, 100 mcg (0.1 mg) two to four times a day. Dosage should then be decreased according to patient response. {08} {10} {77} {174}

Children over 14 years of age: See Usual adult dose . {174}


Usual pediatric prescribing limits
500 mcg (0.5 mg) {77} {174} per day.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


100 mcg (0.1 mg) per capsule (Rx) [Beclovent Rotacaps{174} (lactose)]


200 mcg (0.2 mg) per capsule (Rx) [Beclovent Rotacaps{174} (lactose)]

Packaging and storage:
Store below 30 °C (86 °F) {174} and in a dry place. {174}

Auxiliary labeling:
   • Do not swallow capsule.

Note: Include patient instructions when dispensing.
Demonstrate administration technique.
Use of beclomethasone for oral inhalation (capsules) requires a special device that separates the capsule into halves and releases the medication.
Each capsule should be inserted into the device only immediately prior to use. If this instruction is not followed, the delivery of the medicine may be affected. {174}



BECLOMETHASONE DIPROPIONATE FOR INHALATION (POWDER)

Usual adult dose
See Beclomethasone Dipropionate for Inhalation (Capsules). {63} {172}

Usual adult prescribing limits
1000 mcg (1 mg) per day. {172}

Usual pediatric dose
See Beclomethasone Dipropionate for Inhalation (Capsules). {63} {172}

Usual pediatric prescribing limits
500 mcg (0.5 mg) {63} {172} per day.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


100 mcg (0.1 mg) per blister (Rx) [Beclodisk{172}]


200 mcg (0.2 mg) per blister (Rx) [Beclodisk{172}]

Packaging and storage:
Store below 30 °C (86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Note: Include patient instructions when dispensing.
Demonstrate administration technique.
Use of beclomethasone for oral inhalation (powder) requires a special device that penetrates the blister {63} {172} and releases the medication.



BUDESONIDE


Inhalation Dosage Forms

Note: Bracketed information in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.


BUDESONIDE POWDER FOR INHALATION

Usual adult dose
Antiasthmatic


Previous asthma therapy consisting of bronchodilators alone:
Oral inhalation, 1 to 2 inhalations (200 to 400 mcg) two times a day. {84} {170}



Previous asthma therapy including inhaled corticosteroids:
Oral inhalation, 1 to 2 inhalations (200 to 400 mcg) two times a day. Dosage may be increased as needed and as tolerated to a maximum of 4 inhalations (800 mcg) two times a day. {84} {170}

Note: Once-daily dosing with 200 mcg or 400 mcg may be considered in patients with mild to moderate asthma who are well controlled on inhaled corticosteroids. {181} This dose may be administered once daily either in the morning or in the evening. {181} If the asthma symptoms are not controlled adequately with the once-daily treatment, the total daily dose should be increased and/or administered as a divided dose. {181}




Previous asthma therapy including systemic corticosteroids:
Oral inhalation, 2 to 4 inhalations (400 to 800 mcg) two times a day {84} {167}.



Usual adult prescribing limits
1600 mcg a day for patients previously treated with inhaled or systemic corticosteroids or 800 mcg a day for patients previously treated with bronchodilators alone {84} {170}.

Usual pediatric dose
Antiasthmatic


Children up to 6 years of age:
Use is not recommended {167}. However, studies have shown that [children 3 months to 6 years of age]1 have benefited from inhaled budesonide, at a dosage of 1 to 2 inhalations (200 to 400 mcg) daily, with a spacer (i.e., Nebuhaler, Inhaler), after which the dosage is adjusted as needed and as tolerated, to a maximum of 2 inhalations (400 mcg) daily.{184}



Children 6 years of age and older:
Oral inhalation, 1 inhalation (200 mcg) two times a day. Dosage may be increased as needed and as tolerated to a maximum of 2 inhalations (400 mcg) two times a day. {84} {167}

Note: Once-daily dosing with 200 mcg or 400 mcg may be considered in patients with mild to moderate asthma who are well controlled on inhaled corticosteroids. {181} This dose may be administered once daily either in the morning or in the evening. {181} If the asthma symptoms are not controlled adequately with the once-daily treatment, the total daily dose should be increased and/or administered as a divided dose. {181}




Usual pediatric prescribing limits
800 mcg a day {84} {167}.

Strength(s) usually available
U.S.—


200 mcg (0.2 mg) (Rx) [Pulmicort Turbuhaler{168}{170}]

Note: Product is an inhalation-driven, multi-dose, dry powder inhaler {168}.


Canada—


100 mcg (0.1 mg) (Rx) [Pulmicort Turbuhaler{167}]


200 mcg (0.2 mg) (Rx) [Pulmicort Turbuhaler{167}]


400 mcg (0.4 mg) (Rx) [Pulmicort Turbuhaler{167}]

Packaging and storage:
Store between 20 and 25 °C (68 and 77 °F). {170} Protect from light.

Auxiliary labeling:
   • For oral inhalation only.


BUDESONIDE SUSPENSION FOR INHALATION

Usual adult and adolescent dose
[Antiasthmatic]
Initial: Oral inhalation, 1 to 2 mg, diluted with sterile sodium chloride inhalation solution, if necessary, to a volume of two to four mL, and administered via nebulization over a period of ten to fifteen minutes two times a day. {171}

Note: For severe asthma, dosage may be increased according to patient response. {65} {171}


Maintenance: After the desired clinical effect has been obtained, the maintenance dose should be reduced gradually to the smallest dose necessary for control of symptoms. {61} {171}


Usual pediatric dose
Antiasthmatic
Children 12 months to 8 years of age: Previous Therapy: Bronchodilators alone— 0.5 mg total daily dose via jet nebulizer, either as a single dose or twice daily in divided doses.{01}

Previous Therapy: Inhaled Corticosteroids— 0.5 mg total daily dose via jet nebulizer, either as a single dose or twice daily in divided doses.

Previous Therapy: Oral Corticosteroids—1 mg total daily dose via jet nebulizer, either as a single 1 mg dose or twice daily in divided doses of 0.5 mg.{185}

Children up to 12 months of age: Dosage has not been established.{185}


Note: In Canada, children 3 months to 12 years of age: Initial—Oral inhalation, 250 mcg (0.25 mg) to 1 mg, diluted with sterile sodium chloride inhalation solution, if necessary, to a volume of two to four mL, and administered via nebulization over a period of ten to fifteen minutes two times a day {61} {171}. Maintenance—After the desired clinical effect has been obtained, the maintenance dose should be reduced gradually to the smallest dose necessary for control of symptoms {61} {171}. Dosage has not been established for children younger than 3 months of age.{171}


Strength(s) usually available
U.S.—


125 mcg (0.125 mg) per mL (250 mcg per 2-mL ampul) (Rx) [Pulmicort Respules (disodium edetate) (sodium chloride) (sodium citrate) (citric acid) (polysorbate 80) (water for injection)]{01}


250 mcg (0.25 mg) per mL (500 mcg per 2-mL ampul) (Rx) [Pulmicort Respules (disodium edetate) (sodium chloride) (sodium citrate) (citric acid) (polysorbate 80) (water for injection)]{01}

Canada—


125 mcg (0.125 mg) per mL (250 mcg per 2-mL ampul) (Rx) [Pulmicort Nebuamp{171}]


250 mcg (0.25 mg) per mL (500 mcg per 2-mL ampul) (Rx) [Pulmicort Nebuamp{171}]


500 mcg (0.5 mg) per mL (1000 mcg per 2-mL ampul) (Rx) [Pulmicort Nebuamp{171}]

Packaging and storage:
Store between 5 and 30 °C (41 and 86 °F) in an upright position {171}, unless otherwise specified by manufacturer. Protect from freezing. Protect from light.

Stability:
Ampuls in an opened envelope should be stored in the envelope, protected from light, and used within 2 weeks.{185}

Any opened ampul must be used promptly.{185}

Note: For Canadian products, any unused suspension remaining in an opened ampul may be stored for later use as long as it is protected from light and is used within 12 hours after the ampul was opened.{65} The entire contents of an ampul must be used within 12 hours after it is first opened.{171} Ampuls in an opened envelope should be used within 3 months. {171}


Auxiliary labeling:
   • For oral inhalation only.
   • Shake gently before using.
   • Do not freeze.{185}

Note: When dispensing, include patient instructions for preparation of solution. {65}


Additional information:
For nebulization of budesonide inhalation suspension, a gas flow (oxygen or compressed air) of 6 to 10 liters per minute should be used. Nebulizers with either a facemask or mouthpiece have been used. Ultrasonic nebulizers are not recommended. {133} {171}


FLUNISOLIDE


Inhalation Dosage Forms

FLUNISOLIDE INHALATION AEROSOL

Usual adult and adolescent dose
Antiasthmatic
Oral inhalation, 500 mcg (0.5 mg—2 metered sprays) two times a day, morning and evening. {18} {19} {20} {64} {66} {67} {164}


Usual adult prescribing limits
Oral inhalation, 2 mg per day (4 metered sprays twice a day). {18} {19} {20} {137} {164} At the 2-mg-per-day dosage, the patient should be monitored at appropriate intervals for HPA suppression. {164}

Usual pediatric dose
Antiasthmatic
Children up to 6 years of age: Dosage has not been established. {164}

Children 6 years of age and older: See Usual adult and adolescent dose . {164}


Note: Doses higher than 1 mg per day have not been studied in children 4 to 15 years of age. {18} {19} {20} {64} {66} {67} In Canada the pediatric dosing is established for children 4 years of age and older. {175}


Strength(s) usually available
U.S.—


250 mcg (0.25 mg) per metered spray (Rx) [AeroBid{164}] [AeroBid-M (menthol)]

Canada—


250 mcg (0.25 mg) per metered spray (Rx) [Bronalide{175}]

Note: Each canister delivers at least 100 inhalations. {18} {20} {64} {66} {67} {164} {175}


Packaging and storage:
Store below 49 °C (120 °F) {18} {20}, preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Auxiliary labeling:
   • Shake well {18} {19} {20} {66} {67} before using.
   • For oral inhalation only.

Note: Include patient instructions when dispensing.
Demonstrate administration technique.


Additional information:
These products contain dichlorodifluoromethane, trichloromonofluoromethane, and dichlorotetrafluoroethane, substances that harm public health and the environment by destroying ozone in the upper atmosphere. {164}


TRIAMCINOLONE


Inhalation Dosage Forms

TRIAMCINOLONE ACETONIDE INHALATION AEROSOL

Usual adult and adolescent dose
Antiasthmatic
Initial: Oral inhalation, 200 mcg (0.2 mg—2 metered sprays) three or four times a day {21} {22} {23} {74} {163}, or four inhalations twice a day {163}. For severe asthma: Oral inhalation, 1.2 to 1.6 mg (12 to 16 metered sprays) a day. {21} {22} {74}

Maintenance: Dosage to be decreased according to patient response; maintenance may be achieved in some patients by administering the total daily dose in two divided doses. {21} {22} {74} {163}


Usual adult prescribing limits
1.6 mg (16 metered sprays) per day. {163}

Usual pediatric dose
Antiasthmatic
Children up to 6 years of age: Dosage has not been established. {21} {22} {74} {163}

Children 6 to 12 years of age: Oral inhalation, 100 to 200 mcg (0.1 to 0.2 mg—1 or 2 metered sprays) three or four times a day {21} {22} {23} {26} {74}, or 200 to 400 mcg (2 or 4 metered sprays) twice a day. {163} Dosage must be adjusted according to patient response.


Usual pediatric prescribing limits
1.2 mg (12 metered sprays) per day. {21} {22} {74} {163}

Strength(s) usually available
U.S.—


100 mcg (0.1 mg) per metered spray (Rx) [Azmacort{163} (alcohol 1%)]

Canada—


200 mcg (0.2 mg) per metered spray (Rx) [Azmacort{97}{176} (alcohol 1%)]
{176}
Note: In Canada, metered dose inhalers are labeled according to the amount of medication delivered at the valve; in the U.S., metered dose inhalers are labeled according to the amount of medication delivered from the mouthpiece or actuator. Thus, 200 mcg of triamcinolone delivered at the valve is equivalent to 100 mcg delivered at the mouthpiece. {163} {176}
Each 60 gram canister delivers at least 240 inhalations. Canister should not be used after 240 inhalations. {21} {22} {163} After 240 actuations, the dose may not be accurate. {163}


Packaging and storage:
Store at temperatures below 49 °C (120 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. {23} {74}

Auxiliary labeling:
   • Shake well before using.
   • For oral inhalation only.

Note: Include patient instructions when dispensing.
Demonstrate administration technique.


Additional information:
Each actuation releases approximately 200 mcg of triamcinolone acetonide, of which approximately 100 mcg are delivered from the unit.

This product contains dichlorodifluoromethane, a substance that harms public health and the environment by destroying ozone in the upper atmosphere.



Revised: 09/16/2002



References
  1. Fleeger CA, editor. USAN 1994. USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc. 1993.
  1. No reference
  1. No reference
  1. No reference
  1. Beclovent package insert (Glaxo—US), Rev 3/87.
  1. Beclovent package insert (Glaxo—US), Rev 2/88.
  1. Beclovent package insert (Glaxo—US), Rev 11/88.
  1. Beclovent product monograph (A & H). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 23rd ed. Ottawa: Canadian Pharmaceutical Association, 1988.
  1. Beclovent 100 (box) labeling (A & H—Canada).
  1. Beclovent 200 (box) labeling (A & H—Canada).
  1. Beclovent inhaler (box) labeling (A & H—Canada).
  1. Beclovent patient instruction leaflet (A & H—Canada).
  1. Vanceril package insert (Schering—US), Rev 9/85.
  1. Vanceril package insert (Schering—US), Rev 9/88.
  1. Vanceril (Schering). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 23rd ed. Ottawa: Canadian Pharmaceutical Association, 1988.
  1. Decadron package insert (MSD—US), Rev 4/85.
  1. Decadron package insert (MSD—US), Rev 3/88.
  1. Aerobid package insert (Key—US), Rec 12/7/87, Rev 8/86.
  1. Aerobid (Key). In: PDR Physicians' desk reference. 43rd ed. 1989. Oradell, NJ: Medical Economics Company, 1989.
  1. Bronalide (Syntex). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 23rd ed. Ottawa: Canadian Pharmaceutical Association, 1988.
  1. Azmacort package insert (Rorer—US).
  1. Azmacort package insert (Rorer). In: PDR Physicians' desk reference. 43rd ed. Oradell, NJ: Medical Economics Company, 1989.
  1. Azmacort labeling (box) (Rorer—US), Rec 11/20/87.
  1. Reviewer comment, 10/12/88.
  1. Reviewer comment, 9/26/88.
  1. Lozewicz S, et al. Inflammatory cells in the airways in mild asthma. Br Med J 1988; 297: 1515-6.
  1. Johnson CE. Aerosol corticosteroids for the treatment of asthma. Drug Intell Clin Pharm 1987; 21: 784-90.
  1. Higgins LC. Use of inhaled steroids still lags. Med World News 1988 Jun 27: 55-6.
  1. Simon PA. Asthma in children. Guidelines for pharmacotherapy. Drug Topics 1989 Mar 6: 80-6.
  1. Nassif E, et al. Extrapulmonary effects of maintenance corticosteroid therapy with alternate-day prednisone and inhaled beclomethasone in children with chronic asthma. J Allergy Clin Immunol 1987; 80: 518-29.
  1. Salzman GA, Pyszcynski DR, [Candidiasis: incidence study. In: Ractions 7 May 1988, 5]. J Allergy Clin Immunol 1988; 81(2): 424-8.
  1. Settipane GA et. al. (Beclomethasone: hoarseness and candidiasis-incidence study.) New England and Regional Allergy Proceeding 1987; 8: 95-7.
  1. Kesten S. Esophageal candidiasis associated with beclomethasone dipropionate aerosol therapy. Drug Intell Clin Pharm 1988; 22: 568-9.
  1. Tandon MK. High dose beclomethasone in the management of elderly patients with corticosteroid dependent chronic obstructive pulmonary disease. Med J Aust 1987; 147: 314-5.
  1. Littlewood JM et al. Growth retardation in asthmatic children treated with inhaled beclomethasone dipropionate. Lancet 1988 Jan 16: 115-6.
  1. Law CM, et al. Nocturnal adrenal suppression in asthmatic children taking inhaled beclomethasone dipropionate. Lancet 1986 Apr 26: 944.
  1. Law CM, et al. Nocturnal adrenal suppression in asthmatic children taking inhaled beclomethasone dipropionate. Lancet 1987 Jun 6: 1321.
  1. Ventura A, et al. Systemic effects and inhaled beclomethasone dipropionate. Lancet 1986 Jun 14: 1393.
  1. Munch EP, et al. Dose frequency in the treatment of asthmatics with inhaled topical steroids: comparison between a twice daily and once daily dosing regimen. Eur J Respir Dis 1985; 67: 254-60.
  1. Meltzer, et al. Effect of dosing schedule on efficacy of beclomethasone dipropionate aerosol in chronic asthma. Am Rev Respir Dis 1985; 131: 732-6.
  1. Tukiainen H. Comparison of twice-daily and four-times daily administration of beclomethasone dipropionate in patients with severe chronic bronchial asthma. Eur J Clin Pharmacol 1986; 30: 319-22.
  1. Ebden P, Davies BH. High-dose corticosteroid inhalers for asthma. Lancet 1984 Sep 8: 576.
  1. Henry RL. Dysphonia following inhalation resolving with volumatic spacer device use: 2 case reports. [In: Reactions Annual 1987: 29]. Med J Austr 1987 Oct 5: 147.
  1. Beasley R, et al. Beclomethasone: exacerbation of asthma, follow-up comment. 1986. [In: Reactions Annual 1987: 29]. Lancet 1986 Nov 22; 2: 1277.
  1. Tarlo SM, et al. Six-month double-blind, controlled trial of high dose, concentrated beclomethasone dipropionate in the treatment of severe chronic asthma. Chest 1988; 93(5): 998-1002.
  1. Broder I, et al. Safety and efficacy of long-term treatment with inhaled beclomethasone dipropionate in steroid-dependent asthma. Can Med Assoc J 1987; 136(2): 129-35.
  1. Hollman GA, Allen DB. Overt glucocorticoid excess due to inhaled corticosteroid therapy. Pediatrics 1988; 81(3): 452-5.
  1. Meltzer ED. Flunisolide aerosol for treatment of severe, chronic asthma in steroid-independent children. Pediatrics 1982; 69: 340-5.
  1. Shapiro GG, et al. Short-term double-blind evaluation of flunisolide aerosol for steroid-dependent asthmatic children and adolescents. Chest 1981; 80(6): 671-5.
  1. Panel comment, Panel survey date 7/5/89.
  1. Panel comment, Panel survey date 7/5/89.
  1. Panel comment, Panel survey date 7/5/89.
  1. Panel comment, Panel survey date 7/5/89.
  1. Wyngaarden MD, Smith LH. Cecil textbook of medicine. 18th ed. Philadelphia: W.B. Saunders Company, 1988: 403-10.
  1. Rakel RE, editor. Conn's current therapy 1988. Philadelphia: W.B. Saunders Company, 1988.
  1. Barnes PJ, Rodger IW, Thomson NC. Asthma: basic mechanisms and clinical management. San Diego, CA: Academic Press, 1988: 81-95, 131-42, 653-97.
  1. Panel comment, Panel survey date 7/5/89.
  1. Panel comment, Panel survey date 7/5/89.
  1. Panel comment, Facsimile response 10/3/89.
  1. Panel comment, Panel survey date 7/5/89.
  1. Budesonide suspension for inhalation product monograph (Pulmicort Nebuamp, Astra—Canada), Rev 8/96.
  1. Beclovent package insert (Allen and Hanburys—US), Rev 3/93, Rec 6/30/93.
  1. Beclodisk box/label and patient instructions (Glaxo—Canada), Rec. 9/2/93.
  1. Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 28th ed. Ottawa: Canadian Pharmaceutical Association, 1993: 172-3.
  1. Pulmicort Nebuamp product monograph (Astra—Canada), Rev 8/11/93, Rec 8/31/93.
  1. AeroBid-M package insert (Forest Pharm—US), Rev 11/92, Rec 6/21/93.
  1. AeroBid package insert (Forest Pharm—US), Rev 3/92, Rec 6/21/93.
  1. Vanceril product monograph (Schering—Canada), Rev 8/92, Rec 6/30/93.
  1. Konig P, Hillman L, Cervantes C, et al. Bone metabolism in children with asthma treated with inhaled beclomethasone dipropionate. J Pediatr 1993; 122: 219-26.
  1. Merkus PJFM, van Essen-Zandvliet EEM, Duiverman EJ, et al. Long-term effect of inhaled corticosteroids on growth rate in adolescents with asthma. Pediatrics 1993: 91: 1121-6.
  1. Brogden RN, McTavish D. Budesonide. An updated review of its pharmacological properties, and therapeutic efficacy in asthma and rhinitis. [See errata in Drugs 1992 Dec; 44(6): 1012 and Drugs 1993 Jan; 45(1): 130]. Drugs 1992 Sep; 44 (3): 375-407.
  1. Toogood J. Complications of topical steroid therapy for asthma. Am Rev Respir Dis 1990; 141: S89-96.
  1. Executive Committee, American Academy of Allergy and Immunology. Position statement. Inhaled steroids and severe viral infections. J Allergy Clin Immunol 1993 Aug; 92(2): 223-8.
  1. Azmacort package insert (Rhone-Poulenc—US), Rev 11/91, Rec 11/16/93.
  1. Decadron Respihaler package insert (Merck—US), Rev 3/93, Rec 10/21/93.
  1. Fleeger CA, editor. USAN 1994. USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1993: 72, 100, 200-1, 288-9, 683.
  1. Beclovent Rotacaps box/label and patient information (Glaxo—Canada), Rec 9/2/93.
  1. Beclomethasone inhalation aerosol product labeling (Vanceril 84 mcg Double Strength, Schering—US), Rev 12/96.
  1. Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 28th ed. Ottawa: Canadian Pharmaceutical Association, 1993: 137-8.
  1. Beclomethasone dipropionate product labeling (Vanceril, Schering—US). In: PDR Physicians' desk reference. 51st ed. Montvale, NJ: Medical Economics Data; 1997. p. 2538-9.
  1. Meyboom RHB. Budesonide and psychic side effects. Lancet 1993 Sept 10; 342 (8872): 683-4.
  1. Katsunuma T, Akosawa A, Ikura Y. Adrenal function of children with bronchial asthma treated with beclomethasone dipropionate. Ann Allergy 1992 Dec; 109: 529-32.
  1. Shim CS, Williams MH Jr. Cough and wheezing from beclomethasone dipropionate aerosol are absent after triamcinolone acetonide. Ann Int Med 1987; 106: 700-3.
  1. Budesonide inhalation powder package insert (Pulmicort, Astra—US), Rev 6/97.
  1. Brown PH, Greening AP, Crompton GK. Large volume spacer devices and the influence of high dose beclomethasone dipropionate on hypothalamo-pituitary-adrenal axis function. Thorax 1993; 48: 233-8.
  1. Toogood JH, Markov AE, Baskerville J, Dyson C. Association of ocular cataracts with inhaled and oral steroid therapy during long-term treatment of asthma. J Allergy Clin Immunol 1993; 91: 571-9.
  1. Cochran BM. An integrated patient-specific learning program for pharmacists. Can Pharm J 1993 Apr; Choices: 1-8.
  1. HHS News. US Dept. of Health and Human Services, Dec 2, 1992.
  1. Ninan TK, Russell G. Asthma, inhaled corticosteroid treatment, and growth. Arch Dis Child 1992; 67: 703-5.
  1. Packe GE, Douglas JG, McDonald AF, et al. Bone density in asthmatic patients taking high dose inhaled beclomethasone dipropionate and intermittent systemic corticosteroids. Thorax 1992 Jun; 97(6): 414-7.
  1. Shaikh WA. Pulmonary tuberculosis in patients treated with inhaled beclomethasone. Allergy 1992; 47: 327-30.
  1. Becloforte Inhaler product label/box (Glaxo—Canada), Rec 6/93.
  1. The National Institutes of Health Asthma Education Program and the National Heart, Lung, and Blood Institute. Executive Summary: Guidelines for the diagnosis and management of asthma. Bethesda, MD: National Institutes of Health; 1991. US Dept of Health and Human Services publication 3042.
  1. Nicklas RA. Treatment of the elderly asthmatic patient with heart disease. Immunol Allergy Clin North America 1991 Feb; 11(1): 183-99.
  1. Zehetner W. Suggested Canadian in vitro requirements for MDIs. Highlights Metered-Dose Inhaler Workshops–Ottawa 1990 Feb 19: 11-2.
  1. Federal Register 1993 June 29; 58 (123)/Notices: 34183.
  1. Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 28th ed. Ottawa: Canadian Pharmaceutical Association, 1993: 123-4.
  1. Stead RJ, Cooke NJ. Adverse effects of inhaled corticosteroids. Br Med J 1989 Feb; 298: 403-4.
  1. International Consensus Report on Diagnosis and Management of Asthma. US Dept. of Health and Human Services, US Public Health Service, National Institutes of Health, 1992 Mar: 55.
  1. Ernst P, Spitzer WO, Suissa S, et al. Risk of fatal and near-fatal asthma in relation to inhaled corticosteroid use. JAMA 1992 Dec; 268(24): 3462-4.
  1. Evans P, O'Connor BJ, Fuller RW, et al. Effect of inhaled corticosteroids on peripheral blood eosinophils and density profiles in asthma. J Allergy Clin Immunol 1993 Feb; 91(2): 643-50.
  1. Laitinen LA, Laitinen A, Haahtela T. A comparative study of the effects of an inhaled corticosteroid, budesonide, and a beta-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: A randomized, double-blind, parallel-group controlled trial. J Allergy Clin Immunol 1992; 90: 32-42.
  1. USP DI Allergy Advisory Panel Meeting, 8/3/91.
  1. Suetsugu M, Yamauchi K, Shirato K, et al. Beclomethasone inhalation associated with reduced activated eosinophils in sputum. Drug Invest 1992; 4(6): 492-500.
  1. Wempe JB, Tammeling EP, Koeter GH, et al. Blood eosinophil numbers and activity during 24 hours: Effects of treatment with budesonide and bambuterol. J Allergy Clin Immunol 1992; 90: 757-65.
  1. High-dose inhaled steroids. Clin-Alert 1992; 14: 189.
  1. Haahtela T, Jarvinen M, Kava T, et al. Comparison of a beta-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma. N Engl J Med 1991; 325: 388-92.
  1. Phillip M, Avram M, Leiberman E, et al. Integrated plasma cortisol concentration in children with asthma receiving long-term inhaled corticosteroids. Pediatr Pulmonol 1992; 12: 84-9.
  1. Kamada AK, Parks DP, Szefler S. Inhaled glucocorticoid therapy in children: How much is safe? Pediatr Pulmonol 1992; 12: 71-2.
  1. Pulmicort Turbuhaler product monograph (Astra—Canada), Rev 10/93, Rec 11/93.
  1. Barnes PJ, Pedersen S. Efficacy and safety of inhaled corticosteroids in asthma. Am Rev Respir Dis 1993; 148: S1-26.
  1. Stempel D. Inhaled corticosteroids—Are they all the same? Am J Asthma and Allergy for Pediatricians 1992; 6(1): 41-4.
  1. Barnes PJ. Asthma: what is there left to find out? Br Med J 1993; 307: 814-5.
  1. Konig P. Inhaled corticosteroids—their present and future in the management of asthma. J Allergy Clin Immunol 1988; 82(2): 297-306.
  1. Burke C, Power CK, Norris A, et al. Lung function and immunopathological changes after inhaled corticosteroid therapy in asthma. Eur Respir J 1992; 5: 73-9.
  1. Wolthers OD, Pedersen S. Controlled study of linear growth in asthmatic children during treatment with inhaled corticosteroids. Pediatrics 1992; 89: 839-42
  1. McCubbin M, Milavetz G, Grandgeorge S, et al. A bioassay for topical and systemic effects of three inhaled corticosteroids. Draft.
  1. Svendsen UG, Frolund L, Heinig JH, et al. High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness, and the adrenal function. Allergy 1992; 47: 174-80.
  1. Dompeling E, van Schayck CP, van Grunsven PM, et al. Slowing the deterioration of asthma and chronic obstructive pulmonary disease observed during bronchodilator therapy by adding inhaled corticosteroids. Ann Intern Med 1993; 118: 770-8.
  1. Puolijoki H, Liippo K, Herrala J, et al. Inhaled beclomethasone decreases serum osteocalcin in postmenopausal asthmatic women. Bone 1992; 13: 285-8.
  1. Capewell S, Reynolds, Shuttleworh D, et al. Purpura and dermal thinning associated with high dose inhaled corticosteroids. Br Med J 1990; 300: 1548-51.
  1. Dompeling E, van Grunsven PM, van Schayck CP, et al. Treatment with inhaled steroids in asthma and chronic bronchitis: long-term compliance and inhaler technique. Fam Pract 1992; 9(2): 161-6.
  1. Panelist comment, Dec 1993.
  1. Manufacturer comment, 4/15/94.
  1. Panel comment, 4/25/94.
  1. Panel comment, 4/5/94.
  1. Panel comment, 4/1/94.
  1. Panel comment, 4/13/94.
  1. Panel comment, 4/14/94.
  1. Panel comment, 4/25/94.
  1. Panel comment, 4/4/94.
  1. Panel comment, 4/15/94.
  1. Panel comment, 4/12/94.
  1. Panel comment, 4/18/94.
  1. Panel comment, 4/19/94.
  1. Panel comment, 4/13/94.
  1. Panel comment, 4/4/94.
  1. Panel comment, 4/18/94.
  1. Panel comment, 4/4/94.
  1. Panel comment, 4/13/94.
  1. Panel comment, 4/18/94.
  1. Panel comment, 4/13/94.
  1. Szefler SJ. Glucocorticoid therapy for asthma: clinical pharmacology. J Aller Clin Immunol 1991 Aug; 88(2): 147-65.
  1. The National Institutes of Health National Asthma Education Program and the NHLBI Executive Summary. Management of asthma during pregnancy. Bethesda, MD: NIH; 1992. US Dept of HHS publication 93-3279A.
  1. Dreyer EB. Inhaled steroid use and glaucoma. Letters. N Engl J Med Dec 1993; 329(24):1822.
  1. Regulatory actions. Pharmaceuticals newsletter 1993 Aug; 8: 2.
  1. Panel comment, 7/19/94.
  1. Panel comment, 7/11/94.
  1. Panel comment, 7/7/94.
  1. Panel comment, 7/15/94.
  1. Panel comment, 7/13/94.
  1. Panel comment, 7/6/94.
  1. Panel comment, 6/29/94.
  1. Panel comment, 7/19/94.
  1. Panel comment, 7/6/94.
  1. Panel comment, 7/19/94.
  1. Panel comment, 7/5/94.
  1. Panel comment, 7/20/94.
  1. Panel comment, 7/6/94.
  1. Panel comment, 7/13/94.
  1. Panel comment, 7-8/94.
  1. Panel comment, 10/12/94.
  1. Azmacort (Rhone-Poulenc Rorer). In: PDR Physicians' desk reference. 52nd ed. 1998. Montvale, NJ: Medical Economics Data; 1998. p. 2358-60.
  1. Aerobid, Aerobid-M (Forest Pharmaceuticals). In: PDR Physicians' desk reference. 52nd ed. 1998. Montvale, NJ: Medical Economics Data; 1998. p. 941-2.
  1. Vanceril (Schering). In: PDR Physicians' desk reference. 52nd ed. 1998. Montvale, NJ: Medical Economics Data; 1998. p. 2672-4.
  1. Becloforte Product Monograph (Glaxo Wellcome Inc—US), Rev 1/98, Rec 2/98.
  1. Pulmicort Turbuhaler Product Monograph (Astra Pharmaceuticals—US), Rev 1/98, Rec 3/98.
  1. New Product Bulletin: Pulmicort Turbuhaler. APhA American Pharmaceutical Association. 1998.
  1. Vanceril (Schering). In: PDR Physicians' desk reference. 52nd ed. 1998. Montvale, NJ: Medical Economics Data; 1998. p. 2674-6.
  1. Pulmicort Turbuhaler (Astra—US), Issued 6/97, Rec 12/97.
  1. Pulmicort Nebuamp (Astra) In: CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa, Ontario, Canada: Canadian Pharmacists Association; 1998. p. 1400-2.
  1. Beclodisk, Beclodisk Diskhaler (Glaxo Wellcome) In: CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa, Ontario, Canada: Canadian Pharmacists Association; 1998. p. 176-8.
  1. Becloforte (Glaxo Wellcome) In: CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa, Ontario, Canada: Canadian Pharmacists Association; 1998. p. 178-9.
  1. Beclovent (Glaxo Wellcome) In: CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa, Ontario, Canada: Canadian Pharmacists Association; 1998. p. 179-80.
  1. Bronalide (Boehringer Ingelheim) In: CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa, Ontario, Canada: Canadian Pharmacists Association; 1998. p. 228.
  1. Azmacort (Rhone-Poulenc Rorer) In: CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa, Ontario, Canada: Canadian Pharmacists Association; 1998. p.165-6.
  1. Beclovent (Glaxo Wellcome) In: PDR Physicians' desk reference. 52nd ed. Montvale, NJ: Medical Economics Data; 1998. p. 1004-6.
  1. Beclovent (Glaxo Wellcome—US), Rev 12/97, Rec 6/98.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1997. p. 317.
  1. FDA Talk Paper. Class labeling for intranasal and orally inhaled corticosteroid containing drug products regarding the potential for growth suppression in children. U.S. Food and Drug Administration Center for Drug Evaluation and Research Division of Pulmonary Drug Products. 1998 Nov 9. Available from: URL: http://www.fda.gov/cder/news/cs-label.htm
  1. Pulmicort package insert (Astra—US), Rev 10/98, Rec 10/98.
  1. Panel comment, 1/99.
  1. Panel comment, 1/99
  1. Reviewers' consensus on the use of inhaled budesonide in pediatric patients for the treatment of asthma evidence table, 5/16/00.
  1. Product Information: Pulmicort Respules™, budesonide inhalation suspension. Astra Pharmaceuticals, L.P., Wayne, PA, (PI revised 08/2000) reviewed 11/2000.
  1. Product Information: QVAR, beclomethasone dipropionate HFA. 3M Pharmaceuticals, Northridge, CA (PI revised 11/2000) Reviewed 12/2001.
  1. QVAR product monograph (3M Pharmaceuticals). In: Repchinsky C, editor. CPS Compendium of pharmaceuticals and specialties. 26th ed. Ottawa: Canadian Pharmaceutical Association, 2001.
  1. Expert Committee comment, 9/2002
  1. Product Information: QVAR, beclomethasone dipropionate HFA. 3M Pharmaceuticals, Northridge, CA (PI revised 5/2002) Reviewed 9/2002.
  1. Suissa S, Ernst P. Inhaled corticosteroids: impact on asthma morbidity and mortality. J Allergy Clin Immunol 2001;107:937-44.
  1. Anis AH, Lynd LD, Wang X, et al. Double trouble: impact of inappropriate use of asthma medication on the use of health care resources. CMAJ 2001;164:625-31.
  1. Suissa S, Ernst P, Benayoun S, et al. Low-dose inhaled corticosteroids and the prevention on death from asthma. N Engl J Med 2000;343:332-6.
  1. NAEOO Expert Panel Report. Guidelines for the diagnosis and management of asthma: update on selected topics 2002. NIH 2002 June.
  1. Schuh S, Reisam J, Alshehri M, et al. A comparison of inhaled fluticasone and oral prednisone for children with severe acute asthma. N Engl J Med 2000;343:689-94.
  1. Product Information: Pulmicort Turbuhaler, budesonide inhalation powder. AstraZeneca, Wilmington, DE (PI revised 12/2001) Reviewed 9/2002.
  1. Product Information: Pulmicort Respules, budesonide inhalation suspension. AstraZeneca, Wilmington, DE (PI revised 5/2001) Reviewed 9/2002.
  1. Szefler S, Weiss S, Tonascia J, et al. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med 2000;343:1054-63.
  1. Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med 2000;343:1064-9.
  1. Silverstein MD, Yunginger JW, Reed CE, et al. Attained adult health after childhood asthma: effect of glucocorticoid therapy. J Allergy Clin Immunol 1997;99:466-74.
  1. Wong CA, Walsh LJ, Smith CJP, et al. Inhaled corticosteroids use and bone-mineral density in patients with asthma. Lancet 2000;355:1399-403.
Hide
(web3)