Vanceril

Indications : Asthma; Polyps, nasal, prevention; Rhinitis, perennial allergic; Rhinitis, seasonal allergic; Rhinitis, vasomotor

Pregnancy Category C

Orphan Drugs; WHO Formulary

FDA Approved 1976 May

DRUG CLASS : Corticosteroids; Antiasthmatics

BRAND NAMES : Aerobec (Mexico, Germany, South-Africa); Alanase (New-Zealand); Aldecin (New-Zealand, New-Zealand, Denmark, Switzerland, Hong-Kong, Malaysia, Netherlands, Belgium, Denmark, Bulgaria, Taiwan); Aldecina (Portugal, Costa-Rica, Dominican-Republic, El-Salvador, Guatemala, Honduras, Nicaragua, Panama); Anceron (South-Africa); Andion (Denmark); Atomase (New-Zealand); Beceze (Israel); Beclate (Bahrain, Cyprus, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Oman, Qatar, Republic-of-Yemen, Saudi-Arabia, Syria, United-Arab-Emirates, India, South-Africa); Beclazone (Israel); Beclocort Nasel (Poland); Becloforte (New-Zealand, Hong-Kong, South-Africa); Beclomet (Germany, Switzerland, Malaysia, Taiwan, Bulgaria); Beclomet Nasal (Bahrain, Cyprus, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Libya, Oman, Qatar, Republic-of-Yemen, Saudi-Arabia, Syria, United-Arab-Emirates); Beclo-Rhino (France); Beclorhinol (Germany); Becloturmant (Germany); Beclovent (US); Beconase (Australia, New-Zealand; Benin, Burkina-Faso, Ethiopia, Gambia, Ghana, Guinea, Ivory-Coast, Kenya, Liberia, Malawi, Mali, Mauritania, Mauritius, Morocco, Niger, Nigeria, Senegal, Seychelles, Sierra-Leone, South-Africa, Sudan, Tanzania, Tunia, Uganda, Zambia, Zimbabwe; Bahamas, Barbados, Belize, Bermuda, Curacao, Guyana, Jamaica, Netherland-Antilles, Puerto-Rico, Surinam, Trinidad; Bahrain, Cyprus, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Libya, Oman, Qatar, Republic-of-Yemen, Saudi-Arabia, Syria, United-Arab-Emirates, New-Zealand, Netherlands, Germany, England, Belgium, France, Philippines, Taiwan, Thailand, Hong-Kong, Indonesia, Malaysia, Austria, Hungary, Finland, Portugal, Bulgaria, Spain, Costa-Rica, Dominican-Republic, El-Salvador, Guatemala, Honduras, Nicaragua, Panama, Ecuador, Mexico, Canada, South-Africa, Colombia, Peru); Beconase AQ (US); Becotide (Hong-Kong, Indonesia, Korea, Malaysia, Philippines, Taiwan, Thailand; Bahamas, Barbados, Belize, Bermuda, Curacao, Guyana, Jamaica, Netherland-Antilles, Puerto-Rico, Surinam, Trinidad; Bahrain, Cyprus, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Libya, Oman, Qatar, Republic-of-Yemen, Saudi-Arabia, Syria, United-Arab-Emirates; Benin, Burkina-Faso, Ethiopia, Gambia, Ghana, Guinea, Ivory-Coast, Kenya, Liberia, Malawi, Mali, Mauritania, Mauritius, Morocco, Niger, Nigeria, Senegal, Seychelles, Sierra-Leone, South-Africa, Sudan, Tanzania, Tunia, Uganda, Zambia, Zimbabwe; Australia, New-Zealand; Austria, Belgium, Bulgaria, Czech-Republic, Denmark, England, Finland, France, Greece, Hungary, Italy, Netherlands, Norway, Portugal, Russia, Spain, Sweden, Switzerland, , New-Zealand, Bulgaria, South-Africa, Israel, Mexico, Ecuador, Costa-Rica, Dominican-Republic, El-Salvador, Guatemala, Honduras, Nicaragua, Panama, Peru); Belax (Taiwan); Clenil (Bahrain, Cyprus, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Libya, Oman, Qatar, Republic-of-Yemen, Saudi-Arabia, Syria, United-Arab-Emirates, Hong-Kong, Philippines, Taiwan, South-Africa); Clenil Forte (Philippines); Q Var (New-Zealand); Respocort (New-Zealand, Malaysia, Philippines); Rhino Clenil (Bahrain, Cyprus, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Libya, Oman, Qatar, Republic-of-Yemen, Saudi-Arabia, Syria, United-Arab-Emirates); Rhinocort (Korea, Israel); Rinaze (South-Africa); Vancenase (US); Vanceril (US); Viarex (Bahrain, Cyprus, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Libya, Oman, Qatar, Republic-of-Yemen, Saudi-Arabia, Syria, United-Arab-Emirates; Benin, Burkina-Faso, Ethiopia, Gambia, Ghana, Guinea, Ivory-Coast, Kenya, Liberia, Malawi, Mali, Mauritania, Mauritius, Morocco, Niger, Nigeria, Senegal, Seychelles, Sierra-Leone, South-Africa, Sudan, Tanzania, Tunia, Uganda, Zambia, Zimbabwe, Israel); Viarox (South-Africa); Xiten (Peru);
(International brand names outside U.S. in italics)

Beclomethasone Dipropionate (Intranasal)

DESCRIPTION :

Nasal Inhalation

Beclomethasone dipropionate is a white to creamy white, odorless powder a molecular weight of 521.25 (double strength 521.05). It is very slightly soluble in water, very soluble in chloroform, and freely soluble in acetone and in alcohol.

Beclomethasone dipropionate nasal inhalers are pressurized metered-dose aerosol units containing a microcrystalline suspension of beclomethasone dipropionate-trichloromonofluoromethane clathrate in a mixture of propellants (trichloromonofluoromethane and dichlorodifluoromethane) with oleic acid. Each canister contains beclomethasone dipropionate-trichloromonofluoromethane clathrate having a molecular proportion of beclomethasone dipropionate to trichloromonofluoromethane between 3:1 and 3:2.

Beconase Nasal Inhaler : Each actuation delivers from the compact actuator a quantity of clathrate equivalent to 42 mug of beclomethasone dipropionate. The contents of one 6.7 g-nasal inhaler canister provide at least 80 metered doses and the contents of one 16.8 g-nasal inhaler canister provide at least 200 metered doses.

Nasal Spray

Beclomethasone dipropionate, monohydrate is a white to creamy-white, odorless powder with a molecular weight of 539.06. It is very slightly soluble in water, very soluble in chloroform, and freely soluble in acetone and in alcohol.

This form is a metered-dose, manual pump spray unit containing a microcrystalline suspension of beclomethasone dipropionate, monohydrate equivalent to 0.042% w/w beclomethasone dipropionate calculated on the dried basis in an aqueous medium containing microcrystalline cellulose, carboxymethylcellulose sodium, dextrose, benzalkonium chloride, polysorbate 80, and 0.25% v/w phenylethyl alcohol; hydrochloric acid may be added to adjust pH. The pH is between 4.5 and 7.0.

After initial priming (3 to 4 actuations), each actuation of the pump delivers from the nasal adapter 100 mg of suspension containing beclomethasone dipropionate, monohydrate equivalent to 42 mug of beclomethasone dipropionate. Each bottle of Beconase AQ nasal spray delivers at least 200 metered doses.

CLINICAL PHARMACOLOGY :

Beclomethasone 17,21-dipropionate is a diester of beclomethasone, a synthetic halogenated corticosteroid. Animal studies show that beclomethasone dipropionate has potent glucocorticoid and weak mineralocorticoid activity.

The mechanisms responsible for the anti-inflammatory action of beclomethasone dipropionate are unknown. The precise mechanism of the aerosolized drug’s action in the nose is also unknown. Biopsies of nasal mucosa obtained during clinical studies showed no histopathologic changes when beclomethasone dipropionate was administered intranasally.The effect of beclomethasone dipropionate on hypothalamic-pituitary-adrenal (HPA) function have been evaluated in adult volunteers by other routes of administration. Studies with beclomethasone dipropionate by the intranasal route which may demonstrate that there is more or that there is less absorption by this route of administration. There was no suppression of early morning plasma cortisol concentrations when beclomethasone dipropionate was administered in a dose of 1000 mug per day for 1 month as an oral aerosol or for 3 days by IM injection. However, partial suppression of plasma cortisol concentration was observed when beclomethasone dipropionate was administered in doses of 2000 mug per day either by oral aerosol or intramuscular injection form. Immediate suppression of plasma cortisol concentrations was observed after single doses of 4000 mug of beclomethasone dipropionate. Suppression of HPA function (reduced early morning plasma cortisol levels) has been reported in adult patients who received 1600-mug daily doses of oral beclomethasone dipropionate for 1 month. In clinical studies using beclomethasone dipropionate intranasally, there was no evidence of adrenal insufficiency.

The effect of beclomethasone dipropionate nasal spray on HPA function was not evaluated but would not be expected to differ from intranasal beclomethasone dipropionate aerosol.

In one study in asthmatic children, the administration of inhaled beclomethasone at recommended daily doses for at least 1 year was associated with a reduction in nocturnal cortisol secretion. The clinical significance of this finding is not clear. It reinforces other evidence, however, that topical beclomethasone may be absorbed in amounts that can have systemic effects and that physicians should be alert for evidence of systemic effects, especially in chronically treated patients (see PRECAUTIONS).

Beclomethasone dipropionate is sparingly soluble. When given by nasal inhalation in the form of an aqueous or aerosolized suspension, the drug is deposited primarily in the nasal passages. A portion of the drug is swallowed. Absorption occurs rapidly from all respiratory and gastrointestinal tissues. There is no evidence of tissue storage of beclomethasone dipropionate or its metabolites. In vitro studies have shown that tissue other than the liver (lung slices) can rapidly metabolize beclomethasone dipropionate to beclomethasone 17- monopropionate and more slowly to free becloethasone (which has very weak anti-inflammatory activity). However, irrespective of the route of entry, the principal route of excretion of the drug and its metabolites is the feces. In humans, 12% to 15% of an orally administered dose of beclomethasone dipropionate is excreted in the urine as both conjugated and free metabolites of the drug.

Studies have shown that the degree of binding to plasma proteins is 87%.

INDICATIONS AND USAGE :

Beclomethasone dipropionate nasal inhaler and nasal spray is indicated in the relief of the symptoms of seasonal or perennial allergic and nonallergic (vasomotor) rhinitis in those cases poorly responsive to conventional treatment.

Results from two clinical trials have shown that significant symptomatic relief was obtained within 3 days. However, symptomatic relief may not occur in some patients for as long as 2 weeks. Beclomethasone dipropionate nasal spray should not be continued beyond 3 weeks in the absence of significant symptomatic improvement. Beclomethasone dipropionate nasal spray should not be used in the presence of untreated localized infection involving the nasal mucosa.

Beclomethasone dipropionate nasal inhaler and spray is also indicated for the prevention of recurrence of nasal polyps following surgical removal.

Clinical studies using the nasal inhalation aerosol in patients with seasonal or perennial rhinitis have shown that improvement is usually apparent within a few days. However, symptomatic relief may not occur in some patients for as long as 2 weeks. Although systemic effects are minimal at recommended doses, beclomethasone dipropionate nasal inhaler and nasal spray should not be continued beyond 3 weeks in the absence of significant systematic improvement. Beclomethasone dipropionate nasal inhaler and nasal spray should not be used in the presence of untreated localized infection involving the nasal mucosa.

Clinical studies have shown that treatment of the symptoms associated with nasal polyps may be continued for several weeks or more before a therapeutic result can be fully assessed. Recurrence of symptoms due to polyps can occur after stopping treatment, depending on the severity of the disease.

CONTRAINDICATIONS :

Hypersensitivity to any of the ingredients of this preparation contraindicates its use.

WARNINGS :

The replacement of a systemic corticosteroid with beclomethasone dipropionate nasal inhaler or spray can be accompanied by signs of adrenal insufficiency.

Careful attention must be given when patients previously treated for prolonged periods with systemic corticosteroids are transferred to beclomethasone dipropionate nasal inhaler or spray. This is particularly important in those patients who have associated asthma or other clinical conditions where too rapid a decrease in systemic corticosteroids may cause a severe exacerbation of their symptoms.

Studies have shown that combined administration of alternate-day prednisone systemic treatment and orally inhaled beclomethasone dipropionate increases the likelihood of HPA suppression compared to a therapeutic dose of either one alone. Therefore, nasal forms of beclomethasone dipropionate should be used with caution in patients already on alternate day prednisone regimens for any disease.

If recommended doses of intranasal beclomethasone are exceeded or if individuals are particularly sensitive or predisposed by virtue of recent systemic steroid therapy, symptoms of hypercorticism may occur, including very rare cases of menstrual irregularities, acneform lesions, cataracts, and cushingoid features. If such changes occur, this drug should be discontinued slowly consistent with accepted procedures for discontinuing oral steroid therapy.

Persons who are on drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in nonimmune children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care should be taken to avoid exposure of these infectious agents. How the dose, route, and duration of corticosteroid administration affects the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk of developing a more severe infection is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscualr immunoglobulin (IG), may be indicated. (See the respective product information for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered.

PRECAUTIONS :

General

During withdrawal from oral steroids, some patients may experience symptoms of withdrawal (e.g., joint and/or muscular pain, lassitude, and depression).

Rarely, immediate hypersensitivity reactions may occur after the intranasal administration of beclomethasone (see ADVERSE REACTIONS).

Rare instances of nasal septum perforation have been spontaneously reported.

Rare instances of wheezing, cataracts, glaucoma, and increased intraocular pressure have been reported following the intranasal application of beclamthasone.

In clinical studies with beclomethasone dipropionate administered intranasally, the development of localized infections of the nose and pharynx with Candida albicans has occurred only rarely. When such an infection develops, it may require treatment with appropriate local therapy or discontinued use of treatment.

If persistent nasopharyngeal irritation occurs, it may be an indication for stopping beclomethasone dipropionate administered intranasally.

Beclomethasone dipropionate is absorbed into the circulation. Use of excessive doses may suppress HPA function.

This drug should be used with caution, if at all, in patients with active or quiescent tuberculous infections of the respiratory tract; untreated fungal, bacterial, or systemic viral infections; or ocular herpes simplex.

For intranasal forms of beclomethasone dipropionate to be effective in the treatment of nasal polyps, the aerosol or spray must be able to enter the nose. Therefore, treatment of nasal polyps with beclomethasone dipropionate should be considered adjunctive therapy to surgical removal and/or the use of other medications which will permit effective penetration of this drug into the nose. Nasal polyps may recur after any form of treatment.

As with any long-term treatment, patients using intranasal beclomethasone dipropionate over several months or longer should be examined periodically for possible changes in the nasal mucosa.

Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septal ulcers, nasal surgery, or trauma should not use a nasal corticosteroid until healing has occurred.

Although systemic effects have been minimal with recommended doses, this potential increases with excessive doses. Therefore, larger than recommended doses should be avoided.

Information for the Patient

Patients being treated with beclomethasone dipropionate should receive the following information and instructions. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.

Patients should use beclomethasone dipropionate at regular intervals since its effectiveness depends on their regular use. The patient should take the medication as directed. It is not acutely effective, and the prescribed dosage should not be increased. Instead, nasal vasoconstrictors or oral antihistamines may be needed until the effects of this drug are fully manifested. One to 2 weeks may pass before relief is obtained. The patient should contact the doctor if symptoms do not improve, or if the condition worsens, or if sneezing or nasal irritation occurs. For the proper use of this unit and to attain maximum improvement, the patient should read and follow carefully the accompanying patient’s instructions.

Persons who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles and, if exposed, medical advice should be sought without delay.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Treatment of rats for a total of 95 weeks, 13 weeks by inhalation and 82 weeks by the oral route, resulted in no evidence of carcinogenic activity. Mutagenic studies have not been performed.

Impairment of fertility, as evidenced by inhibition of the estrous cycle in dogs, was observed following treatment by the oral route. No inhibition of the estrous cycle in dogs was seen following treatment by the inhalation route.

Pregnancy Category C

Teratogenic Effects : Like other corticoids, parenteral (subcutaneous) beclomethasone dipropionate has shown to be teratogenic and embryocidal in the mouse and rabbit when given in doses approximately 10 times the human dose. In these studies beclomethasone was found to produce fetal resorption, cleft palate, agnathia, microstomia, absence of tongue, delayed ossification, and agenesis of the thymus. No teratogenic or embryocidal effects have been seen in the rat when beclomethasone dipropionate was administered by inhalation at 10 times the human dose or orally at 1000 times the human dose. There are no adequate and well-controlled studies in pregnant women. Beclomethasone dipropionate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects : Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully observed.

Nursing Mothers

It is not known whether beclomethasone dipropionate is excreted in human milk. Because other corticosteroids are excreted in human milk, caution should be exercised when beclomethasone dipropionate nasal spray is administered to a nursing woman.

Pediatric Use

Nasal Spray : The safety and effectiveness of beclomethasone dipropionate nasal spray have been established in children aged 6 years and above through evidence from extensive clinical use in adult and pediatric patients. The safety and effectiveness of beclomethasone dipropionate nasal spray in children below 6 years of age have not been established.

Glucocorticoids have been shown to cause a reduction in growth velocity in children and teenagers with extended use. If a child or teenager on any glucocorticoid appears to have growth suppression, the possibility that they are particularly sensitive to this effect of glucocorticoids should be considered.

Nasal Inhalation : Safety and effectiveness in children below 6 years of age have not been established.

ADVERSE REACTIONS :

Nasal Inhaler

In general, side effects in clinical studies have been primarily associated with the nasal mucous membranes.

Adverse reactions reported in controlled clinical trials and long-term open studies in patients treated with beclomethasone dipropionate nasal inhaler are described below.

Sensations of irritation and burning in the nose (11 per 100 patients) following the use of beclomethasone dipropionate nasal inhaler have been reported. Also, occasional sneezing attacks (10 per 100 adult patients) have occurred immediately following the use of the intranasal inhaler. This symptom may be more common in children. Rhinorrhea may occur occasionally (1 per 100 patients).

Localized infections of the nose and pharynx with Candida albicans have occurred rarely (see PRECAUTIONS).

Transient episodes of epistaxis have been reported in 2 per 100 patients.

Rare cases of ulceration of the nasal mucosa and instances of nasal septum perforation have been spontaneously reported (see PRECAUTIONS).

Reports of headache, light-headedness, dryness and irritation of the nose and throat, and unpleasant taste and smell have been received. There are rare reports of loss of taste and smell.

Rare instances of wheezing, cataracts, glaucoma and increased intraocular pressure have been reported following the intranasal application of aerosolized corticosteroids (see PRECAUTIONS).

Rare cases of immediate and delayed hypersensitivity reactions, including urticaria, angioedema, rash, and bronchospasm, have been reported following the oral and intranasal inhalation of beclomethasone.

Systemic corticosteroid side effects were not reported during the controlled clinical trials. If recommended doses are exceeded, however, or if individuals are particularly sensitive, symptoms of hypercorticism (i.e., Cushing’s syndrome, could occur).

Nasal Spray

In general, side effects in clinical studies have been primarily associated with irritation of the nasal mucous membranes. Rare cases of immediate and delayed hypersensitivity reactions, including urticaria, angioedema, rash, and bronchospasm, have been reported following the oral and intranasal inhalation of beclomethasone dipropionate.

Adverse reactions reported in controlled clinical trials and open studies in patients treated with beclomethasone dipropionate nasal spray are described below.

Mild nasopharyngeal irritation following the use of beclomethasone aqueous nasal spray has been reported in up to 24% of patients treated, including occasional sneezing attacks (about 4%) occurring immediately following use of the spray. In patients experiencing these symptoms, none had to discontinue treatment. The incidence of transient irritation and sneezing was approximately the same in the group of patients who received placebo in these studies, implying that these complaints may be related to vehicle components of the formulation.

Fewer than 5 per 100 patients reported headache, nausea, or lightheadedness following the use of beclomethasone dipropionate nasal spray. Fewer than 3 per 100 patients reported nasal stuffiness, nosebleeds, rhinorrhea, or tearing eyes.

Rare cases of ulceration of the nasal mucosa and instances of nasal septum perforation have been spontaneously reported (see PRECAUTIONS).

Reports of dryness and irritation of the nose and throat, and unpleasant taste and smell have been received. There are rare reports of loss of taste and smell.

Rare instances of wheezing, cataracts, glaucoma, and increased intraocular pressure have been reported following the use of intranasal beclomethasone (see PRECAUTIONS).

OVERDOSAGE :

When used at excessive doses, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. If such changes occur, beclomethasone dipropionate intranasal should be discontinued slowly consistent with accepted procedures for discontinuing oral steroid therapy. The oral LD50 of beclomethasone dipropionate is greater that 1 g/kg in rodents. One canister of beclomethasone dipropionate nasal inhaler contains 8.4 mg of beclomethasone dipropionate, and one bottle of beclomethasone dipropionate nasal spray contains beclomethasone dipropionate, monohydrate equivalent to 10.5 mg of beclomethasone dipropionate; therefore, acute overdosage is unlikely.

DOSAGE AND ADMINISTRATION :

In patients who respond to beclomethasone dipropionate nasal inhaler and nasal spray, an improvement of the symptoms of seasonal or perennial rhinitis usually becomes apparent within a few days after the start of therapy. However, symptomatic relief may not occur in some patients for as long as 2 weeks. Beclomethasone dipropionate nasal inhaler and nasal spray should not be continued beyond 3 weeks in the absence of significant symptomatic improvement.

The therapeutic effect of corticosteroids, unlike those of decongestants, are not immediate. This should be explained to the patient in advance in order to ensure cooperation and continuation of treatment with the prescribed dosage regimen.

In the presence of excessive nasal mucous secretion or edema of the nasal mucosa, the drug may fail to reach the site of intended action. In such cases it is advisable to use a nasal vasoconstrictor during the first 2 to 3 days of beclomethasone dipropionate therapy.

Nasal Inhaler

Adults and Children 12 Years of Age and Older : The usual dosage is one inhalation (42 mug) in each nostril two to four times a day (total dose, 168 to 336 mug per day). Patients can often be maintained on a maximum dose of one inhalation in each nostril three times a day (252 mug per day).

Children 6 to 12 Years of Age : The usual dosage is one inhalation in each nostril three times a day (252 mug per day). This product is not recommended for children under 6 years of age since safety and efficacy studies have not been conducted in this age-group.

Nasal Spray

Adults and Children 12 Years of Age and Older : The usual dosage is one or two inhalations (42 to 84 mug) in each nostril twice a day (total dose, 168 to 336 mug per day).

Children 6 to 12 Years of Age : Patients should be started with one inhalation in each nostril twice a day; patients not adequately responding to 168 mug or those with more severe symptoms may use 336 mug (two inhalations in each nostril). Beclomethasone dipropionate nasal spray is not recommended for children below 6 years of age.

HOW SUPPLIED :

Nasal Inhalers : CONTENTS UNDER PRESSURE. Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw container in fire or incinerator. Keep out of reach of children.
Store between 2-30°C (36-86°F). As with most inhaled medications in aerosol canisters, the therapeutic effect of this medication may decrease when the canister is cold. Shake well before using.
Nasal Spray : Store between 15-30°C (59-86°F). Shake well before each use.

Beclomethasone Dipropionate (Oral)

DESCRIPTION :

Beclomethasone dipropionate is an anti-inflammatory corticosteroid having the chemical name 9-chloro-11beta,17,21-trihydroxy-16beta-methylpregna-1,4-diene-3,20-dione17,21-dipropionate. Beclomethasone 17,21-dipropionate is a diester of beclomethasone, a synthetic corticosteroid which is chemically related to dexamethasone. Additional Information for Vanceril 84 mug Oral Inhalation: Beclomethasone differs from dexamethasone only in having a chlorine at the 9alpha carbon in place of fluorine and in having a 16beta-methyl group instead of a 16alpha-methyl group.

Beclomethasone dipropionate is a white to creamy-white, odorless powder with a molecular formula of C28H37ClO7 and a molecular weight of 521.05. It is very slightly soluble in water, very soluble in chloroform, and freely soluble in acetone and in alcohol.

Beclomethasone dipropionate oral and nasal inhalers are pressurized metered-dose aerosol units containing a microcrystalline suspension of beclomethasone dipropionate-trichloromonofluoromethane clathrate in a mixture of propellants (trichloromonofluoromethane and dichlorodifluoromethane) with oleic acid. Each canister contains beclomethasone dipropionate-trichloromonofluoromethane clathrate having a molecular proportion of beclomethasone dipropionate to trichloromonofluoromethane between 3:1 and 3:2.

Beclovent 42 mug Inhalation Aerosol : Each actuation delivers a quantity of clathrate equivalent to 42 mug of beclomethasone dipropionate from the mouthpiece and 50 mug from the valve. The contents of one 6.7-g canister provide at least 80 oral inhalations, and the contents of one 16.8-g canister provide at least 200 oral inhalations.

Vanceril 84 mug Inhalation Aerosol : Each actuation delivers a quantity of clathrate equivalent to 84 mug of beclomethasone dipropionate from the mouthpiece and 100 mug of beclomethasone dipropionate from the valve. The contents of the 5.4 g and 12.2 g canisters provide at 40 and 120 oral inhalations, respectively (see HOW SUPPLIED).

CLINICAL PHARMACOLOGY :

42 mug Inhalation Aerosol

Animal studies show that beclomethasone dipropionate has potent anti-inflammatory activity. When beclomethasone dipropionate was administered systemically to mice, the anti-inflammatory activity was accompanied by other features typical of glucocorticoid action, including thymic involution, liver glycogen deposition, and pituitary-adrenal suppression. After systemic administration of beclomethasone dipropionate to rats, the anti-inflammatory action was associated with little or no effect on other tests of glucocorticoid activity.

Beclomethasone dipropionate is sparingly soluble and is poorly mobilized from subcutaneous or intramuscular injection sites. However, systemic absorption occurs after all routes of administration. When given to animals in the form of an aerosolized suspension of the trichloromonofluoromethane clathrate, the drug is deposited in the mouth and nasal passages, the trachea and principal bronchi, and in the lung; a considerable portion of the drug is also swallowed. Absorption occurs rapidly from all respiratory and gastrointestinal tissues, as indicated by the rapid clearance of radioactively labeled drug from local tissues and appearance of tracer in the circulation. There is no evidence of tissue storage of beclomethasone dipropionate or its metabolites. Lung slices can metabolize beclomethasone dipropionate rapidly to beclomethasone 17-monopropionate and more slowly to free beclomethasone (which has very weak anti-inflammatory activity). However, irrespective of the route of administration (injection, oral, or aerosol), the principal route of excretion of the drug and its metabolites is the feces. Less than 10% of the drug and its metabolites is excreted in the urine. In humans, 12% to 15% of an orally administered dose of beclomethasone dipropionate was excreted in the urine as both conjugated and free metabolites of the drug.

The precise mechanisms of glucocorticoid action in asthma are unknown. Inflammation is recognized as an important component in the pathogenesis of asthma. Glucocorticoids have been shown to inhibit multiple cell types (e.g., mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils) and mediator production or secretion (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in the asthmatic response. These anti-inflammatory actions of glucocorticoids may contribute to their efficacy in asthma.

CLINICAL STUDIES :

42 mug Inhalation Aerosol

The effects of beclomethasone dipropionate on HPA function have been evaluated in adult volunteers. There was no suppression of early morning plasma cortisol concentrations when beclomethasone dipropionate was administered in a dose of 840 mug per day for 1 month as an aerosol or 1000 mug/day for 3 days by intramuscular injection. However, partial suppression of plasma cortisol concentration was observed when beclomethasone dipropionate was administered in doses of 2000 mug/day intramuscularly or 1680 mug/day by aerosol. Immediate suppression of plasma cortisol concentrations was observed after single doses of 4000 mug of beclomethasone dipropionate.

In one study the effects of beclomethasone dipropionate on HPA function were examined in patients with asthma. There was no change in basal early morning plasma cortisol concentrations or in the cortisol responses to tetracosactin (ACTH 1:24) stimulation after daily administration of 336, 672, or 1008 mug of beclomethasone dipropionate for 28 days. After daily administration of 1344 mug for 28 days, there was a slight reduction in basal cortisol concentrations and a statistically significant (P <0.01) reduction in plasma cortisol responses to tetracosactrin stimulation. Following 52 weeks of aerosol treatment with 840 mug of beclomethasone dipropionate daily, 7/115 (6%) of patients exhibited a plasma cortisol measurement below the lower limit of normal (150 nmol-1).

Clinical experience has shown that some patients with asthma who require corticosteroid therapy for control of symptoms can be partially or completely withdrawn from systemic corticosteroids if therapy with beclomethasone dipropionate aerosol is substituted. Beclomethasone dipropionate aerosol is not effective for all patients with asthma or at all stages of the disease in a given patient.

84 mug Inhalation Aerosol

The efficacy of beclomethasone dipropionate 84 mug double strength inhalation aerosol was compared with beclomethasone dipropionate inhaler (42 mug/actuation) in a 28-day randomized parallel group, double-blind, placebo-controlled study in patients with moderate to severe asthma. A total of 336 mug/day of each beclomethasone dipropionate formulation or placebo was administered based on twice daily dosing. FEV1 at endpoint (last valid visit for each patient) was regarded as the primary measure of efficacy. Beclomethasone dipropionate 84 mug double strength inhalation aerosol and beclomethasone dipropionate inhaler were both significantly more effective (p0.01) than placebo in improving FEV1 at all time points, but were not significantly different from each other at any time point (p>0.05). Thus beclomethasone dipropionate 84 mug double strength inhalation aerosol administered twice daily to give a total daily dose of 336 mug was comparable in efficacy to beclomethasone dipropionate inhaler when administered at the same total daily dose.

The effects of beclomethasone dipropionate on hypothalamic-pituitary-adrenal (HPA) function have been evaluated in adult volunteers. There was no suppression of early morning plasma cortisol concentrations when beclomethasone dipropionate was administered at a dose of 840 mug/day for 1 month as an aerosol or 1000 mug/day for 3 days by intramuscular injection. However partial suppression of plasma cortisol concentration was observed when beclomethasone dipropionate was administered at doses of 2000 mug/day intramuscularly or 1680 mug/day by aerosol. Immediate suppression of plasma cortisol concentrations was observed after single doses of 4000 mug of beclomethasone dipropionate intramuscularly.

The potential for beclomethasone dipropionate 84 mug double strength inhalation aerosol (84 mug/actuation) to cause HPA axis suppression was compared with beclomethasone dipropionate inhaler (42 mug/actuation) in a randomized, parallel, placebo- and positive controlled study. Sixty-four adult patients with moderate asthma received doses of either: 1) 420 mug twice daily of beclomethasone dipropionate 84 mug double strength; 2) 420 mug twice daily of beclomethasone dipropionate inhaler; 3) 10 mg of prednisone orally; or 4) placebo for 35.5 days. The potential for HPA axis suppression was evaluated via a cosyntropin stimulation test administered on the 36th day. In response to a 6-hour cosyntropin 250 mug infusion, there was no evidence of HPA axis suppression associated with either beclomethasone dipropionate 84 mug double strength inhalation aerosol or beclomethasone dipropionate inhaler preparations as compared with placebo. However, there were sioniflunt (p0.01) attenuations of the plasma cortisol concentration responses to cosyntropin stimulation in the prednisone-treated group compared with the placebo-treated group.

In another study with beclomethasone dipropionate inhaler, the effects of beclomethasone dipropionate on HPA function were examined in patients with asthma. There was no change in basal early morning plasma cortisol concentrations or in the cortisol responses to tetracosactrin (ACTH 1:24) stimulation after daily aerosol administration of 336, 672, or 1008 mug of beclomethasone dipropionate for 28 days. After daily aerosol administration of 1344 mug for 28 days. There was a slight reduction in basal cortisol concentrations and a statistically significant (p<<0.01) reduction in plasma cortisol responses to tetracosactrin stimulation. The effects of a more prolonged period of beclomethasone dipropionate administration on HPA function have not been evaluated.

Clinical experience has shown that some patients with asthma who require corticosteroid therapy for control of symptoms can be partially or completely withdrawn from systemic corticosteroid if therapy with beclomethasone dipropionate aerosol is substituted. Beclomethasone dipropionate aerosol is not effective for all patients with asthma or at all stages of the disease in a given patient.

INDICATIONS AND USAGE :

Beclomethasone dipropionate inhalation aerosol is indicated in the maintenance treatment of asthma as prophylactic therapy. Beclomethasone dipropionate inhalation aerosol is also indicated for asthma patients who require systemic corticosteroid administration, where adding beclomethasone dipropionate may reduce or eliminate the need for systemic corticosteroids.

Beclomethasone dipropionate is NOT indicated for the relief of acute bronchospasm.

CONTRAINDICATIONS :

Beclomethasone dipropionate inhaler is contraindicated in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required.

Hypersensitivity to any of the ingredients of this preparation contraindicates its use.

WARNINGS :

Particular care is needed in patients who are transferred from systemically active corticosteroids to beclomethasone dipropionate because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to aerosol beclomethasone dipropionate . After withdrawal from systemic corticosteroids a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infections, particularly gastroenteritis. Although beclomethasone dipropionate may provide control of asthmatic symptoms during these episodes, it does NOT provide the systemic steroid that is necessary for coping with these emergencies.

During periods of stress or a severe asthmatic attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume systemic steroids (in large doses) immediately and to contact their physician for further instruction. These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic steroids during periods of stress or a severe asthma attack. To assess the risk of adrenal insufficiency in emergency situations, routine tests of adrenal cortical function, including measurement of early morning resting cortisol levels, should be performed periodically in all patients. An early morning resting cortisol level may be accepted as normal only if it falls at or near the normal mean level.

Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in nonimmune children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care should be taken to avoid exposure of these infectious agents. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk of developing a more severe infection is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscualr immunoglobulin (IG), may be indicated. (See the respective product information for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered.

Localized infections with Candida albicans or Aspergillus niger have occurred frequently in the mouth and pharynx and occasionally in the larynx. Positive cultures for oral Candida may be present in up to 75% of patients. Although the frequency of clinically apparent infection is considerably lower, these infections can develop with any inhaled corticosteroid and may require treatment with appropriate antifungal therapy or discontinuation of treatment with beclomethasone dipropionate inhaler.

Beclomethasone dipropionate inhaler is not a bronchodilator and is not indicated for rapid relief of bronchospasm.

Patients should be instructed to contact their physicians immediately when episodes of asthma that are not responsive to bronchodilators occur during the course of treatment with beclomethasone dipropionate. During such episodes, patients may require therapy with systemic corticosteroids.

Transfer of patients from systemic steroid therapy to beclomethasone dipropionate inhaler may unmask allergic conditions previously suppressed by the systemic steroid therapy (e.g., rhinitis, conjunctivitis, and eczema).

Avoid spraying in eyes.

Additional Information for 84 mug Inhalation Aerosol

Studies have shown that the combined administration of alternate-day prednisone systemic treatment and orally inhaled beclomethasone increases the likelihood of HPA suppression compared to a therapeutic dose of either one alone.

Because of the possibility of systemic absorption of orally inhaled corticosteroids, including beclomethasone, patients should be monitored for symptoms of systemic effects such as mental distrubances, increased bruising, weight gain, cushingoid features, acneiform lesions, and cataracts. Therefore, if such changes occur, beclomethasone dipropionate inhaler should be discontinued slowly, consistent with accepted procedures for discontinuing oral steroids.

There is no evidence that control of asthma can be achieved by the administration of beclomethasone dipropionate inhalation aerosol in amounts greater than the recommended doses.

The management of asthma should follow a stepwise program, and patient response should be monitored clinically and by lung function tests. Increasing use of short-acting inhaled beta2–agonists to control symptoms indicates deterioration of asthma control. Under these conditions, the patient’s therapy plan should be reassessed. In patients considered at risk, daily flow monitoring may be instituted.

If patients find that short-acting relief bronchodilator treatment becomes less effective or they need more inhalations than usual, medical attention must be sought.

PRECAUTIONS :

General

During withdrawal from oral steroids, some patients may experience symptoms of systemically active steroid withdrawal (e.g., joint and/or muscular pain, lassitude and depression) despite maintenance or even improvement of respiratory function (see DOSAGE AND ADMINISTRATION).

In responsive patients, beclomethasone dipropionate may permit control of asthmatic symptoms without suppression of HPA function, as discussed in CLINICAL PHARMACOLOGY. Since beclomethasone dipropionate is absorbed into the circulation and can be systemically active, the beneficial effects of beclomethasone dipropionate inhalation aerosol in minimizing or preventing HPA dysfunction may be expected only when recommended dosages are not exceeded.

Pulmonary infiltrates with eosinophilia may occur in patients receiving orally inhaled beclomethasone dipropionate. Although it is possible that in some patients this state may become manifest because of systemic corticosteroid withdrawal when inhalational corticosteroids are administered, a causative role for beclomethasone dipropionate and/or its vehicle cannot be ruled out.

Additional Information for 42 mug Inhalation Aerosol

Because of the possibility of systemic absorption of orally inhaled corticosteroids, including beclomethasone, patients should be monitored for symptoms of systemic effects such as mental disturbances, increased bruising, weight gain, cushingoid features, acneiform lesions, and cataracts. Therefore, if such changes occur, beclomethasone dipropionate should be discontinued slowly, consistent with accepted procedures for discontinuing oral steroids.

Additional Information for 84 mug Inhalation Aerosol

Children should be monitored for a reduction in growth velocity, although the relationship between growth velocity and final adult height is not known.

The long-term effects of beclomethasone dipropionate in human subjects are still unknown. In particular, the local effects of the agent on developmental or immunologic processes in the mouth, pharynx, trachea, and lung are unknown. There is also no information about the possible long-term systemic effects of the agent.

This drug should be used with caution, if at all, in patients with active or quiescent tuberculous infection of the respiratory tract; untreated systemic fungal, bacterial, parasitic, or viral infections; or ocular herpes simplex.

Pregnancy Category C

42 mug Inhalation Aerosol : Like other corticosteroids, beclomethasone dipropionate was teratogenic and embryocidal in the mouse and rabbit at a subcutaneous dose of 0.1 mg/kg in mice or 0.025 mg/kg in rabbits (approximately ½ the maximum recommended daily inhalation dose in adults on a mg/m2 basis). No teratogenicity or embryocidal effects were seen in rats when exposed to an inhalation dose of 0.1 mg/kg plus oral doses of up to 10 mg/kg per day for a combined dose of 10.1 mg/kg (approximately 80 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis). There are no adequate and well-controlled studies in pregnant women. Beclomethasone dipropionate inhalation aerosol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

84 mug Inhalation Aerosol : Like other corticosteriods, parenteral (subcutaneous) beclomethasone dipropionate was teratogenic and embryocidal in the mouse or rabbit when given at a dose of 0.1 mg/kg/day in mice or at a dose of 0.025 mg/kg/day in rabbits. These doses in rats and rabbits were approximately one-half the maximum recommended human daily inhalation dose on a mg/m2 basis. No teratogenicity or embryocidal effects were seen in rats when exposed to an inhalation dose of 0.1 mg/kg plus oral doses of up to 10 mg/kg/day for combined daily dose of 10.1 mg/kg (approximately 97 times the maximum recommended human daily inhalation dose on mg/m2 basis). There are no adequate and well-controlled studies in pregnant women. Beclomethasone dipropionate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Information for the Patient

Patients being treated with beclomethasone dipropionate should receive the following information and instructions. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.

Patients should be warned to avoid exposure to chickenpox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay.

Patients should use beclomethasone dipropionate double strength inhalation aerosol at regular intervals as directed. Results of clinical trials indicated significant improvement may occur within the first day or two of treatment; however, the full benefit may not be achieved until treatment has been administered for 1 to 2 weeks or longer. The patient should not increase the prescribed dosage but should contact the physician if symptoms do not improve or if condition worsens.

Patients should also be advised that beclomethasone dipropionate double strength inhalation aerosol is not intended for use in the treatment of acute asthma. Patients should be instructed to contact their physician immediately if there is any deterioration of their asthma. Additional Information for 42 mug Inhalation Aerosol: Patients should be made aware of the prophylactic nature of therapy with inhaled beclomethasone dipropionate and that it should be taken regularly even when they are asymptomatic.

Patients should be advised to rinse his/her mouth each time after using beclomethasone dipropionate inhalation aerosol.

Beclomethasone dipropionate inhalation aerosol should not be stopped abruptly. If discontinuing use of beclomethasone dipropionate is necessary, the patient’s physician should be contacted immediately.

Additional Information for 42 mug Inhalation Aerosol : Patients should use beclomethasone dipropionate inhalation aerosol at regular intervals as directed. Results of clinical trials indicated significant improvement may occur within the first day or two of treatment; however, the full benefit may not be achieved until treatment has been administered 1 or 2 weeks or longer. The patient should not increase the prescribed dosage but should contact the physician if symptoms do not improve or if the condition worsens.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

The carcinogenicity of beclomethasone dipropionate was evaluated in rats which were exposed for a total of 95 weeks, 13 weeks at inhalation doses up to 0.4 mg/kg/day and the remaining 82 weeks at combined oral and inhalation doses up to 2.4 mg/kg/day. There was no evidence of carcinogenicity in this study at the highest dose which is approximately, for the 42 mug inhalation aerosol, 20 or 36 times the maximum recommended human daily inhalation dose on a mg/m2 basis, and 23 times for the 84 mug inhalation aerosol.

Impairment of fertility, as evidenced by inhibition of the estrous cycle in dogs, was observed following treatment by the oral route at a dose of 0.5 mg/kg/day which is approximately 16 times the maximum recommended human daily inhalation dose on a mg/m2 basis. No inhibition of the estrous cycle in dogs was seen following 12 months of exposure to beclomethasone dipropionate by the inhaltion route at an estimated daily dose of 0.33 mg/kg (approximately 11 times the maximum recommended human daily inhalation dose on a mg/m2 basis).

Additional Information for 42 mug Inhalation Aerosol

Beclomethasone dipropionate did not induce gene mutation in bacterial cells or mammalian Chinese Hamster ovary (CHO) cells in vitro . No significant clastogenic effect was seen in cultured CHO cells in vitro or in the mouse micronucleus test in vivo.

In rats, beclomethasone dipropionate caused decreased conception rates at an oral dose of 16 mg/kg (approximately 130 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis). Inhibition of the estrous cycle in dogs was observed following oral dosing at 0.5 mg/kg (approximately 15 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis). No inhibition of the estrous cycle in dogs was seen following 12 months’ exposure at an estimated daily inhalation dose of 0.33 mg/kg (approximately 9 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis).

Nursing Mothers

Corticosteriods are secreted in human milk. Because of the potential for serious adverse reactions in nursing infants from beclomethasone dipropionate, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in children below 6 years of age have not been established.

Additional Information for 42 mug Inhalation Aerosol : The safety and effectiveness of beclomethasone dipropionate inhalation aerosol have been established in children aged 6 years and above. The safety and effectiveness of beclomethasone dipropionate inhalation aerosol in children below 6 years of age have not been established. Corticosteroids have been shown to cause a reduction in growth velocity in children and teenagers with extended use. If a child or teenager on any corticosteroid appears to have growth suppression, the possibility that they are particularly sensitive to this effect of corticosteroids should be considered.

ADVERSE REACTIONS :

Deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to aerosol beclomethasone dipropionate (see WARNINGS).

Suppression of HPA function (reduction of early morning plasma cortisol levels) has been reported in adult patients who received 1344-mug daily doses (approximately twice the maximum recommended daily dose) of beclomethasone dipropionate by oral inhalation for 1 month. Some patients receiving orally inhaled beclomethasone dipropionate have complained of hoarseness or dry mouth.

42 mug Inhalation Aerosol

The following adverse events have been reported spontaneously during worlwide postmarketing surveillance. Therefore, the frequency of events and causality cannot be reliably determined. The adverse events reported in association with beclomethasone dipropionate inhalation aerosol include:

General : Immediate and delayed hypersensitivity reactions including anaphylactic/anaphylactoid reactions, angioedema, bronchospasm, rash, urticaria.
Ear, Nose, and Throat : Dryness and irritation of the nose, throat, and mouth; hoarseness; localized infections with Candida or Aspergillus ; unpleasant taste and smell; loss of taste and smell.
Endocrine and Metabolic : Cushingoid features, growth velocity reduction in children/adolescents, weight gain.
Eye : Cataracts, glaucoma, increased intraocular pressure.
Gastrointestinal : Nausea, vomiting.
Nervous : Dizziness, headache, lightheadedness.
Psychiatry : Agitation, depression, mental disturbances.
Respiratory : Paradoxical bronchospasm, wheezing.
Skin : Acneiform lesions, atrophy, bruising, pruritus, purpura, striae.

84 mug Inhalation Aerosol

In a 4-week, randomized, double-blind, placebo-controlled clinical trial, the incidence of adverse events reported for beclomethasone dipropionate double strength inhalation aerosol was similar to that reported for placebo. Adverse event rates did not appear to differ significantly based on age, sex, or race. Adverse events that were reported by 2% or more of patients receiving this drug (regardless of relationship to treatment) and that occurred more frequently than placebo are displayed in TABLE 1.

In a 4-week, randomized, double-blind clinical study, there were no reports of oral candidasis in patients receiving this drug. (See WARNINGS).

TABLE 1 Adverse Events from 4-Week Placebo-Controlled Clinical Trial in Patients With Asthma
Percent of Patients Reporting
Beclomethasone Dipropionate
84 mug
Placebo
n=103
n=109
Headache
22
18
Pharyngitis
14
8
Coughing
9
4
Infection (viral)
8
6
Nasal congestion
6
2
Dysmenorrhea
4
3
Sinusitis
4
3
Dyspepsia
3
2
Fatigue
3
2
Influenza-like symptoms
3
0
Sneezing
3
0
Eczema
2
0
Pruritus
2
<1
Respiratory disorder
2
0

 

In addition to those adverse events reported in TABLE 1, the following adverse events have been reported in fewer than 2% of patients receiving double strength beclomethasone dipropionate (regardless of relationship to treatment).

Autonomic Nervous System : Lacrimation.
Body as a Whole : Increased allergy symptoms, chest pain, fever, rigors.
Gastrointestinal: Diarrhea, nausea, rectal hemorrhage.
Hearing and Vestibula : Earache.
Heart Rate and Rhythm : Tachycardia.
Musculoskeletal : Arthralgia, pain.
Psychiatric : Depression, insomnia.
Respiratory: Bronchitis, bronchospasm, chest congestion, dysphonia, upper respiratory infection.
Skin and Appendages : Rash, skin discoloration, urticaria.
Special Senses : Taste perversion.
Urinary : Urinary tract infection.
Vascular (Extracardiac) : Migraine.
White Cell and Reticuloendothelia l: Lymphadenopathy.

Deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to aerosol beclomethasone dipropionate. (See WARNINGS.)

Rare cases of immediate and delayed hypersensitivity reactions, including urticaria, angioedema, rash, and bronchospasm, have been reported following the oral and intranasal inhalation of beclomethasones.

Rare instances of wheezing, cataracts, glaucoma, and increased intraocular pressure have been reported following the oral inhalation of beclomethasone dipropionate.

Reports of headache, light-headedness, dryness and irritation of the nose and throat, and unpleasant taste and smell have been received. There are rare reports of loss of taste and smell.

Rare case of hypercorticism, adrenal insufficiency, growth inhibitory effects, cataracts, glaucoma, and hyperglcemia have been reported with inhaled corticosteriods.

OVERDOSAGE :

42 mug Inhalation Aerosol : For maximum doses studies in humans, see CLINICAL STUDIES. Chronic overdosage may result in signs/symptoms of hypercorticism (see PRECAUTIONS). No deaths occurred when beclomethasone dipropionate was given as single oral doses of 3000 mg/kg to mice and 2000 mg/kg to rats (approximately 12,000 and 16,000 times, respectively, the maximum recommended human daily inhalation dose on a mg/m2 basis.

84 mug Inhalation Aerosol : There were no deaths over 15 days following the oral administration of a single dose of 3000 mg/kg in mice, 2000 mg/kg in rats, and 1000 mg/kg in rabbits. The doses in mice, rats, and rabbits were 14,500, 19,300, and 19,300 times, respectively, the maximum recommended human daily inhalation dose on a mg/m2 basis.

DOSAGE AND ADMINISTRATION :

42 mug Inhalation Aerosol

Adults and Children 12 Years of Age and Older : The usual recommended dosage is 2 inhalations (84 mug) given 3 or 4 times a day. Alternatively, 4 inhalations (168 mug) given twice daily has been shown to be effective in some patients. In patients with severe asthma, it is advisable to start with 12 to 16 inhalations a day (504 to 672 mug) and adjust the dosage downward according to the response of the patient. The maximal daily intake should not exceed 20 inhalations, 840 mug (0.84 mg), in adults.

Children 6 to 12 Years of Age : The usual recommended dosage is 1 or 2 inhalations (42 to 84 mug) given 3 or 4 times a day according to the response of the patient. Alternatively, 4 inhalations (168 mug) given twice daily has been shown to be effective in some patients. The maximal daily intake should not exceed 10 inhalations, 420 mug (0.42 mg), in children 6 to 12 years of age . Insufficient clinical data exist with respect to the administration of beclomethasone dipropionate inhalation in children below the age of 6.

Rinsing the mouth after inhalation is advised.

Patients receiving bronchodilators by inhalation should be advised to use the bronchodilator before beclomethasone dipropionate inhaler in order to enhance penetration of beclomethasone dipropionate into the bronchial tree. After use of an aerosol bronchodilator, several minutes should elapse before use of the beclomethasone dipropionate inhaler to reduce the potential toxicity from the inhaled fluorocarbon propellants in the two aerosols.

Different considerations must be given to the following groups of patients in order to obtain the full therapeutic benefit of beclomethasone dipropionate inhalation aerosol.

Patients Not Receiving Systemic Corticosteroids : Patients who require maintenance therapy of their asthma may benefit from treatment with beclomethasone dipropionate inhalation aerosol at the doses recommended above. In patients who respond to beclomethasone dipropionate, improvement in pulmonary function is usually apparent within 1 to 4 weeks after the start of therapy. Once the desired effect is achieved, consideration should be given to tapering to the lowest effective dose.

Patients Receiving Systemic Corticosteroids : Clinical studies have shown that beclomethasone dipropionate inhalation aerosol may be effective in the management of asthmatics dependent or maintained on systemic corticosteroids and may permit replacement or significant reduction in the dosage of systemic corticosteroids.

The patient’s asthma should be reasonably stable before treatment with beclomethasone dipropionate inhalation aerosol is started. Initially, beclomethasone dipropionate inhalation aerosol should be used concurrently with the patient’s usual maintenance dose of systemic corticosteroid. After approximately 1 week, gradual withdrawal of the systemic corticosteroid is started by reducing the daily or alternate-daily dose. Reductions may be made after an interval of 1 or 2 weeks, depending on the response of the patient. Generally, these decrements should not exceed 2.5 mg of prednisone or its equivalent. During withdrawal, some patients may experience symptoms of systemic corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, and depression) despite maintenance or even improvement of pulmonary function. Such patients should be encouraged to continue with the inhaler but should be monitored for objective signs of adrenal insufficiency, such as hypotension. If evidence of adrenal insufficiency occurs, the systemic corticosteroid doses should be increased temporarily and thereafter withdrawal should continue more slowly.

During periods of stress or a severe asthma attack, transfer patients may require supplementary treatment with systemic steroids.

Directions for Use : See the PATIENT PACKAGE INSERT.

CONTENTS UNDER PRESSURE : Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw container into fire or incinerator. Keep out of reach of children.

84 mug Inhalation Aerosol

Double strength oral inhalation aerosol should be test sprayed 2 times into the air before using for the first time and in cases where the product has not been used for more than 7 days.

Adults : The usual recommended dosage is two inhalations (168 mug) given twice daily. In patients with severe asthma, it is advisable to start with 6 to 8 inhalations a day and adjust the dosage downward according to the response of the patient. The maximal daily intake should not exceed 10 inhalations, 840 mug (0.84 mg), in adults.

Children 6 to 12 Years of Age : The usual recommended dosage is two inhalations (168 mug) given twice daily. The maximal daily intake should not exceed 5 inhalations, 420 mug (0.42 mg), in children 6 to 12 years of age. Insufficient clinical trial data exist with respect to the administration of beclomethasone dipropionate in children below the age of 6.

Rinsing the mouth after inhalation is advised.

Treatment with beclomethasone dipropionate inhalation aerosol should not be stopped abruptly.

Different considerations must be given to the following groups of patients in order to obtain the full therapeutic benefit of beclomethasone dipropionate inhaler.

Patients Not Receiving Systemic Steroids : Patients who require maintenance therapy of their asthma may benefit from treatment with 84 mug beclomethasone dipropionate inhalation aerosol at the doses recommended above. In patients who respond to beclomethasone dipropionate, an improvement in pulmonary function is usually apparent within 1 to 4 weeks after the start of beclomethasone dipropionate inhaler. Once the desired effect is achieved, consideration should be given to tapering to the lowest effective dose.

Patients Receiving Systemic Steroids : Clinical studies have shown that beclomethasone dipropionate may be effective in the management of asthmatics dependent or maintained on systemic corticosteriods and may permit replacement or significant reduction in the dosage of systemic corticosteriods.

The patient’s asthma should be reasonably stable before treatment with beclomethasone dipropionate inhaler is started. Initially, the aerosol should be used concurrently with the patient’s usual maintenance dose of systemic corticosteroid. After approximately 1 week, gradual withdrawal of the systemic corticosteroid is started by reducing the daily or alternate-daily dose. The next reduction is made after an interval of 1 or 2 weeks, depending on the response of the patient. Generally, these decrements should not exceed 2.5 mg of prednisone or its equivalent. A slow rate of withdrawal cannot be overemphasized. During withdrawal some patients may experience symptoms of systemical corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, and depression) despite maintenance or even improvement in pulmonary function. Such patients should be encouraged to continue with the inhaler but should be monitored carefully for objective signs of adrenal insufficiency, such as hypotension and weight loss. If evidence of adrenal insufficiency occurs, the systemic corticosteroid dose should be increased temporarily and thereafter further withdrawal should continue more slowly.

During periods of stress or a severe asthma attack, transfer patients will require supplementary treatment with systemic steroids.

PATIENT PACKAGE INSERT :

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

The refill canister is to be used only with the tan Beclovent inhalation aerosol mouthpiece.

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

The Beclovent inhalation aerosol canister should only be used with the Beclovent inhalation aerosol mouthpiece. This mouthpiece should not be used with any other inhalation drug product. Similarly, the canister should not be used with other mouthpieces.

2. It is recommended to “test spray” into the air before using for the first time and in cases where the aerosol has not been used for a prolonged period of time.

3. Avoid spraying in the eyes.

4. BREATHE OUT FULLY THROUGH THE MOUTH, expelling as much air from your lungs as you comfortably can. Place the mouthpiece fully into the mouth, holding the inhaler in the mouthpiece down position and closing the lips around it.

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

6. When you have finished breathing in, HOLD YOUR BREATH AS LONG AS you comfortably can. Before breathing out, remove the inhaler from your mouth and release your finger from the canister.

7. Wait 1 minute and SHAKE the inhaler again. Repeat steps 4 through 6 for each inhalation prescribed by your doctor.

8. It is recommended that you rinse your mouth thoroughly with water, gargle, or drink water after inhalation(s), whenever possible.

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

10. DISCARD THE CANISTER AFTER the date calculated by your doctor or pharmacist. The correct amount of medication in each inhalation cannot be assured after 200 actuations from the 16.8 g-canister or 80 actuations from the 6.7 g-canister even though the canister is not completely empty. You should keep track of the number of actuations used form each canister of Beclovent inhalation aerosol, and discard the canister after 200 actuations from the 16.8 g-canister or 80 actuations from the 6.7 g-canister. Before the discard date you should consult your doctor to determine whether a refill is needed. Just as you should not take extra doses without consulting doctor, you also should not stop Beclovent inhalation aerosol without consulting your doctor.

Dosage : Use only as directed by your doctor.

Warning : This inhaler contains medication that is intended for treatment of your asthma. It does not contain medication intended to provide rapid relief of your breathing difficulties during an asthma attack. It is essential that you use this medication regularly at the intervals recommended by your doctor, and not as an emergency measure. Your doctor will decide whether other medication is needed should you require immediate relief. If you also use another medicine by inhalation, you should consult your doctor for instructions on when to use it in relation to using Beclovent inhalation aerosol.

Contents Under Pressure : Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw container into fire or incinerator. Keep out of reach of children. Avoid spraying in eyes.

Store between 2-30°C (36-86°F). As with most medications in aerosol canisters, the therapeutic effect of this medication may decrease when the canister is cold. For best results, the canister should be at room temperature before use. Shake well before using.

Note : The warning below is required by the Federal government’s Clean Air Act for all products containing or manufactured with Chlorofluorocarbons (CFCs).

WARNING : Contains trichloromonofluoromethane (CFC-11) and dichlorodifluoromethane (CFC-12), substances which harm public health and environment by destroying ozone in the upper atmosphere.

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

PATIENT INFORMATION :

Beclomethasone Dipropionate is a corticosteroid. The oral inhaler is used to prevent the symptoms of asthma. Beclomethasone will not treat an acute asthma attack. The nasal inhaler and nasal spray are used to relieve the symptoms of hayfever and to prevent nasal polyps from growing back after they have been surgically removed. Immediate results do not occur with this medication. To be effective, beclomethasone needs to be used on a regular basis. It is important that beclomethasone oral inhaler, nasal inhaler, and nasal spray are administered using the proper technique. Please obtain detailed administration directions from your pharmacist or physician. Inform your physician if you are pregnant or nursing. Rinse your mouth or drink a glass of water after using the oral inhaler. Blow your nose before using the nasal inhaler or nasal spray. The oral inhaler my cause a sore throat or sore mouth. The nasal inhaler or spray may irritate and dry the nasal mucosa. Notify your physician if these occur.

HOW SUPPLIED :

Beclovent 42 mug Inhalation Aerosol

Each actuation delivers a quantity of clathrate equivalent to 42 mug of belomethasone dipropionate from the mouthpiece and 50 mug form the valve.

The Beclovent inhalation aerosol canister should only be used with the tan Beclovent inhalation aerosol mouthpiece, and this mouthpiece should not be used with any other inhalation product. A dark brown cap fits over the mouthpiece when not in use.

The correct amount of medication in each inhalation cannot be assured after 80 inhalations from the 6.7 g-canister or 200 inhalations from the 16.8 g-canister even though the canister is not completely empty. The canister should be discarded when the labeled number of actuations have been used.

Storage : Store between 2-30°C (36-86°F). As with most inhaled medications in aerosol canisters, the therapeutic effect of this medication may decrease when the canister is cold. For optimal results, the canister should be at room temperature before use. Shake well before using.

Note : The warning below is required by the Federal government’s Clean Air Act for all products containing or manufactured with Chlorofluorocarbons (CFCs).

WARNING : Contains trichloromonofluoromethane (CFC-11) and dichlorodifluoromethane (CFC-12), substances which harm public health and environment by destroying ozone in the upper atmosphere.

Vanceril 84 mug Double Strength Inhalation Aerosol

12.2 g-canisters contain 120 metered inhalations. 5.4 g-canisters contain 40 metered inhalations for instutional use only. Each canister is supplied with a dark-pink plastic actuator with a maroon cap and Patient’s Instructions for Use. Each actuation delivers an amount of beclomethasone dipropionate-trichloromonofluoromethane clathrate equivalent to 84 mug of beclomethasone dipropionate from the mouthpiece and 100 mug of beclomethasone dipropionate from the valve.

Vanceril 84 mug double strength inhalation aerosol should only be used with the Vanceril 84 mug double strength inhalation aerosol mouthpiece and this mouthpiece should not be used with any other inhalation drug product.

The correct amount of medication in each inhalation cannot be assured after 120 actuations from the 12.2 g-canister or 40 actuations from the 5.4 g-canister even though the canister is not completely empty. The canister should be discarded when the labeled number of actuations have been used.

Store at 15-30°C (59-86°F). Protect from moisture and unusual temperature fluctuations. Failure to use the product within this temperature range may result in improper dosing. For optimal results, the canister should be at room temperature before use. Shake well before using. Once canister is removed from the moisture protective package the product must be used within 6 months.

Store between 2-30°C (36-86°F). As with most inhaled medications in aerosol canisters, the therapeutic effect of this medication may decrease when the canister is cold. Shake well before using.

WARNING : Contains trichloromonofluoromethane (CFC-11) and dichlorodifluoromethane (CFC-12), substances which harm public health and environment by destroying ozone in the upper atmosphere.

CONTENTS UNDER PRESSURE. Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw container in fire or incinerator. Keep out of reach of children.

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