Beclomethasone Dipropionate

AHFS Class: Adrenals (68:04)

ATC Class: H02AB
Molecular Formula: C₂₈H₃₇ClO₇

View the associated Essentials monograph.

Introduction

Beclomethasone dipropionate is a synthetic corticosteroid. ^{1 2 149}

See Uses in the associated General Statement for more information.

Uses

Asthma

Beclomethasone dipropionate is used by oral inhalation for the long-term prevention of bronchospasm in patients with asthma. ^{1 2 8 21 24 25 26 103 112 113 116 144 147 149 152} In the stepped-care approach to antiasthmatic drug therapy, maintenance therapy with low doses of an inhaled corticosteroid is the preferred treatment for adults and children with mild persistent asthma (i.e., patients with daytime symptoms of asthma more than twice per week, but less than once daily, and nocturnal symptoms of asthma more than twice per month).^{147 152} When daily asthmatic symptoms (moderate persistent asthma) develop, a long-acting β₂-agonist (e.g., formoterol, salmeterol) added to low- to medium-dose inhaled corticosteroids is the preferred therapy; alternatively, maintenance dosage of the inhaled corticosteroid can be increased (e.g., doubled) within the medium-dosage range.^{147 152} Maintenance therapy with an inhaled corticosteroid in high dosages, an inhaled long-acting β₂-agonist, and, if needed, oral corticosteroids is the preferred treatment for adults and children with severe persistent asthma (i.e., patients with continuous daytime and frequent nocturnal symptoms of asthma).¹⁵² Use of orally inhaled beclomethasone dipropionate as adjunctive therapy in patients who require chronic administration of systemic corticosteroids to control asthma symptoms may permit a reduction in dosage or discontinuance of systemic corticosteroids.^{1 24 70 103 116} For additional details on the stepped-care approach to drug therapy in asthma,^{145 146 147 148 152} seeAsthma under Uses: Bronchospasm, in Albuterol 12:12.08.12 and see Asthma under Uses: Respiratory Diseases, in the Corticosteroids General Statement 68:04.

Well-controlled clinical studies have shown that oral inhalation of beclomethasone dipropionate relieves symptoms of bronchial asthma (cough, dyspnea, wheezing) and improves lung function (e.g., forced expiratory volume in 1 second [FEV₁]) in most adults and children.^{6 7 8 9 10 11 12 13 14 15 16 17 103 116 149 155 156} Although some improvement may occur shortly after therapy is initiated,^{101 149} optimum symptomatic relief may require 1–4 weeks of continuous beclomethasone dipropionate oral inhalation therapy in patients who have not previously received systemic corticosteroid therapy.^{1 2 61 77 100 112 113 144 149} In corticosteroid-dependent asthmatic patients being switched to beclomethasone dipropionate oral inhalation therapy, withdrawal of systemic corticosteroid therapy and management of asthma with orally inhaled beclomethasone dipropionate may be delayed, since recovery from hypothalamic-pituitary-adrenal (HPA) axis suppression occurs slowly.^{1 2 100 103 112 113 149} Clinical studies have shown that therapy with orally inhaled beclomethasone dipropionate may allow eventual dosage reduction or total replacement of systemic corticosteroid therapy.^{1 2 6 8 9 10 11 12 18 21 22 23 24 25 26 27 100 103 112 113 116 144 149}

Beclomethasone dipropionate oral inhalation therapy should not be used in the treatment of nonasthmatic bronchitis.^{1 28 112 113 144} Oral inhalation of beclomethasone dipropionate is contraindicated in the primary treatment of severe acute asthmatic attacks or status asthmaticus when intensive measures^{1 2 29 112 113 149} (e.g., oxygen, parenteral bronchodilators, IV corticosteroids)¹⁴⁷ are required. Beclomethasone dipropionate oral inhaler is not a bronchodilator, and patients should be warned that the drug should not be used for rapid relief of bronchospasm.^{1 2 103 112 113 144 149} Beclomethasone dipropionate oral inhalation therapy is not effective for all patients with bronchial asthma^{1 2 103 112 113 144 149} (e.g., in patients with bronchorrhea or severe pulmonary obstruction when proper penetration of the drug into the lungs is prevented).¹⁰⁵ In addition, the drug is not always effective at all stages of the disease in a particular patient.^{1 2 112 113 144 149}

When beclomethasone dipropionate is administered by oral inhalation, the principal sites of action are the bronchi and bronchioles.¹⁴⁹ Limited data suggest that substantially more drug is deposited into the airways of the lung and less reaches the oropharynx with beclomethasone dipropionate inhalation aerosols containing tetrafluoroethane (HFA-134a, a non-chlorofluorocarbon [CFC] propellant) (QVAR^®) than with inhalation aerosols containing CFC propellant (e.g., Beclovent^®, Vanceril ^®, Vanceril ^® Double Strength; all no longer commercially available in the US).^{153 154 155 159} In clinical studies of 6 weeks’ to 12 months’ duration, treatment with beclomethasone dipropionate with non-CFC propellant, administered at approximately half the daily dosage of beclomethasone dipropionate with CFC propellant, ¹⁴⁹ was associated with similar efficacy (i.e., control of moderate or moderately severe asthma) and safety; however, a definitive comparative therapeutic ratio has not been demonstrated to date.^{149 153 154 155 157} Unlike dexamethasone sodium phosphate, beclomethasone dipropionate appears to have higher topical anti-inflammatory activity with fewer adverse systemic effects following oral inhalation;^{14 29 30} however, no direct comparison of the adverse effects of these drugs has been performed.

In corticosteroid-dependent patients, use of beclomethasone dipropionate oral inhalation therapy usually permits a substantial reduction in the daily maintenance dosage of the systemic corticosteroid,^{1 2 6 8 9 10 11 12 18 21 22 23 24 25 26 27 100 103 112 113 116 144 149} conversion from daily to alternate-day corticosteroid therapy,^{24 25 26 149} or gradual discontinuance of corticosteroid maintenance dosages.^{6 8 9 18 21 22 23 24 25 26 27 103 116 149} (See Cautions: Hypothalamic-Pituitary-Adrenal [HPA] Axis Suppression.)

In the management of asthma, the need for single- vs multiple-drug therapy must be determined on an individual basis.^{56 103} Beclomethasone dipropionate oral inhalation therapy has been administered to patients receiving bronchodilator and/or cromolyn sodium therapy.^{6 7 12 13 32 87 88 109 124} In a well-controlled study in corticosteroid-dependent asthmatic patients receiving either orally inhaled beclomethasone dipropionate or alternate-day prednisone, the addition of theophylline to either regimen at dosages that maintained therapeutic serum theophylline concentrations resulted in greater symptomatic relief and improved pulmonary function compared with therapy that did not include theophylline.⁸⁷ In several controlled studies in asthmatic patients, concurrent therapy with orally inhaled beclomethasone dipropionate and cromolyn sodium did not provide a clinical advantage over beclomethasone dipropionate therapy alone;^{88 109} however, in an uncontrolled study, symptomatic relief of bronchial asthma was greater during concurrent therapy with orally inhaled beclomethasone dipropionate and cromolyn sodium than with either drug alone.³²

Other Uses

The efficacy of orally inhaled beclomethasone dipropionate in the management of patients with chronic obstructive pulmonary disease (e.g., bronchitis)† who are stabilized with oral corticosteroids^{33 34 37 117} or whose disease is corticosteroid responsive^{117 118} remains to be fully evaluated. Limited data suggest that orally inhaled beclomethasone dipropionate may be useful in some patients with chronic obstructive pulmonary disease,^{117 118} but is probably not an adequate substitute for oral corticosteroid therapy in patients with steroid-responsive disease.¹¹⁷ Whether orally inhaled beclomethasone can maintain improvement in pulmonary function initially produced by oral corticosteroid therapy has not been established.^{117 118}

Beclomethasone dipropionate has been used as an oral solution³⁵ or rectal suspension³⁶ in the management of inflammatory diseases of the GI tract†.^{35 36} In a group of patients with inflammatory bowel disease†, treatment with enemas containing beclomethasone dipropionate resulted in symptomatic improvement without producing adverse systemic effects.³⁶ In a patient with eosinophilic gastroenteritis†, administration of an oral solution of beclomethasone dipropionate improved intestinal absorptive function.³⁵ The role of beclomethasone dipropionate in the management of inflammatory conditions of the GI tract remains to be established.^{35 36}

For other uses of beclomethasone dipropionate, see 52:08.08.

See Dosage and Administration in the associated General Statement for more information.

Dosage and Administration

Administration

Beclomethasone dipropionate is administered by oral inhalation using an oral aerosol inhaler.¹⁴⁹ Patients should be carefully instructed in the use of the oral inhaler.¹⁴⁹ To obtain optimum results, patients should also be given a copy of the patient instructions provided by the manufacturer.¹⁴⁹ An adult should carefully supervise a child in the administration of beclomethasone dipropionate for oral inhalation.^{71 74} The manufacturer states that beclomethasone dipropionate oral inhaler should be used by oral inhalation only.¹⁴⁹ The manufacturer states that the regular- (40 mcg/metered dose) and double-strength inhalation aerosols with tetrafluoroethane (non-CFC) propellant (QVAR^®)¹⁴⁹ should be tested by spraying twice into the air before using the device for the first time or whenever the aerosol has not been used for more than 10 days.¹⁴⁹

Because the commercially available beclomethasone dipropionate oral inhalation aerosol with tetrafluoroethane (non-CFC) propellant (QVAR^®) is formulated as a solution, it is not necessary to shake the inhaler prior to use.¹⁴⁹ After exhaling as completely as possible, the mouthpiece of the inhaler should be placed well into the mouth and the lips closed firmly around it, keeping the tongue below the mouthpiece.¹⁴⁹ The patient should then inhale slowly and deeply through the mouth while pressing the metal canister down with the forefinger.¹⁴⁹ After holding the breath for as long as possible (about 5–10 seconds), the mouthpiece should be removed and the patient should exhale slowly.¹⁴⁹ If additional inhalations are required, the patient should repeat the procedure.¹⁴⁹ Following each treatment, the patient should rinse the mouth thoroughly with water to remove drug deposited in the oropharyngeal area.^{33 48 49 52 59} The patient instructions provided by the manufacturer should be referred to for further information regarding use of beclomethasone dipropionate for oral inhalation.¹⁴⁹

Weekly cleansing of the mouthpiece of the beclomethasone dipropionate oral inhaler is recommended.¹⁴⁹ The mouthpiece should be cleaned using a clean, dry tissue or cloth.¹⁴⁹ The patient should be instructed not to wash or place any part of the inhaler canister in water. ¹⁴⁹

According to the manufacturer of beclomethasone dipropionate inhalation aerosol with tetrafluoroethane (non-CFC) propellant (QVAR^®), lung deposition does not differ when the drug is administered with or without a spacer device, and administration with a spacer device is not necessary.¹⁶⁰ However, the manufacturer states that the QVAR^® inhaler is compatible with the AeroChamber^® spacer device, which may be used if preferred by the clinician or patient.^{153 160}

Dosage

The commercially available 7.3-g regular- or double-strength oral inhalation aerosol with tetrafluoroethane (non-CFC) propellant (QVAR^®) delivers about 40 or 80 mcg of beclomethasone dipropionate per metered spray and provides 100 metered sprays.¹⁴⁹ Dosage of orally inhaled beclomethasone dipropionate must be carefully adjusted according to individual requirements and response.^{1 2 61 83 112 113 144 149}

The recommended dosage of orally inhaled beclomethasone dipropionate administered via metered-dose aerosol with tetrafluoroethane (non-CFC) propellant (QVAR^® is lower than that with inhalation aerosols containing CFC propellant (e.g., Beclovent^®, Vanceril ^®, Vanceril ^® Double Strength; all no longer commercially available in the US), although a definitive comparative therapeutic ratio between non-CFC and CFC-containing beclomethasone preparations has not been demonstrated.¹⁴⁹ The usual initial dosage of beclomethasone dipropionate oral inhalation aerosol with tetrafluoroethane (non-CFC) propellant (QVAR^®) for adults and children 12 years of age or older in whom previous asthma therapy consisted of bronchodilators alone is 40 or 80 mcg twice daily.¹⁴⁹ The usual initial dosage of the drug for adults and children 12 years of age or older in whom previous asthma therapy consisted of inhaled corticosteroids is 40–160 mcg twice daily.¹⁴⁹ In children 5–11 years of age in whom previous asthma therapy consisted of bronchodilators alone or inhaled corticosteroids, the usual initial dosage of the drug is 40 mcg twice daily.¹⁴⁹ After a satisfactory response is obtained, dosage should be decreased gradually to the lowest dosage that maintains an adequate clinical response, particularly in children, since inhaled corticosteroids have the potential to affect growth.^{149 150} (See Cautions: Pediatric Precautions.) The manufacturer of QVAR^® states that the safety and efficacy of dosages exceeding 320 mcg twice daily in adults and children 12 years of age and older or 80 mcg twice daily in children 5–11 years of age have not been established.¹⁴⁹

Patients who respond to beclomethasone dipropionate oral inhalation usually show improvement in pulmonary function within 1–4 weeks of continuous therapy.^{1 2 61 77 100 112 113 144 149}

Conversion to Orally Inhaled Therapy in Patients Receiving Systemic Corticosteroids

When orally inhaled beclomethasone dipropionate is administered to patients receiving systemic corticosteroids, the patient’s asthma should be reasonably stable before treatment with the oral inhalation begins.^{1 2 112 113 144 149} Initially, the aerosol is given concurrently with the maintenance dosage of the systemic corticosteroid.^{1 2 112 113 144 149} After about 1 week, gradual withdrawal of the systemic corticosteroid is begun.^{1 2 112 113 144 149} (See Dosage and Administration in the Corticosteroids General Statement 68:04.) Gradual withdrawal of systemic corticosteroids following long-term therapy is strongly recommended, since death has occurred in some individuals in whom systemic corticosteroids were withdrawn too rapidly.^{1 2 112 113 144 149} (See Cautions: Hypothalamic-Pituitary-Adrenal [HPA] Axis Suppression.)After systemic corticosteroids have been withdrawn, if exacerbations of asthma occur during beclomethasone dipropionate oral inhalation therapy, short courses of systemic corticosteroids should be given, then tapered as symptoms subside.^{1 2 112 113 144 149}

See Cautions in the associated General Statement for more information.

Cautions

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression

Suppression of hypothalamic-pituitary-adrenal (HPA) axis function below the clinical normal range was not observed with beclomethasone dipropionate inhalation aerosol with tetrafluoroethane (non-CFC) propellant (QVAR^®) at dosages up to 640 mcg daily during clinical trials; however, a dose-dependent reduction in adrenal cortisol production was detected.¹⁴⁹ In a comparative study, corticosteroid-naïve patients receiving beclomethasone dipropionate inhalation aerosol with tetrafluorethane (non-CFC) propellant (320 mcg twice daily) or the drug formulated with CFC propellant (336 mcg twice daily; preparation no longer commercially available in the US) experienced a reduction in 24-hour urinary free cortisol concentrations of approximately 37 or 47%, respectively.¹⁴⁹ In an open-label study of 354 patients receiving beclomethasone oral inhalation aerosol with tetrafluoroethane (non-CFC) propellant at recommended dosages for 1 year, less than 1% had an abnormal response to rapid corticotropin (ACTH) stimulation tests.^{149 154} Mean changes from baseline in morning plasma cortisol concentrations were similar in patients receiving beclomethasone dipropionate inhalation aerosol with tetrafluoroethane (non-CFC) propellant (>320 – 640 mcg daily) or CFC propellant (>420-840 mcg daily; preparation no longer commercially available in the US) after 12 months of treatment and were not considered clinically meaningful.¹⁵⁴

Reductions in plasma cortisol concentrations did not occur in adults when beclomethasone dipropionate was administered by IM injection at dosages of 1000 mcg daily for 3 days.^{1 2 112 113 144} Partial suppression of adrenal function has been observed when beclomethasone dipropionate was administered by IM injection at dosages of 2000 mcg daily.^{1 2 112 113} Follwoing IM administration of single 4000-mcg doses of beclomethasone dipropionate, immediate adrenal suppression has been observed.^{1 2 112 113 144}

Concurrent administration of a systemic and orally inhaled corticosteroid may increase the risk of HPA-axis suppression.^{45 47} Following concurrent therapy with alternate-day prednisone and orally inhaled beclomethasone dipropionate in a group of asthmatic children, reductions in plasma cortisol concentrations were greater than those produced by therapeutic dosages of either drug alone;⁴⁵ however, studies have not been performed to date comparing the systemic effects of alternate-day systemic corticosteroid therapy alone with therapeutically equivalent doses of orally inhaled beclomethasone dipropionate.¹⁰¹ Reductions in plasma cortisol concentrations have occurred when intranasal and orally inhaled beclomethasone dipropionate were used concomitantly.¹¹¹

Because beclomethasone dipropionate is absorbed into circulation and can be systemically active, HPA axis suppression could occur when recommended dosages are exceeded or in particularly sensitive individuals.¹⁴⁹ Since recommended dosages of orally inhaled beclomethasone dipropionate provide less than normal physiologic amounts of glucocorticoid systemically and do not provide mineralocorticoid activity, the drug will not compensate for insufficient endogenous cortisol production caused by previous systemic corticosteroid therapy. ¹⁴⁹

In most patients, a number of months are required for recovery of HPA function following withdrawal of long-term systemic corticosteroid therapy.^{1 40 80 112 113 149} Since death resulting from acute adrenal insufficiency or an exacerbation of the underlying asthma has occurred rarely in asthmatic patients during and after transfer from systemic corticosteroid to beclomethasone dipropionate oral inhalation therapy,^{1 2 13 23 28 40 112 113 144 149} systemic corticosteroid therapy should be withdrawn gradually.^{1 2 112 113 144 149} Several deaths in asthmatic children have occurred about 6 months after conversion from oral corticosteroid to beclomethasone dipropionate oral inhalation therapy.⁴⁰ Although adrenal stimulation tests performed in some of these children shortly before death indicated normal HPA function, adrenal atrophy was observed on postmortem examination.⁴⁰

Respiratory Effects

Infectious Complications

Increased colonization and/or localized infections with Candida albicans have occurred frequently in the mouth or pharynx and occasionally in the larynx, bronchus, or esophagus of patients receiving orally inhaled beclomethasone dipropionate;^{1 2 14 27 29 30 44 48 49 50 51 52 59 60 70 89 100 112 113 116 144} Aspergillus niger infections or overgrowth also have occurred.^{1 2 7 105 112 113 144} The frequency of positive oral Candida cultures in patients receiving orally inhaled beclomethasone dipropionate is variable.^{33 48 49 103}

The manufacturer of orally inhaled beclomethasone dipropionate aerosol with tetrafluoroethane (non-CFC) propellant states that no patient developed symptomatic oropharyngeal candidiasis during clinical development with this preparation.¹⁴⁹ In an open-label study in 354 patients receiving beclomethasone dipropionate oral inhalation aerosol with tetrafluoroethane (non-CFC) propellant (160–640 mcg daily) or CFC propellant (336–1344 mcg daily; no longer commercially available in the US) for 1 year, oropharyngeal candidiasis was not reported in either treatment group.¹⁵⁴ Approximately 4 or 8% of patients receiving the drug containing non-CFC (HFA) or CFC propellant, respectively, were instructed to use a spacer device either positive oral Candida cultures or dysphonia; however, the difference between the treatment groups was not statistically significant.¹⁵⁴

Most clinicians recommend that patients rinse their mouth and throat with water after each dose of beclomethasone dipropionate to remove residual medication in the oropharyngeal area and to minimize the development of fungal overgrowth and/or infection.^{33 48 49 52 59} If a fungal infection is suspected, appropriate local anti-infective therapy and/or discontinuance of beclomethasone dipropionate therapy should be considered,¹⁴⁹ but usually oropharyngeal Candida or Aspergillus infections are of little clinical importance.^{33 89}

Monilial esophagitis has occurred in several asthmatic patients receiving concomitant therapy with oral prednisone and orally inhaled beclomethasone dipropionate; however, predisposing factors, other than therapy with orally inhaled beclomethasone dipropionate, were present in these patients.⁵¹ The development of esophagitis resulting from concurrent infection with Candida and herpes simplex has been reported in at least one corticosteroid-dependent patient receiving orally inhaled beclomethasone dipropionate.⁹⁷

Although not directly attributable to the drug, clinical tuberculosis developed in one patient during a 6-month period of beclomethasone dipropionate oral inhalation therapy.³⁸ However, concurrent administration of beclomethasone dipropionate oral inhalation did not appear to have an adverse effect on resolution of tuberculosis in this patient.³⁸ In a previous 10-month period, the patient received an oral corticosteroid without any clinical evidence of tuberculosis.³⁸

Eosinophilic pneumonia has occurred in several patients receiving orally inhaled beclomethasone dipropionate.^{2 53 54 55 98 112 113} A possible relationship of this adverse effect to systemic corticosteroid withdrawal has been suggested.^{2 53 54 55 98 112 113} A causal relationship to beclomethasone dipropionate and/or the contents of the vehicle (e.g., fluorocarbons, oleic acid) in the preparation has been suggested but remains to be established.^{2 53 54 55 112 113}

Dysphonia

Dysphonia (sometimes persistent and severe) has occurred in patients receiving orally inhaled beclomethasone dipropionate;^{1 2 27 44 48 56 60 84 103 112 113 116 149} a direct causal relationship to therapy with orally inhaled beclomethasone dipropionate and to chronic voice stress has been shown in at least one study.⁴⁸ A causal relationship has not been ruled out, but in one controlled study, dysphonia did not appear to be related to the contents of the vehicle (e.g., fluorocarbons, oleic acid) in the preparation of beclomethasone dipropionate oral inhalation that was used.⁴⁸ Dysphonia may result from dysfunction of the bilateral adductor muscles that control phonation.¹⁰² It has been suggested that this adverse effect may result from a local steroid myopathy.¹⁰² Dysphonia has occurred concomitantly with candidiasis in some patients.^{44 116} Although dysphonia and candidiasis were related to beclomethasone dipropionate oral inhalation therapy in some patients, they apparently were not related to each other and required different treatment (voice rest or nystatin).⁴⁸

Other Adverse Respiratory Effects

Bronchospasm,^{1 2 57 112 113 133 149} cough,^{20 25 58 131 132 149} and/or wheezing^{57 58 131 132 133 149} may occur in some patients following oral inhalation of beclomethasone dipropionate, especially in asthmatic patients with hyperactive airways.^{20 25 57 58 101 131 132 133} Administration of an orally inhaled β₂-agonist a few minutes before oral inhalation of beclomethasone dipropionate has prevented or minimized these adverse respiratory effects in some patients;^{20 101 131 132} other patients may require a course of oral corticosteroid therapy to tolerate oral inhalation of the steroid.^{131 132}

The long-term and systemic effects of beclomethasone dipropionate in humans, particularly local effects on developmental or immunologic processes in the mouth, pharynx, trachea, and lung, are unknown.¹⁴⁹ Although not reported to date in patients receiving orally inhaled beclomethasone dipropionate, the possibility of atrophic changes in the respiratory epithelium during prolonged therapy with orally inhaled corticosteroids should be considered, since atrophic dermatitis has occurred in patients treated with topical corticosteroids to the skin for prolonged periods.⁸⁶ In a limited number of patients receiving beclomethasone dipropionate oral inhalation for 12–18 months, light and electron microscopic studies of bronchial and pharyngeal biopsy material did not reveal any changes attributable to the drug.³⁹ Long-term studies using high doses of orally inhaled beclomethasone dipropionate in cushingoid animals also did not reveal any evidence of pulmonary changes as determined by light or electron microscopy.¹¹⁴ Following therapy with orally inhaled beclomethasone dipropionate, bronchial biopsies did not show any evidence of atrophic changes in asthmatic patients receiving the drug for up to 32 months; however, an increased number of mastocytes was observed when biopsies from these patients were compared with those from asthmatic patients not receiving therapy with the drug.⁹⁶

Other Adverse Effects

In addition to bronchospasm, other immediate or delayed hypersensitivity reactions, including anaphylactic/anaphylactoid reactions,² urticaria, angioedema, and rash, have occurred rarely following oral or intranasal inhalation of beclomethasone dipropionate.^{1 2 112 113 149} Other adverse effects reported with oral inhalation of beclomethasone dipropionate include flushing,¹⁵ dry mouth^{1 112 113} or throat,^{2 58} irritation of the tongue⁵⁸ or throat,^{25 27} and dysgeusia;^{15 25} however, a causal relationship to the drug has not been established. Headache, pharyngitis, rhinitis, sinusitis, pain/back pain, and dysmenorrhea were also reported during clinical trials with beclomethasone dipropionate oral inhalation therapy.¹⁴⁹

Glaucoma, increased intraocular pressure, and cataracts have been reported rarely with administration of inhaled corticosteroids.¹⁴⁹ Prolonged therapy with orally inhaled beclomethasone dipropionate has been associated with the development of bilateral posterior subcapsular cataracts in at least one patient.⁹⁹ Several months following discontinuance of corticosteroid therapy in this patient, normal lenses were observed.⁹⁹ In a group of asthmatic children who developed cataracts during systemic corticosteroid therapy, cataracts resolved within 6 months in 2 patients when prednisone dosage was reduced or discontinued and beclomethasone dipropionate oral inhalation therapy was initiated.¹⁰⁴

A bullous eruption of the lips and oral mucosa has been reported in at least one patient receiving oral inhalation of beclomethasone dipropionate.⁹² Since rechallenge with the drug produced the same adverse reaction in this patient, a causal relationship to beclomethasone dipropionate or an ingredient in the vehicle of the preparation has been suggested.⁹²

Precautions and Contraindications

In patients being switched from systemic corticosteroids to orally inhaled beclomethasone dipropionate, systemic corticosteroid therapy should be withdrawn gradually since a life-threatening exacerbation of asthma or adrenal insufficiency could occur.^{1 2 112 113 144 149} Patients who have been maintained on 20 mg or more of prednisone (or its equivalent) daily may be most susceptible to such adverse events, particularly when their systemic corticosteroid therapy has been almost completely withdrawn.¹⁴⁹ In most patients, up to 12 months may be required for total recovery of HPA function following withdrawal of systemic corticosteroid therapy.^{1 2 40 80 112 113} These patients should be carefully monitored during and for a number of months after withdrawal of systemic corticosteroids because of the risk of corticosteroid withdrawal symptoms (e.g., joint pain, muscular pain, lassitude, depression);^{1 2 112 113 144 149} acute adrenal insufficiency during exposure to trauma, surgery, or infection (particularly gastroenteritis or other conditions associated with acute electrolyte loss);^{1 2 112 113 144} pulmonary infiltrates with eosinophilia;^{1 112 113} or symptomatic exacerbation of allergic conditions previously controlled by systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema).^{1 2 27 44 52 58 70 112 113 144} In asthmatic patients, death, possibly resulting from acute adrenal insufficiency or an exacerbation of the underlying asthma, has occurred rarely during and after transfer from systemic corticosteroid to beclomethasone dipropionate oral inhalation therapy.^{1 2 13 23 28 40 112 113 144} Systemic corticosteroid dosage should be carefully tapered and patients should be monitored during dosage reduction for objective signs of adrenal insufficiency (e.g., hypotension, weight loss).^{1 2 112 113 144 149} In general, the greater the dosage and duration of systemic corticosteroid therapy, the greater the time required for withdrawal of systemic corticosteroids and replacement by orally inhaled corticosteroids.⁷³

The manufacturer of beclomethasone dipropionate oral inhalation containing tetrafluoroethane (non-CFC) propellant (QVAR^®) states that higher than recommended dosages of the drug should be avoided, since suppression of HPA function may occur.¹⁴⁹ If higher than recommended dosages are used, the relative risks of adrenal suppression and potential therapeutic benefits must be carefully considered; systemic corticosteroids will likely be necessary during prolonged periods of stress (e.g., infection, trauma, surgery),¹⁴⁹ particularly in patients who received continuous oral corticosteroid therapy within the previous 12 months.^{1 2 119 130} Orally inhaled beclomethasone dipropionate should be used with caution in patients receiving systemic prednisone or another systemic corticosteroid in an alternate-day or daily dosing regimen for any disease, since concomitant use of the drugs could increase the likelihood of HPA-axis suppression compared with therapeutic dosages of either drug alone.^{45 47}

Although signs and symptoms of Cushing’s syndrome (e.g., hypertension, glucose intolerance, cushingoid features) have not been associated with beclomethasone dipropionate oral inhalation therapy to date, the possibility of their occurrence should be considered in patients who are particularly sensitive to corticosteroid effects or when usual dosages of the drug are exceeded.^{100 149}

Patients should be advised that oral inhalation of beclomethasone dipropionate must be used at regular intervals to be therapeutically effective.^{100 103 144 149} In addition, patients should be advised that the drug usually will not provide immediate symptomatic relief, but 1–4 weeks of continuous therapy may be required for optimum effects to be achieved.^{1 2 61 77 100 112 113 144 149} Patients should be advised that orally inhaled beclomethasone dipropionate should not be used as a bronchodilator and is not indicated for emergency use (e.g., relief of acute bronchospasm).^{1 2 103 112 113 144 149} Patients should be instructed not to exceed the prescribed dosage,⁷¹ and to rinse their mouth after the inhalation procedure.^{1 2 112 113 144} (See Dosage and Administration: Administration.) Patients receiving beclomethasone dipropionate oral inhalation therapy should also be advised to contact their physician immediately when asthmatic attacks that are not controlled by bronchodilator therapy occur.^{1 2 112 113 149} The manufacturer of beclomethasone dipropionate containing tetrafluoroethane (non-CFC) propellant (QVAR^®) states that if bronchospasm occurs following dosing with the drug, it should be treated immediately with a short-acting bronchodilator, treatment with beclomethasone dipropionate should be discontinued, and alternative therapy should be instituted.¹⁴⁹ Patients being transferred from systemic corticosteroid to beclomethasone dipropionate oral inhalation therapy should carry special identification (e.g., card, bracelet) indicating the need for supplementary systemic corticosteroids during periods of stress.^{1 2 112 113 144} Patients receiving orally inhaled beclomethasone dipropionate who are currently being withdrawn or who have been withdrawn recently from systemic corticosteroids should be advised to immediately resume full therapeutic dosages of systemic corticosteroids and to contact their physician for further instructions during stressful periods (e.g., severe infection, severe asthmatic attack).^{1 2 112 113 144 149}

Patients receiving beclomethasone dipropionate oral inhalation with tetrafluoroethane (non-CFC) propellant (QVAR^®) should be advised that this preparation may have a different taste and inhalation sensation than that of an inhaler containing CFC propellants (no longer commercially available in the US).¹⁴⁹

Patients who become immunosuppressed while receiving corticosteroids have increased susceptibility to infections compared with healthy individuals, and certain infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome in such patients, particularly in children.^{113 134 135 136 137 138 139 140 141 142 143 144} Patients receiving corticosteroids who are potentially immunosuppressed should be warned of the risk of exposure to certain infections (e.g., chickenpox, measles) and of the importance of obtaining medical advice if such exposure occurs.^{113 134 135 136 142 143 144 149} For additional information, see Cautions: Increased Susceptibility to Infection and also see Precautions and Contraindications, in the Corticosteroids General Statement 68:04.

The effect of beclomethasone dipropionate oral inhalation therapy on acute, recurrent, or chronic pulmonary infections, including active or latent Mycobacterium tuberculosis infections, is not known.^{1 112 113} Orally inhaled beclomethasone dipropionate should be used with caution, if at all, in patients with clinical tuberculosis or latent M. tuberculosis infection of the respiratory tract; untreated systemic fungal, bacterial, or parasitic infections; or ocular herpes simplex or untreated, systemic viral infections.^{1 2 100 144}

Oral inhalation of beclomethasone dipropionate is contraindicated in the primary treatment of severe acute asthmatic attacks or status asthmaticus when intensive measures (e.g., oxygen, parenteral bronchodilators, IV corticosteroids) are required.^{1 2 61 112 113 144 149} Oral inhalation of beclomethasone dipropionate is also contraindicated in patients who are hypersensitive to the drug or any ingredient in the formulation.^{1 2 112 113 144 149}

Pediatric Precautions

The safety and efficacy of beclomethasone dipropionate oral inhaler with non-CFC (tetrafluoroethane) propellant (QVAR^®) have not been established in children younger than 5 years of age.¹⁴⁹ In several studies in children 5–12 years of age not previously treated with corticosteroids, no overall differences in the pattern, severity, or frequency of adverse events were observed compared with those in adults, with the exception of conditions that are more prevalent in the pediatric population generally.¹⁴⁹ In a 12-month comparative study in children 5–11 years of age receiving 8–320 mcg daily of orally inhaled non-CFC tetrafluoroethane propellant beclomethasone dipropionate (without a spacer) or 160–640 mcg daily of the drug with CFC propellant with a spacer (no longer commercially available in the US), a small reduction in growth velocity (0.5 cm/year) was observed with the non-CFC inhalation aerosol and no spacer compared with the CFC-containing inhalation aerosol and a spacer. ^{149 150} Children receiving prolonged therapy with orally inhaled beclomethasone dipropionate should be monitored periodically for possible adverse effects on growth and development.^{62 149} (See Pediatric Precautions in the Corticosteroids General Statement 68:04.)

Geriatric Precautions

Clinical studies of beclomethasone dipropionate did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients.¹⁴⁹ While clinical experience generally has not revealed age-related differences in response to the drug, care should be taken in dosage selection of beclomethasone dipropionate.¹⁴⁹ Because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy in geriatric patients, the manufacturer suggests that patients in this age group receive initial dosages of the drug at the lower end of the usual range.¹⁴⁹

Mutagenicity and Carcinogenicity

Beclomethasone dipropionate did not exhibit mutagenic potential in vitro in bacterial or mammalian (Chinese hamster ovary) test systems.¹⁴⁹ No evidence of clastogenic potential was found in in vitro tests using cultured CHO cells or in vivo in the mouse micronucleus test.¹⁴⁹

No evidence of carcinogenicity was observed when rats were given the drug for 95 weeks (13 weeks by oral inhalation and 82 weeks by the oral route).^{68 69 149}

Pregnancy, Fertility, and Lactation

Pregnancy

Orally inhaled beclomethasone dipropionate should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.^{1 2 112 113 144 149}

Although there are no adequate and controlled studies to date in humans, 20 asthmatic patients who became pregnant and were receiving oral inhalation of beclomethasone dipropionate at usual dosages delivered healthy children.⁷⁰ Other women with severe asthma who received orally inhaled beclomethasone dipropionate during pregnancy to reduce systemic corticosteroid dosage requirements also delivered healthy children;^{90 122} however, a cardiac malformation was reported in an infant whose mother had complications and was receiving other drugs.⁹⁰ Several of these pregnancies resulted in premature deliveries and low birthweight infants,^{90 122} but evidence of neonatal adrenal insufficiency was not observed.⁹⁰ Infants born to women who received substantial doses of corticosteroids during pregnancy should be carefully monitored for manifestations of hypoadrenalism.^{2 61 112 144 149} Subcutaneous beclomethasone dipropionate has been shown to be teratogenic and embryocidal in mice and rabbits at dosages about one-half the maximum recommended daily inhalation dose in adults on a mg/m² basis.¹⁴⁹ Teratogenic effects in these animals included fetal resorption, cleft palate, agnathia, microstomia, aglossia, delayed ossification, and agenesis of the thymus gland.^{1 112 113} Teratogenic or embryocidal effects were not observed following oral inhalation of beclomethasone dipropionate at 190 times the maximum recommended daily human dosage on a mg/m² basis ¹⁴⁹ or following oral administration at 1000 times the usual human dosage in rats.^{68 69}

Fertility

It is not known whether beclomethasone dipropionate affects fertility in humans.^{68 69} Reproduction studies in female dogs given oral beclomethasone dipropionate dosages of 500 mcg/kg daily have shown evidence of impaired fertility (inhibition of the estrus cycle); however, no inhibition of the estrus cycle was observed in dogs following administration of orally inhaled beclomethasone dipropionate for 12 months as an estimated daily dosage of 0.33 mg/kg (about 15 times the maximum recommended daily dosage in humans on a mg/m² basis).¹⁴⁹

Lactation

Since corticosteroids are distributed into milk and potentially may cause serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.^{144 149}

See Drug Interactions in the associated General Statement for more information.

See Lab Test Interferences in the associated General Statement for more information.

See Pharmacology in the associated General Statement for more information.

Pharmacology

For a discussion of the pharmacology of beclomethasone dipropionate, see Pharmacology in the Corticosteroids General Statement 68:04 and in Beclomethasone Dipropionate 52:08.08.

See Pharmacokinetics in the associated General Statement for more information.

Pharmacokinetics

For a discussion of the absorption, distribution, and elimination of beclomethasone dipropionate, see Pharmacokinetics in the Corticosteroids General Statement 68:04 and in Beclomethasone Dipropionate 52:08.08.

See Chemistry and Stability in the associated General Statement for more information.

Chemistry and Stability

Chemistry

Beclomethasone dipropionate, a diester of beclomethasone, is a synthetic corticosteroid.^{1 2} Beclomethasone and beclomethasone dipropionate are 21-carbon steroids and are structurally related to dexamethasone.^{1 2 149} Esterification of the hydroxyl group at positions 17 and 21 of the beclomethasone molecule enhances the topical anti-inflammatory activity of beclomethasone dipropionate compared with beclomethasone.⁴ (See Chemistry in the Corticosteroids General Statement 68:04.)

Beclomethasone dipropionate occurs as a white to creamy white powder^{3 5 144} and is slightly soluble in water and freely soluble in alcohol.¹⁴⁹

Beclomethasone dipropionate is commercially available for oral inhalation in a vehicle containing a fluorocarbon propellant (tetrafluoroethane [HFA-134a], which is not a CFC) and alcohol (QVAR^®).¹⁴⁹ Beclomethasone dipropionate oral inhaler containing non-CFC (tetrafluoroethane) propellant (QVAR^®) produces a metered spray containing 50 or 100 mcg of beclomethasone dipropionate per spray at the valve and delivers a beclomethasone dipropionate dose of 40 or 80 mcg, respectively, from the actuator.¹⁴⁹

Stability

The manufacturer of beclomethasone dipropionate oral inhaler with non-CFC (tetrafluoroethane) propellant (QVAR^®) states that the aerosol should be stored at 25°C but may be exposed to temperatures ranging from 15–30°C.¹⁴⁹ Because the contents of beclomethasone dipropionate oral inhalers are under pressure, the aerosol containers should not be punctured, used or stored near heat or an open flame, exposed to temperatures greater than 49°C, or placed into a fire or incinerator for disposal.^{1 112 113 144 149}

For further information on chemistry, pharmacology, pharmacokinetics, cautions, and dosage and administration of beclomethasone dipropionate, see the Corticosteroids General Statement 68:04.

Preparations

Beclomethasone Dipropionate

Routes	Forms	Strengths	Brand Names	Manufacturer
Oral Inhalation	Aerosol	40 mcg/metered spray	QVAR® Oral Inhaler (with tetrafluoroethane propellants and ethanol)	Teva
		80 mcg/metered spray	QVAR® Oral Inhaler (with tetrafluoroethane propellants and ethanol)	Teva

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

Selected Revisions March 2006, © Copyright, October 1983, American Society of Health-System Pharmacists, Inc. 7272 Wisconsin Avenue, Bethesda, MD 20814.

References

1. Schering Corporation. Vanceril^® 42 mcg (beclomethasone dipropionate, 42 mcg) inhalation aerosol prescribing information. Kenilworth, NJ; 2000 Aug.

2. Glaxo Wellcome. Beclovent^® (beclomethasone dipropionate) inhalation aerosol prescribing information. Research Triangle Park, NC; 1997 Dec.

3. Schering Corporation. Vanceril^® basic data book. Kenilworth, NJ; 1976 May.

4. Harris DM. Clinical pharmacology of beclomethasone dipropionate. In: Mygind N, Clark TJH, eds. Topical steroid treatment for asthma and rhinitis. London: Bailliere Tindall; 1980:34-47.

5. Wade A, ed. Martindale: the extra pharmacopeia. 27th ed. London: The Pharmaceutical Press; 1977:401-2.

6. Bondarevsky E, Shapiro MS, Schey G et al. Beclomethasone dipropionate use in chronic asthmatic patients: effect on adrenal function after substitution for oral glucocorticoids. JAMA. 1976; 236:1969-71.

7. Smith AP, Booth M, Davey AJ. A controlled trial of beclomethasone dipropionate for asthma. Br J Dis Chest. 1973; 67:208-14.

8. Harvey LL, Nair SV, Kass I. Beclomethasone dipropionate aerosol in the treatment of steroid-dependent asthma. Chest. 1976; 70:345-50.

9. Pines A. Beclomethasone dipropionate used as an aerosol in the treatment of asthma. Practitioner. 1975; 211:86-90.

10. Cayton RM, Soutar CA, Stanford CF et al. Double-blind trial comparing two dosage schedules of beclomethasone dipropionate aerosol in the treatment of chronic bronchial asthma. Lancet. 1974; 2:303-7.

11. Brown HM, Storey G. Beclomethasone dipropionate steroid aerosol in the treatment of perennial allergic asthma in children. Br Med J. 1973; 3:161-4.

12. Dickson W, Hall CE, Ellis M et al. Beclomethasone dipropionate aerosol in childhood asthma. Arch Dis Child. 1973; 48:671-5.

13. Gwynn CM, Smith JM. A one year follow-up of children and adolescents receiving regular beclomethasone dipropionate. Clin Allergy. 1974; 4:325-30.

14. Kerrebijn KF. Beclomethasone dipropionate in long-term treatment of asthma in children. J Pediatr. 1976; 89:821-6.

15. Vogt F, Chervinsky P, Dwek J et al. Beclomethasone dipropionate aerosol in the treatment of chronic bronchial asthma. J Allergy Clin Immunol. 1976; 58:316-21.

16. Choovoravech P, Preeyasombat C. Trial of beclomethasone dipropionate aerosol in the treatment of severe chronic asthma. Practitioner. 1978; 220:639-42.

17. Klein R, Waldman D, Kershnar H et al. Treatment of chronic childhood asthma with beclomethasone dipropionate aerosol. Part I: a double-blind crossover trial in nonsteroid-dependent patients. Pediatrics. 1977; 60:7-13.

18. Mackay JB. The impact of beclomethasone dipropionate aerosol on patients with reversible airways obstruction attending a chest clinic. Postgrad Med J. 1975; 51(Suppl 4):37-41.

19. Zwi S, Van As A, Goldman HI et al. The measurement of response to beclomethasone dipropionate treatment for asthma. Postgrad Med J. 1975; 51(Suppl 4):64-7.

20. Johannessen H, Halvorsen FJ, Kommedal TM. Long-term treatment of patients with perennial bronchial asthma with beclomethasone dipropionate aerosol: a 24 month follow-up study. Curr Ther Res. 1979; 26:592-600.

21. Vandenberg R, Tovey E, Love I et al. Beclomethasone dipropionate: trial of a new inhalational steroid preparation in the treatment of steroid-dependent chronic asthmatics. Med J Aust. 1975; 1:189-93.

22. Webb DR. Corticosteroid aerosols in the treatment of asthma. Bull Mason Clin. 1975; 29:98-106.

23. Brown HM, Storey G, George WHS. Beclomethasone dipropionate: a new steroid aerosol for the treatment of allergic asthma. Br Med J. 1972; 1:585-90.

24. Bacal E, Patterson R. Long-term effects of beclomethasone dipropionate on prednisone dosage in the corticosteroid asthmatic. J Allergy Clin Immunol. 1978; 62:72-5.

25. Richards W, Platzker A, Church JA et al. Steroid-dependent asthma treated with inhaled beclomethasone dipropionate in children. Ann Allergy. 1978; 41:274-7.

26. Toogood JH, Lefcoe NM, Haines DSM et al. Minimum dose requirements of steroid-dependent asthmatic patients for aerosol beclomethasone and oral prednisone. J Allergy Clin Immunol. 1978; 61:355-64.

27. Kershnar H, Klein R, Waldman D et al. Treatment of chronic childhood asthma with beclomethasone dipropionate aerosols. Part II: effect on pituitary-adrenal function after substitution for oral corticosteroids. Pediatrics. 1978; 62:189-97.

28. Anon. Beclomethasone dipropionate (Vanceril^®) for asthma. Med Lett Drugs Ther. 1976; 18:76.

29. Anon. Steroid aerosols for asthma. Med Lett Drugs Ther. 1975; 17:88.

30. Ballin JC. Evaluation of a new aerosolized steroid for asthma therapy. JAMA. 1976; 236:2891-3.

31. Willey RF, Godden DJ, Carmichael J et al. Comparison of twice daily administration of a new corticosteroid budesonide with beclomethasone dipropionate four times daily in the treatment of chronic asthma. Br J Dis Chest. 1982; 76:61-8.

32. Kennedy MCS, Posner E, Thursby-Pelham DC. Long-term treatment of asthma with beclomethasone dipropionate. Postgrad Med J. 1975; 51(Suppl 4):84-6.

33. Williams MH Jr. Beclomethasone dipropionate. Ann Intern Med. 1981; 95:464-7.

34. Shim C, Stover DE, Williams MH Jr. Response to corticosteroids in chronic bronchitis. J Allergy Clin Immunol. 1978; 62:363-7.

35. Elkon KB, Sher R, Seftel HC. Immunological studies of eosinophilic gastroenteritis and treatment with disodium cromoglycate and beclomethasone dipropionate. S Afr Med J. 1977; 52:834-41.

36. Kumana CR, Meghji M, Seaton T et al. Beclomethasone dipropionate enemas for treating inflammatory bowel disease without producing Cushing’s syndrome or hypothalamic-pituitary-adrenal suppression. Lancet. 1982; 1:579-83.

37. Matthews JI, Hooper RG. Idiopathic bronchial stenosis in a young woman. Chest. 1978; 74:690-1.

38. Horton DJ, Spector SL. Clinical pulmonary tuberculosis in an asthmatic patient using a steroid aerosol. Chest. 1977; 71:540-2.

39. Andersson E, Smidt CM, Sikjaer B et al. Bronchial biopsies after beclomethasone dipropionate aerosol. Br J Dis Chest. 1977; 77:35-43.

40. Mellis CM, Phelan PD. Asthma deaths in children—a continuing problem. Thorax. 1977; 32:29-34.

41. Bhan GL, Gwynn CM, Smith JM. Growth and adrenal function of children on prolonged beclomethasone dipropionate treatment. Lancet. 1980; 1:96-7.

42. Smith JM. Hazards of prolonged use of beclomethasone spray. JAMA. 1982; 248:1449.

43. Siegel SC, Katz RM, Rachelefsky GS. Prednisone and beclomethasone for treatment of asthma. N Engl J Med. 1979; 300:986.

44. Clark TJH. Beclomethasone dipropionate treatment of asthma in adults. In: Mygind N, Clark TJH, eds. Topical steroid treatment for asthma and rhinitis. London: Bailliere Tindall; 1980:94-106.

45. Wyatt R, Waschek J, Weinberger M et al. Effects of inhaled beclomethasone dipropionate and alternate-day prednisone on pituitary-adrenal function in children with chronic asthma. N Engl J Med. 1978; 299:1387-92.

46. Vaz R, Senior B, Morris M et al. Adrenal effects of beclomethasone inhalation therapy in asthmatic children. J Pediatr. 1982; 100:660-2.

47. Toogood JH, Lefcoe NM, Haines DSM et al. A graded dose assessment of the efficacy of beclomethasone dipropionate aerosol for severe chronic asthma. J Allergy Clin Immunol. 1977; 59:298-308.

48. Toogood JH, Jennings B, Greenway RW et al. Candidiasis and dysphonia complicating beclomethasone treatment of asthma. J Allergy Clin Immunol. 1980; 65:145-53.

49. Chiu JT, Wells I, Novey HS. Incidence of fungal precipitins in patients treated with beclomethasone dipropionate aerosol. Ann Allergy. 1981; 46:137-9.

50. Milne LJR, Crompton GK. Beclomethasone dipropionate and oropharyngeal candidiasis. Br Med J. 1974; 3:797-8.

51. Stein MR, Shay SS, Jacobson K. Monilial esophagitis in asthmatic patients treated with beclomethasone. J Allergy Clin Immunol. 1979; 63:172.

52. Imbeau SA, Geller M. Aerosol beclomethasone treatment of chronic severe asthma—a one-year experience. JAMA. 1978; 240:1260-2.

53. Klotz LR, Klotz SD, Moeller RK. The use of beclomethasone dipropionate inhaler complicated by the development of an eosinophilic pneumonia reaction. Ann Allergy. 1977; 39:133-6.

54. Hudgel DW, Spector SL. Pulmonary infiltration with eosinophilia—recurrence in an asthmatic patient treated with beclomethasone dipropionate. Chest. 1977; 72:359-60.

55. Friedman H, Tworag JF, Voss HE et al. Eosinophilic pneumonia in association with the use of beclomethasone dipropionate aerosol. J Allergy Clin Immunol. 1978; 61:150.

56. Brogden RN, Pinder RM, Sawyer PR et al. Beclomethasone dipropionate inhaler: a review of its pharmacology, therapeutic value and adverse effects. Part I: asthma. Drugs. 1975; 10:166-210.

57. Bryant DH, Pepys J. Bronchial reactions to aerosol inhalant vehicle. Br Med J. 1976; 1:1319-20.

58. Kass I, Nair SV, Patil KD. Beclomethasone dipropionate aerosol treatment of steroid-dependent asthmatic patients: an assessment of 18 months of therapy. Chest. 1977; 71:703-7.

59. Lee-Hong E, Collins-Williams C. The long-term use of beclomethasone dipropionate for the control of severe asthma in children. Ann Allergy. 1977; 38:242-4.

60. Cooper EJ, Grant IWB. Beclomethasone dipropionate aerosol in treatment of chronic asthma. Q J Med. 1977; 46:295-308.

61. USPDI: 1983 drug information for the health care provider. Johnson KW, ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1983; I:177-8.

62. Freigang B. New method of beclomethasone aerosol administration to children under 4 years of age. Can Med Assoc J. 1977; 117:1308-9.

63. Freigang B. Long-term follow-up of infants and children treated with beclomethasone aerosol by a special inhalation device. Ann Allergy. 1980; 45:13-7.

64. Soderberg-Warner M, Siegel S, Katz R et al. Treatment of chronic childhood asthma with beclomethasone dipropionate aerosols (BDP). IV. long-term effects on growth. J Allergy Clin Immunol. 1979; 63:164.

65. Godfrey S, Balfour-Lynn L, Tooley M. A three- to five-year follow-up of the use of the aerosol steroid beclomethasone dipropionate, in childhood asthma. J Allergy Clin Immunol. 1978; 62:335-9.

66. Godfrey S. Beclomethasone dipropionate treatment of childhood asthma. In: Mygind N, Clark TJH, eds. Topical steroid treatment for asthma and rhinitis. London: Bailliere Tindall; 1980:123-36.

67. Anon. Management of asthma in the child aged under 6 years. BMJ. 1981; 283:863-4.

68. Schering Corporation. Vancenase^® prescribing information. Kenilworth, NJ; 1981 Sep.

69. Glaxo Inc. Beconase^® prescribing information. Fort Lauderdale, FL; 1981 Aug.

70. Brown HM, Storey G. Beclomethasone dipropionate aerosol in long-term treatment of perennial and seasonal asthma in children and adults: a report of five-and-half years exper