Beclomethasone (Systemic, Oral Inhalation)

AHFS Class: Adrenals (68:04)

VA Class: NT200
Molecular Formula: C₂₈H₃₇ClO₇

View the associated AHFS monograph.

Brands: QVAR^®

Introduction

Synthetic corticosteroid;^{2 149} minimal mineralocorticoid activity.^{149 a}

Uses

Asthma

Used 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}

Should not be used in the treatment of nonasthmatic bronchitis.^{1 28 112 113 144}

Chronic Obstructive Pulmonary Disease

Efficacy in 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.

Inflammatory Conditions of the GI Tract

Has been used as an oral solution³⁵ or rectal suspension³⁶ (these dosage forms not commercially available in the US) in the management of inflammatory diseases of the GI tract† (e.g., inflammatory bowel disease†, eosinophilic gastroenteritis†).^{35 36} However, the role of beclomethasone dipropionate in the management of inflammatory conditions of the GI tract remains to be established.^{35 36}

Dosage and Administration

General

• Adjust dosage carefully according to individual requirements and response.^{1 2 61 83 112 113 144 149}

• After a satisfactory response is obtained, decrease dosage gradually to the lowest dosage that maintains an adequate clinical response.^{149 150} Achieve the lowest effective dosage, particularly in children, since inhaled corticosteroids have the potential to affect growth. (See Pediatric Use under Cautions.)^{149 150}

• When switching from systemic corticosteroids to orally inhaled beclomethasone dipropionate, asthma should be reasonably stable before initiating treatment with the oral inhalation.^{1 2 112 113 144 149}

• Initially, administer the aerosol concurrently with the maintenance dosage of the systemic corticosteroid.^{1 2 112 113 144 149} After about 1 week, gradually withdraw the systemic corticosteroid.^{1 2 112 113 144 149}

• Death has occurred in some individuals in whom systemic corticosteroids were withdrawn too rapidly.^{1 2 112 113 144 149} (See Withdrawal of Systemic Corticosteroid Therapy under Warnings.)

• If exacerbations of asthma occur after transfer to oral inhalation therapy, administer short courses of systemic corticosteroids, then taper dosage as symptoms subside.^{1 2 112 113 144 149}

Administration

Administer by oral inhalation using an oral aerosol inhaler.¹⁴⁹

Test-spray inhalation aerosol (2 times) before first use or whenever the aerosol has not been used for prolonged periods (>10 days).^{149 b}

Oral inhalation aerosol is formulated as a solution, which does not require shaking.¹⁴⁹

Exhale slowly and completely and place the mouthpiece of the inhaler well into the mouth with the lips closed firmly around it; keep the tongue below the mouthpiece.^b Inhale slowly and deeply through the mouth while actuating the inhaler.^b Hold the breath for as long as possible (about 5–10 seconds), withdraw the mouthpiece, and exhale gently.^b If additional inhalations are required, repeat the procedure.^b

Rinse the mouth thoroughly with water to remove drug deposited in the oropharyngeal area.^{33 48 49 52 59 149 b}

Clean the mouthpiece weekly^b using a clean, dry tissue or cloth.^b Do not wash or place any part of the inhaler canister in water.^b

Dosage

Available as beclomethasone dipropionate; dosage expressed in terms of the salt.^{b 149}

Oral inhalation aerosol releases 50 or 100 mcg of beclomethasone dipropionate, and delivers 40 or 80 mcg, respectively, from the actuator (mouthpiece) per metered spray.¹⁴⁹

Asthma.

> Oral Inhalation— Children 5–11 years of age receiving bronchodilators alone or inhaled corticosteroids previously: Initially, 40 mcg twice daily.¹⁴⁹ If required, dosage may be increased to a maximum 80 mcg twice daily.¹⁴⁹ Children ≥12 years of age receiving bronchodilators alone previously: Initially, 40–80 mcg twice daily.¹⁴⁹ If required, dosage may be increased to a maximum 320 mcg twice daily.¹⁴⁹ Children ≥12 years of age receiving inhaled corticosteroids previously: Initially, 40–160 mcg twice daily. If required, dosage may be increased to a maximum 320 mcg twice daily.

Asthma.

> Oral Inhalation— In adults receiving bronchodilators alone previously: Initially, 40–80 mcg twice daily.^{149 149} If required, dosage may be increased to a maximum 320 mcg twice daily.¹⁴⁹ Adults receiving inhaled corticosteroids: Initially, 40–160 mcg twice daily. If required, dosage may be increased to a maximum of 320 mcg twice daily.

Prescribing Limits

Asthma.

> Oral Inhalation— Children 5–11 years of age: Maximum 80 mcg twice daily.¹⁴⁹ Children ≥12 years of age: Maximum 320 mcg twice daily.¹⁴⁹

Asthma.

> Oral Inhalation— Maximum 320 mcg twice daily.¹⁴⁹

Special Populations

Consider initial dosages at the lower end of the usual range due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹⁴⁹

Cautions

Contraindications

• 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.

• Known hypersensitivity to the drug or any ingredient in the formulation.^{1 2 112 113 144 149}

Warnings/Precautions

Withdrawal Of Systemic Corticosteroid Therapy. Possible corticosteroid withdrawal symptoms (e.g., joint pain, muscular pain, lassitude, depression);^{1 2 112 113 144 149} acute adrenal insufficiency;^{1 2 112 113 144} life-threatening exacerbation of asthma;^{1 2 112 113 144 149} pulmonary infiltrates with eosinophilia;^{1 112 113} or symptomatic exacerbation of allergic conditions^{1 2 27 44 52 58 70 112 113 144} if prolonged systemic corticosteroid therapy is replaced with oral inhalation corticosteroid therapy.^{1 2 112 113 144 149} Such symptoms may be observed especially in patients maintained on ≥20 mg of prednisone (or its equivalent) daily and particularly during the later part of the transfer.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

Taper the dosage of the systemic corticosteroid, and carefully monitor patients during dosage reduction for objective signs of adrenal insufficiency (e.g., hypotension, weight loss).^{1 2 112 113 144 149}

Immunosuppressed Patients. Increased susceptibility to infections in patients who are taking immunosuppressant drugs compared with healthy individuals.^{113 134 135 136 137 138 139 140 141 142 143 144} 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}

Exposure to varicella and measles should be avoided in previously unexposed patients.^b If exposure to varicella (chickenpox) or measles occurs in susceptible patients, consider administering varicella zoster immune globulin (VZIG) or immune globulin (IG) respectively.^b Consider treatment with an antiviral agent if varicella develops.^b

Concomitant Therapy. Use with caution in patients receiving systemic prednisone for any disease.^{45 47} Concomitant use with prednisone in an alternate-day or daily dosing regimen could increase the likelihood of HPA-axis suppression compared with therapeutic dosages of either drug alone.^{45 47}

Resume systemic corticosteroids during periods of stress (e.g., infection, trauma, surgery) or a severe asthma exacerbation in patients who were attempting a switch from systemic to orally inhaled corticosteroid therapy.¹⁴⁹

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression. Avoid higher than recommended dosages of the drug, since suppression of HPA function may occur.¹⁴⁹ If higher than recommended dosages are used, carefully consider the relative risks of adrenal suppression and potential therapeutic benefits.¹⁴⁹ Recommended dosages of orally inhaled drug provide less than normal physiologic amounts of glucocorticoid systemically and do not provide mineralocorticoid activity.¹⁴⁹ Orally inhaled drug will not compensate for insufficient endogenous cortisol production caused by previous systemic corticosteroid therapy.¹⁴⁹

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, especially in asthmatic patients with hyperactive airways.^{20 25 57 58 101 131 132 133}

If bronchospasm occurs, treat immediately with a short-acting bronchodilator, and discontinue treatment with beclomethasone dipropionate and institute alternative therapy.¹⁴⁹

Infection. Use 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 2 100 144 149}

Immediate or delayed hypersensitivity reactions, including bronchospasm, anaphylactic/anaphylactoid reactions,² urticaria, angioedema, and rash reported rarely.^{1 2 112 113 149}

Systemic Corticosteroid Effects. Possible signs and symptoms of Cushing’s syndrome (e.g., hypertension, glucose intolerance, cushingoid features) in patients who are particularly sensitive to corticosteroid effects or when usual dosages of the drug are exceeded.^{100 149}

Carefully monitor neonates exposed to prenatal corticosteroids for manifestations of hypoadrenalism.^{2 61 112 144 149}

Ocular Effects. Glaucoma, increased intraocular pressure, and cataracts reported rarely.¹⁴⁹

Other Effects. Unknown long-term, systemic, and local effects of the drug in humans, particularly developmental or immunologic processes in the mouth, pharynx, trachea, and lung.¹⁴⁹

Pregnancy.

Category C.¹⁴⁹ (See Systemic Corticosteroid Effects under Cautions.)

Lactation. Distributed into milk.^{144 149} Discontinue nursing or the drug.^{144 149}

Pediatric Use. Safety and efficacy not established in children <5 years of age.¹⁴⁹ No overall differences in the pattern, severity, or frequency of adverse events in children 5–12 years of age compared with those in adults.¹⁴⁹ Monitor periodically children receiving prolonged therapy for possible adverse effects on growth and development.^{62 149}

Geriatric Use. Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹⁴⁹

Use caution due to the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy in geriatric patients.¹⁴⁹ (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

Headache, pharyngitis, upper respiratory tract infection, rhinitis.¹⁴⁹

Interactions

Metabolized by CYP3A4.¹⁴⁹

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: potential pharmacokinetic interaction (increased plasma beclomethasone dipropionate concentrations).^a

Inducers of CYP3A4: potential pharmacokinetic interaction (decreased plasma beclomethasone dipropionate concentrations).^a

Specific Drugs

Pharmacokinetics

Absorption

Absorbed into circulation following oral inhalation, ¹⁴⁹ with peak plasma concentrations usually attained at 0.5 hour.¹⁴⁹ After oral inhalation, 51–60% of the dose is deposited in the respiratory tract.¹⁵⁴

Relief of respiratory symptoms usually is evident within 24 hours; however, about 1–4 weeks of continuous therapy may be required for optimum effectiveness.¹⁴⁹

Distribution

Glucocorticoids cross the placenta and are distributed into milk.^{144 149 a} No evidence of tissue storage of parent drug or metabolites.¹⁴⁹

Elimination

Metabolized to active metabolites via CYP3A4.¹⁴⁹

Beclomethasone dipropionate and its metabolites eliminated principally in feces and to a lesser extent in the urine (<10%).¹⁴⁹

2.8 hours.¹⁴⁹

Stability

Storage

25°C (may be exposed to 15–30°C).¹⁴⁹

Do not puncture aerosol containers, use or store near heat or an open flame, expose to temperatures >49°C, or place into a fire or incinerator for disposal.^{1 112 113 144 149}

Actions

• Potent glucocorticoid and minimal mineralocorticoid activity.^{149 a c} At recommended dosages, provides less than normal physiologic amounts of glucocorticoid systemically.¹⁴⁹

• Inhibits inflammatory cells and release of inflammatory mediators in the respiratory tract.¹⁴⁹ Improves lung function (e.g., forced expiratory volume in 1 second [FEV₁], morning peak expiratory flow).¹⁴⁹

• Principal sites of action are the bronchi and bronchioles.¹⁴⁹

• May reduce the following: number of mediator cells (basophils, leukocytes, and mast cells) at the epithelial level, number of eosinophils, sensitivity of sensory nerves to mechanical stimuli, secretory response to cholinergic receptor stimulation, and fibroblast activity.^c

• May inhibit capillary dilation and permeability, stabilize lysosomal membranes, and prevent subsequent release of proteolytic enzymes.^c

Advice to Patients

• Importance of providing the patient a copy of the manufacturer's patient information.¹⁴⁹

• Importance of understanding of proper storage, preparation, and administration techniques.^{149 b}

• Advise that oral inhalation must be used at regular intervals to be therapeutically effective.^{100 103 144 149}

• Importance of understanding that although improvement may occur within the first 24 hours, at least 1–4 weeks of continuous therapy may be required for optimal effectiveness.^{1 2 61 77 100 112 113 144 149}

• Importance of rinsing the mouth after inhalation and not exceeding the recommended dosage.^{1 2 71 112 113 144 149 b}

• Importance of not using orally inhaled beclomethasone dipropionate as a bronchodilator or for emergency use (e.g., relief of acute bronchospasm).^{1 2 103 112 113 144 149}

• Importance of contacting a clinician immediately when asthmatic attacks that are not controlled by bronchodilator therapy occur.^{1 2 112 113 149}

• Advise patients being transferred from systemic corticosteroid to beclomethasone dipropionate oral inhalation therapy to carry special identification (e.g., card, bracelet) indicating the need for supplementary systemic corticosteroids during periods of stress. (See Concomitant Therapy under Cautions.)^{1 2 112 113 144 149}

• Importance of immunosuppressed patients avoiding exposure to certain infections (e.g., chickenpox, measles) and if exposed, of immediately consulting their clinician.^{113 134 135 136 142 143 144 149}

• Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.¹⁴⁹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹⁴⁹

• Importance of advising patients of other important precautionary information.¹⁴⁹ (See Cautions.)

Preparations

Beclomethasone Dipropionate

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

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

© Copyright, July 2005, American Society of Health-System Pharmacists, Inc. 7272 Wisconsin Avenue, Bethesda, MD 20814.

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