Prescription Drugs

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 mcg 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 mcg per day either by oral aerosol or intramuscular injection form. Immediate suppression of plasma cortisol concentrations was observed after single doses of 4000 mcg of beclomethasone dipropionate. Suppression of HPA function (reduced early morning plasma cortisol levels) has been reported in adult patients who received 1600-mcg 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%.

DESCRIPTION Beclomethasone dipropionate is an anti-inflammatory corticosteroid having the chemical name 9-chloro-11b,17,21-trihydroxy-16b-methylpregna-1,4-diene-3,20-doine17,21-dipropionate. 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 (beclomethasone nasal) Nasal Inhaler: Each actuation delivers from the compact actuator a quantity of clathrate equivalent to 42 mcg 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 mcg of beclomethasone dipropionate. Each bottle of Beconase (beclomethasone nasal) AQ nasal spray delivers at least 200 metered doses.

INDICATIONS 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. 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 mcg) in each nostril two to four times a day (total dose, 168 to 336 mcg per day). Patients can often be maintained on a maximum dose of one inhalation in each nostril three times a day (252 mcg per day). Children 6 to 12 Years of Age: The usual dosage is one inhalation in each nostril three times a day (252 mcg 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 mcg) in each nostril twice a day (total dose, 168 to 336 mcg 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 mcg or those with more severe symptoms may use 336 mcg (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.

PATIENT INFORMATION 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.

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

SIDE EFFECTS 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). DRUG INTERACTIONS No information provided.