Beclometasone Dipropionate
(British Approved Name Modified, rINNM)
Drug Nomenclature
Pharmacopoeias. In China, Europe, International, and Japan US allows either the anhydrous or monohydrate form. Europe also includes a separate monograph for the monohydrate.
European Pharmacopoeia, 6th ed. (Beclometasone Dipropionate, Anhydrous). A white or almost white, crystalline powder. Practically insoluble in water sparingly soluble in alcohol freely soluble in acetone. Protect from light.
European Pharmacopoeia, 6th ed. (Beclometasone Dipropionate Monohydrate). A white or almost white powder. Practically insoluble in water sparingly soluble in alcohol freely soluble in acetone. Protect from light.
The United States Pharmacopeia 31, 2008 (Beclomethasone Dipropionate). It is anhydrous or contains one molecule of water of hydration. A white to cream white, odourless powder. Very slightly soluble in water freely soluble in alcohol and in acetone very soluble in chloroform.
Adverse Effects, Treatment, Withdrawal, and Precautions
As for corticosteroids in general. Adrenal suppression may occur in some patients treated with high-dose long-term inhalation therapy for asthma. It has been stated that in the majority of patients no significant suppression is likely to occur when total daily doses of less than 1.5 mg are used (but see Adrenal Suppression, below).
When applied topically, particularly to large areas, when the skin is broken, or under occlusive dressings, corticosteroids may be absorbed in sufficient amounts to cause systemic effects. Systemic absorption may also follow nasal use, particularly after high doses or prolonged treatment.
Adrenal suppression. The problem of adrenal suppression with corticosteroids is discussed. Listed below are some references and correspondence concerning adrenal suppression due to beclometasone inhalation therapy in some cases occurring with doses below 1.5 mg daily. However, one study found that function of the hyp othalamic-pituitary-adrenal axis remained normal in most patients at beclometasone doses below 3 mg daily.
Candidiasis. Results of a study involving 229 asthmatic children indicated that the presence of a sore throat or a hoarse voice was not related to the presence of Candida or to treatment with inhaled beclometasone. The occurrence of only one clinical case of oral candidiasis in 129 of the children receiving beclometasone confirmed previous observations that it is an uncommon finding in children compared with the reported incidence of between 4.5 and 13% in adults. The incidence of colonisation with Candida was greater in those children who received corticosteroids than in those who did not but was not affected by either the dose or type of inhaler used.
Effects on the bones. The adverse effects of corticosteroids in general on bones are discussed. Studies in healthy subjects have shown that inhaled beclometasone dipropionate can suppress bone metabolism. These studies measured biochemical markers such as serum-osteocalcin concentrations, serum alkaline phosphatase activity, and urinary hydroxyproline-creatinine ratio, over short periods of time. Another study found that markers of collagen turnover, but not osteocalcin, were reduced by beclometasone or budesonide 800 micrograms daily in mildly asthmatic children. Results are difficult to interpret since osteocalcin concentrations are reduced in patients with asthma regardless of treatment, and it is uncertain whether significant bone loss does occur in practice. One 12-month study in adults with asthma found that biochemical markers showed suppressed bone formation from inhaled beclometasone, and that there was some loss of bone mineral density from the hip. This study also found that inhaled fluticasone, in equivalent therapeutic doses, may have less adverse effect on bone. Another, smaller, study found no adverse effects from beclometasone or fluticasone on bone mass or metabolism. In a study of asthmatic children, comparing those treated with inhaled budesonide with those who received no corticosteroids, an average daily dose of about 500 micrograms budesonide for 3 to 6 years did not adversely affect bone density and mineral measures.
Effects on growth. Meta-analysis of 3 eligible studies (out of 92 examined) concluded that inhaled beclometasone therapy at a dose of 400 micrograms daily may cause a 1.54 cm/year decrease in growth in children with mild to moderate asthma. The long-term effects of treatment are unknown, and therefore it is not clear whether catch-up growth will occur on stopping therapy. The lowest possible dose of corticosteroid therapy should be used in asthma, and growth should be monitored. There is also evidence that long-term intranasal beclometasone for the treatment of allergic rhinitis can slow growth in children the effect on final height is unknown. For further details of the effects of corticosteroids on growth.
Effects on the lungs. Pulmonary eosinophilia has occurred in patients treated with inhaled beclometasone.
Hypersensitivity. There have been reports of asthmatic reactions to beclometasone dipropionate inhalations, possibly associated with materials used in their formulation, or with the containers.
Reformulation. Reformulation of some metered-dose inhalers to use a chlorofluorocarbon (CFC)-free propellant has resulted in a change of efficacy. One CFC-free product (Qvar, UK) is reported to be effective at about half the dose required with the standard product (see Uses and Administration, below) and the UK CSM has issued a reminder of the need for dosage reduction when converting from the conventional formulation to this product. An open-label, crossover study in healthy subjects also found higher beclometasone plasma concentrations after use of another brand (Beclozone, Eire) of CFC-free product. However, this dose reduction does not apply to all CFC-free formulations of beclometasone. A review concluded that good studies on the bioequivalence between the reference beclometasone preparation and the newer CFC-free formulations are not available.
Interactions
The interactions of corticosteroids in general are described.
Pharmacokinetics
For a brief outline of the pharmacokinetics of corticosteroids. Beclometasone is stated to be readily absorbed from sites of local application, and rapidly distributed to all body tissues. It is metabolised principally in the liver, but also in other tissues including gastrointestinal tract and lung enzymatic hydrolysis rapidly produces the monopropionate (which has some glucocorticoid activity), and, more slowly, the free alcohol, which is virtually devoid of activity. Only a small proportion of an absorbed dose is excreted in urine, the remainder being excreted in the faeces mainly as metabolites.
Uses and Administration
Beclometasone dipropionate is a corticosteroid with mainly glucocorticoid activity that is stated to exert a topical effect on the lungs without significant systemic activity at recommended doses (but see Adrenal Suppression under Adverse Effects, above). It is used by inhalation, generally from a metered-dose aerosol, for the prophylaxis of asthma (see below).
Many formulations are now available, with differing dosage regimens, and the appropriate product literature should be consulted before starting therapy or changing to another formulation. Furthermore in the UK the doses of beclometasone dipropionate for asthma and rhinitis are expressed in units of 50 micrograms or multiples thereof (dose supplied into the mouthpiece per actuation) whereas in the USA the dose-unit is 42 micrograms or multiples thereof (dose emitted from the mouthpiece) recommended doses therefore appear somewhat lower in the USA than the UK doses given below, although in practical terms there is probably no difference.
In the UK the adult dosage of the conventional aerosol and some dry powder inhalers is usually 400 micrograms daily, inhaled in 2 to 4 divided doses for maintenance treatment if necessary, 600 to 800 micrograms may be inhaled daily initially, subsequently adjusted according to the patient’s response. In patients with severe asthma or in those showing only a partial response to standard inhalation doses, high-dose inhalation therapy may be considered doses of 1 mg daily (250 micrograms four times daily or 500 micrograms twice daily) may be used and may be increased to 1.5 to 2 mg daily (500 micrograms three or four times daily) if necessary a maximum of 2 mg daily should not be exceeded. In children, 50 or 100 micrograms may be inhaled 2 to 4 times daily according to the response or alternatively, 100 or 200 micrograms may be inhaled twice daily.
Although beclometasone dipropionate is generally inhaled in aerosol form, inhalation capsules or discs containing powder for inhalation are available for patients who experience difficulty in using the aerosol. Owing to differences in the relative bioavailability to the lungs a 100-microgram dose from an inhalation capsule or disc is approximately equivalent in activity to a 50-microgram dose from a conventional aerosol. Recommended maintenance doses of beclometasone dipropionate from inhalation capsules or discs are therefore higher. 200 micrograms inhaled 3 or 4 times daily or 400 micrograms inhaled twice daily for adults, and 100 micrograms inhaled 2 to 4 times daily or 200 micrograms inhaled twice daily for children. Up to 800 micrograms twice daily may be inhaled if necessary in adults requiring high-dose therapy.
In some countries beclometasone dipropionate is now available as a CFC-free aerosol. Because of changes in particle size the dose required from some such inhalers may be lower than that from a conventional aerosol: typical UK doses for one product (Qvar) range from 100 to 200 micrograms daily in mild asthma to 400 to 800 micrograms daily in severe asthma, given as 2 divided doses.
Inhalation of nebulised beclometasone dipropionate has also been used in the management of asthma in children.
Beclometasone dipropionate is also used as a nasal spray in the prophylaxis and treatment of allergic and non-allergic rhinitis. Usual doses are 100 micrograms in each nostril twice daily or 50 micrograms in each nostril 3 or 4 times daily a total of 400 micrograms daily should not generally be exceeded. A dose of 50 micrograms in each nostril twice daily may be sufficient for prophylaxis. The nasal spray is also used to prevent recurrence of nasal polyps after surgical removal. Beclometasone dipropionate is also used topically in the treatment of various skin disorders. It is generally applied as a cream or ointment containing 0.025%. Beclometasone salicylate has also been used topically. For recommendations concerning the correct use of corticosteroids on the skin, and a rough guide to the clinical potencies of topical corticosteroids.
Adenoidal hypertrophy. Although normally managed by surgery (or if less severe simply by symptomatic relief) adenoidal hypertrophy in children was reported to respond to aqueous nasal beclometasone 336 micrograms daily in an 8-week crossover study. Improvements in adenoidal obstruction and symptom scores were enhanced in a subsequent 16-week follow-on study using 168 micrograms daily. Another similar study, of an initial 4-week crossover period followed by 24 weeks of open-label treatment, found symptomatic improvements in about half of the patients, and at 100 weeks there was a decrease in the rate of adenotonsillectomy in children who had responded to beclometasone compared with nonresponders.
Asthma. Corticosteroids and beta2-adrenoceptor agonists form the cornerstone of the management of asthma. Patients requiring only occasional relief from symptoms may be managed with an inhaled short-acting beta2 agonist, and an inhaled corticosteroid such as beclometasone is added if symptomatic relief is needed more than once daily. In more severe asthma other drugs may be added (combination with a long-acting beta2 agonist may have synergistic benefits), or the dose of inhaled corticosteroid may be increased.
High-dose regimens may pose problems of compliance if beclometasone must be inhaled several times daily. However, one study found once-daily inhalation to be as effective as the same dose divided into 2 daily inhalations in short-term control of moderate asthma. Also there have been doubts that increasing the dose of inhaled beclometasone brings about increased benefits, but guidelines and clinical practice suggest that improved control can often be achieved by increasing the dose. A systematic review noted that while there was little evidence of an effect of dose titration above 400 micrograms daily in those with mild to moderate asthma, evidence was lacking in patients with more severe disease (who are more likely to be given high-dose therapy), and studies were needed to resolve the question. Inhalation of beclometasone dipropionate as a nebulised solution has been found to be useful in the management of severe asthma in children aged 2 years or under previously unresponsive to other drugs Nebulised beclometasone dipropionate was also effective in the management of recurrent episodes of bronchopulmo-nary obstruction following bronchiolitis in children under 2 years of age. However, in other reports nebulised beclometasone dipropionate, although more effective than saline in pre-school children, produced a response less than that usually observed with inhalation of beclometasone from an aerosol or capsules, or no benefit at all. This may have been due to beclometasone somehow failing to reach the lungs. In pre-school children able to use a spacer device with a metered aerosol, intermittent therapy with high-dose beclometasone dipropionate, given at the first sign of symptoms, reduced the severity of acute episodic asthma.
Chronic obstructive pulmonary disease. For discussion of the value of inhaled corticosteroids in chronic obstructive pulmonary disease.
Cough. In children with recurrent cough inhalation of beclometasone 200 micrograms twice daily from a conventional aerosol or salbutamol 200 micrograms twice daily had no effect on cough frequency or severity. However, in another study of 200 adults, use of beclometasone, salbutamol, or sodium cromoglicate (all in aerosol formulation) given 15 minutes before anaesthesia, significantly decreased coughing caused by fentanyl when compared with placebo. Of the 50 patients given beclometasone, none experienced coughing.
Graft-versus-host disease. Beclometasone is under investigation for its topical effect in the treatment of intestinal graft-versus-host disease (GVHD). A study in patients with acute intestinal GVHD after bone marrow transplantation (see Haematopoietic Stem Cell Transplantation) found that addition of oral beclometasone to prednisolone therapy was associated with a greater proportion of durable responses after 30 days. Repeated courses may be needed in some patients to achieve and maintain response, but prolonged therapy appears to be feasible.
Inflammatory bowel disease. Beclometasone 500 micrograms given nightly as an enema was as effective as betamethasone 5 mg enemas in the treatment of acute attacks of distal ulcerative colitis. Although betamethasone produced slightly superior histological improvement and faster disappearance of blood from the stools, systemic adverse effects observed with betamethasone therapy were absent in patients treated with beclometasone.
Comparisons of beclometasone dipropionate enemas (3 mg) with prednisolone sodium phosphate enemas (30 mg) or me-salazine enemas (1 g) found them to be equally effective. Treatment was well tolerated. Beclometasone dipropionate has also been investigated for the oral treatment of ulcerative colitis. For a review of the management of inflammatory bowel disease, including the role of corticosteroids.
Preparations
British Pharmacopoeia 2008: Beclometasone Cream; Beclometasone Nasal Spray; Beclometasone Ointment; Beclometasone Powder for Inhalation; Beclometasone Pressurised Inhalation
Proprietary Preparations
Australia:: Aldecin † Becloforte † Beconase Beconase Hayfever Becotide Qvar
Austria: Aerocortin Beclomet Beconase Becotide
Belgium: Beclometatop Beclophar Beconase Becotide † Qvar
Brazil: Alerfin Beclosol Genii Miflasona
Canada: Gen-Beclo Propaderm Qvar Rivanase
Czech Republic: Aldecin Beclazone † Becloforte Beclomet Becodisks Beconase Becotide Clenil Ecobec Miflason-P Nasobec
Denmark: AeroBec Beclomet Beconase
Finland: AeroBec Beclomet Beclonasal Beconase Becotide †
France: Asmabec Beclo-Rhino Beclojet Beclone Beclospin Beconase Becotide Bemedrex Ecobec Humex Rhume des Foins Niflasone Nexxair Prolair Qvar Spir †
Germany: AeroBec Beclo Beclo Siozwo † Beclobreathe Beclohexal Beclomet Beclorhinol Becloturmant Beconase Aquosum Bronchocort Junik ratioAllerg Rhinivict Sanasthmax Sanasthmyl Ventolair Viarox †
Hungary: Aldecin † Beclomet † Beclonasal Ecobec †
India: Beclate
Indonesia: Beclomet Beconase Becotide Geniderm
Ireland: AeroBec † Asmabec Beclazone Beclo-Rhino Becodisks † Beconase Becotide Nasobec Qvar
Israel: Becloforte Beconase † Becotide † Rhinocort Viarex
Italy: Becotide Becotide A † Bronco-Turbinal † Clenil Genilexx Clipper Klostenal Nenaderm Simplex Prontinal Rino Clenil Topster Propaderm Rhinocort Salcoat
Malaysia: Atomase † Beclate Beclazone Becloforte † Beclomet Beconase Becotide † Clenil Qvar
Mexico: Beclazone Beconase Becotide Dobipro Riferina
The Netherlands: AeroBeec Aldecin Beclodin Becloforte Beconase Becotide Clenil Qvar Viarin
Norway: AeroBec Beclomet Becotide
New Zealand: Alanase Atomase Atomide † Beclazone Beconase Hayfever Niflasone † Qvar Respocort
Philippines: Qvar
Poland: Becodisk Cortare Nasobec
Portugal: Beclotaide Beconase Clenil Ecobec
Russia: Aldecin Beclazone Becloforte Beclojet Becodisk Beconase † Becotide Clenil Nasobec
Spain: Asmabec † Beclo Asma Beclo Rino Becloenema Becloforte Beclomet Beclosona Beconase Becotide Betsuril † Broncivent † Decasona † Dereme Nenaderm Simple Qvar † Recto Nenaderm N †
Sweden: AeroBec Beclomet Becotide
Switzerland: AeroBec † BECeco Becloforte † Beclomet † Beclonarin Becodisk Beconase Beconasol Becotide †
Thailand: Atomase Becloforte † Beclomet Becodisk † Beconase Becotide † Bemase Clenil Rino Clenil
Turkey: Becloforte Becodisks Becotide Bekamet Beklazon Filair
UAE: Beclohale
UK: AeroBec Asmabec Beceze Beclazone Becloforte † Beclogen Becodisks Beconase Becotide † Clenil Clipper Filair Hayfever Relief Nasal-Beec Nasobec Pollenase Nasal Propaderm † Pulvinal Beclometasone Dipropionate Qvar Vivabec
USA: Beclovent Beconase Qvar Vancenase †
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